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CAS No. : | 106-22-9 | MDL No. : | MFCD00002935 |
Formula : | C10H20O | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | QMVPMAAFGQKVCJ-UHFFFAOYSA-N |
M.W : | 156.27 | Pubchem ID : | 8842 |
Synonyms : |
(±)-β-Citronellol;Dihydrogeraniol;(±)-Citronellol
|
Num. heavy atoms : | 11 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.8 |
Num. rotatable bonds : | 5 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 50.87 |
TPSA : | 20.23 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -4.48 cm/s |
Log Po/w (iLOGP) : | 2.72 |
Log Po/w (XLOGP3) : | 3.91 |
Log Po/w (WLOGP) : | 2.75 |
Log Po/w (MLOGP) : | 2.7 |
Log Po/w (SILICOS-IT) : | 2.51 |
Consensus Log Po/w : | 2.92 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.94 |
Solubility : | 0.179 mg/ml ; 0.00114 mol/l |
Class : | Soluble |
Log S (Ali) : | -4.03 |
Solubility : | 0.0145 mg/ml ; 0.0000926 mol/l |
Class : | Moderately soluble |
Log S (SILICOS-IT) : | -2.21 |
Solubility : | 0.964 mg/ml ; 0.00617 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 2.0 |
Synthetic accessibility : | 2.61 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H317-H319 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With N,N-diphenylchloromethyleneiminium chloride; triethylamine In dichloromethane for 3h; Ambient temperature; | |
82% | With 4-methoxy-benzoyl chloride; N,N-dimethyl-formamide In 1,4-dioxane at 80℃; for 2h; Sealed tube; | 4.4.6.5 Synthesis of rac-1-Chloro-3,7-dimethyl-6-octene (citronellyl chloride, 237) According to general procedure II (chapter 2.1.2) rac-3,7-dimethyl-6-octen-1-ol(137, 247 ilL, 252 mg, 2.00 mmol, 1.00 equiv, 95% purity), DMF (62 ilL, 0.80 mmol,59 mg, 40 mol%), dioxane (2 mL, 1 M) and 4-MeD BzCI (328 ilL, 414 mg,2.40 mmol, 1.2 equiv) were combined at ambient temperature and allowed to stirfor 2 h at 80 °C. ‘H-N MR of the crude product (440 mg) revealed full conversionand a chloride 237 to ester 337 ratio of 88:12. Finally chromatographic purification on silica gel (mass of crude material/Si02 1:11) with Et20/nPen 1:99 lead to the isolation of chloride 237 as a colorless oil in 82% yield (285 mg, 1.63 mmol).M (C,0H,9C1) = 174.71 g/mol; rf (Si02, Et20/n Pen 1:99) = 0.55; HR-MS (Cl, PH451, [C,0H,9C135]j174.1175 u found 174.1134 u, ([C,0H,7C135]j calc. 172.1019 found 172.1021 u. |
With pyridine; thionyl chloride |
With pyridine; Petroleum ether; phosphorus trichloride | ||
With p-toluenesulfonyl chloride In pyridine at 20℃; for 72h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With Zn(BH4)2(Ph3P)2 In tetrahydrofuran at 20℃; | |
100% | With hydrogen In isopropanol at 90℃; for 0.75h; | |
99% | With trimethylamine-N-oxide; anhydrous sodium formate; C34H44FeN4O4(2+)*2I(1-) In water monomer at 80℃; for 24h; Inert atmosphere; Schlenk technique; | General procedure A for reduction of aldehydes by hydrogen transfer reaction General procedure: In a dried flamed Schlenk tube under argon, the corresponding aldehyde (1 equiv.) and sodiumformate (170 mg, 5 equiv.) were mixed in water (0.5 M). The iron complex Fe4 (5 mg, 2 mol%) and Me3NO (1 mg, 2.5 mol %) were then added. The mixture was stirred and heated at 80°C for 24 h. After cooling-down to room temperature, the resulting solution was quenchedwith a saturated aqueous solution of sodium bicarbonate and extracted three times with ethylacetate. The organic phase was dried over MgSO4, filtrated and concentrated under vacuumto afford the crude product. A purification by flash chromatography on silica gel furnished thealcohol. |
99% | With trimethylamine-N-oxide; (1,4-dimethyl-5,7-diphenyl-1,2,3,4-tetrahydro-6H-cyclopenta[b]pyrazin-6-one) irontricarbonyl complex3; potassium methylate In ethanol at 45 - 60℃; for 24h; Inert atmosphere; Schlenk technique; | General procedure A for chemoselective reduction of aldehydesor C = C bond by hydrogen transfer reaction General procedure: In a driedflamed Schlenk tube under argon, aldehyde or enone (1 equiv.) andpotassium formate (5 equiv.) were added in ethanol (0.5 M) followedby the addition of the iron complex Fe (2 mol%) and trimethylamineN-oxide (2.5 mol%). The mixturewas heated at 45e60 Cfor 24 h. After cooling-down to room temperature, the reactionmixture was hydrolyzed with a saturated aqueous solution of sodiumbicarbonate and extracted three times with ethyl acetate. Theorganic phase was dried over MgSO4, filtrated and the solventevaporated in vacuo to give the crude product, which was purifiedby flash chromatography. |
98% | With (ethylenediamine)[1,2-bis(diphenylphosphino)ethane]ruthenium(II)(bisbenzoate); hydrogen In isopropanol at 90℃; for 3h; Inert atmosphere; Autoclave; | 2 Influence of Nature of Ruthenium Precursor on Catalytic Activity in 3,7-dimethyloct-6-enal (Citronellal) Selective Hydrogenation General procedure: 3,7-dimethyloct-6-enal (8.4 g, 0.05 mol), isopropanol (8.4 g, 100 wt. %), ruthenium catalyst (0.0025 mmol, 0.005 mol.%) and, whenever required tBuOK as additive (28 mg, 0.25 mmol, 0.5 mol.%) were loaded altogether in a 60 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 30 bars hydrogen. It was then heated to 90° C. and hydrogen pressure was maintained to 30 bars for several hours. Upon reaction completion or after 24 h, autoclave was then cooled down to 25° C. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and solvent was removed under vacuum. Crude product was then flash distilled in order to determine the quantity of residues formed during the reaction and yield was calculated based on GC purity of distilled product. |
98% | Stage #1: 3,7-dimethyl-oct-6-enal With [Fe(CO)(1,3-bis(diphenylphosphino)propane)H(NO)]; phenylsilane; triethylamine In tetrahydrofuran at 80℃; for 18h; Schlenk technique; Stage #2: With sodium hydroxide In tetrahydrofuran; methanol; water monomer at 20℃; for 1h; Schlenk technique; | |
97% | With trimethylamine-N-oxide; (N,N,N-trimethyl-2-(5-oxo-4,6-bis(trimethylsilyl)cyclopenta[c]pyrrol-2-(1H,3H,5H)-yl)ethanaminium) iron tricarbonyl; hydrogen In water monomer at 85℃; for 14h; Autoclave; Inert atmosphere; chemoselective reaction; | |
96% | In water monomer; N,N-dimethyl-formamide for 4h; Ambient temperature; | |
96% | With water monomer; antimony(III) chloride; zinc powder In N,N-dimethyl-formamide for 4h; Ambient temperature; | |
96% | With zirconium(IV) hydrous oxide hydroxide; isopropanol at 120℃; for 0.3h; | |
95% | With bis-tri-n-butylstannane In benzene at 80℃; for 8h; | |
95% | With water monomer; nickel (II) chloride; zinc powder In N,N-dimethyl-formamide for 5h; Ambient temperature; | |
95% | With cobalt(II) chloride; zinc powder In water monomer; N,N-dimethyl-formamide for 5h; Ambient temperature; | |
95% | With carbon monoxide; C12H10FeO4; potassium carbonate In water monomer; dimethyl sulfoxide at 100℃; for 20h; Inert atmosphere; | |
95% | With hydrogen In tetrahydrofuran at 150℃; for 12h; Autoclave; chemoselective reaction; | |
94% | With Ba(BH2S3)2 In tetrahydrofuran at 20℃; for 1h; | |
92% | With sodium tetrahydridoborate In water monomer for 0.00833333h; microwave irradiation; | |
92% | With C31H34N2O4P2Ru; hydrogen In neat (no solvent) at 100℃; for 24h; Inert atmosphere; Glovebox; Autoclave; chemoselective reaction; | |
91% | With sodium tetrahydridoborate; water monomer; titanium(IV) dioxide In acetonitrile at 20℃; for 0.05h; regioselective reaction; | |
90% | With anhydrous sodium formate In water monomer at 80℃; for 4h; | |
89% | With tris(triphenylphosphine)ruthenium(II) chloride; formic acid; triethylamine In tetrahydrofuran for 0.5h; Ambient temperature; | |
89% | With Escherichia coli JW0317 for 20h; Enzymatic reaction; | |
89% | With Co-doped ammonia borane In methanol at 20℃; for 0.0833333h; chemoselective reaction; | |
88% | With trans-[OsCl2(1,1'-bis(diphenylphosphino)ferrocene)(2-aminomethylpyridine)]; sodium isopropanolate; isopropanol at 100℃; for 2h; Inert atmosphere; | |
88% | With isopropanol at 90℃; for 20h; | |
87% | With dmap; formic acid; hexarhodium hexadecacarbonyl; carbon monoxide In tetrahydrofuran at 30℃; for 5h; | |
85% | With 2,2'-bi(1,3,6,2-dioxazaborocane); water monomer at 20℃; for 18h; Inert atmosphere; Sealed tube; | |
85% | Stage #1: 3,7-dimethyl-oct-6-enal With lithium aluminium hydride In tetrahydrofuran at 20℃; Stage #2: With water monomer; Potassium sodium tartrate In tetrahydrofuran at 20℃; for 1h; | |
84% | With isopropanol; potassium hydroxide at 85℃; for 10h; | |
80% | With Triethoxysilane at 25℃; for 1h; | |
80% | With potassium fluoride; Triethoxysilane at 25℃; for 1h; | |
79% | With C48H43ClN2P2Ru; ammsnium formate In water monomer; toluene at 90℃; for 9h; Schlenk technique; | 31 Example 31 Transfer hydrogenation in a biphasic system with formate salts as hydride donor on aldehyde substrates The selected aldehyde (2.5 mmol), HCOONH4 (10 mmol, 0.63 g) and complex (e.g. 1 .25 μηιοΙ, 1 mg; S/C = 2000) are transferred into a 50 ml Schlenk tube. Then toluene (1 .2 ml) and water (5 ml) are sequentially added. The biphasic mixture is subjected to four vacuum-argon cycles under vigorous stirring and then put into an oil bath at 90°C for the desired time. The reaction is sampled by removing ~1 ml of the mixture, diethyl ether (4 ml) is added, the organic phase separated, dried over MgS04, filtered and the solvent gently removed under reduced pressure. The crude residue was dissolved with CDCI3 and analyzed by H-NMR. Alternatively, the dried organic fraction is filtered over a short silica pad and the conversion determined by GC analysis. Table 11. TH of aldehydes catalyzed by complexes 13-15 with HC02NH4 in toluene/H20 at 90°C Aldehyde Complex S/C Substrate NH4-formate Time Alcohol By- molar molar;equivalents (h) (%) products (%L_ 13 5000 0.5 1 ; 2 16 60 0 13 5000 0.5 1 ; 2 22 76 0 14 5000 0.5 1 ; 2 15 96 0 14 5000 0.5 1 ; 2 24 97 0 14 5000 1 .0 1 ; 2 15 86 0 14 5000 1.0 1; 2 24 95 0 14 5000 0.5 1; 4 15 96 0 14 5000 0.5 1; 4 24 96 0 14 5000 1.0 1; 4 15 96 0 14 5000 1.0 1; 4 24 96 0 14 20000 2.0 2; 4 24 94 0 14 20000 2.0 2; 4 48 96 0 15 5000 0.5 1; 2 16 96 0 15 10000 2.0 1; 2 20 86 0 15 20000 2.0 1; 2 40 96 0 14 2000 0.5 1; 2 10 97 0 14 20000 2.0 2; 4 24 62 0 14 20000 2.0 2; 4 48 72 0 14 2000 0.5 2; 4 10 >99 0 14 2000 0.5 1; 2 3.5 >99 0 14 2000 0.5 1; 1.5 9 57: 83 0 58: 17 14 2000 0.5 1; 2 10 57: 71 0 58: 21 0 14 2000 0.5 1;4 10 57: 0 58: 99 14 2000 0.5 1; 2 10 97 54:10 14 5000 2.0 2; 4 16 78 0 14 5000 2.0 2; 4 24 86 0 14 5000 2.0 2; 4 48 97 0 14 5000 2.0 4; 4 16 84 0 14 5000 2.0 4; 4 24 91 0 14 5000 2.0 4; 4 48 94 0 14 10000 0.5 1;2 24 38 0 14 10000 0.5 1;2 38 49 0 With complexes 13-15 the transfer hydrogenation of aldehydes with NH4-formate is an improvement compared to using 2-propanol as hydride donor and K2C03 as base (examples 28 and 29). The use of less complex (higher S/C ratio) is possible and less by-products are formed. It is important to note that no primary amines are produced by reductive amination of the aldehyde. Interestingly, the presence of the toluene solvent as co-solvent is not entirely required, as shown in the table below. Toluene was not added to the reactions carried out on a 2.5 mmol substrate scale. Table 12. TH of aldehydes catalyzed by complex 14 with HC02NH4in H20 at 90°C Aldehyde Complex S/C Substrate NH4-formate Time Alcohol By- molar molar;equivalents (h) (%) products (%) 13 5000 0.5 1; 2 16 60 13 5000 0.5 1; 2 22 76 14 2000 2.5 mmol 1; 2 2 50 14 2000 2.5 mmol 1; 2 4 76 14 2000 2.5 mmol 1; 2 7 97 14 5000 2.5 mmol 1; 2 14 53 14 5000 2.5 mmol 1; 4 24 97 14 5000 2.5 mmol 2; 4 24 90 45 14 5000 0.5 1; 2 15 96 14 5000 0.5 1; 2 24 97 14 5000 1.0 1; 2 15 86 14 5000 1.0 1; 2 24 95 14 5000 0.5 1; 4 15 96 14 5000 0.5 1; 4 24 96 14 5000 1.0 1; 4 15 96 14 5000 1.0 1; 4 24 96 14 20000 2.0 2; 4 24 94 14 20000 2.0 2; 4 48 96 0 15 5000 0.5 1; 2 16 96 0 15 10000 2.0 1; 2 20 86 0 15 20000 2.0 1; 2 40 96 0 14 2000 2.5 mmol 1; 2 14 33 6 14 2000 2.5 mmol 1; 2 16 61 0 14 2000 0.5 1; 2 10 97 0 46 14 2000 2.0 2;4 11 97 0 14 10000 2.0 2;4 24 24 0 14 20000 2.0 2; 4 24 62 0 14 20000 2.0 2; 4 48 72 0 14 5000 2.0 2; 4 15 96 0 47 >99, 14 2000 0.5 2; 4 10 0 48 65[bl 14 2000 0.5 1; 2 3.5 >99 0 55 14 2000 2.0 2;4 3.5 99, 65[bl 0 14 2000 0.5 1; 1.5 9 57: 83 0 56 58: 17 14 2000 0.5 1; 2 10 57: 71 0 58: 21 14 2000 0.5 1;4 10 57: 0 0 58: 99 14 2000 0.5 1; 2 10 97 54:10 14 5000 2.0 2; 4 16 78 54:6 14 5000 2.0 2; 4 24 86 0 52 14 5000 2.0 2; 4 48 97 54:12 14 5000 2.0 4; 4 16 84 0 14 5000 2.0 4; 4 24 92 54:5 14 5000 2.0 4; 4 48 94 54:7 14 10000 0.5 1 ; 2 24 38 14 10000 0.5 1 ; 2 38 49 59 14 10000 2.0 4; 4 20 98 0 60 14 10000 2.0 2; 4 24 65 0 60 14 10000 2.0 4; 4 24 97 0 61 14 5000 2.0 4;4 20 98, 88[bl 62 14 5000 2.0 2;4 8 95 63 14 2000 2.0 4;4 9 96, 79[bl Conversion and product content were determined by GC analysis or by -NMR spectroscopy. Isolated yield. On 2.5 mmol scale, reduction of benzaldehyde 45 (0.5 molar in toluene) at S/C =2000, 90°C and 4 equivalents of 2M aqueous Na-formate gave only traces of benzylalcohol after 14 hours. Use of 4 equivalents of (NEt3H)-formate improves the yield to 50 % in 22 hours. Use of 5 equivalents of (NEt3H)-formate on frans-cinnamaldehyde 52 gives after 18 hours 80 % of allylic alcohol 53 and 15 % of saturated alcohol 54. NH4-formate is preferred over the other formate reagents. |
78% | With water monomer; magnesium In tetrahydrofuran for 7h; Ambient temperature; | |
78% | With water monomer; 1,8-diazabicyclo[5.4.0]undec-7-ene; 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl-4',4',5',5'-tetramethyl-1,3,2-dioxaborolane at 20℃; for 10h; Sealed tube; chemoselective reaction; | |
77% | With tetraethylammonium borohydride In dichloromethane at 25℃; for 20h; | |
72% | With butan-1-ol at 115℃; for 4h; | |
70% | With lithium aluminium hydride; antimony(III) chloride In tetrahydrofuran at 0℃; for 4h; | |
70% | With lithium aluminium hydride; antimony(III) chloride In tetrahydrofuran at 0℃; for 4h; competition experiment with ethyl levulinate (recovered unchanged); | |
69% | With MnBr(CO)2[NH(CH2CH2P(iPr)2)2]; hydrogen; sodium tertiary butoxide In toluene at 100℃; for 24h; Autoclave; chemoselective reaction; | |
65% | With manganese powder; water monomer; 2,4,6-trimethylpyridinium chloride In tetrahydrofuran at 20℃; chemoselective reaction; | |
With copper oxide-chromium oxide at 130℃; Hydrogenation; | ||
With tris isopropylate aluminium; isopropanol | ||
13 % Chromat. | With sodium tetrahydridoborate; erbium(III) chloride In ethanol; water monomer The reaction was carried out in the presence of citral. Condition used was described in ref. 3. (J. Am. Chem. Soc. (1979), 44, 4187).; | |
99 % Chromat. | With carbon monoxide; water monomer In 2-ethoxy-ethanol at 60℃; for 5h; | |
320 g | With hydrogen at 120 - 130℃; | |
With methanol; methyltriphenylphosphonium tetrahydroborate 1) CH2Cl2, room temperature, 1 min, 2) 1 h; Yield given. Multistep reaction; | ||
With potassium fluoride; PMHS; N,N,N-tributylbutan-1-aminium fluoride 1.) THF, -70 deg C, 10-15 min, 2.) acetone, diethyl ether, room temperature, 4 h; Yield given. Multistep reaction; | ||
With hydrotalcite; isopropanol at 82℃; for 4h; Yield given; | ||
100 % Chromat. | With methyltriphenylphosphonium tetrahydroborate at 60℃; for 0.08h; | |
95 % Chromat. | With potassium hydroxide; isopropanol at 82℃; for 30h; | |
With hydrogen; trimethylamine In methanol at 80℃; | ||
> 99 %Chromat. | With hydrogen; Cs2CO3 In tetrahydrofuran at 150℃; for 6h; Autoclave; chemoselective reaction; | |
97 %Chromat. | With formic acid; iron(II) tetrafluoroborate hexahydrate; tris(2-diphenylphosphinoethyl)phosphine In tetrahydrofuran at 60℃; for 2h; Schlenk technique; Inert atmosphere; | 2. Experimental General procedure: Fe(BF4)2·6H2O (0.7 mg; 0.002 mmol) and tris[2-(diphenyl-phosphino)-ethyl]phosphine [P(CH2CH2PPh2)3; tetraphos] (1.4 mg; 0.002 mmol) are placed in a Schlenk-tube under argon atmosphere. 1 mL dry tetrahydrofurane is added and the purple solution is stirred for 2 min. Cinnamaldehyde (63 μL; 0.5 mmol) and 100 μL n-hexadecane as an internal GC-standard are injected and a sample is taken for GC-analysis. The solution is heated to 60 °C and the reaction starts by addition of 1.1 equiv formic acid (22 μL; 0.55 mmol). After 2 h, a second sample is taken for GC-analysis and conversion and yield are determined by comparison with authentic samples. For the isolation, the reaction is scaled up by a factor of 20. When the reaction is completed, the reaction solution is diluted with a mixture of n-hexane and ethyl acetate (3:1), filtered through a plug of silica and the solvent removed in vacuum. |
With tropinone reductase of Cochlearia officinalis; NADPH In methanol at 30℃; for 1h; Enzymatic reaction; | ||
86 %Chromat. | With methyl ammonia borane In water monomer at 20℃; for 0.5h; Green chemistry; chemoselective reaction; | General Procedure for the Hydrogenation of Carbonyl Compounds to Alcohols General procedure: A mixture of carbonyl compound (1 mmol) and MeAB (1 mmol) in neat water (2 mL) was stirred at room temperature for an appropriate time. The reaction was monitored by TLC and gas chromatography (GC). After completion, the reaction mixture was extracted with ethyl acetate (310 mL). Then, the organic extracts were concentrated by rotary evaporation, and the residue was purified by silica-gelcolumn chromatography (elution by using petroleum ether=ethyl acetate 5:1) to obtain the alcohol product. |
With [{RuCl2(sodium 3-diphenylphosphinobenzenesulfonate)2}2]; water monomer; anhydrous sodium formate; diphenylphosphinobenzene-3-sulfonic acid sodium salt In propan-1-ol at 30℃; for 1h; Inert atmosphere; | 2.1. Catalytichydrogenationofcinnamaldehyde General procedure: In a typical reaction, 408mg (6mmol) sodiumformate and 126 L (1mmol) cinnamaldehyde were added to a mixture of 4.0mL water and 3.5m L2-propanolat T=30C. 5mg (0.005mmol) [{RuCl2(mtppms)2}2] and 16mg(0.04mmol) mtppms weredis-solved in the deoxygenated solution and the mixture was stirred vigorously. Samples(0.2mL) were withdrawn periodically and diluted with 1mL of water before extraction by chlorobenzene.The organic layers were filtered through short silica plugs and analyzed by gas chromatography. | |
93 %Spectr. | With C16H26AlNO; isopropanol for 0.25h; Reflux; Inert atmosphere; Schlenk technique; | 4.3 Typical procedure employed for MPV reactions General procedure: A 25mL Schlenk flask was charged with aluminum complex (0.2mmol) and the carbonyl compound (4.0mmol) was added, followed by the addition of 2-propanol (0.37mL, 4.8mmol). The reaction mixture was then refluxed for 15min, and the yield was determined by 1H NMR spectroscopic studies based on the integration in the methylene and the CHO region of the benzyl group. |
97 %Spectr. | With [Fe(PNPMe-iPr)(CO)(H)(Br)]; hydrogen; 1,8-diazabicyclo[5.4.0]undec-7-ene In ethanol at 40℃; for 16h; chemoselective reaction; | |
99 %Chromat. | With hydrogen In ethanol at 100℃; for 20h; Autoclave; | |
With C39H51AlN6; isopropanol In toluene at 110℃; for 2h; Inert atmosphere; Schlenk technique; | 2.5. Typical procedure employed for the Meerwein-Ponndorf-Verley(MPV) reduction General procedure: To a solution of catalyst (0.4 mmol) in toluene (10 mL) wasadded 2-propanol (8.0 mmol), followed by the addition of the aldehyde(4.0 mmol). The reaction mixture was then refluxed for therequired reaction time under an atmosphere of nitrogen. The reactionwas then cooled to room temperature and the conversionyield was determined by 1H NMR spectroscopic study based onthe integration in the methylene and the CHO region. | |
With RuCl(4-phenyl-2-aminomethylbenzo[h]quinoline-H)(1,4-bis(diphenylphosphino)butane); ammsnium formate In water monomer; toluene at 90℃; for 18h; chemoselective reaction; | ||
Multi-step reaction with 2 steps 1: 1.06 wtpercent platinum loading 17 wtpercent tungsten supported on technische universiteit delft-1 / toluene / 5 h / 80 °C / 15001.5 Torr / Autoclave; Inert atmosphere 2: hydrogen / toluene / 16 h / 80 °C / 15001.5 Torr / Autoclave | ||
91.7 %Spectr. | With C40H86Li2Mg2N4O2; isopropanol In neat (no solvent) for 4h; Inert atmosphere; Schlenk technique; Reflux; | |
99 %Spectr. | With [{(C5H10N)C(NCy)2}AlMe(μ-OMe)]2; isopropanol In toluene at 110℃; for 8h; Reflux; Inert atmosphere; Schlenk technique; | 2.6 General procedure employed for the MPV reaction General procedure: To a solution of catalyst in toluene was added aldehyde or ketone, followed by the addition of 2-propanol. The reaction mixture was then refluxed for the required reaction time under an atmosphere of nitrogen. The reaction was then cooled to room temperature and the conversion yield was determined by 1H NMR spectroscopic study based on the integration in the methylene and the CHO region. |
With hydrogen In isopropanol at 149.84℃; for 1h; Autoclave; chemoselective reaction; | ||
With hydrogen; 1,8-diazabicyclo[5.4.0]undec-7-ene In n-heptane at 25℃; for 1h; Ionic liquid; chemoselective reaction; | ||
74 %Chromat. | With isopropanol at 200℃; for 6h; Autoclave; | |
97.9 %Chromat. | With hafnium phytate; isopropanol at 100℃; for 4h; Inert atmosphere; chemoselective reaction; | |
85 %Spectr. | With [(N,N'-bis(diisopropylphosphino)-2,6-diaminopyridine)Mn(CO)2H]; hydrogen In ethanol at 25℃; for 18h; chemoselective reaction; | |
With C33H27Cl2N2OPRu; sodium isopropanolate; potassium carbonate In isopropanol at 82℃; for 0.166667h; Inert atmosphere; Schlenk technique; | ||
91 %Chromat. | With C28H35ClCoN5(1+)*Cl(1-); potassium-t-butoxide; hydrogen In tetrahydrofuran at 20℃; for 16h; Autoclave; | General procedure for Hydrogenation of Ketones General procedure: In an argon filled glove box, the cobalt catalyst (LNHC/CoCl2 or Co-2a) and the base wereweighted into a 4mL vial equipped with a magnetic stir bar, followed by addition of the solvent.After shaking of the vial for 30 seconds, the carbonyl substrate was then added. The vial wasplaced into a Parr Instruments autoclave, which was then sealed, removed from the glove boxand purged with hydrogen gas. The autoclave was heated to certain temperature. After reactionfor 16 hours, the autoclave was cooled down to 0 oC before releasing the hydrogen gas. Forquantitative GC analysis, biphenyl (1.0 mmol) as internal standard was added. The organiclayer was then filtrated and diluted for GC analysis. The stereo-selectivity of the hydrogenatedproducts of cyclohexanones were determined by NMR with mesitylene as the internal standard.The desired hydrogenation product was further isolated by flash column chromatography. |
With [Fe(N,N′-bis(diisopropylphosphino)-N,N′-dimethyl-2,6-diaminopyridine)(H)(CO)Br]; hydrogen; 1,8-diazabicyclo[5.4.0]undec-7-ene In n-heptane at 25℃; for 1h; Autoclave; | ||
98 %Chromat. | With hydrogen In methanol at 110℃; for 2h; Autoclave; chemoselective reaction; | |
99 %Spectr. | With formic acid; (RuCl<SUB>2</SUB>(p-cymene))<SUB>2</SUB>(dppf); tetrabutylammonium bromide; triethylamine at 40℃; for 6h; | 4.1 General procedure for the catalytic TH of carbonyl compounds and imines General procedure: The selected substrate (0.2-1.0mmol, 1 eq), [RuCl2(p-cymene)}2-μ-dppf] (6) (0.002-0.01mmol, 0,01-0,05 eq, 2.3-58.3mg), NEt3 (1.4-8.6mmol, 0.2-1.2mL) and CPME (0.5-1.5mL) were transferred into a 4mL vial. The mixture was heated at the selected temperature (40-80°C) under stirring for ca. 15min and finally the DES-5 (0.45-1.7mL) was added. After the addition of the DES, the vial was put into the oil bath and the Teflon cap pierced with a needle to help the emission of the CO2 produced. The reaction was then leaved to react at the selected temperature from 2 to 24h, depending on the substrate. The reaction mixture was worked taken up with water (1.5mL) and extracted with diethyl ether (4×1.5mL), then the combined organic layers washed with brine (1.5mL). The organic phase was then separated, dried over Na2SO4 and filtered. The solvent was removed and the crude was analysed by 1H and, when pure products were afforded, by 13C NMR spectroscopy. |
93.8 %Chromat. | With C6H4B2O4(4-)*Zr(4+); isopropanol at 100℃; for 4h; Sealed tube; | |
With hydrogen; C27H41IrN3P In 2-methyltetrahydrofuran at 25℃; for 24h; Inert atmosphere; Glovebox; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With hydrogen In ethyl acetate | |
99% | With hydrogen In ethyl acetate at 80℃; for 0.0833333h; microwave irradiation; | |
93% | With hydrogen In methanol at 20℃; for 50h; |
88% | With cobalt In tetrahydrofuran Heating; High pressure; | |
86% | With zinc In water; acetic acid for 17h; Ambient temperature; | |
83% | With iron(III) chloride hexahydrate; hydrazine hydrate In ethanol at 80℃; for 30h; | |
81% | With sodium tetrahydroborate; ruthenium(III) trichloride hydrate In 1-methyl-pyrrolidin-2-one; water at 0℃; for 1h; chemoselective reaction; | General procedure for alkene reduction General procedure: To a 15-mL 1-neck reaction flask fitted with a glass stopper [Note: A larger-scale reaction may require the use of a pressure vessel and/or addition of NaBH4 in small portions.] were added a small spin bar, 0.18-0.20 mmol of substrate, 0.60 mL of 5:1 (v/v) [10:1 (v/v) in Table 1, entry 3] liquid amide(s)/H2O, and 7.0 mg (0.034 mmol) of ruthenium(III) chloride hydrate (Sigma-Aldrich Catalog No. 206229). After cooling the latter mixture to 0 C (external ice-H2O bath), 9.0 mg (0.24 mmol) of NaBH4 powder was added in one portion; and the mixture was subsequently stirred at 0 C for 60 min. The reaction was then quenched by addition of 2.0 mL of 2 M aqueous HCl to the reaction flask, followed by 1.0 mL of pentane and subsequent stirring of the mixture at 0 C for 15 min. The product was then isolated by dilution of the reaction mixture with 10 mL of 4:1 (v/v) pentane/dichloromethane; and solid material was removed by filtration through a small pad of Hyflo Super-Cel filtering aid. After dilution of the filtrate with 10 mL of pentane, removal of the liquid amide(s) was accomplished by washing the filtrate with 10% (w/v) aqueous NaCl (4 15 mL portions). The organic layer was subsequently dried over anhydrous MgSO4, filtered, and the volatile organic solvents were removed by evaporation at reduced pressure. |
79% | With ruthenium trichloride; sodium tetrahydroborate In N,N-dimethyl acetamide; water at 0℃; for 1h; | |
68% | With 4-methyl-morpholine; tetrahydroxydiboron; 5%-palladium/activated carbon In 1,2-dichloro-ethane at 50℃; for 24h; | |
61% | With palladium 10% on activated carbon; hydrogen In ethanol at 40℃; | |
With ethanol; water; hydrogen in Gegenwart von Katalysatoren der Platingruppe; | ||
With nickel at 60 - 120℃; Hydrogenation.Druckhydrierung; | ||
With hydrogen In isopropyl alcohol at 80℃; also in cyclohexanol; also at 21 and 41 bar H2 pressure; initial citronellol concentration varied; | ||
With hydrogen; nickel at 150 - 160℃; citronellol dihydride; | ||
With hydrogen In methanol | ||
With hydrogen In hexane at 99.85℃; | ||
With hydrogen | ||
With hydrogen In ethyl acetate at 80℃; for 0.0833333h; Microwave irradiation; | A number of hydrogenation reactions were conducted using the present apparatus and method. Several of these reactions, along with their reaction conditions and yields, are listed below. Unless otherwise noted, each reaction proceeded with a stoichiometric amount of hydrogen with respect to the reactant to be hydrogenated and 1% catalyst loading.As used in the drawings, the abbreviation Pd/C refers to a palladium metal catalyst on a carbon support. The abbreviation EtOH refers to ethyl alcohol and the abbreviation EtOAc refers to ethyl acetate. The abbreviation μλ refers to the application of microwaves. Simultaneous cooling was carried out using the PowerMAX single mode capacity microwave instrument available from the assignee herein, CEM Corporation of Matthews, N.C., USA. | |
With 5%-palladium/activated carbon; hydrogen In toluene at 40℃; Autoclave; | ||
With ethanol; water; hydrogen in Gegenwart von Katalysatoren der Platingruppe; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With carbon tetrabromide; triphenylphosphine In dichloromethane at 0℃; for 2h; | |
93% | With 1H-imidazole; iodine In dichloromethane at 20℃; for 0.75h; | |
89% | With pyridine; bromine; triphenylphosphine In Carbon tetrachloride; N,N-dimethyl-formamide at 45℃; |
85% | With carbon tetrabromide; triphenylphosphine In dichloromethane at 0 - 20℃; for 5h; | Diethyl (3,7-dimethyloct-6-en-1-yl)phosphonate 26 Citronellol 25 (1 eq., 2.0 mL, 11 mmol) and CBr4 (1.1 eq., 4.0 g, 12 mmol) were dissolved in2 mL CH2Cl2. Triphenylphosphine (1.2 eq, 3.5 g, 13 mmol) dissolved in 2 mL CH2Cl2 was addedat 0 °C. The reaction mixture was stirred at room temperature for 5 h. The solvent wasremoved under reduced pressure. Purification by chromatography on silica (pentane) gave2.03 g (9.35 mmol, 85%) 8-bromo-2,6-dimethyloct-2-ene6 as a colorless oil.1H NMR (300 MHz, CDCl3) δ = 5.09 (t, 3J = 7.1 Hz, 1 H, 6-H), 3.5 - 3.37 (m, 2 H, 1-H), 2.08 - 1.80(m, 3 H, 2-H, 5a-H), 1.74 - 1.52 (m, 8 H, 9a-H, 9b-H, 3-H, 5b-H), 1.32 - 1.08 (m, 2 H, 4-H), 0.9(d, 3J = 6.3 Hz, 3 H, 9-H).13C NMR (150 MHz, CDCl3) δ = 131.6 (C7), 124.6 (C6), 40.2 (C5), 36.8 (C4), 32.3 (C1), 31.5 (C3),25.9 (C8b), 25.5 (C2), 19.0 (C9), 17.8 (C8a). |
83% | With allyl bromide; 1,1'-carbonyldiimidazole In acetonitrile for 2h; Heating; | |
83.2% | With bromine; triethylamine; triphenylphosphine In dichloromethane at 0℃; | |
82% | With triphenylphosphine monolith functionalized with carbon tetrabromide In dichloromethane at 0℃; Flow reactor; | |
80% | With carbon tetrabromide In N,N-dimethyl-formamide at 23 - 35℃; for 0.25 - 1h; UV-irradiation; | |
67% | With 1H-imidazole; carbon tetrabromide; triphenylphosphine In dichloromethane at 0 - 20℃; for 0.5h; Inert atmosphere; | |
62% | With pyridine; bromine; triphenylphosphine In dichloromethane at 0 - 20℃; for 2h; | |
With phosphorus tribromide | ||
With pyridine; phosphorus tribromide; Petroleum ether | ||
With pyridine; phosphorus tribromide | ||
With bromine; phenylphosphane | ||
With N-Bromosuccinimide; triphenylphosphine In dichloromethane at 20℃; for 12h; Glovebox; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With hydrogen In isopropyl alcohol at 90℃; for 12h; | |
96% | With hydrogen In dichloromethane for 10h; | |
71% | With 1,1'-bis(diphenylphosphino)ferrocene; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; Butane-1,4-diol; potassium <i>tert</i>-butylate at 110℃; for 24h; Inert atmosphere; |
With nickel at 80 - 95℃; Hydrogenation.auf Bimsstein; <i>dl</i>-citronellol; | ||
With platinum at 130℃; Hydrogenation.auf Bimsstein; <i>dl</i>-citronellol; | ||
With ethanol; platinum Hydrogenation; <i>dl</i>-citronellol; | ||
With ethanol; iron(II) sulfate; platinum Hydrogenation; <i>dl</i>-citronellol; | ||
With wool fat; platinum (II) hydroxide Hydrogenation.3-4 Atm. Ueberdruck; <i>dl</i>-citronellol; | ||
With palladium dihydroxide Hydrogenation.3-4 Atm. Ueberdruck; <i>dl</i>-citronellol; | ||
With nickel at 150℃; Hydrogenation.auf Bimsstein; <i>dl</i>-citronellol; | ||
With diethyl ether; platinum Hydrogenation; <i>dl</i>-citronellol; | ||
With ethanol; zinc diacetate; platinum Hydrogenation; <i>dl</i>-citronellol; | ||
With sodium tetrahydroborate; water In toluene at 100℃; for 22h; | ||
With nickel Hydrogenation.in der Kaelte bei niedrigem Druck; | ||
With nickel at 100℃; Hydrogenation; | ||
With hydrogen; sodium | ||
With hydrogen; sodium; xylene | ||
97 % Chromat. | With isopropyl alcohol at 82℃; for 24h; | |
98 %Chromat. | With dichloro(η3:η2:η3-dodeca-2,6,10-triene-1,12-diyl)ruthenium(IV); caesium carbonate; isopropyl alcohol at 82℃; for 24h; Inert atmosphere; chemoselective reaction; | |
31 %Chromat. | With (S,S)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane; potassium hydroxide at 100℃; for 20h; Inert atmosphere; enantioselective reaction; | |
With Rh-SBA-15 In methanol at 20℃; for 0.2h; | ||
With (bis-1,2-diethylphosphinoethane)Co(CH<SUB>2</SUB>SiMe<SUB>3</SUB>)<SUB>2</SUB>; hydrogen In toluene at -196.15 - 25℃; for 14h; Sealed tube; | ||
With nicotinamide-dependent cyclohex-2-en-1-one reductase (NCR) at 30℃; for 24h; | ||
With ethanol; hydrogen; palladium | ||
With ethanol; hydrogen; platinum |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With iron(III)-acetylacetonate; methyl 4-nitrobenzenesulfonate; phenylsilane; sodium hydrogencarbonate In methanol at 0 - 20℃; for 12h; Schlenk technique; Inert atmosphere; regioselective reaction; | |
68% | With sodium tetrahydroborate; ferric(III)oxalate hexahydrate; oxygen In water; acetonitrile at 0℃; for 0.583333h; | |
57% | With sodium tetrahydroborate; iron(II) phthalocyanine; oxygen In ethanol at 0 - 25℃; for 3h; Inert atmosphere; |
(i) Hg(OAc)2, THF, H2O, (ii) NaBH4, aq. NaOH; Multistep reaction; | ||
With sodium tetrahydroborate In methanol at 20℃; for 14h; | ||
Multi-step reaction with 2 steps 1: MCPBA 2: LiAlH4 | ||
Stage #1: Citronellol With water at 20℃; for 18h; Stage #2: With potassium hydroxide In water |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With iodine; triphenylphosphine In 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran at 20℃; for 1h; chemoselective reaction; | 2.2 General procedure for the iodination of alcohols General procedure: To a stirred solution of triphenylphosphine (1.5 mmol) in dry dichloromethane was added iodine (1.5 mmol)and polymer supported 4-DMAP (0.4 mmol, 40 mol%). Stirring was continued for 2 min; alcohol (1mmol) was then added. The reaction was monitored by TLC. After complete conversion of the alcohol (as indicated byTLC), the reaction was quenched with an aqueous solution of sodium thiosulfate (20 mL). The organic solventswere removed and the aqueous solution extracted with ethylacetate (50 mL). The combined organic layers weredried using sodium sulfate (anhydrous), filtered and concentrated. The residue was purified by column chromatography (2% EtOAc in hexane) to get the desired iodide product. |
90% | With 1H-imidazole; iodine; triphenylphosphine In dichloromethane for 0.75h; Ambient temperature; | |
89% | With 1H-imidazole; iodine; triphenylphosphine In tetrahydrofuran Inert atmosphere; Darkness; Sealed tube; |
84% | With 1,1'-carbonyldiimidazole; methyl iodide In acetonitrile for 2h; Heating; | |
72% | With 1H-imidazole; iodine; triphenylphosphine In tetrahydrofuran at 20℃; for 24h; Schlenk technique; Inert atmosphere; | 8-Iodo-2,6-dimethyloct-2-ene 8-Iodo-2,6-dimethyloct-2-ene: To a stirring solution ofi citronellol (8.7 g, 55.6 mmol 1.0 equiv.) in THF (150 mL) was added triphenylphosphine (16.0 g, 61.2 mmol, 1.1equiv.), imidazole (4.16 g, 61.2 mmol, 1.1 equiv.) and iodine (15.5 g, 61.2 mmol, 1.1 equiv.). The mixture was stirred at room temperature for 24 h and then concentrated in vacuo. Purification via dry flash chromatography (hexane, R = 0.61) afforded 8-iodo-2,6-dimethyloct-2-ene as a colorless liquid (10.6 g, 72%). 1H NMR (400 MHz, CDCI3) 6:0.88 (d, J= 6.8 Hz, 3H), 1.12-1.21 (m, 1H), 1.25-1.38 (m, 1H), 1.53-1.71 (m, 1H), 1.61(s, 3H), 1.68 (d, J= 1.2 Hz, 3H), 1.83-2.05 (m, 3H), 3.13-3.28 (m, 2H), 5.06-5.11 (m,1 H). |
72% | With 1H-imidazole; iodine; triphenylphosphine In tetrahydrofuran at 20℃; for 24h; Inert atmosphere; Schlenk technique; | |
With phosphorus; iodine at 150℃; | ||
With 1H-imidazole; iodine; triphenylphosphine In dichloromethane at 0 - 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With sodium hydrogencarbonate; 3-chloro-benzenecarboperoxoic acid In dichloromethane | |
98% | With oxygen; cobalt(II) acetate; isobutyraldehyde In dichloromethane at 20℃; for 5h; | General procedure: Reaction conditions: A 50 mL round bottomed flask is charged with alkene (20 mmol), isobutyraldehyde (100 mmol), metal salt, (0.18 mmol), CH2Cl2 (15 mL) attached to a O2 filled balloon and stirred at room temperature. At the end of the reaction the mixture is filtered, diluted with CH2Cl2, washed with NaHCO3 solution (10%) to remove the acid and dried (Na2SO4). The residue is purified by column chromatography (hexane-ethyl acetate) to afford the corresponding epoxides. |
95% | With (NMe4)(Co-ortho-phenylenebis(N'-methyloxamidate)*2H2O*CH3CN; oxygen; pivalaldehyde In fluorobenzene for 2.5h; Ambient temperature; |
90% | With <NMe4>2<Ni(Me2opba)>*4H2O; oxygen; pivalaldehyde In fluorobenzene for 2.5h; | |
85% | With sodium hydrogencarbonate; 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 1h; | |
82% | With 1,1-diethoxypropane; bis(3-methyl-2,4-pentanedionato)cobalt(II); 4 A molecular sieve; oxygen at 45℃; for 10h; | |
82% | With 1,1-diethoxypropane; bis(3-methyl-2,4-pentanedionato)cobalt(II); 4 A molecular sieve; oxygen at 45℃; for 10h; | |
62% | With {(N,N',N''-trimethyl-1,4,7-triazacyclononane)2Mn(IV)2(μ-O)3}(PF6)2*H2O; dihydrogen peroxide; salicylic acid In water; acetonitrile at 0 - 20℃; for 16h; | |
45% | With fluorine In dichloromethane at 0℃; for 0.0166667h; | |
36% | With 1-(tert-butylperoxy)-1,2-benziodoxol-3(1H)-one In dichloromethane at 25℃; for 168h; | |
30% | With 3-chloro-benzenecarboperoxoic acid | |
With oxygen; isobutyraldehyde In 1,2-dichloro-ethane for 4.5h; Ambient temperature; Yield given; | ||
With 3-chloro-benzenecarboperoxoic acid | ||
0.061 g | With monoperoxyphthalic acid; sodium hydrogencarbonate In water at 0℃; for 2h; | |
With dihydrogen peroxide; sodium acetate In phenol at 60℃; for 8h; | ||
97 % Chromat. | With dihydrogen peroxide In dichloromethane at 10℃; for 4h; | |
Multi-step reaction with 2 steps 1: 100 mg / CH2Cl2 / 30 h 2: 82 percent / 35percent aq. H2O2 / CH2Cl2 | ||
With 3-Methylpyrazole; dihydrogen peroxide; methyltrioxorhenium(VII) at 10℃; for 2h; | ||
With 3-chloro-benzenecarboperoxoic acid | ||
With peracetic acid; sodium carbonate In dichloromethane at 0℃; for 4h; | 1.1 Citronellol (15.6 g, 0.10 mol) was dissolved in CH2Cl2 (200 mL), Na2CO3 (15. 0 g) was added. A solution of 15% peracetic acid (60.8 g, 0.12 mol) was slowly added dropwise at 0 °C. The reaction was carried out at low temperature for 4 hours. The product was extracted with CH2Cl2 (200 mL). The organic phase was washed with saturated Na2SO4 solution and brine, dried over anhydrous Na2SO4, the solvent was distilled off under reduced pressure to obtain an epoxy compound. | |
Multi-step reaction with 2 steps 1: N-Bromosuccinimide; cerium(IV) oxide / water; acetone / 0.25 h / 20 °C 2: diethylamine / 2 h / 20 °C | ||
With 2-Picolinic acid; manganese(II) perchlorate hexahydrate; dihydrogen peroxide; sodium acetate; dimethylglyoxal In water; acetonitrile at 0 - 20℃; for 1h; | ||
With sodium undecatungstophosphate; dihydrogen peroxide In acetonitrile at 24.84℃; | ||
Multi-step reaction with 2 steps 1: N-Bromosuccinimide; water / acetone / 0.5 h / 20 °C 2: sodium carbonate / ethanol | ||
Multi-step reaction with 2 steps 1: N-Bromosuccinimide; N,N-dimethyl-formamide / 10 h / 0 - 70 °C 2: sodium carbonate / ethanol | ||
With dibutylamine; iron(III) oleate; cobalt(II) oleate at 120℃; | 1-7; 1-2 Epoxidation reaction: Pack 5g of catalyst CAT1 into the fixed bed,The upper and lower spaces of the catalyst layer are filled with fillers such as quartz sand to achieve a supporting effect.After the reactor temperature stabilized at 120,The raw material citronellol was pumped in from the feed port above the reactor at a space velocity of 45 g/h.At the same time, compressed air was introduced into the reactor to maintain the reactor pressure at 3MPaG. Sampling for GC analysis, the results are shown in Table 1. | |
With peracetic acid; sodium carbonate; acetic acid In toluene at 15 - 25℃; for 6h; | I Example I: Preparation of 5- (3,3-Dimethyloxiran-2-yl)3- methylpentan-1-ol (Structure la) A mixture of 3,7-dimethyloct-6-en-l-ol (655 g, 3.98 mol) and sodium carbonate (Na2C03) (150 g, 1.41 mol) was stirred in toluene (2 L) and cooled to 15°C using an ice bath. To this mixture was added peracetic acid (CH3COOOH) (32% in acetic acid) (994 g, 4.18 mol) over 3 hours while maintaining the temperature at 20-25°C. After the feed was complete, the reaction was aged at 25°C for another 3 hours. The reaction mixture was washed sequentially with sodium carbonate solution (10%) (1 L), sodium sulfite solution (Na2S03) (10%) (1 L) and brine solution (NaCl) (1L) to afford a crude reaction mixture. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With pyridine chromium peroxide In dichloromethane for 1.25h; Ambient temperature; effect of various chromium(VI) based oxidants; | |
99% | With pyridine chromium peroxide In dichloromethane for 1.25h; Ambient temperature; | |
99% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; 3-[4'-(diacetoxyiodo)phenoxy]-1-propyl-N,N,N-trimethylammonium 4-methylbenzenesulfonate In dichloromethane at 20℃; for 2h; |
99% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; 3-[4-(diacetoxyiodo)phenoxy]-1-propyl-N,N,N-trimethylammonium 4-methylbenzenesulfonate In dichloromethane at 20℃; for 2h; Inert atmosphere; | |
96% | With 2,2,6,6-tetramethyl-piperidine-N-oxyl; oxygen In chlorobenzene at 80℃; for 9h; | |
95% | Stage #1: Citronellol With bis(trichloromethyl) carbonate; dimethyl sulfoxide In dichloromethane at -78℃; for 0.25h; Stage #2: With triethylamine at -78 - 20℃; for 0.166667h; | |
94% | With pyridine; oxygen In toluene at 80℃; for 4.5h; | |
92% | With 2,2,6,6-tetramethyl-piperidine-N-oxyl; dimethylsulfide; oxygen In chlorobenzene at 90℃; for 1h; | |
91% | Stage #1: Citronellol With 1-methyl-1H-imidazole; [2,2]bipyridinyl; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; oxygen; copper(II) bis(trifluoromethanesulfonate); 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 20℃; for 0.25h; Stage #2: In acetonitrile at 20℃; for 2h; Molecular sieve; Stage #3: In acetonitrile | |
90% | With bis(pyridine)silver(I) permanganate In benzene for 1h; | |
90% | With barium permanganate In benzene for 24h; Heating; | |
90% | With 2,2,6,6-tetramethyl-piperidine-N-oxyl; [bis(acetoxy)iodo]benzene In dichloromethane for 0.5h; | |
90% | With cis-[Os(VIII)O4(OH)2](2-); [Fe(CN)6](3-); acetonitrile at 20℃; for 2h; | |
90% | With tris(2-methoxyphenyl)bismuth oxide In dichloromethane at 20℃; for 0.166667h; | |
89% | Stage #1: Citronellol With oxalyl dichloride; 3-methyl-1-[10-(methanesulfinyl)decan-1-yl]-1H-imidazolium p-toluenesulfonate In dichloromethane at -70℃; for 0.5h; Stage #2: With triethylamine In dichloromethane at -70 - 20℃; for 5.5h; | 4.7. General procedure for the Swern oxidation using ion-supported methyl sulfoxide A-1 or B-1 General procedure: Oxalyl chloride (0.34 mL) was added dropwise to a solution of ion-supported methyl sulfoxide A-1 (C6) (1.60 g, 4.0 mmol) in CH2Cl2 (6 mL) at -70 °C and the mixture was stirred for 30 min at the same temperature. Then, a solution of alcohol (2.0 mmol) in CH2Cl2 (3 mL) was added dropwise at -70 °C and the obtained mixture was stirred for 30 min. Triethylamine (1.66 mL, 12 mmol) was added dropwise at -70 °C and the mixture was stirred for 1 h at the same temperature. The resulting mixture was warmed to -60 °C and stirred for 1.5 h at the same temperature. Then, the mixture was warmed to -50 °C and stirred for 1 h at the same temperature. Finally, the mixture was warmed to room temperature and stirred for 2 h at the same temperature. The reaction mixture was quenched with water (10 mL), neutralized (pH=6-7) with aq 1 M HCl solution, and extracted with diethyl ether (40 mL×2). The organic layer was washed with water (10 mL), dried over Na2SO4, and filtered. After removal of the solvent, aldehyde or ketone was obtained. The purity was estimated by 1H NMR measurements. |
89% | With dmap; tetrakis(actonitrile)copper(I) hexafluorophosphate; N,N'-di-tert-butylethylenediamine; oxygen In dichloromethane at 20℃; for 6h; Schlenk technique; Molecular sieve; Sealed tube; | |
88% | With quinolinium monofluorochromate(VI) In hexane for 3h; Heating; | |
85% | With pyridinium chlorochromate In dichloromethane for 2h; | |
85.5% | With quinolinium monofluorochromate(VI) In dichloromethane for 0.833333h; | |
85% | With oxygen In toluene at 80℃; for 4h; | |
85% | With C23H35N3O3(1+)*Br(1-); copper In chlorobenzene at 80℃; for 15h; | |
85% | With isoamyltriphenylphosphonium perruthenate; 4-methylmorpholine N-oxide In dichloromethane at 20℃; Molecular sieve; Inert atmosphere; | |
83% | With bis(2,2'-bipyridyl) copper(II) permanganate In dichloromethane for 1h; Ambient temperature; | |
83% | With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -78 - 20℃; for 1h; | |
83% | With oxalyl dichloride; 3-methyl-1-[6-(methanesulfinyl)hexan-1-yl]-1H-imidazolium p-toluenesulfonate; triethylamine In dichloromethane at -78 - 20℃; | |
82% | With aluminum oxide; pyridinium chlorochromate In hexane for 4h; Ambient temperature; | |
82% | With aluminium trichloride; benzyltriphenylphosphonium periodate In acetonitrile for 9h; Heating; | |
82% | With di-tert-butyl-diazodicarboxylate; potassium <i>tert</i>-butylate; oxygen In fluorobenzene Heating; | |
82% | With pyridine; air In toluene at 65℃; for 15h; | |
81% | With molecular sieve; <PPh4><RuO2(OCOMe)Cl2> In dichloromethane for 0.5h; Ambient temperature; | |
81% | With pyridine; oxygen In toluene at 80℃; for 6h; | |
75% | With 4-methylmorpholine N-oxide In dichloromethane for 5h; Ambient temperature; | |
75% | With 2-Picolinic acid; sodium nitrate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; manganese (II) nitrate tetrahydrate; oxygen; acetic acid at 16℃; for 3h; | |
74.7% | Stage #1: Citronellol With pyridine; dimethyl sulfoxide; trifluoroacetic acid In toluene at 25℃; for 0.166667h; Stage #2: In toluene at 23 - 25℃; for 5h; Stage #3: With acetic acid In water; toluene | 4 Example 4 In a reactor equipped with a stirrer, a cooling condenser, a dropping funnel and a thermometer, citronellol (46.9 g, 0.30 mol), dimethyl sulfoxide (352 g, 4.50 mol) and toluene (120 g) were added, and the resulting reaction solution was stirred at a temperature of 20 to 23° C. To this reaction solution, pyridine (23.7 g, 0.30 mol) was added dropwise, followed by trifluoroacetic acid (17.1 g, 0.15 mol). The resulting mixture was maintained at a temperature of 25° C. or lower and was stirred for 10 minutes. After stirring, Carbodilite V-03 (manufactured by Nisshinbo Chemical Inc., 431.1 g/mol) (258.7 g, 0.60 mol) was added dropwise to the reaction liquid, while the reaction liquid was maintained at 25° C. or below. After the dropwise addition, the reaction liquid was stirred for 5 hours at 23 to 25° C., and the reaction was terminated with a 1.0% aqueous solution of acetic acid (48 g). After the reaction was terminated, a urea compound precipitated from the reaction liquid was separated by filtration. The filtrate was partitioned to remove the aqueous phase, and then the organic phase was washed with an aqueous sodium chloride solution.The resulting organic phase was treated such that the solvent was removed under reduced pressure, and the residue was distilled under reduced pressure. Thus, citronellal (bp: 76 to 78° C./0.27 kPa, 34.6 g, 0.22 mol) was obtained (yield 74.7%). The aldehyde compound thus obtained was confirmed by using NMR, mass spectrometry and IR spectroscopy. |
73% | With 2-Picolinic acid; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; manganese (II) nitrate tetrahydrate; oxygen; acetic acid at 15℃; for 3h; | |
71% | With imidazolium fluorochromate In acetonitrile at 20℃; for 3.5h; | |
70% | With iodosylbenzene In dichloromethane for 2.5h; Heating; | |
70% | With 3,5-dimethylpyrazolium fluorochromate(VI) In dichloromethane at 20℃; for 1h; | |
63% | In ethyl acetate at 45℃; for 10h; Inert atmosphere; Irradiation; | A representative procedure B: synthesis of aldehydes 2 (Table 2, entry 1) General procedure: To a three-necked, cylindrical Pyrex glass reaction vessel equipped with a rubber balloon, rubberseptum, and glass stopper, a N2 atmosphere was introduced by flowing via cannula for 5 min. Au(0.6 wt %)/TiO2 (117.3 mg, 0.17 mol % Au), 1a (271.5 mg, 1.99 mmol), and dehydrated ethylacetate (25 mL) were added successively to the vessel. After N2 gas was reintroduced more than 5min, the rubber balloon was connected to the vessel and the mixture was sonicated. The vessel wasimmersed in a oil bath (kept at 45 oC) and stirred for 10 h under irradiation (λ = 300-470 nm). 1HNMR analysis of this crude mixture using mesitylene as an internal standard indicated 97%conversion of 1a and the formation of 2a in 86% yield, as determined based on the signals at δ 3.61ppm and 2.94 ppm (shifted from 2.89 ppm due to the presence of ethyl acetate), respectively. Theproduct was purified by silica gel column chromatography (n-hexane/ethyl acetate 3:1) to afford 2a(180 mg, 66% yield, with inclusion of small amounts of unidentified impurities). |
62% | With potassium trichromate(VI) In acetonitrile for 2h; | |
47% | With tetrapropylammonium perruthennate; N,N,N′,N′-tetramethylethylenediamine dioxide In dichloromethane at 20℃; for 4h; Molecular sieve; Inert atmosphere; | |
40% | With barium ferrate(VI) In benzene for 24h; Heating; | |
40% | With barium ferrate(VI) In benzene for 24h; Heating; | |
35% | With oxygen at 30℃; for 24h; Irradiation; | |
32% | With <PPh4>2<Mo2O3(O2)4> In dichloromethane for 15h; Ambient temperature; | |
10% | With 1,10-Phenanthroline; oxygen; potassium carbonate; copper(l) chloride In benzene for 2h; Heating; | |
10% | With silver ferrate In benzene for 2h; Heating; | |
10% | With oxygen; potassium carbonate In water at 100℃; for 7h; | Typical oxidation of alcohols General procedure: Into a reaction vessel with a reflux condenser were placed Pd-pol (23.1 mg, Pd%w = 2.3), benzyl alcohol (108.1 mg, 1.0 mmol), K2CO3 (138.2 mg, 1.0 mmol) and water (5 mL). The resulting mixture was stirred at 100°C under 1 atm of air. After 6 h, the mixture was cooled down to room temperature and the organic product was extracted with ethyl acetate (3 mL). The water phase was washed with ethyl acetate (2×5 mL) and the organic layers were collected. GLC analysis of the ethyl acetate solution using biphenyl as an internal standard gave a 98% yield of benzyl aldehyde with >99% selectivity. |
With sodium hypochlorite In tetrachloromethane; water at 60 - 65℃; Yield given; | ||
With chromium trioxide-pyridine complex In dichloromethane | ||
74 % Chromat. | With tert.-butylhydroperoxide In tetrachloromethane for 1h; Heating; | |
49 % Chromat. | With oxygen; 2-ethoxycarbonyl-1-cyclopentanone In acetonitrile at 60 - 70℃; | |
With tert.-butylhydroperoxide; 3 A molecular sieve In dichloromethane; toluene at 60℃; for 1h; other catalyst: silica gel/Zr(OR)x; | ||
With isoquinolinium chlorochromate In dichloromethane | ||
With potassium hydroxide In tetrahydrofuran | ||
With pyridine; N-(2,2,6,6-tetramethyl-1-oxopiperidin-1-ium-4-yl)acetamide tetrafluoroborate In dichloromethane at 20℃; | ||
88 % Chromat. | With N-chloro-succinimide; N-(phenylthio)-N-(tert-butyl)amine; potassium carbonate In dichloromethane at 20℃; for 1h; | |
With benzimidazolium fluorochromate at 20℃; for 4h; | ||
With [2,2]bipyridinyl; oxygen; 4-methoxy-2,2,6,6-tetramethylpiperidin-1-oxyl radical In water; acetonitrile at 25℃; for 29h; | ||
With quinoxalinium fluorochromate In dichloromethane for 0.00555556h; Microwave irradiation; | ||
90 % Turnov. | With 2,2,6,6-tetramethyl-piperidine-N-oxyl; trichloroisocyanuric acid In dichloromethane at 20℃; for 0.25h; | |
With 4-benzylpyridinium fluorochromate at 20℃; for 2.16667h; | ||
With oxygen In toluene at 100℃; for 9h; chemoselective reaction; | 2.4. Catalytic oxidation experiments General procedure: The reactions were carried out in a stainless steel reactor equipped with a magnetic stirrer. In a typical run, a mixture of the substrate (1.0 mmol), toluene (5 mL), and the catalyst (0.02-0.2 g; ca. 0.45-4.5 wt.%; Ru: 0.28-2.80 mol%) was transferred in the reactor. The reactor was pressurized with oxygen to the total pressure of 10 atm and placed in an oil bath; then, the solution was intensively stirred at 80-120 °C for the reported time. The reactions were followed by gas chromatography (GC) (Shimadzu 17 instrument, Carbowax 20 M capillary column). To take the aliquots for the GC analysis at appropriate time intervals, stirring was stopped and the catalyst was quickly settled by the application of an external permanent magnet. The structures of the products were confirmed by GC/MS (Shimadzu QP2010-PLUS instrument, 70 eV). | |
88 %Chromat. | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium <i>tert</i>-butylate; copper(ll) bromide In water; acetonitrile for 4h; air; | |
With pyridine; oxygen; palladium diacetate; potassium carbonate In toluene at 80℃; chemoselective reaction; | ||
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; [bis(acetoxy)iodo]benzene | ||
With 3,5-dimethylpyrazolium chlorochromate at 20℃; for 0.0833333h; Neat (no solvent); | ||
With oxygen In methanol at 120℃; for 8h; Stainless steel reactor; | 2.3. Catalytic oxidation experiments General procedure:The reactions were carried out in a stainless steel reactor equipped with a magnetic stirrer. In a typical run, a mixture of the substrate (0.4-1.2 mmol), solvent (if any) (2 mL), and the catalyst (10-40 mg; ca. 0.6-2.4 wt.%; Au: 0.01-0.75 mol%) was transferred in the reactor. The reactor was pressurized with oxygen to the total pressure of 10 atm and placed in an oil bath; then, the solution was intensively stirred at 80-130 °C for the reported time. The reactions were followed by gas chromatography (GC) (Shimadzu 17 instrument, Carbowax 20 M capillary column). At appropriate time intervals, stirring was stopped and after catalyst settling aliquots were taken and analyzed by GC. To ensure correct GC results in solvent-free reactions and in those with high initial substrate concentrations, the aliquots were diluted with methanol before the analysis. The structures of the products were confirmed by GC/MS (Shimadzu QP2010-PLUS instrument, 70 eV). | |
With [Rh((5-H-dibenzo[a,d]cyclohepten-5-yl)2NH)(PPh3)]OTf; potassium carbonate; Nitrosobenzene In tetrahydrofuran at 20℃; | ||
With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium bromide In dichloromethane at 0℃; | ||
With oxygen In toluene at 100℃; for 1.5h; Green chemistry; | ||
With oxygen In toluene at 100℃; for 1.5h; | 2.3. Typical Procedure for Alcohol Oxidation. General procedure: Liquid-phaseoxidation of 1-phenylethanol was performed in glass flaskequipped with a magnetic stirrer, reflux condenser, andthermometer. In a typical experiment, a mixture of the1-phenylethanol (2mmol), toluene (10 mL), and the catalyst(0.3 g) was transferred in a glass three-necked roundbottomedflask (100 mL); the resulting mixture was thenheated to desired temperature with vigorous stirring. Theoxidation experiment was started by bubbling oxygen gas ata flow rate of 20 mL/min into the reaction mixture. After thereaction, the solid catalyst was filtered off by centrifugationand the liquid productswere analyzed by gas chromatographyto determine the conversion of the alcohol and productselectivity by GC, 7890A,Agilent Technologies Inc., equippedwith a flame ionization detector (FID) and a 19019S-001 HPPONAcolumn. | |
With oxygen In water at 80℃; for 4h; Inert atmosphere; Schlenk technique; | ||
With oxygen In toluene at 100℃; for 1.33333h; | ||
With 2,2'-azinobis(3-ethylbenzthiazolinesulfonate); horse-radish peroxidase; choline oxidase from Arthrobacter cholorphenolicus In aq. phosphate buffer at 30℃; for 24h; Enzymatic reaction; | ||
With rhodococcus hoagii NBRC 3730; sodium chloride In decane for 336h; | 2.4. Oxidation of citronellol, 2-methylcyclohexanol, and 2-octanol by R.hoagii NBRC 3730 General procedure: Oxidation activities to these substrates by R. horgii NBRC 3730 werecompared among submerged cultivation (SmC), organic-aqueous twoliquid-phase (TLP), and L-L IBRtac systems. The strain was cultivated in25 ml of B-medium at 30 °C with rotation (200 rpm) for 1 day as a seedbroth. Concerning the SmC, the seed broth (225 μl) was inoculated into15 ml of B-medium prepared in a 100 ml-Erlenmeyer flask. After precultivationat 30 °C with rotation (200 rpm) for 1 day, 150 μl of citronellol,2-methylcyclohexanol or 2-octanol was added and the incubationwas continued for 14 days. Two ml of a broth was sampled,added excess NaCl, and thrice extracted with ethyl acetate. The productswere determined by gas chromatography (GLC). As for the TLP,each substrate was added into the 1-day broth as 3 ml of a 5% solutionin n-decane, and incubation was continued for 14 days. The organicphase was directly analyzed by the GLC. | |
93 %Chromat. | With 1-methyl-1H-imidazole; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; C23H16CuF5N2O5S In acetonitrile at 20℃; for 24h; | 2.3. Oxidations General procedure: A series of catalytic oxidation reactions was performed in 5 ml/3 mlMeCN solutions at room temperature under open air. The reaction wasset up by adding 1 mmol of 1-octanol, 5 mol % of copper(I)catalyst,5 mol % of TEMPO and 10 mol % of NMI into a 20 ml test tube, whichwas equipped with a magnetic stirrer bar. The reaction was stirred1500 rpm for 24 h for 1-octanol, 3 h for cinnamyl alcohol and 3-phenyl-1-propanol and 1 h for benzyl alcohol. After the reaction, 0.7 ml of thereaction solution and an internal standard (acetophenon 40 μl or 1,2-dichlorobenzene 40 μl, more information see ESI) were diluted withEtOAc (100 ml). GC samples (1.5 ml) were prepared by filtrating thesolution through a layer of silica gel (1 cm thick). The yields were determinedusing GC-MS with calibration curves. |
0.98 g | With polystyrene-loaded 2-iodylbenzoic acid resin In dichloromethane at 20℃; for 0.5h; | 3 Example 3 The polymer-loaded oxidant containing high valence iodine prepared by the present invention is mainly used for alcohol oxidation. The reaction formula of polymer-loaded oxidant containing high-valency iodine and alcohol oxidation is shown in FIG. 2.Specifically, in this example, 50 ml of methylene chloride, 10 g of polymer-loaded oxidant resin and 1.1 g of citronellol (molecular weight 156) were added to the reaction bottle equipped with a mechanical stirrer, and stirred at room temperature for 30 Minutes; gas chromatography monitoring, citronellol completely converted to citronellal; filtered, filtered resin was washed with 10 ml of dichloromethane, the combined clear solution was concentrated to obtain citronellal 0.98 g, purity>98%. |
With oxygen at 100℃; for 1.75h; Green chemistry; | ||
91 %Chromat. | With 1-methyl-1H-imidazole; copper(l) iodide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; C12H8F3NOS In acetonitrile at 20℃; for 24h; | 2.3. Oxidations General procedure: Oxidation reactions were performed in 3 ml or 5 ml MeCN solutionsat room temperature under open air conditions. The reaction was set upby adding 4 mol% of copper(I)iodine, 4 mol% of ligand, solvent, 5 mol%of TEMPO, 1 mmol of alcohol and 10 mol% of NMI into a 20 ml test tube,which was equipped with a magnetic stir bar. The reaction was stirred at 1500 rpm for 1 h, 3 h or 24 h depending on the substrate.After the reaction, the reaction solution and an internal standard(acetophenone 40 μL or 1,2-dichlorobenzene 40 μL, see ESI for moreinformation) were diluted with EtOAc (50 mL). GC samples (1.5 mL)were prepared by filtrating the solution through a layer of silica gel (1cm thick). The yields were determined using GC-FID with calibration curves and identified using GC-MS and/or 1H/13C/HMBC/HSQC NMR. |
99 %Chromat. | With copper(l) iodide; di(pyridin-2-yl)amine; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In acetonitrile at 20℃; for 24h; | Oxidations General procedure: Oxidation reactions were performed in 3 mL MeCN or in a mixture of2 mL MeCN and 1 mL H2O solutions at room temperature under open airconditions. The reaction was set up by adding 2.5 mol% of copper(I)iodine, 2.5 mol% of ligand, 3 mL solvent, 4 mol% of TEMPO and 1 mmol of alcohol into a 20 ml test tube, which was equipped with a magneticstir bar. The reaction was stirred at 1500 rpm for 1 h, 3 h or 24 h depending on the substrate. After the reaction, the reaction solution andan internal standard (acetophenone 40 μL or 1,2-dichlorobenzene 40 μL,see ESI for more information) were diluted with EtOAc (50 mL). GCsamples (1.5 mL) were prepared by filtrating the solution through alayer of silica gel (1 cm thick). The yields were determined using GC-FIDwith calibration curves and identified using GC-MS and/or 1H/13C/HMBC/HSQC NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.84 g | With dihydrogen peroxide; sodium bromide In <i>tert</i>-butyl alcohol at 25℃; for 1h; aq. buffer; Enzymatic reaction; regioselective reaction; | |
With cerium(IV) oxide; N-Bromosuccinimide In water; acetone at 20℃; for 0.25h; | 2.2. General Procedure for Bromohydroxylation of Terpenes. General procedure: In a typical experiment, N-bromosuccinimide (1.3 equiv.)and 0.04 g of catalyst were added to a vigorously stirredsolution of terpene (0.4 g) in aqueous acetone (4 : 1, v/v). (emixture was stirred at room temperature for 15 min. (ereaction was monitored by GC. At the end of the reaction,the mixture was diluted with water and extracted three timeswith EtOAc (10 mL). (e organic layer was dried overNa2SO4 and then concentrated, and the residue was puriedby column chromatography using silica gel with EtOAcheptane(3 : 7, v/v) as eluent. the obtained pure bromoalcoholswere characterized by mass spectrometry, ATRIR,MS/ESI measurements, and NMR spectroscopy. Characterizationdata can be found in ESI | |
1.1 g | With N-Bromosuccinimide; water In acetone at 20℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 8 % Chromat. 2: 18 % Chromat. | With methanol; samarium diiodide In tetrahydrofuran for 24h; Ambient temperature; Yields of byproduct given. Title compound not separated from byproducts; | |
With methanol; samarium diiodide In tetrahydrofuran for 24h; Ambient temperature; Yields of byproduct given. Title compound not separated from byproducts; | ||
With hydrogen In hexane at 174.84℃; for 2.5h; |
With hydrogen In carbon dioxide at 49.84℃; for 0.25 - 3h; | ||
With hydrogen In hexane | ||
With hydrogen | ||
With hydrogen In hexane | ||
With hydrogen In carbon dioxide at 35 - 70℃; for 0.25 - 6h; | ||
With hydrogen | ||
With hydrogen In toluene at 70℃; for 4h; | ||
With hydrogen In hexane at 70℃; for 4h; | ||
With hydrogen In benzene at 70℃; for 4h; | ||
With hydrogen In ethanol at 70℃; for 4h; | ||
With hydrogen In carbon dioxide at 35 - 80℃; for 0.25 - 6h; | ||
With hydrogen at 70℃; for 4h; | ||
With Pt/MCM-41; carbon dioxide; hydrogen at 70℃; for 4h; Supercritical conditions; Autoclave; | ||
With dichloro(benzene)ruthenium(II) dimer; sodium formate In water at 70℃; for 3h; Sealed glass reactor; | ||
With hydrogen In water at 80℃; Autoclave; | ||
1: 43.5 %Chromat. 2: 19.4 %Chromat. 3: 16.2 %Chromat. 4: 15.1 %Chromat. | With C54H42ClO9P3RhS3(3-)*3Na(1+); sodium formate; sodium 3-(diphenylphosphanyl)benzenesulfonate In water; isopropyl alcohol at 70℃; for 1h; Inert atmosphere; | |
With hydrogen In ethanol at 80℃; for 3.5h; Autoclave; | ||
With hydrogen In isopropyl alcohol at 160℃; Sealed tube; | ||
With hydrogen; sodium hydroxide In ethanol at 25℃; for 1h; chemoselective reaction; | Catalytic Testing The liquid-phase hydrogenation of citral was carriedout at P = 1 atm and T = 25°C. The catalyst (13 or 25 mg) was placed in a two-necked flask, and the systemwas purged with hydrogen for 30 min. A solutionof 0.3 mmol of citral in 1.5 mL of EtOH was then poured into the reactor using a feed valve. Depending on the content of platinum in the catalyst, the amount of Pt in the reaction mixture was 0.8-0.2 mol %. The reaction mixture was stirred with a magnetic stirrer at a speed of 1400 rpm. At the end of each experiment, the liquid phase was separated from the catalyst via centrifugation and the supernatant was sampled to analyze the reaction products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic acid In water; N,N-dimethyl-formamide electochemical reduction, various reaction conditions; | ||
With dichloro(benzene)ruthenium(II) dimer; sodium formate In water at 80℃; for 3h; Sealed glass reactor; | ||
With Pt(5wt%)Sn(3wt%)/Al2O3; hydrogen In isopropyl alcohol at 70℃; for 2h; |
1: 39.8 %Chromat. 2: 8.9 %Chromat. 3: 7.2 %Chromat. | With C54H42ClO9P3RhS3(3-)*3Na(1+); sodium formate; sodium 3-(diphenylphosphanyl)benzenesulfonate In water; isopropyl alcohol at 40℃; for 1h; Inert atmosphere; | |
With hydrogen In ethanol at 80℃; for 3.5h; Autoclave; | ||
With hydrogen In n-heptane at 90℃; chemoselective reaction; | 2.4. Catalytic performance The citral hydrogenation was carried out in 100 ml heptanesolution at a constant hydrogen pressure of 8.3 bar and 90 °C usinga Parr reactor model 5500. The experimental conditions such ascitral concentration, catalyst weight and stirring speed, were previouslyoptimized in order to avoid mass transfer limitations (resultsnot showed) and fixed in 0.05 M, 500 mg and 1500 rpm, respectively.A small volume of the sample (1 mL) was periodically withdrawnand analysed by chromatography using a Bruker 430-GCequipped with a FID detector and a Varian GC Capillary ColumnCP7485 (25 m 0.32 mm 0.45 μm). Citral and all possible productswere previously calibrated. | |
With hydrogen; zinc(II) acetylacetonate at 85℃; for 5h; Autoclave; | 2 Comparative Example 2 Under the anaerobic and anhydrous atmosphere,Into a 1 L hydrogenation kettle, 0.009 g of zinc acetylacetonate and 500 g of citral were successively added.Seal the autoclave, replace with nitrogen and hydrogen three times, and start heating and stirring.When the temperature rose to 85 , hydrogen gas was charged to 2MPa, and maintained for 5h until the end of the reaction.The results of the reaction were analyzed by GC and the results are shown in Table 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With lithium aluminium tetrahydride In tetrahydrofuran for 4h; 0 to 20 deg C; Yield given; | ||
With C30H34Cl2N2P2Ru; potassium methanolate; hydrogen In tetrahydrofuran at 100℃; for 5h; Glovebox; Autoclave; chemoselective reaction; | 28 Example 28: Chemoselective hydrogenation of ester compounds catalyzed by ruthenium complex Ia General procedure: In a glove box, add a ruthenium complex Ia (0.7 mg, 0.001 mmol),Potassium methoxide (35-175 mg, 0.5-2.5 mmol), tetrahydrofuran (5-20 mL), and ester compounds (10-50 mmol).After sealing the autoclave, take it out of the glove box and fill it with 50atm of hydrogen.The reaction kettle was heated and stirred in an oil bath at 100 ° C for 10 to 24 hours.After the reaction kettle was cooled in an ice-water bath for 1.5 hours, the excess hydrogen was slowly released.The solvent was removed from the reaction solution under reduced pressure, and the residue was purified with a short silica gel column to obtain an alcohol compound. The results are shown in Table 6. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With [RuCl2((E)-N-(2-(diphenylphosphino)benzyl)-1-(6-((diphenylphosphino)methyl)pyridin-2-yl)methanimine)]; hydrogen; sodium ethanolate at 80℃; for 5h; Autoclave; | 10 General hydrogenation reaction procedure: General procedure: Ester, ruthenium catalyst , metal alkoxide co-catalyst (used as a solid or some alcoholic solution) and optionally solvent (see Table 1) were loaded altogether in an 100 mL or 1L autoclave equipped with a mechanical stirring device, pressure and internal temperature sensors and a heating/cooling system for internal temperature regulation. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to required hydrogen pressure via an hydrogen tank equipped with a way out pressure regulator and also an internal pressure sensor to follow and determine hydrogen consumption. Reaction mixture was then heated to required temperature and hydrogen pressure into the autoclave was maintained to the desired value during the whole reaction. Upon reaction completion also determined by GC analysis with complete disappearance of both starting material and mixed ester coming from transesterification reaction with product and eventually with metal alkoxide co-catalyst and/or alcoholic solvent, autoclave was then cooled down to 25 °C. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and lights compounds were removed under vacuum. Crude product was then flash distilled in order to determine the quantity of residues formed during the reaction and yield was calculated based on GC purity of distilled product. |
With lithium aluminium tetrahydride Yield given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With hydrogen; benzyl bromide In methanol for 0.5h; | |
98% | With aluminium trichloride; <i>N</i>,<i>N</i>-dimethyl-aniline In dichloromethane for 1.5h; Ambient temperature; | |
89% | With naphthalene; lithium In tetrahydrofuran; methanol at -78℃; for 40h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | Stage #1: Citronellol With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Stage #2: benzyl bromide With sodium iodide In tetrahydrofuran for 5h; Heating; | |
58% | Stage #1: Citronellol With sodium hydride In tetrahydrofuran; hexane for 2h; Heating; Stage #2: benzyl bromide With tetra-(n-butyl)ammonium iodide In tetrahydrofuran; hexane for 18h; Heating; Further stages.; | |
With sodium hydride 1.) dimethoxyethane, room temperature, 2 h, 2.) room temperature, 40 h; Yield given. Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With pyridine at 0 - 5℃; for 1h; | 2 4.2. 2,6-Dimethyl-2-icosene (10) (+-)-Citronellol (8, 8.0 g, 53 mmol) in dry C5H5N (30 mL) was treated with TsCl (11.5 g, 72 mmol) with stirring and ice-cooling (0-5 °C) for 1 h. Subsequent work-up gave 17.9 g (quant.) of 9, νmax (film): 2963 (s), 2925 (s), 1598 (m), 1362 (s), 1189 (s), 1176 (s), 946 (s), 890 (m), 815 (m), 764 (m), 664 (s). A Grignard reagent was prepared from n-C12H25Br (19.1 g, 76.5 mmol) and Mg (2.0 g, 82 mmol) in dry THF (20 mL). A solution of 9 (17.9 g, 53 mmol) in dry THF (30 mL) was added to the stirred and cooled Grignard reagent at -70 °C under argon. A solution of Li2CuCl4 in THF (0.1 M, 3 mL, 0.3 mmol) was added to the stirred mixture at -70 °C. The mixture was stirred at -60 to -70 °C for 2 h, and left to stand overnight with gradual raise of the temperature. Usual work-up gave 22.4 g of crude 10 as an oil, νmax (film): 2956 (s), 2925 (s), 2853 (s), 1465 (m), 1377 (m), 1072 (m), 721 (m), 676 (w). |
93% | With potassium hydroxide; potassium carbonate for 0.05h; | |
92% | With pyridine In chloroform for 0.5h; sonication; |
91.3% | In pyridine at 0℃; for 72h; | |
83% | With trimethylamine hydrochloride; triethylamine In dichloromethane at 0℃; for 2h; Inert atmosphere; | |
75% | With pyridine In chloroform for 3.5h; | |
58% | Stage #1: Citronellol With dmap; triethylamine In dichloromethane for 0.0833333h; Inert atmosphere; Stage #2: p-toluenesulfonyl chloride In dichloromethane at 0 - 20℃; for 12h; Inert atmosphere; | The 3,7-dimethyloct-6-en-1-ol (1.56 g, 10 mmol) and a stir bar were added to a 100 mL round flask, thenDCM (20 mL), Et3N (2.6 mL, 20 mmol, 2 eq) and DMAP (0.18 g, 1.5 mmol, 0.2 eq) were added. Themixture was stirred for 5 min and cooled to 0 °C, then TsCl (2.1 g, 11 mmol, 1.1 eq) was added. Afteraddition, the ice bath was removed and the mixture was kept stirring for 12 hours. The full consumption ofthe starting alcohol was confirmed by TLC. Water (20 mL) was added to the mixture and extracted withDCM (10 mL×3), the organic layers were combined and dried over Na2SO4 and concentrated undervacuum. Column chromatography gave a colorless oil (1.8 g, 58%). 1H NMR (CDCl3, 400 MHz): δ 7.79 (d, J = 8.4 Hz, 2H), 7.36 - 7.32 (m, 2H), 5.02 (dddd, J = 7.1, 5.7, 2.9,1.4 Hz, 1H), 4.12-4.01 (m, 2H), 2.45 (s, 3H), 1.99-1.79 (m, 2H), 1.73-1.63 (m, 4H), 1.57 (s, 3H), 1.54-1.37(m, 2H), 1.24 (m, 1H), 1.10 (m, 1H), 0.81 (d, J = 6.5 Hz, 3H). 13C{1H} NMR (CDCl3, 101 MHz): δ 144.60,133.24, 131.44, 129.77, 127.86, 124.29, 69.02, 36.68, 35.63, 28.84, 25.66, 25.23, 21.60, 19.01, 17.59.The NMR spectra are consistent with literature report4. CAS registry No. 41144-01-8 |
55% | With triethylamine In dichloromethane at 0 - 20℃; for 14h; Inert atmosphere; | |
49% | With pyridine at 0 - 20℃; for 12h; | |
With pyridine at 0℃; | ||
30.2 g | With pyridine for 5h; | |
With pyridine at 0 - 4℃; Yield given; | ||
19.4 g | With pyridine at 0 - 20℃; | |
With pyridine In dichloromethane at 4℃; for 17h; | ||
With pyridine at 5℃; for 4h; | ||
With pyridine | ||
In pyridine at 0℃; for 24h; | ||
With pyridine at 0℃; for 3.5h; | ||
With potassium carbonate In neat (no solvent) for 0.0833333h; Milling; Green chemistry; | ||
12.2 g | Stage #1: Citronellol With pyridine for 0.5h; Stage #2: p-toluenesulfonyl chloride at 0℃; | 3,7-Dimethyl-6-octenyltosylate (4). To a solution of citronellol(10 g, 64.1 mmol), dry pyridine (61 mL, 769 mmol)was addedand stirred for 30 min. Then the temperature was brought down to 0 C and p-toluenesulfonyl chloride (18.26 g, 96.15 mmol) wasadded. Upon completion of the reaction, the solution was pouredinto a mixture of ice cold water and HCl (50 mL) and extracted withethyl acetate (2 50 mL). The organic phase was washed withdilute HCl (50 mL), water (50 mL), saturated aqueous NaHCO3(50 mL) and brine (50 mL) and dried in Na2SO4, concentrated invacuo to give an oil which was purified by column chromatography (SiO2, Hexane: EtOAc, 9.5: 0.5) to give as an oil in 61% Yield (12.2 g).IR (KBr, cm1): y1599, 1362, 1177, 815, 664. 1HNMR (400 MHz,CDCl3): d 7.80 (d, J 8.8 Hz, 2H), 7.35 (d, J 8.8 Hz, 2H), 5.02 (t, J 8.4 Hz, 1H), 4.09e4.03 (m, 2H), 2.45 (d, J 2.8 Hz, 3H), 1.98e1.84(m, 2H), 1.71e1.65 (m, 6H), 1.54e1.40 (m, 2H), 1.26e1.22 (m, 1H),1.13e1.03 (m, 2H), 0.85e0.79 (m, 3H) ppm. 13CNMR (100 MHz,CDCl3): d144.6, 133.1, 131.4, 129.8, 127.8, 124.3, 69.1, 36.6, 35.6, 28.8,25.7, 25.2, 21.6, 19.0, 17.6 ppm. ESI-MS (m/z): 328 (M NH4). |
With pyridine; dmap In dichloromethane at 0 - 20℃; for 25h; | ||
With dmap; triethylamine In dichloromethane at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With 1H-imidazole In N,N-dimethyl-formamide for 2h; Ambient temperature; | |
89% | With 1H-imidazole In dichloromethane at 0 - 20℃; Inert atmosphere; | |
With 1H-imidazole; dmap In dichloromethane for 5h; Ambient temperature; Yield given; |
With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With triethylamine In dichloromethane at 0℃; for 3h; Inert atmosphere; | 6 4.6 5-(Benzyloxy)pentyl methanesulfonate (7a) [47] General procedure: Freshly distilled methanesulphonyl chloride (2.3 mL, 30.9 mmol) was added drop wise to a stirred solution of 5-(benzyloxy)pentane-1-ol (4 g, 20.6 mmol) and Et3N (4.3 mL, 31 mmol) in dry dichloromethane (45 mL) at 0 °C. After 3 h, the reaction mixture was diluted with water, and extracted with dichloromethane. The organic extract was concentrated under vacuum to give mesylate 7a (5.3 g, 95%). IR (film): υυ 3427, 3034, 2943, 2860, 2519, 2315, 1959, 1732, 1460, 1352, 1172, 1096, 952, 832, 741, 695, 612, 521 cm-1. 1H NMR (200 MHz, CDCl3): δ 1.50-1.85 (m, 6H, 3 × CH2), 2.99 (s, 3H, OSO2CH3), 3.48 (t, 2H, 3JHH = 6.0 Hz, CH2OCH2Ph), 4.22 (t, 2H, 3JHH = 6.4 Hz, SO2CH2), 4.50 (s, 2H, PhCH2), 7.27-7.35 (m, 5H, Ph). 13C NMR (50 MHz, CDCl3): δ 22.0, 28.6, 28.8, 36.9, 69.6, 69.9, 72.6, 127.3, 127.4 (2C), 128.1 (2C), 138.3. |
97% | With triethylamine In dichloromethane at 0 - 20℃; for 24.3h; | |
94% | With triethylamine In dichloromethane at 0 - 20℃; for 16h; Inert atmosphere; |
91% | With pyridine In pentane at 20℃; Inert atmosphere; Cooling with ice; | |
75% | With triethylamine In acetonitrile at 40℃; for 0.333333h; Flow reactor; | |
With triethylamine In dichloromethane at 0℃; for 1h; | ||
With triethylamine In tetrahydrofuran at 0 - 20℃; for 2.5h; | A typical one-pot preparation of sulfide 3 (entry 1 in Table 1) General procedure: To a solution of n-pentanol (0.440 g, 5.0 mmol) in THF (20.0 mL) at 0 C were added methansulfonyl chloride (0.465 mL, 6.0 mmol) and triethylamine (0.906 mL, 6.5 mmol). After the mixture was stirred at RT for 1.5 h, a solution of 5-mercapto-1-phenyl-1H-tetrazole (0.891 g, 5.0 mmol) and NaH (0.46 g, 11.5 mmol) in THF (5.0 mL) was added at 0 C. The resulting mixture was stirred at RT for 16 h. The reaction was quenched with sat. NH4Cl aq., and the mixture was extracted with AcOEt (3 10 mL). The combined extracts were washed with brine, dried (MgSO4), and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hex:AcOEt = 8:1) to afford 3a (1.076 g, 86%) as a colorless oil. 1 H NMR (400 MHz, CDCl3) d 0.91 (3H, t, J = 7.3 Hz), 1.31-1.47 (4H, m), 1.83 (2H, quin, J = 7.3 Hz), 3.40 (2H, t, J = 7.3 Hz), 7.51-7.61 (5H, m) [16]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With pyridine In dichloromethane at 20℃; | |
99% | With C12H8N2*2CH4O3S at 60℃; for 3h; | |
98% | With iodine at 25℃; for 0.0166667h; |
96% | With silica-supported phosphomolybdic acid at 20℃; for 0.133333h; | |
95% | With lanthanum(III) nitrate at 20℃; for 0.166667h; | |
95% | With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 16h; | 44 PREPARATION 44: 3,7-dimethyloct-6-en-1-yl acetate To a solution of 3,7-dimethyloct-6-en-1-ol (10 g, 63.99 mmol) in DCM (100 mL) were added DIPEA (24.81 g, 191.98 mmol, 33.44 mL) and Ac2O (7.19 g, 70.39 mmol, 6.59 mL). The mixture was stirred at 20°C for 16 hours. TLC (petroleum ether/EtOAc = 10:1, Rf =0.79) indicated the starting material was consumed and one major new spot with lower polarity was detected. The reaction mixture was concentrated under reduced pressure and purified by column chromatography (SiO2) using a gradient of petroleum ether/EtOAc (1:0 to 100:1) to give the title compound as a colorless oil (12 g, 95%).1H NMR (CDCl3) δ ppm 5.06 - 5.10 (m, 1H), 4.06 - 4.13 (m, 2H), 2.03 (s, 3H), 1.68 - 1.95 (m, 2H), 1.64 - 1.65 (m, 1H), 1.53 - 1.60 (m, 4H), 1.44 - 1.45 (m, 3H), 1.34 - 1.42 (m, 1H), 1.17 - 1.19 (m, 2H), 0.92 - 1.17 (d, 1H), 0.90 (d, 3H). |
95% | With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 16h; | 44 PREPARATION 44: 3,7-dimethyloct-6-en-1-yl acetate To a solution of 3,7-dimethyloct-6-en-1-ol (10 g, 63.99 mmol) in DCM (100 mL) were added DIPEA (24.81 g, 191.98 mmol, 33.44 mL) and Ac2O (7.19 g, 70.39 mmol, 6.59 mL). The mixture was stirred at 20°C for 16 hours. TLC (petroleum ether/EtOAc = 10:1, Rf =0.79) indicated the starting material was consumed and one major new spot with lower polarity was detected. The reaction mixture was concentrated under reduced pressure and purified by column chromatography (SiO2) using a gradient of petroleum ether/EtOAc (1:0 to 100:1) to give the title compound as a colorless oil (12 g, 95%).1H NMR (CDCl3) δ ppm 5.06 - 5.10 (m, 1H), 4.06 - 4.13 (m, 2H), 2.03 (s, 3H), 1.68 - 1.95 (m, 2H), 1.64 - 1.65 (m, 1H), 1.53 - 1.60 (m, 4H), 1.44 - 1.45 (m, 3H), 1.34 - 1.42 (m, 1H), 1.17 - 1.19 (m, 2H), 0.92 - 1.17 (d, 1H), 0.90 (d, 3H). |
92% | With nickel dichloride at 20℃; for 0.416667h; Neat (no solvent); | |
92% | In pyridine at 0 - 30℃; for 12h; | |
90% | at 20℃; for 6h; | |
62% | With nickel dichloride for 0.133333h; microwave irradiation; | |
With pyridine; dmap | ||
With pyridine | ||
With triethylamine In dichloromethane at 20℃; for 16h; | ||
With immobilized enzyme Novozym 435<SUP>®</SUP> at 150℃; Enzymatic reaction; | ||
93.1 %Spectr. | With sulfonated biochar at 20.1℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With mesoporous p-hydroxybenzenesulphonic acid-formaldehyde polymer resin In neat (no solvent) at 20℃; for 1.3h; chemoselective reaction; | 2.3. Typical procedure for tetrahydropyranylation of alcohol using PAFR catalyst General procedure: As a pilot protocol, a mixture of 1-octanol (0.130 g, 1 mmol), DHP (0.084 g, 2 mmol) and PAFR catalyst (0.025 g, 7.48 mol%) was mechanically stirred in a small reaction vessel at room temperature. The progress of the reaction was monitored by thin layer chromatography (TLC). After completion of the reaction as indicated by TLC, the catalyst was separated by simple filtration and the reaction mixture was extracted with ethyl acetate, the extracted compound thus obtained was then charged into a short silica gel chromatography column using hexane/ethyl acetate (9:1 ratio) as eluent to afford 98% of isolated yield of desired product. |
90% | With lanthanum(III) nitrate at 20℃; for 2.5h; | |
89% | With 1-butyl-3-methylimidazolium hydrogen sulfate for 0.025h; microwave irradiation; |
84% | With Fe3O4 supported silica sulphuric acid nanoparticle In neat (no solvent) at 20℃; for 0.833333h; Green chemistry; | |
82% | With tin(ll) chloride In chloroform for 0.333333h; Ambient temperature; | |
96 % Spectr. | With Ersorb-4 zeolite at 20℃; for 1.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 88% 2: 10% | With hydrogen; silver In tetrahydrofuran at 150℃; for 72h; | 13 (Selective Hydrogenation of Aldehyde Group) Catalysts E to G for Examples obtained in Production Example 4 were each 0.008 mmol in terms of metal equivalent of silver, incidentally, as a substrate having a carbon-carbon double bond and an aldehyde group, 0.25 mmol of citral (a mixture of cis-trans isomers geranial and neral 2: 1), solvent 5 ml of tetrahydrofuran (THF), hydrogen pressure 1.5 MPa, Hydrogenation reduction treatment was carried out at a reaction temperature of 150 ° C reaction time is In each of Examples 11 to 13, it was 72 hours, by using gas chromatograph, yield, selectivity was measured. The results are shown in Table 5. |
1: 54% 2: 46% | With sodium cyanoborohydride at 20℃; for 0.05h; | |
With (triphenylphosphine)copper(I) hydride hexamer; hydrogen; Dimethyl(phenyl)phosphine In <i>tert</i>-butyl alcohol; benzene at 20℃; for 15h; Title compound not separated from byproducts; |
With hydrogen In isopropyl alcohol at 119.84℃; | ||
With [Ru(H)(CO)(CH3CN)(TPPMS)3][BF4]; hydrogen In water; toluene at 100℃; for 24h; chemoselective reaction; | ||
With hydrogen In tetrahydrofuran at 150℃; for 3h; Autoclave; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With 2,5-bis(perfluorobutyl)-1,4-benzoquinone In water; acetonitrile at 20℃; for 6h; | |
80% | With oxone In methanol at 20℃; for 15h; | |
76% | With bismuth(III) chloride; sodium iodide In acetonitrile at 20℃; for 1.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.9% | With Candida antarctica lipase B at 50℃; for 4h; Molecular sieve; Ionic liquid; Green chemistry; Enzymatic reaction; | |
95% | With ZrCl4-Mg(ClO4)2 composite In neat (no solvent) at 20℃; for 0.133333h; | Typical experimental procedure for the onepotsynthesis of benzyl acetate General procedure: A mixture of 4-methoxy benzyl alcohol (1b, 1 mmol),acetic acid (3 mmol), 2 mol% ZrCl4-Mg(ClO4)2 catalyst was stirred at room temperature for the time specified inTable 5. After completion of reaction (monitored by TLC),the solid or liquid product was filtered and washed with25 ml diethyl ether and water. The organic layer wassuccessively washed with saturated NaHCO3 solution. Theorganic layer was dried over anhydrous sodium sulfateand evaporated of the solvent under reduced pressure toprovide a residue which was passed through a short padof silica gel (60-120 mesh) using hexane as eluent to providethe analytically pure acylated product (please seeAppendix S1).Note that as we know that esterification is a reversiblereaction, to avoid this reversible we used every time activatedmolecular sieves as dehydrating agent/waterabsorbing agent. We have not mentioned it in our actualexperimental procedure. |
90% | With cetyltrimethylammonium chloride; potassium hexacyanoferrate(III) at 80℃; for 1h; |
With molecular sieve at 120℃; for 8h; | ||
With tin(II) chloride dihdyrate In acetonitrile at 24.84℃; for 6h; | ||
With N,N′,N′′,N′′′-hexadecyltrimethylammonium bis(trifluoromethylsulfonyl)imide; Novozym 435 (immobilized Candida antarctica lipase B) at 50℃; for 4h; Green chemistry; Enzymatic reaction; | Lipase-catalyzed synthesis of flavour esters in sponge-like ionic liquid (SLILs) Three mmol of citronellol, geraniol, nerol or anisyl alcohol, and 1, 2 or 3mmol of acetic acid were added to 3mL screw-capped vials with teflon-lined septa. Then, the corresponding amount of [C16tma][NTf2] was added to reach a final IL concentration of 60 or 70% (w/w) with respect to the mass substrates. Reaction mixtures were pre-incubated at 50°C for 10min, resulting in fully clear monophasic systems. Then, 80mg of MS13× per mmol of carboxylic acid were also added. The reaction was started by adding Novozym 435 (40mg/mmol of carboxylic acid) and the reaction was incubated for 4h at 50°C while shaking (300rpm), or under 4W microwave irradiation (which provided a 50°C constant temperature). For products analysis, aliquots (20μL) were taken at selected times and suspended in 500μL octane, and the resulting biphasic mixture was shaken to extract the products. The resulting mixture was centrifuged at 14,000rpm for 10min. Finally, 300μL of the octane extract were added to 100μL of a 100mM ethyl propionate (internal standard) solution in octane, and the final solution was analyzed by CG. For full recovery of the flavour ester products at 4h, the reaction mixtures were consecutively centrifuged four times at 14,000rpm (15min) and at room temperature, 21, 10 and 4°C, which resulted in a top liquid phase of flavour ester and a bottom solid phase containing the SLIL. For the case of anisyl acetate, the reaction mixture was cooled in an ice bath for 3h, and the resulting solid mixture was placed in a centrifugal filter, then centrifuged at 16,000rpm (10min) and at 0°C. This resulted in a top SLIL solid phase, which was retained inside the filter, and a bottom liquid phase of anisyl acetate. For all cases, a sample (10μL) of the resulting flavour ester phase was dissolved in 1mL acetone-δ6, then analyzed by 300MHz 1H NMR and 282MHz 19F NMR, in a Brucker AC 300E spectrometer for SLIL detection. All experiments were carried out in duplicate. | |
With Iron(III) nitrate nonahydrate In acetonitrile at 64.84℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 12h; | |
65% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 12h; | 13 To a solution of 4-(3-adamantan-l-yl-ureido)butyric acid 822 (0.10 g, 0.36 mmol), 4-(dimethylamino)pyridine (DMAP; 44 mg, 0.36 mmol), and 3,7-dimethyl-oct-6-en-l-ol (61 mg, 0.39 mmol) in methylene chloride (20 mL) was added l-[3-(dimethylamino)propyl]-3- ethylcarbodiimide hydrochloride (EDCI; 75 mg, 0.39 mmol) at room temperature. After stirring for 12 h, the reaction mixture was washed with 1 N NaOH aqueous solution (15 mL) and water (30 mL), and the organic layer was dried over Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel eluting with hexane and ethyl acetate (3:1) to give 798 (97 mg, 65%) as a solid: 1H NMR (CDCl3) 0.91 (3H, d, J = 6.9 Hz), 1.34-1.37 (2H, m), 1.56-1.60 (9H, m), 1.67-1.69 (8H, m), 1.81 (2H, quint, J = 6.9 Hz), 1.94- 1.97 (6H, m), 2.05-2.07 (3H, m), 2.35 (2H, t, J = 6.9 Hz), 3.16 (2H, q, J = 6.9 Hz), 4.05 (IH, s), 4.11 (2H, t, J = 6.9 Hz), 4.21 (IH, s), 5.09 (IH, t, J = 6.9 Hz); LC-MS (ESI) m/z calcd for C25H42N2O3 [M + H]+ 419.32, found [M + H]+ 419.22; mp 49 C. Anal. Calcd for C25H42N2O3: C, 71.73; H, 10.11; N, 6.69. Found: C, 70.27; H, 9.83; N5 6.39. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | Stage #1: Citronellol With 1H-imidazole; iodine; triphenylphosphine at 20℃; for 0.166667h; Stage #2: With sodium azide In dimethyl sulfoxide at 345℃; for 0.75h; | |
85% | With di-tert-butyl-diazodicarboxylate; diphenyl-phosphinic acid; triphenylphosphine In tetrahydrofuran at 23℃; | |
Multi-step reaction with 2 steps 1: potassium carbonate / neat (no solvent) / 0.08 h / Milling; Green chemistry 2: sodium azide; potassium carbonate / N,N-dimethyl-formamide / 0.03 h / Microwave irradiation |
Multi-step reaction with 2 steps 1.1: pyridine / 0.5 h 1.2: 0 °C 2.1: sodium azide / N,N-dimethyl-formamide / 40 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | ||
90% | With N-ethyl-N,N-diisopropylamine In diethyl ether at 20℃; for 48h; | |
With pyridine In dichloromethane for 22h; Heating / reflux; | 43 EXAMPLE 43 Succinic acid mono-(3,7-dimethyl-oct-6-enyl) ester A solution of 30.0 g succinic anhydride, 46.9 g citronellol, 36.0 g pyridine and 2.2 g 4-dimethylaminopyridine in 300 ml of dichloromethane was refluxed for 22 hours. Then the solution was cooled, ether was added and the organic phase was washed with 2N HCl and water to neutrality, dried and evaporated to dryness. The residue was wipe-film distilled to yield 36.4 g of a colourless liquid. ; NMR (CDCl3)δ 10.0 (s, 1H), 5.08 (t, 1H), 4.13 (t, 2H), 2.75-2.54 (m,4H), 2.08-1.88 (m, 2H), 1.69 (s, 3H), 1.60 (s, 3H), 1.80-1.00 (m, 5H), 0.91 (d, 3H) ppm. |
With dmap In dichloromethane at 23 - 27℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With hydrogen In isopropyl alcohol at 90℃; for 12h; | |
95 %Chromat. | With dichloro(η3:η2:η3-dodeca-2,6,10-triene-1,12-diyl)ruthenium(IV); caesium carbonate; isopropyl alcohol at 82℃; for 23h; Inert atmosphere; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With rose bengal; sodium sulfite; In methanol; at 70.0℃; for 3.0h;Irradiation; | 500 ml (429 g, 2.7 mol) citronellol (I) [00045] 400 ml methanol (J) [00046] 30 g rose bengal (K) [00047] I, J and 6g of K were mixed and irradiated with sunlight in a flat-bed solar light collector by passing continuously air through the reaction solution. If the dark red solution turned brown during irradiation, again 6 g of K were added. Such additions were four times necessary during the three days of irradiation with sunlight (weather: approx. 50% cloudy and 50% direct sunshine). [00048] The course of the reaction was monitored by thin layer chromatography. [00049] After irradiation 800 ml conc. Na2SO3 solution (L) was added to the irradiated solution which was then heated in the flat-bed solar light collector to 70 C. for 3 hours (which can also be performed by direct solar radiation). After cooling of the solution to room temperature, the lower (aqueous) layer was removed and 500 ml of 5% sulfuric acid (M) were added to the remaining organic layer. After 30 min. water steam was passed through the solution and the distillate (mixture of oxides) was collected. 210 g of rose oxide (N) were collected after removal of the water. [00050] For analytical data and structure assignments of I and N, see EP0842926 by Dragoco Gerberding & Co AG (1998).Example 9 [00051] Application of Connected Flat-bed Solar Light Collectors in Series: [00052] Production of rose oxide (N) with sunlight. [00053] As in most of the previous examples, solar reactors of identical size (apperture 1 m2) were employed in the following runs. [00054] 200 ml (172 g, 1.1 mol citronellol (I) [00055] 1 l methanol (J) [00056] 4 g rose bengal (K) [00057] A mixture of I, J and K (3 g) was irradiated with sunlight in two flat-bed solar light collectors (each 0.5 m2), connected in series, by passing air through the solution. The reaction solution was pumped through the reactors (approx. 2 l/hour) to enable continuous production. As soon as the dark red reaction medium turned brown during irradiation with sunlight, additional 1 g of K were added. The reaction time was 11 hours (weather: 70% cloudy and 30% direct sunshine). [00058] After irradiation 300 ml conc. Na2SO3 solution (L) was added to the irradiated solution and which was then heated in the flat-bed solar light collector to 70 C. for 3 hours (which can be performed by direct solar radiation. After cooling of the solution to room temperature, the lower (aqueous) layer was removed and 200 ml of 5% sulfuric acid (M) were added to the organic layer. After 30 min., water steam was passed through the solution and the distillate (mixture of oxides) was collected. 88 g of rose oxide (N) were obtained after removal of the water. [00059] For analytical data and structure assignments of I and N, see EP0842926 by Dragoco Gerberding & Co AG (1998). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen; sodium methylate In tetrahydrofuran at 100℃; for 2.5h; Title compound not separated from byproducts.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 75% 2: 12% | With sodium tetrahydroborate; sodium azide; ferric(III)oxalate hexahydrate In water; acetonitrile at 0℃; for 0.583333h; Inert atmosphere; | |
1: 75% 2: 12% | With sodium tetrahydroborate; sodium azide; ferric tartrate In water at 0℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | Stage #1: Citronellol With sodium hydride In toluene at 20 - 85℃; for 2.58333h; Stage #2: coumarin In toluene at 80℃; for 2.75h; | 1 To a suspension of NaH (114 g of a 60%-dispersion in mineral oil, 2.85 mol) in toluene (500 ml) is added at room temperature a solution of citronellol (468 g, 3.0 mol) in toluene (800 ml) over 50 min via dropping funnel. The temperature is raised to 85°C (bath) over 60 min and stirring continued for further 45 min. Then a solution of coumarin (219 g, 1.5 mol) in toluene (800 ml) is added over 75 min. After further 90 min stirring at 80°C (inside temperature), the deep orange suspension is cooled to 55°C and poured on a mixture of 2.5 kg crushed ice and 280 mi 37% aq. HCI-solution. The reaction flask is rinsed twice with 500 ml toluene. Upon stirring for 10 min the colour of the organic layer fades to a pale yellow. The organic layer is washed twice with water, then with brine/water 1: 1 and dried over MgS04. After concentrating in the rotary evaporator the excess citronellol is distilled off using a short path apparatus (110-125°C/0. 03 mbar, head 82°C) to obtain 240 g of citronellol and 463 g of a brownish residue. The latter is dissolved in 600 ml hexane containing 18 ml acetone and crystallized at-25°C. After filtration and drying 320 g (71 %) of product are obtained as white crystals, m. p. 37- 39°C. IR (film) : 3500-3100br, 1673vs, 1633w, 1619w, 1598s, 1450s. 'H-NMR (400 MHz, CDCI3) : 8.10 (d, J=16,2H), 7.79 (s, 1H), 7.44 (dd, J=7.6, 1.2, 1H), 7.22-7. 18 (m, 1H), 6.69 (d, J=16, 2H), 5.09 (sym. m, 1H), 4.28 (sym. m, 24H), 2.00 (sym. m, 2H), 1.80-1. 15 (series of m, 5H), 1.68 (d, J=0.4, 3H), 1.60 (s, 3H), 0.95 (d, J=6.8, 3H). '3C-NMR (100 MHz, CDCI3) : 169.1 (s), 155.9 (s), 141.3 (d), 131.4 (d), 131.2 (s), 129.1 (d), 124.5 (d), 121.5 (s), 120.3 (d), 117.8 (d), 116.4 (d), 63.4 (t), 36.9 (t), 35.3 (t), 29.4 (d), 25.6 (q), 25.3 (t), 19.3 (q), 17.6 (q). MS (El 70 eV): 302 (<1, M+), 165 (15), 147 (83), 138 (45), 81 (100). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With palladium 10% on activated carbon; sodium formate In toluene at 80℃; for 0.5h; Microwave irradiation; Sealed tube; | General procedures for the reduction of citral with microwave irradiation General procedure: The reduction of citral was carried out in a quartz tube (10 mL) under microwave irradiation. The order of addition of the reagents plays an important role in the reactions [27]. We selected the following standard protocol. Hydrogen donor was first dissolved in a solvent in the reactor, catalyst was then added, and finally the substrate was added. Then, the reaction vessel was sealed and the reaction was carried out under microwave irradiation at 300 W with a stirring speed of 900 r/min. The reaction time was started to count when the reaction mixture reached the desired temperature. After the reaction, the mixture was extracted with n-hexane and the resulting solution was analyzed with gas chromatography (GC-Shimadzu-14C, FID, Capillary column Rtx-Wax 30 m-0.53 mm- 0.25 mm) and gas chromatography/mass spectrometry (GC/MS, Agilent 5890). The gas phases were analyzed by Shimadzu GC-14C with TCD and a TDX-01 packed column. The reactions in the autoclave (50 mL) were also carried out in a water-bath with the same procedures. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.5% | With triethylamine at 20℃; | Example 6: For Ex.6, the following procedure is carried out using the twin-screw extruder at ambient temperature. A blend of CiOH (15.6 g) and TEA (50 g) is prepared as a first addition stream (Stream I) and incorporated through a first addition port of the extruder at a flow speed of 7.5ml/min. Pure ACL is incorporated as a second addition stream (Stream II) through a second addition port of the extruder at a flow speed of 4.5ml/min. The equivalent ratios of CiOH: ACL:TEA incorporated into the reaction chamber are 1: 1.1:2.9. The screw speed of the extruder is set to 200 rpm. The resulting reaction product stream is a solid material. The concentration of citronellyl acrylate is determined by NMR as detailed in Table 4. |
64% | With triethylamine In dichloromethane at 0℃; for 3h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 5h; Inert atmosphere; | 1 Production of 3,7-Dimethyl-6-Octenyl-9-Decenoate In a 100mL flask, 3,7-dimethyl-6-octene-1-ol ((6)-citronellol, manufactured by Wako Pure Chemical Industries,Ltd., Purity: 90%, 2.1g, 12.1 mmol) and 9-decenoic acid (2.4 g, 14.0 mmol) were placed and then were dissolved indichloromethane (25 mL). Subsequently, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (3.2 g, 16.5mmol, 136 mol% with respect to 3,7-dimethyl-6-octene-1-ol and 118 mol% with respect to 9-decenoic acid) and N,N’-dimethylaminopyridine (146 mg, 1.2 mmol, 10 mol% with respect to citronellol) were added to the flask.This was allowed to react under a nitrogen gas stream at room temperature for five hours. An ammoniumchloride aqueous solution was added to a reaction solution obtained after the reaction was completed, which then wasstirred. Thereafter, it was subjected to settled separation and thereby an aqueous layer was extracted and an oil layerwas washed with saturated saline. Then sodium sulfate was added to the oil layer to dehydrate to dryness. After filtrationthereof, dichloromethane was evaporated to dryness from the oil layer and thereby 3,7-dimethyl-6-octenyl-9-decenoate(3.7 g, 12.0 mmol, the yield in terms of 3,7-dimethyl-6-octene-1-ol: 100%) was obtained.[0107] The measurement results of respective spectrum analyses of 3,7-dimethyl-6-octenyl-9-decenoate are shownbelow.(1) 1H-NMR (CDCl3, 400 MHz); δ (ppm): 0.91 (d, 3H, J=6.4 Hz), 1.18 (m, 1H), 1.30-1.47 (m, 10H), 1.50-1.70 (m,4H), 1.60 (s, 3H), 1.68 (s, 3H), 1.92-2.05 (m, 4H), 2.28 (t, 2H, J=7.6 Hz), 4.09 (m, 2H), 4.92 (d, 1H, J=10.0 Hz), 4.98(d, 1H, J=17.2 Hz), 5.08 (t, 1H, J=7.0 Hz), 5.79 (m, 1H).(2) 13C-NMR (CDCl3, 100 MHz); δ (ppm): 174.1, 139.3, 131.5, 124.8, 114.4, 63.1, 37.4, 35.9, 34.8, 34.2, 29.9, 29.5,29.5, 29.4, 29.3, 26.2, 25.8, 25.4, 19.9, 18.1.(3)MS(CI) m/Z: 309(M+), 171, 139, 83, 71 |
88% | With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 22h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 16h; | General procedure for the synthesis of esters 1b-i, 2b-j, 3b-e. General procedure: A solution of the appropriate carboxylic acid (0.55 mmol), geraniol or nerol or citronellol (0.50 mmol), EDC (0.90 mmol), and DMAP (0.82 mmol) in dry CH2Cl2 (3 mL) was stirred at room temperature overnight. The mixture was diluted with 2 N HCl and extracted with AcOEt. The organic phase was washed with saturated NaHCO3 and brine, dried (Na2SO4), and evaporated under vacuum. The residue was purified by column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 81% 2: 8% 3: 8% 4: 1% | With chloro(1,5-cyclooctadiene)rhodium(I) dimer; hydrogen; ammonium hydroxide; 1-methyl-3-decylimidazolium bromide In toluene at 130℃; for 6h; Autoclave; | 2.1. Typical synthetic procedure General procedure: All reactants, catalysts and solvents were commercially available and were used without further purification. In a typical experiment chloro(1,5-cyclooctadiene) rhodium(I) (0.03 mmol14.8 mg), triphenylphosphine trisulfonate (TPPTS, aq. saturated, 0.12 mmol, 68.2 mg) and hexadecyltrimethylammonium chloride(CTAC, aq. 25%, 0.031 mol, 60.7 mg) were dissolved in an aqueous ammonia solution (28%, 216.0 mmol, 13.14 g NH3). Nexy, toluene(5.0 ml, 4.3 g) and citronellal (6.0 mmol, 925.5 mg) were added to the solution, which was sonicated for 5 min. The solution was transferred to an evacuated stainless steel autoclave with a volume of 70 ml (Parr Instrument Company). The autoclave was pressurised at 60 bar of H2, mechanically stirred with 800 rpm and heated up to 130° C. At the end of the reaction time, the autoclave was allowed to allowed to cool to room temperature, the pressure was released, the two layers were separated using a separating funnel, and the solution was analysed by gas chromatography. |
1: 41% 2: 21% 3: 20% 4: 2% | With chloro(1,5-cyclooctadiene)rhodium(I) dimer; hydrogen; ammonium hydroxide; 1-octyl-3-methyl-imidazolium bromide In toluene at 130℃; for 6h; Autoclave; | 2.1. Typical synthetic procedure General procedure: All reactants, catalysts and solvents were commercially available and were used without further purification. In a typical experiment chloro(1,5-cyclooctadiene) rhodium(I) (0.03 mmol14.8 mg), triphenylphosphine trisulfonate (TPPTS, aq. saturated, 0.12 mmol, 68.2 mg) and hexadecyltrimethylammonium chloride(CTAC, aq. 25%, 0.031 mol, 60.7 mg) were dissolved in an aqueous ammonia solution (28%, 216.0 mmol, 13.14 g NH3). Nexy, toluene(5.0 ml, 4.3 g) and citronellal (6.0 mmol, 925.5 mg) were added to the solution, which was sonicated for 5 min. The solution was transferred to an evacuated stainless steel autoclave with a volume of 70 ml (Parr Instrument Company). The autoclave was pressurised at 60 bar of H2, mechanically stirred with 800 rpm and heated up to 130° C. At the end of the reaction time, the autoclave was allowed to allowed to cool to room temperature, the pressure was released, the two layers were separated using a separating funnel, and the solution was analysed by gas chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 51% 2: 26% 3: 11% | With chloro(1,5-cyclooctadiene)rhodium(I) dimer; hydrogen; cetyltrimethylammonim bromide; ammonium hydroxide In toluene at 130℃; for 6h; Autoclave; | 2.1. Typical synthetic procedure General procedure: All reactants, catalysts and solvents were commercially available and were used without further purification. In a typical experiment chloro(1,5-cyclooctadiene) rhodium(I) (0.03 mmol14.8 mg), triphenylphosphine trisulfonate (TPPTS, aq. saturated, 0.12 mmol, 68.2 mg) and hexadecyltrimethylammonium chloride(CTAC, aq. 25%, 0.031 mol, 60.7 mg) were dissolved in an aqueous ammonia solution (28%, 216.0 mmol, 13.14 g NH3). Nexy, toluene(5.0 ml, 4.3 g) and citronellal (6.0 mmol, 925.5 mg) were added to the solution, which was sonicated for 5 min. The solution was transferred to an evacuated stainless steel autoclave with a volume of 70 ml (Parr Instrument Company). The autoclave was pressurised at 60 bar of H2, mechanically stirred with 800 rpm and heated up to 130° C. At the end of the reaction time, the autoclave was allowed to allowed to cool to room temperature, the pressure was released, the two layers were separated using a separating funnel, and the solution was analysed by gas chromatography. |
1: 43% 2: 35% 3: 9% | With chloro(1,5-cyclooctadiene)rhodium(I) dimer; hydrogen; cetyltrimethylammonim bromide; ammonium hydroxide In toluene at 130℃; for 6h; Autoclave; | 2.1. Typical synthetic procedure General procedure: All reactants, catalysts and solvents were commercially available and were used without further purification. In a typical experiment chloro(1,5-cyclooctadiene) rhodium(I) (0.03 mmol14.8 mg), triphenylphosphine trisulfonate (TPPTS, aq. saturated, 0.12 mmol, 68.2 mg) and hexadecyltrimethylammonium chloride(CTAC, aq. 25%, 0.031 mol, 60.7 mg) were dissolved in an aqueous ammonia solution (28%, 216.0 mmol, 13.14 g NH3). Nexy, toluene(5.0 ml, 4.3 g) and citronellal (6.0 mmol, 925.5 mg) were added to the solution, which was sonicated for 5 min. The solution was transferred to an evacuated stainless steel autoclave with a volume of 70 ml (Parr Instrument Company). The autoclave was pressurised at 60 bar of H2, mechanically stirred with 800 rpm and heated up to 130° C. At the end of the reaction time, the autoclave was allowed to allowed to cool to room temperature, the pressure was released, the two layers were separated using a separating funnel, and the solution was analysed by gas chromatography. |
1: 40% 2: 36% 3: 3% | With bis(1,5-cyclooctadiene)diiridium(I) dichloride; hydrogen; cetyltrimethylammonim bromide; ammonium hydroxide In toluene at 130℃; for 6h; Autoclave; | 2.1. Typical synthetic procedure General procedure: All reactants, catalysts and solvents were commercially available and were used without further purification. In a typical experiment chloro(1,5-cyclooctadiene) rhodium(I) (0.03 mmol14.8 mg), triphenylphosphine trisulfonate (TPPTS, aq. saturated, 0.12 mmol, 68.2 mg) and hexadecyltrimethylammonium chloride(CTAC, aq. 25%, 0.031 mol, 60.7 mg) were dissolved in an aqueous ammonia solution (28%, 216.0 mmol, 13.14 g NH3). Nexy, toluene(5.0 ml, 4.3 g) and citronellal (6.0 mmol, 925.5 mg) were added to the solution, which was sonicated for 5 min. The solution was transferred to an evacuated stainless steel autoclave with a volume of 70 ml (Parr Instrument Company). The autoclave was pressurised at 60 bar of H2, mechanically stirred with 800 rpm and heated up to 130° C. At the end of the reaction time, the autoclave was allowed to allowed to cool to room temperature, the pressure was released, the two layers were separated using a separating funnel, and the solution was analysed by gas chromatography. |
1: 29% 2: 17% 3: 1% | With bis(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate; hydrogen; cetyltrimethylammonim bromide; ammonium hydroxide In toluene at 130℃; for 6h; Autoclave; | 2.1. Typical synthetic procedure General procedure: All reactants, catalysts and solvents were commercially available and were used without further purification. In a typical experiment chloro(1,5-cyclooctadiene) rhodium(I) (0.03 mmol14.8 mg), triphenylphosphine trisulfonate (TPPTS, aq. saturated, 0.12 mmol, 68.2 mg) and hexadecyltrimethylammonium chloride(CTAC, aq. 25%, 0.031 mol, 60.7 mg) were dissolved in an aqueous ammonia solution (28%, 216.0 mmol, 13.14 g NH3). Nexy, toluene(5.0 ml, 4.3 g) and citronellal (6.0 mmol, 925.5 mg) were added to the solution, which was sonicated for 5 min. The solution was transferred to an evacuated stainless steel autoclave with a volume of 70 ml (Parr Instrument Company). The autoclave was pressurised at 60 bar of H2, mechanically stirred with 800 rpm and heated up to 130° C. At the end of the reaction time, the autoclave was allowed to allowed to cool to room temperature, the pressure was released, the two layers were separated using a separating funnel, and the solution was analysed by gas chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 29% 2: 12% | With carbonylhydridetris(triphenylphosphine)rhodium(I); hydrogen; cetyltrimethylammonim bromide; ammonium hydroxide In toluene at 130℃; for 6h; Autoclave; | 2.1. Typical synthetic procedure General procedure: All reactants, catalysts and solvents were commercially available and were used without further purification. In a typical experiment chloro(1,5-cyclooctadiene) rhodium(I) (0.03 mmol14.8 mg), triphenylphosphine trisulfonate (TPPTS, aq. saturated, 0.12 mmol, 68.2 mg) and hexadecyltrimethylammonium chloride(CTAC, aq. 25%, 0.031 mol, 60.7 mg) were dissolved in an aqueous ammonia solution (28%, 216.0 mmol, 13.14 g NH3). Nexy, toluene(5.0 ml, 4.3 g) and citronellal (6.0 mmol, 925.5 mg) were added to the solution, which was sonicated for 5 min. The solution was transferred to an evacuated stainless steel autoclave with a volume of 70 ml (Parr Instrument Company). The autoclave was pressurised at 60 bar of H2, mechanically stirred with 800 rpm and heated up to 130° C. At the end of the reaction time, the autoclave was allowed to allowed to cool to room temperature, the pressure was released, the two layers were separated using a separating funnel, and the solution was analysed by gas chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 45% 2: 34% 3: 9% | With chloro(1,5-cyclooctadiene)rhodium(I) dimer; hydrogen; cetyltrimethylammonium bromide; ammonium hydroxide In toluene at 130℃; for 6h; Autoclave; | 2.1. Typical synthetic procedure General procedure: All reactants, catalysts and solvents were commercially available and were used without further purification. In a typical experiment chloro(1,5-cyclooctadiene) rhodium(I) (0.03 mmol14.8 mg), triphenylphosphine trisulfonate (TPPTS, aq. saturated, 0.12 mmol, 68.2 mg) and hexadecyltrimethylammonium chloride(CTAC, aq. 25%, 0.031 mol, 60.7 mg) were dissolved in an aqueous ammonia solution (28%, 216.0 mmol, 13.14 g NH3). Nexy, toluene(5.0 ml, 4.3 g) and citronellal (6.0 mmol, 925.5 mg) were added to the solution, which was sonicated for 5 min. The solution was transferred to an evacuated stainless steel autoclave with a volume of 70 ml (Parr Instrument Company). The autoclave was pressurised at 60 bar of H2, mechanically stirred with 800 rpm and heated up to 130° C. At the end of the reaction time, the autoclave was allowed to allowed to cool to room temperature, the pressure was released, the two layers were separated using a separating funnel, and the solution was analysed by gas chromatography. |
1: 45% 2: 36% 3: 7% | With chloro(1,5-cyclooctadiene)rhodium(I) dimer; hydrogen; cetyltrimethylammonium chloride; ammonium hydroxide In toluene at 130℃; for 6h; Autoclave; | 2.1. Typical synthetic procedure General procedure: All reactants, catalysts and solvents were commercially available and were used without further purification. In a typical experiment chloro(1,5-cyclooctadiene) rhodium(I) (0.03 mmol14.8 mg), triphenylphosphine trisulfonate (TPPTS, aq. saturated, 0.12 mmol, 68.2 mg) and hexadecyltrimethylammonium chloride(CTAC, aq. 25%, 0.031 mol, 60.7 mg) were dissolved in an aqueous ammonia solution (28%, 216.0 mmol, 13.14 g NH3). Nexy, toluene(5.0 ml, 4.3 g) and citronellal (6.0 mmol, 925.5 mg) were added to the solution, which was sonicated for 5 min. The solution was transferred to an evacuated stainless steel autoclave with a volume of 70 ml (Parr Instrument Company). The autoclave was pressurised at 60 bar of H2, mechanically stirred with 800 rpm and heated up to 130° C. At the end of the reaction time, the autoclave was allowed to allowed to cool to room temperature, the pressure was released, the two layers were separated using a separating funnel, and the solution was analysed by gas chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 33% 2: 21% | With Wilkinson's catalyst; hydrogen; cetyltrimethylammonim bromide; ammonium hydroxide In toluene at 130℃; for 6h; Autoclave; | 2.1. Typical synthetic procedure General procedure: All reactants, catalysts and solvents were commercially available and were used without further purification. In a typical experiment chloro(1,5-cyclooctadiene) rhodium(I) (0.03 mmol14.8 mg), triphenylphosphine trisulfonate (TPPTS, aq. saturated, 0.12 mmol, 68.2 mg) and hexadecyltrimethylammonium chloride(CTAC, aq. 25%, 0.031 mol, 60.7 mg) were dissolved in an aqueous ammonia solution (28%, 216.0 mmol, 13.14 g NH3). Nexy, toluene(5.0 ml, 4.3 g) and citronellal (6.0 mmol, 925.5 mg) were added to the solution, which was sonicated for 5 min. The solution was transferred to an evacuated stainless steel autoclave with a volume of 70 ml (Parr Instrument Company). The autoclave was pressurised at 60 bar of H2, mechanically stirred with 800 rpm and heated up to 130° C. At the end of the reaction time, the autoclave was allowed to allowed to cool to room temperature, the pressure was released, the two layers were separated using a separating funnel, and the solution was analysed by gas chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With carbon dioxide at 46.02℃; for 3.5h; High pressure; Supercritical conditions; Green chemistry; | 2.3.3.2.4. Synthesis of laurate esters in SC-CO2 General procedure: The enzymatic synthesis of citronellyl laurate esters was carried out in 50 mL high pressure reactor vessel. The instrument was equipped with the pressure reading controller and regulator model JASCO-PU-2080-CO2 plus. At first, given amount of vinyl laurate was added followed by addition of given amount of citronellol in the 50 mL reaction vessel. Finally, the reaction was started by addition of immobilized PVA/CHI lipase and the reactor vessel was closed appropriately and assembled to SC-CO2 high pressure reactor. The liquid SC-CO2 was pumped inside the reactor vessel with a flowrate of 3.5 mL/min. The reaction was conducted at given pressure (MPa) and temperature (°C) designed by RSM software for given period. After, the completion of reaction, the SC-CO2 was slowly depressurized through a thermostat restrictor having temperature 50°C which leaves back the residual reaction mass inside the reactor by leaving CO2. The reaction mass was then analyzed using the Perkin-Elmer, Clarus-400 Gas Chromatography (GC) equipped with a flame ionizing detector (FID) and capillary column. The oven temperature of GC was kept at 90°C for 4 min and then rises at 10°C/min up to 240°C. The product formed was also confirmed by the gas-chromatography-mass spectroscopy analysis (GC-MS) by Shimadzu QP-2010 instrument. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 6h; | 4.9.2 Citronellyl citronellate 2 Dicyclohexylcarbamide (2.67 g, 12.92 mmol, 1.1 eq.) was added to a solution of citronellic acid (2.00 g, 11.75 mmol, 1 eq.), citronellol (1.84 g, 11.75 mmol, 1 eq.) and DMAP (0.15 g, 1.18 mmol) in dichloromethane (20 mL) and stirred at room temperature for 6 h. The mixture was poured on water and extracted with diethyl ether. The combined organic phase was washed with brine and dried over MgSO4. The solvent was removed to give 3.91 g of crude product. The residue was purified by flash-chromatography using 2% diethyl ether in pentane, yielding pure product (2.63 g, 73%, GC-MS purity 97%) after bulk-to-bulk distillation (160 °C, 0.056 mbar). 1H NMR (400 MHz, CDCl3): δ 5.09 (br t, J = 7.05, 2 H); 4.04-4.17 (m, 2 H); 2.30 (dd, J = 5.9, 14.5, 1 H); 2.10 (dd, J = 8.2, 14.5, 1H); 1.98 (m, 1.89-2.07, 5 H); 1.68 (s, 6 H); 1.60 (s, 6 H); 1.49-1.72 (m, 2 H); 1.13-1.48 (m, 5 H); 0.94 (d, J = 6.5, 3 H); 0.91 (d, J = 6.5, 3 H). 13C NMR (100 MHz, CDCl3): δ 173.3 (C), 131.5 (C), 131.3 (C), 124.6 (CH), 124.3 (CH), 62.7 (CH2), 41.9 (CH2), 37.0 (CH2), 36.8 (CH2), 35.6 (CH2), 30.1 (CH), 29.5 (CH), 25.7 (2CH3), 25.4 (CH2), 25.4 (CH2), 19.6 (CH3), 19.4 (CH3), 17.6 (2 CH3). MS (EI, 70 eV), m/z (%): 308 (2, M+); 170 (2); 153 (10); 152 (8); 139 (5); 138 (42); 136 (5); 124 (5); 123 (45); 110 (19); 109 (42); 97 (7); 96 (11); 95 (49); 94 (12); 83 (26); 82 (33); 81 (54); 80 (6); 71 (5); 70 (9); 69 (100); 68 (8); 67 (20); 57 (9); 56 (6); 55 (26); 53 (5); 43 (7); 41 (32). HR-GC-TOF-MS: 308.2713 (C20H36O, -0.6 ppm). LRI (SPB-1) 2025; LRI (SWax) 2360. In cv. Judy’s Everbearing and Durham’s Emerald extracts: LRI (SPB-1) 2022; LRI (SWax) 2352. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With (4-Ph)Triaz(NHP<SUP>i</SUP>Pr<SUB>2</SUB>)<SUB>2</SUB>Mn(CO)<SUB>2</SUB>Br; potassium <i>tert</i>-butylate In tetrahydrofuran at 80℃; for 18h; | |
92% | With dimanganese decacarbonyl; potassium <i>tert</i>-butylate In toluene at 20℃; for 48h; Inert atmosphere; Sealed tube; | |
89% | With bis(3,5-di-(tert-butyl)-2-hydroxyazobenzolato)nickel(II); potassium <i>tert</i>-butylate In toluene at 130℃; for 24h; chemoselective reaction; |
75% | With potassium hydroxide In water at 100℃; for 10h; Schlenk technique; | |
71% | With 1,10-Phenanthroline; potassium <i>tert</i>-butylate; nickel dibromide In toluene at 130℃; for 48h; chemoselective reaction; | |
65% | With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; 1-(2,2-dimethoxyethyl)-3-(propyl-3-sulfonate)benzimidazoluim; potassium <i>tert</i>-butylate In neat (no solvent) at 120℃; for 24h; Schlenk technique; Sealed tube; | 2.2. Catalytic reactions General procedure: The alcohol derivative (1.6mmol) was added to a stirred solution of aromatic amine (1mmol) in a Schlenk tube. Subsequently, tBuOK (1mmol), the preligand (L) (1mol%) and [RuCl2(p-cymene)]2 (0.5mol%) were added and the sealed Schlenk tube was stirred at 120°C for 24h. The crude mixture was collected by the addition of CH2Cl2 (2ml) for GC analysis, and the product was then purified by column chromatography (petroleum ether/Et2O or EtOAc) to afford the pure secondary amine. |
50% | Stage #1: Citronellol With sodium hydride In mineral oil for 0.0833333h; Schlenk technique; Inert atmosphere; Stage #2: aniline In mineral oil at 160℃; for 28h; Schlenk technique; Inert atmosphere; | |
40% | With potassium <i>tert</i>-butylate; benzonitrile In 1,4-dioxane at 130℃; for 48h; Inert atmosphere; Glovebox; Sealed tube; | |
90 %Chromat. | With (1-(3-methoxybenzyl)-3-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-ylidene)p-cymeneruthenium(II) chloride; potassium <i>tert</i>-butylate at 120℃; for 20h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With dichloro-[1-(2-(2-ethoxyphenoxy)ethyl)-3-(3-methoxylbenzyl)benz-imidazol-2-ylidene](p-cymene)ruthenium (II) In neat (no solvent) at 120℃; for 16h; | 4.3. General procedure for the ruthenium-carbene catalyzed N-alkylation of amines General procedure: Amine (1.0mmol) and alcohol (1.5mmol), (and tBuOK (1.5mmol) for 4-methylaniline), were added to a Schlenk tube under argon atmosphere. Subsequently, the ruthenium-carbene catalyst (2a-2e) (0.01mmol, 1mol%) was added to stirred solution in a Schlenk tube, and the closed Schlenk tube was stirred at 120°C (oil bath temperature). End of the reaction, the solution was cooled to room temperature and dichloromethane (2mL) was then added to the crude mixture. This solution was used for GC analysis and the resulting N-monoalkylated amines were purified and isolated by column chromatography (eluent: chloroform/MeOH). Yields (%) were calculated according to amines using dodecane as an internal standard. The 3a [10b,29,31a], 3b [31b], 3c [10b,10d], 3d [10d,29,31c], 3e [29,31d], 3g [31e], 3h [31f], 4a [29,31g,31h], 4b [31i], 4c [29], 4d [31j,31k], 5a [31l], 5b [31l] and 5c [31l] N-monoalkylated amines have already been reported in the literature. Only N-(2-hexyl) pyrrolidine (3f) is new. The chemical characterizations of the all the N-monoalkylated amines were made by NMR spectroscopy. NMR spectrums of the corresponding N-monoalkylated amines are available in the SI file, pages S15-S29. |
51% | With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; 1-(2,2-dimethoxyethyl)-3-(propyl-3-sulfonate)benzimidazoluim; potassium <i>tert</i>-butylate In neat (no solvent) at 120℃; for 24h; Schlenk technique; Sealed tube; | 2.2. Catalytic reactions General procedure: The alcohol derivative (1.6mmol) was added to a stirred solution of aromatic amine (1mmol) in a Schlenk tube. Subsequently, tBuOK (1mmol), the preligand (L) (1mol%) and [RuCl2(p-cymene)]2 (0.5mol%) were added and the sealed Schlenk tube was stirred at 120°C for 24h. The crude mixture was collected by the addition of CH2Cl2 (2ml) for GC analysis, and the product was then purified by column chromatography (petroleum ether/Et2O or EtOAc) to afford the pure secondary amine. |
90 %Chromat. | With (1-(3-methoxybenzyl)-3-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-ylidene)p-cymeneruthenium(II) chloride; potassium <i>tert</i>-butylate at 120℃; for 20h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; oxygen; Ru(bpy)<SUB>3</SUB>(PF<SUB>6</SUB>)<SUB>2</SUB>; copper(II) bis(trifluoromethanesulfonate) In N,N-dimethyl acetamide at 20℃; for 4.5h; Irradiation; | III. General Procedure for the Oxygenation of Trisubstituted Olefin General procedure: A test tube was charged with trisubstituted olefin 4 (1.0 equiv.), Ru(bpy)3(PF6)2 (1 mol%), Cu(OTf)2 (10 mol%),and TEMPO (1.0 equiv.). It was evacuated and backfilled with O2. To this vessel, an oxygen balloon wasattached, and DMA (0.1 M) was added by a syringe. The mixture was irradiated by a pair of 5 W blue LEDs(lmax = 450 nm) at 3-5 cm distance blown by a fan to keep room temperature. The reaction was monitored byTLC. After the completion of the reaction, water was added to quench the reaction. The aqueous layer wasextracted with diethyl ether for three times. The combined organic layers were washed with H2O, dried overNa2SO4, filtered through a plug of cotton, and concentrated under reduced pressure. The residue was purifiedby flash column chromatography. |
Multi-step reaction with 2 steps 1.1: sodium carbonate; peracetic acid / dichloromethane / 4 h / 0 °C 2.1: aluminum isopropoxide / 5,5-dimethyl-1,3-cyclohexadiene / 20 h / Inert atmosphere; Reflux 2.2: 24 h / 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With boron trifluoride diethyl etherate In dichloromethane at -15℃; for 0.5h; Molecular sieve; | 1.iv Methyl 2,3,4-tri-O-acetyl-1-O-(2,2,2-trichloroethanimidoyl)-D-glucopyranuronate (190 mg, 0.397 mmol) and citronellol (62 mg, 0.397 mmol) were stirred 1 hour in CH2Cl2 (7 mL), in presence of molecular sieves 4A. The reaction was cooled down at -15° C., 1 hour. Then BF3Et2O (25.4 mg, 0.179 mmol) was added. The reaction was monitored by TLC (thin layer chromatography, SiO2). After 30 min. the whole imidate was consumed. EtOAc was added (30 mL) and the organic phase was washed with NaHCO3 aqueous saturated solution, then with brine. The solvent was removed on rotary evaporator under vacuum. The crude product was purified by flash chromatography on SiO2 (13 g), elution with pentane/Et2O and we obtained 85 mg (yield 45%) of the protected sugar, 100% 13 isomer |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: Citronellol; 4-(4-hydroxyphenyl)-2-oxobutane With tetraethoxy orthosilicate; sodium methylate In methanol at 150℃; for 2h; Inert atmosphere; Stage #2: In methanol for 3h; Inert atmosphere; | 2 Comparative Example 2 Synthesis of fragrance-releasing agent containing Si(ORasp)(OCitronellyl)3 Into 200 ml four-mouth flask, add 20.83g (0.10 mol) tetraethoxysilane, 14.78g (0.09 mol) raspberry ketone, 42.19g (0.27 mol) citronellol, 0.15g 5.6% methanol solution of sodium methoxide. Under the nitrogen flow, distill off ethanol and at about 150 °C stir for about 2 hours. After 2 hours, the pressure inside the tank slowly drops to 8kPa. Distill off ethanol and further stirring 3 hours. After, cooling, after the lifting of the pressure, filtering, to obtain the 48.39g containing raspberry ketone and Citronellol molar ratio of 1:3 of the silicic acid ester compound [Si (ORasp) (OCitronellyl)3] Of light yellow oily matter. The obtained oily matter with the gas chromatograph analysis, to obtain the table 7 is shown of a fragrance releaser. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With (4-Me)Triaz(NHP<SUP>i</SUP>Pr<SUB>2</SUB>)<SUB>2</SUB>Mn(CO)<SUB>2</SUB>Br; potassium hydroxide In tert-Amyl alcohol; toluene at 135℃; for 48h; Inert atmosphere; Sealed tube; | |
66% | With manganese(IV) oxide; potassium hydroxide In tert-Amyl alcohol at 140℃; for 48h; Inert atmosphere; regioselective reaction; | General procedure for synthesis of products (1)substrates General procedure for MnO2 catalyzed oxidation/olefination reaction (3a-3n, 5a-5y, 7a-7b) General procedure: Using a nitrogen-filled glove box, an oven-dried Schlenk tube (100mL volume) was charged with a magnetic stirring bar, MnO2 (0.05mmol), KOH (0.5mmol), alcohols (1) (0.55mmol), heteroarenes (2) (0.5mmol) and t-AmOH (1mL). Then the Schlenk tube was closed tightly with a Teflon cap, removed from the glove box. A reflux condenser was evacuated and refilled with dry air and then attached to the Schlenk tube maintaining dry air stream. A bubble counter was attached to the top of the condenser and the whole system was purged with dry air for 15s. The Schlenk tube was immersed into a pre-heated oil bath (design temperature). After design time the reaction was cooled, a small aliquot of the organic phase was analyzed by GC or GC-MS to monitor product formation. Purification of the remainder by column chromatography on silica gel (petroleum ether/ethyl acetate=20/1-5/1) gave the corresponding products in the reported yield. |
48% | With 1,10-Phenanthroline; potassium <i>tert</i>-butylate; iron(II) acetate In toluene at 140℃; for 24h; Inert atmosphere; chemoselective reaction; |
46% | With 1,10-Phenanthroline; potassium hydroxide; nickel dibromide In toluene at 140℃; for 24h; Schlenk technique; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: disulfanediyldiacetic acid With acetic anhydride at 20℃; for 2h; Inert atmosphere; Stage #2: Citronellol With dmap In dichloromethane; toluene at 20℃; for 1h; Inert atmosphere; Stage #3: taxol Further stages; | 1 Example 1: Synthesis of a paclitaxel-citronellol small molecule prodrug (α-PTX-SS-CIT) with a disulfide bond at the alpha position of the carbonyl group Add an appropriate amount of 2,2 dithiodiacetic acid to a 50 mL round bottom flask.And dissolved with 3 mL of acetic anhydride,Stir at room temperature for 2 hours.The reaction process was monitored by thin layer chromatography.Then 20 mL of toluene was added to the system three times.And vacuum distillation was carried out under reduced pressure.The obtained product was dissolved in 30 mL of dichloromethane.And add the right amount of citronellol and DMAP,Stir at room temperature for 1 hour.The reaction process was monitored by thin layer chromatography.Purification by silica gel column chromatography gave the intermediate.Finally, the intermediate product,EDCI,H0Bt and DMAP were dissolved in 50 mL of anhydrous dichloromethane.Ice bath for 1 hour,Then add the right amount of paclitaxel,Stir for another 24 hours at room temperature.The reaction process was monitored by thin layer chromatography.The target product is obtained by preparative liquid chromatography separation and purification.The above reaction was carried out under the protection of N2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With Cp*Ir(6,6'-dionato-2,2'-bipyridine)(H2O); caesium carbonate In tert-Amyl alcohol at 125℃; for 12h; Inert atmosphere; | 4.2. Procedure for the a-alkylation of ketones with alkenyl alcohols catalyzed by [Cp*Ir(2,2'-bpyO)(H2O)] (cat. 10) (Tables 1-3) General procedure: To an oven-dried, N2-purged 25 mL Schlenk tube were added ketone (1 mmol), alkenyl alcohol (1.2 mmol), cat. 10 (5.3 mg,0.01 mmol, 1 mol%), Cs2CO3 (98 mg, 0.3 mmol, 0.3 equiv) and tert amylalcohol (1 mL). The mixture of reaction was heated under 125 °C in an oil bath for 12 h. The reaction mixture was cooled to ambient temperature, concentrated in vacuo and purified by flash column chromatography with ethyl acetate/hexanes to afford the corresponding product.1-Phenylhept-6-en-1-one (3aa) [3e]. Purified by flash column chromatography on silica gel (ethyl acetate/hexanes = 1/100);Pale-yellow oil; |
30% | With 1,10-Phenanthroline; potassium <i>tert</i>-butylate; nickel dibromide In toluene at 140℃; for 36h; Schlenk technique; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With potassium carbonate In toluene at 90℃; for 16h; | 57 General procedure D: O-acylation of alcohols General procedure: Alcohol (1.0 mmol) was added to the acylation reagent (1.5 mmol) and K2CO3 (0.270 g, 2.0 mmol). Toluene (2mL) was added as a cosolvent when the alcohol substrate was insoluble in the formylating reagent at 60°C. The reaction was then stirred at 90°C for 16 or 24 h. The crude reaction mixture was then purified by column chromatography to give the isolated ester. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium carbonate In toluene at 90℃; for 16h; | 57 General procedure D: O-acylation of alcohols General procedure: Alcohol (1.0 mmol) was added to the acylation reagent (1.5 mmol) and K2CO3 (0.270 g, 2.0 mmol). Toluene (2mL) was added as a cosolvent when the alcohol substrate was insoluble in the formylating reagent at 60°C. The reaction was then stirred at 90°C for 16 or 24 h. The crude reaction mixture was then purified by column chromatography to give the isolated ester. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With potassium carbonate at 90℃; for 16h; | 21 General procedure B: O-Acetylation of alcohols General procedure: Alcohol (1.0 mmol) was added to phenylmethylene diacetate 3a (0.291 g, 1.5 mmol) and K2CO3 (0.270 g, 2.0 mmol) and the reaction stirred at 90°C for 16 or 24h. Toluene or water (2 mL) was added as a cosolvent when the alcohol substrate was insoluble in the formylating reagent at 60°C. The crude reaction mixture was then purified by column chromatography to give the isolated ester. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With sodium hydrogencarbonate In neat (no solvent) at 60℃; for 16h; | 7 General procedure A: O-formylation of alcohols General procedure: Alcohol (1.0 mmol) was added to (formyloxy)(phenyl)methyl acetate 1 (0.291 g, 1.5 mmol) and NaHCO3 (0.168 g, 2.0 mmol), and the reaction stirred at 60°C for 16 h. EtOAc (2 mL) was added as a cosolvent when the alcohol substrate was insoluble in the fomylating reagent at 60°C. The crude reaction mixture was then purified by column chromatography to give the desired formate ester. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With copper(II) 2-ethylhexanoate; rhodium(III) chloride trihydrate In toluene at 110℃; for 24h; Green chemistry; | 43 Example 43 Preparation 3aw indole-7-carboxylic acid ester derivative The synthetic route is as follows: The N-pyrimidyl indoline 1a (0.2 mmol), RhCl3 • 3H2O (0.01 mmol), Cu (EtCO2) 2 (0.4 mmol) and3,7 -dimethyloct-6-en-1-ol2w (1.0 mmol) was added to 2.0 mL of toluene and replaced in a Young's tube. After carbon three times, charged with carbon monoxide (1 atm), reacted in an oil bath at 110 ° C for 24 hours, then stopped the reaction, and the reaction liquid was cooled. To room temperature, directly load, column chromatography ethyl acetate / petroleum ether (1:20 ~ 1: 1), to obtain pure porphyrin-7-carboxylate derivatives 3aw 66 mg, product as a yellow oil fluid, yield 86%. |
86% | With rhodium(III) chloride trihydrate; copper(II) propionate In toluene at 110℃; for 24h; Inert atmosphere; Schlenk technique; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With rhodium(III) chloride trihydrate; copper diacetate In N,N-dimethyl-formamide at 90℃; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With pyridine; dmap In toluene at 10 - 20℃; for 20.25h; | 1 Example 1 : Preparation of 3,7-dimethyloct-6-en-1 -yl methyl carbonate A solution of racemic Citronellol (3,7-dimethyloct-6-en-1 -ol; 20.0 g, 128 mmol. 1 equiv.), pyridine (30.4 g, 384 mmol, 3 equiv) and 4-dimethylamino pyridine (0.4 g, 3.3 mmol, 2.5 mol%) in toluene (300 ml_) was cooled to I O'. Then a solution of methyl chloroformate (24.2 g, 256 mmol, 2.0 equiv.) in toluene (100 ml_) was added dropwise over 15 min at an inside temperature of 15-1 d'. The resulting white suspension was stirred at room temperature during 20 h, then cooled to d' by means of an icebath before the addition of 2 N aqueous HCI-solution (220 ml_, 440 mmol). The resulting biphasic mixture was stirred intensely at room temperature for 10 min., then the phases were separated and the aqueous layer was extracted with toluene. The combined organic layers were washed with water, then saturated aqueous NaHC03-solution and finally three times with brine, dried over MgS04 and concentrated in a rotatory evaporator under reduced pressure to yield a colorless liquid (28.8 g). The crude product was purified by a short path distillation over a 5 cm Vigreux column at 86/0.02 mbar followed by a second fine distillation over a 15 cm Widmer column at 82°C/0.02 mbar to yield the olfactorily pure product as a colorless oil (14.8 g, 54%) exhibiting a fruity-rosy odor with hints of pear and citronella. 1 H-NMR (400 MHz, CDCI3) 5.08 (m, 1H), 4.10 - 4.25 (m, 2 H), 3.77 (s, 3 H), 1.88 - 2.10 (m, 2 H), 1.68 - 1.77 (m, 1H), 1.68 (d, J= 1.0 Hz, 3 H), 1.60 (s, 3 H), 1.13 - 1.58 (series of m, 4 H), 0.92 (d, =6.6 Hz, 3 H). 13C-NMR (100 MHz, CDCy 155.8 (s), 131.3 (s), 124.5 (d), 66.6 (t), 54.5 (q), 36.9 (t), 35.5 (t), 29.2 (d), 25.7 (q), 25.3 (t), 19.3 (q), 17.6 (q). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
21.3 % ee | With dicarbonylacetylacetonato rhodium (I); (1S,1′S)(+)(9,9-dimethyl-9H-xanthene-4,5-diyl)bis((2-methylphenyl)(phenyl)phosphine); hydrogen In toluene at 25℃; for 3.5h; Autoclave; | 5; 6 Hydrogenation of Neral and Geranial Under Standard Conditions General procedure: The individual hydrogenation experiments were carried out on a laboratory scale under the following conditions. In an autoclave (AK), the corresponding amounts of rhodium precursor [Rh(acac)(COD)] or Rh(acac)(CO)2), compound of the formula I and neral or geranial are initially introduced and, by means of flushing several times, treated with argon under an inert atmosphere. Then, by means of a corresponding inlet valve, 7.5 ml of toluene are added by means of a syringe. The Ar atmosphere is exchanged for hydrogen by flushing several times. A hydrogen pressure of 1 bar at 25° C. was established. The reaction is terminated following expiry of the desired time for the hydrogenation of the first C═C bond in the neral or geranial or optionally after visible ending of the hydrogen absorption. Then, the hydrogen atmosphere was again automatically replaced by argon. The qualitative and quantitative evaluation of the reaction was carried out by means of NMR spectroscopy. The results are summarized in table 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17.2 % ee | With (1S,1′S)(+)(9,9-dimethyl-9H-xanthene-4,5-diyl)bis((2-methylphenyl)(phenyl)phosphine); [Ru(acac)(cod)]; hydrogen In toluene at 25℃; for 7.33333h; Autoclave; | 7 Hydrogenation of Neral and Geranial Under Standard Conditions General procedure: The individual hydrogenation experiments were carried out on a laboratory scale under the following conditions. In an autoclave (AK), the corresponding amounts of rhodium precursor [Rh(acac)(COD)] or Rh(acac)(CO)2), compound of the formula I and neral or geranial are initially introduced and, by means of flushing several times, treated with argon under an inert atmosphere. Then, by means of a corresponding inlet valve, 7.5 ml of toluene are added by means of a syringe. The Ar atmosphere is exchanged for hydrogen by flushing several times. A hydrogen pressure of 1 bar at 25° C. was established. The reaction is terminated following expiry of the desired time for the hydrogenation of the first C═C bond in the neral or geranial or optionally after visible ending of the hydrogen absorption. Then, the hydrogen atmosphere was again automatically replaced by argon. The qualitative and quantitative evaluation of the reaction was carried out by means of NMR spectroscopy. The results are summarized in table 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With sodium carbonate In cyclohexane at 80℃; for 24h; Schlenk technique; | 2.4. General procedure for the synthesis of alkyl/aryl mixed phosphates General procedure: A flame-dried Schlenk tube equipped with a magnetic stir bar wassuccessively charged with phosphoryl azides (0.50 mmol, 1.0 equiv.),aliphatic alcohols (excess amount), CSCuCl (30 mg, 10 mol% of [Cu]loading), and Na2CO3 (26 mg, 0.25 mmol, 0.5 equiv.) in indicated solventor mixture (2.0 mL, 0.25 M). The reaction mixture was stirred atthe indicated temperature and time. The reaction was monitored byTLC. After completion of the reaction, the reaction mixture was allowedto cool to room temperature and filtered. The solid stuff was washedwith cyclohexane, dried in the oven, and collected to reuse for furthercatalytic reactions. The filtrate was diluted with ethyl acetate (25 mL)and washed with 1% HCl (aq, 5 mL) and H2O (5 mL). The organic phasewas dried over anhydrous Na2SO4 and concentrated under reducedpressure. Purification by flash column chromatography on silica gelusing mixtures of petroleum ether and ethyl acetate as eluents affordedthe analytically pure product. |
With sodium carbonate; copper(l) chloride In cyclohexane at 20 - 100℃; for 24h; Inert atmosphere; | 10 Synthesis of 3,7-dimethyl-6-octenyl diphenyl phosphate: Weigh 108 μL (0.5 mmol) of diphenyl azide phosphate,Citronella 0.2mL (1.10mmol),Cuprous chloride, sodium carbonate, cyclohexane;The amount of the substance of diphenyl azide phosphate and cuprous chloride is 1: 0.1;The quantity ratio of the substance of diphenyl azide phosphate and sodium carbonate is 1: 0.5;The volume ratio of cyclohexane to citronellol is 9: 1;Add the weighed reactants in sequence to the 25mL reaction tube with magnetons,Stir on a magnetic stirrer at room temperature, then slowly heat to 100 ° C.The progress of the reaction was monitored by thin layer chromatography. Stop reaction at 0.1MPa after 24h,Cool to room temperature.The mixture was diluted with 0.1 mol / L hydrochloric acid (5 mL) and extracted with ethyl acetate (10 mL x 3).Combine the organic phases. The organic phase was washed with saturated brine (5 mL), dried over anhydrous sodium sulfate, filtered and concentrated, and separated by column chromatography. Silica gel with 300-400 mesh was used as the stationary phase.The mixed solvents of ethyl acetate and petroleum ether in different proportions were used as eluents to purify and isolate the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With Bromoform; N-benzyl-N,N,N-triethylammonium chloride; sodium hydroxide In ethanol; dichloromethane; water at 20℃; for 0.833333h; | 3.2. Representative Procedure, Synthesis of (2,2-Dibromo-3,3-dimethylcyclopropyl)methanol (1) General procedure: A 1.0 mL sample loop (PTFE) containing a solution of 3-methyl-2-buten-1-ol (1.43 mmol), CHBr3 (2.86 mmol), 4.3 mol% TEBA (relative to the alkene) and 0.6 vol.% ethanol (absolute) in CH2Cl2, and a 5 mL sample loop (PTFE, Syrris Ltd.) containing 40% (w/w) NaOH (aq) solution, was used. The filling of the 40% (w/w) NaOH (aq) solution into the sample loop was done very slowly and with great care, due to the high viscosity of the strongly basic NaOH solution and danger of spillage due to pressure build-up. The two solutions were simultaneously introduced into the flow system at a total flow rate of 0.50 mL/min (flow rate NaOH (aq): 0.40 mL/min, flow rate organic solution: 0.10 mL/min) at room temperature, i.e., a residence time of 50 min and an AO flow ratio of 4. The mixture was fed into brine (50 mL), and the flow was collected for 77 min at this flow rate, and then for 4 min at 2 × 1.5 mL/min (to flush the system). The pressure in the system was 1-4 bar. The reaction mixture was extracted with ethyl acetate (100 mL + 3 × 50 mL), and the combined organic phases were washed with brine (2 × 50 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by filtering it through a plug made of 0.5 cm silica and 0.5 cm Celite 545 coarse (calcined) using ethyl acetate as the eluent. Concentration in vacuo yielded a mixture (0.31 g) containing (2,2-dibromo-3,3- dimethylcyclopropyl)-methanol (1): 3-methyl-2-buten-1-ol: bromoform; 88:2:10 according to 1H NMR. Estimated yield of 1: 0.27 g, 74%, corresponding to a space time yield of ~0.25 mol L-1 h-1. The spectral data were in accordance with the literature [46]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With (4,4′-di-tert-butyl-2,2′-dipyridyl)Ni(o-tolyl)(Br); 1,8-diazabicyclo[5.4.0]undec-7-ene In toluene at 80℃; for 12h; Inert atmosphere; Sealed tube; UV-irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With sodium t-butanolate In toluene at 150℃; for 36h; Sealed tube; | General procedure for NaOtBu-catalyzed esterification ofamides. General procedure: To a dry 35 mL sealed tube with a stir bar, amide (0.5 mmol), NaOtBu (0.1 mmol), phenol/alcohol (1.0 mmol) and toluene (5.0 mL) were added. After sealed with a Teflon-lined cap, the reaction mixture was stirred at 150 °C for 24 h. Then the mixture was cooled to room temperature and quenched with H2O (5.0 mL). The mixture was separated and extracted with ethyl acetate (EA) (15 mL×3). The combined organic layer was dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography with ethyl acetate/petroleum ether to give the desired product. More experimental details and characterizations are available in the Supporting Information online. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With sodium t-butanolate In toluene at 150℃; for 24h; Sealed tube; | General procedure for NaOtBu-catalyzed esterification ofamides. General procedure: To a dry 35 mL sealed tube with a stir bar, amide (0.5 mmol), NaOtBu (0.1 mmol), phenol/alcohol (1.0 mmol) and toluene (5.0 mL) were added. After sealed with a Teflon-lined cap, the reaction mixture was stirred at 150 °C for 24 h. Then the mixture was cooled to room temperature and quenched with H2O (5.0 mL). The mixture was separated and extracted with ethyl acetate (EA) (15 mL×3). The combined organic layer was dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography with ethyl acetate/petroleum ether to give the desired product. More experimental details and characterizations are available in the Supporting Information online. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With sodium t-butanolate In toluene at 150℃; for 24h; Sealed tube; | General procedure for NaOtBu-catalyzed esterification ofamides. General procedure: To a dry 35 mL sealed tube with a stir bar, amide (0.5 mmol), NaOtBu (0.1 mmol), phenol/alcohol (1.0 mmol) and toluene (5.0 mL) were added. After sealed with a Teflon-lined cap, the reaction mixture was stirred at 150 °C for 24 h. Then the mixture was cooled to room temperature and quenched with H2O (5.0 mL). The mixture was separated and extracted with ethyl acetate (EA) (15 mL×3). The combined organic layer was dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography with ethyl acetate/petroleum ether to give the desired product. More experimental details and characterizations are available in the Supporting Information online. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With Selectfluor In water; acetonitrile at 20℃; for 0.25h; | Synthesis of 6-fluoro-3,7-dimethyl-oct-7-en-1-ol (2a) To a stirred solution of β-citronellol (15.6 mg, 0.1 mmol) in CH3CN: H2O (7: 3, 1.0 mL) was added reagent selectfluor (53.0 mg, 0.15 mmol, 1.5 eq.). The reaction was stirred at ambient temperature for 15 minitues. Solvents were removed and the crude residue was purified by silica gel flash chromatography to give compound 2a (13.3 mg, 0.076 mmol) in 76% yield. 1H-NMR (400 MHz, CDCl3) δ 4.98 (s, 1H), 4.93 (s, 1H), 4.86-4.83 (m, 0.5H), 4.74-4.71 (m, 0.5H), 3.74-3.63 (m, 2H), 1.73 (s, 3H), 1.62-1.59 (s, 5H), 1.47-1.35 (m, 2H), 1.28-1.25 (m, 2H), 0.92 (d, J = 8.0 Hz, 3H). 19F-NMR (376 MHz, CDCl3) δ -177.05 (m, 1F), -177.60 (m, 1F); MS (ESI): calculated: [2M+Na] + = 371.51; found: [M+H] + = 371.27. HRMS (ESI): calculated [2M+H] + = 371.5011; found: 371.2713. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With (η5-C5Me5)Rh(ppy)H; hydrogen In methanol at 20℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With dmap; dicyclohexyl-carbodiimide In acetonitrile at -15 - 25℃; for 14h; | General procedure 5 (GP5) - monoesterification: General procedure: A 50 mL RBF equipped with a stirring bar was charged with the methyl malonic acid(9a, 0.50 g, 4.2 mmol, 1.0 equiv), DMAP (26 mg, 0.21 mmol, 5 mol %), CH3CN (10 mL), and the requisite alcohol 8 (1.1 equiv) and cooled at -15 °C (ice/salt bath). A solution of DCC (0.87 g, 4.2 mmol, 1.0 equiv) in CH3CN (10 mL) was added dropwise to the stirred mixture with a pressure-equalizing dropping funnel. The reaction was allowed to warm to rt and stirred for 14 h. Then, the reaction mixture was filtered through a fritted funnel (rinsed with CH2Cl2), and the filtrate was evaporated. To the resulting crude oil were added 30 mL of sat aq NaHCO3. The resulting solution was washed with Et2O (2 × 10 mL), acidified to pH 1 with 1 M aq HCl, and extracted with CH2Cl2 (2 × 20 mL). The combined organic layers were dried (Na2SO4) and evaporated to afford the expected product 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With methanesulfonic acid; calcium chloride at 20℃; for 5h; | Hydrochlorination Reaction (General Procedure A) General procedure: A solution of the alkene (0.2 mmol, 1 equiv) in acetic acid (1 mL, 0.2M) was added on calcium chloride (111.0 mg, 5 equiv). Methanesulfonicacid (65 L, 5 equiv) was added and the mixture was stirred atroom temperature. After 5 hours, the reaction was quenched withsaturated aqueous NaHCO3 and the mixture was extracted withCH2Cl2 (3×). The organic layers were combined and then washed witha saturated aqueous Na2CO3, dried with Na2SO4, and concentrated underreduced pressure. The desired product was obtained without furtherpurification unless otherwise noted. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With methanesulfonic acid; lithium bromide at 20℃; for 4h; | Hydrobromination Reaction (General Procedure B) General procedure: To a solution of the alkene (0.2 mmol, 1 equiv) in acetic acid (1 mL,0.2 M) was added on lithium bromide (86.9 mg, 5 equiv). Methanesulfonic acid (65 L, 5 equiv) was added and the reaction was stirred atroom temperature. After 4 hours, the reaction was quenched withsaturated aqueous NaHCO3 and the mixture was extracted withCH2Cl2 (3×). The organic layers were combined and then washed withsaturated aqueous Na2CO3, dried with Na2SO4, and concentrated underreduced pressure. The desired product was obtained without furtherpurification unless otherwise noted |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With methanesulfonic acid; lithium iodide at 20℃; for 4h; | Hydroiodination Reaction (General Procedure C) General procedure: To a solution of the alkene (0.2 mmol, 1 equiv) in acetic acid (1 mL,0.2 M) was added lithium iodide (133.9 mg, 5 equiv). Methanesulfonicacid (65 L, 5 equiv) was added, and the reaction was stirred at roomtemperature. After 4 hours, the mixture was extracted with hexane(3×). The organic layers were combined, dried with Na2SO4, and concentratedunder reduced pressure. The desired product was obtainedwithout further purification unless otherwise noted |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen In cyclohexane at 70℃; for 4h; | 2.3. Catalytic experiments General procedure: Citronellal (Sigma Aldrich, ≥95.0 wt%) and citral (Sigma-Aldrich,cis-/trans-isomer ~ 1/1, ≥ 95.0%) transformations were investigated ina trickle bed reactor (the tube diameter 1.25 cm), in which both liquidand gas were flowing from top to bottom in a co-current mode. The liquid flow which rate was varied from 0.2 to 0.3 mL/min contained0.086 mol/l citronellal or citral in cyclohexane. The hydrogen (AGA,99.999%) flow rate was 150 mL/min at the total pressure of 20 bar, while with 10 and 15 bar it was 100 mL/min. The experiments were performed as follows: 5 wt% Ni/(H-Beta-38 +sepiolite) extrudates (1 g)with the length varying from 0.6 to 1.0 cm and the diameter of 1.5 mmwere loaded to gether with 15 g of inert quartz of the size 0.2-0.8 mm. Prior to the reaction, the catalyst was reduced in situ using the followingtemperature program: 2 C/min - 350 C (120 min). The reaction temperature was set to 70 C and the pressure was adjusted to 20 bar. The reaction was started when the cyclohexane was first pumped though the catalyst bed in order to wet it. There after, the liquid flow was changed tothe feed flow. The contact time was varied in the range of 3.2-6.4 mincorresponding to the residence times of 11.5-23 min. The liquid residencetime was 16.7 min. After 180 min TOS, the pressure was adjusted first to 15 bar and finally after 5 h TOS to 10 bar. The total time-onstreamwas 7 h. The reduced fresh catalyst was first used in citronellaltransformation to menthol followed by in situ reduction of the spentcatalyst using the same temperature program as described above andthereafter citral transformation to menthol was started by adjusting thetemperature and pressure initially to 70 C and 20 bar respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With potassium-t-butoxide In 1,4-dioxane at 140℃; for 12h; Schlenk technique; | 25 Example 25 The N-alkyl-substituted pyrrolone compound in this embodiment is 5,9-dimethyl-1-(N-methyl-pyrrol-2-yl)dec-8-en-1-one, For the preparation route of the N-alkyl-substituted pyrrolone compounds of the present embodiment, reference may be made to example 1, and the following steps are specifically adopted: 1) Take 0.2 mmol of 1-methyl-2-acetylpyrrole, 0.4 mmol of citronellol and 0.2 mmol of potassium tert-butoxide, add 1 ml of 1,4-dioxane to prepare a mixture, and place the mixture in put it in a 5ml schlenk tube, put it in a heating module at 140 °C, react for 12h, and cool it to room temperature to obtain a reaction solution; 2) Concentrate the reaction solution to obtain a concentrate, use the mixed solvent composed of petroleum ether and ethyl acetate in a volume ratio of 5:1 as a developing solvent, and use silica gel as an adsorbent, carry out thin-layer chromatography separation, and obtain 39 mg target product. The yield of the target product in this example is 74%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With [2-(di-tert-butylphosphinomethyl)-6-(diethylaminomethyl)pyridine]ruthenium(II) chlorocarbonyl hydride; potassium-t-butoxide; ammonia In tert-Amyl alcohol; toluene at 120 - 150℃; for 36h; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With trimethylsilylazide; 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluoroborate) In lithium hydroxide monohydrate; acetonitrile at 20℃; for 18h; Schlenk technique; | 6-Azido-7-fluoro-3,7-dimethyloctan-1-ol (2c) Compound 1c (15.6 mg, 0.1 mmol) and Selectfluor (71 mg, 0.2 mmol) were placed ina Schlenk tube. TMSN3 (23 mg, 0.2 mmol), CH3CN (0.4 mL) and H2O (0.1 mL) were then added successively at R.T. The reaction mixture was stirred at R.T. for 18 h. The residue was purified by silica gel to give 2c (18.5 mg, 85%) as colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With 4-dimethylaminopyridine; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride In dichloromethane at 20℃; for 18h; | 3.1 Step 1: Synthesis of Compound 3-1 8-Bromooctanoic acid (1.139 g, 5.13 mmol)and 3,7-dimethyloct-6-en-1-ol (citronellol, 1.599 g, 10.25 mmol) in dichloromethane (60 mL),After fully dissolved, EDC hydrochloride (0.98 g, 5.13 mmol) was addedand DMAP (0.125 g, 1.03 mmol).The mixture was stirred at normal temperature for 18 hours.After the reaction was completed, it was diluted with DCM (200 mL),and washed with saturated NaHCO3 (100 mL) and brine (100 mL).The combined organic layers were dried over anhydrous Na2SO4, the solvent was removed in vacuo,The crude product was obtained, and the crude product was purified by chromatography (silica gel column, eluent was petroleum ether containing 0.5% EA (volume percent)),The pure product was evaporated to give compound 3-1 (3,7-dimethyloct-6-enyl 6-bromohexanoate) as a pale yellow oil(0.648 g, 35%) |
35% | With 4-dimethylaminopyridine; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride In dichloromethane at 20℃; for 18h; | 3.1 Step 1: Synthesis of compounds 3-1 8-Bromocaprylic acid (1.139g, 5.13 mmol) and 3,7-dimethyloctano-6-en-1-ol (citronellol, 1.599 g, 10.25 mmol) were dissolved in dichloromethane (60 mL), and after full solubilization, EDC hydrochloride (0.98 g, 5.13 mmol) and DMAP (0.125 g, 1.03 mmol) were added. The mixture was stirred at room temperature for 18 hours. After the reaction is over, dilute with DCM (200 mL) and wash with saturatedNaHCO3(100 mL) and brine (100 mL). The combined organic layer was dried with anhydrousNa2SO4, the solvent was removed in vacuo, the crude product was obtained by chromatography (silica gel column, eluent is petroleum ether containing 0.5% EA (volume percentage)), and the pure product was evaporated to give a light yellow oily compound 3-1 (6-bromohexanoic acid 3,7-dimethyloct-6-enyl ester) (0.648g, 35%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With silver hexafluoroantimonate; bis[dichlorido(η5-1,2,3,4,5-pentamethyl-cyclopentadienyl)rhodium (III)]; benzoic acid In toluene at 80℃; for 20h; Inert atmosphere; | Genaral procedure for synthesis of 4aa General procedure: A mixture of 1-(2-pyrimidinyl)-indole 1a (39.0 mg, 0.2 mmol, 1.0 equiv), 2 (86.1 mg, 1 mmol, 5.0 equiv), 3a (64.1 mg, 2 mmol, 10.0 equiv), [Cp*RhCl2]2 (6.2 mg, 0.01 mmol, 5 mol%), AgSbF6 (14 mg, 0.04 mmol, 20 mmol%), and PhCO2H (12.2 mg, 0.1 mmol, 50 mmol%) in toluene (1.0 mL) was stirred under argon at 80 °C for 20 hours. After cooled to room temperature, the solvent was removed under reduced pressure. The contents were subjected to flash chromatography (petrol ether/ethyl acetate, 6:1) to give the product 4aa as a white solid (47.5 mg, 0.18 mmol, 89%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With bis(3,5-di-(tert-butyl)-2-hydroxyazobenzolato)nickel(II); potassium-t-butoxide In toluene at 120℃; for 24h; Inert atmosphere; |
Tags: 106-22-9 synthesis path| 106-22-9 SDS| 106-22-9 COA| 106-22-9 purity| 106-22-9 application| 106-22-9 NMR| 106-22-9 COA| 106-22-9 structure
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