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CAS No. : | 505-48-6 | MDL No. : | MFCD00004428 |
Formula : | C8H14O4 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | TYFQFVWCELRYAO-UHFFFAOYSA-N |
M.W : | 174.19 | Pubchem ID : | 10457 |
Synonyms : |
Octanedioic acid
|
Num. heavy atoms : | 12 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.75 |
Num. rotatable bonds : | 7 |
Num. H-bond acceptors : | 4.0 |
Num. H-bond donors : | 2.0 |
Molar Refractivity : | 44.11 |
TPSA : | 74.6 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.63 cm/s |
Log Po/w (iLOGP) : | 1.15 |
Log Po/w (XLOGP3) : | 1.03 |
Log Po/w (WLOGP) : | 1.5 |
Log Po/w (MLOGP) : | 0.93 |
Log Po/w (SILICOS-IT) : | 0.88 |
Consensus Log Po/w : | 1.1 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.56 |
Log S (ESOL) : | -1.11 |
Solubility : | 13.6 mg/ml ; 0.0782 mol/l |
Class : | Very soluble |
Log S (Ali) : | -2.19 |
Solubility : | 1.13 mg/ml ; 0.00651 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -1.05 |
Solubility : | 15.4 mg/ml ; 0.0885 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.47 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P305+P351+P338 | UN#: | N/A |
Hazard Statements: | 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 |
---|---|---|
88.58%Chromat. | With Amberlyst 35 In water; acetic acid at 95℃; for 20 h; Inert atmosphere | Example 5: Saponification of dimethyl suberate to yield suberic acid To a 250 mL round bottom flask equipped with a stir bar, heating mantle, temperature probe, and short path distillation head was added crude dimethyl suberate (1.15 g), Amberlyst 35 (0.2 g, pre-washed with methanol), acetic acid (10 mL), and DI water (2 mL). The reaction was heated to 95 °C for 20 hours with a gentle stream of nitrogen (0.05 SCFH) passing through the headspace. GC analysis showed high conversion of dimethyl suberate to suberic acid as shown in Table 6.Table 6 - GC analysis of crude reaction mixture[0093] The product solution was cooled and filtered to remove catalyst using a syringe filter (0.45 u, polypropylene). The clear product solution was loaded to a 250 mL round bottom flask equipped with a stir bar, heating mantle, temperature probe, and short path distillation head. The acetic acid was distilled out under atmospheric pressure to leave an oily residue. To the residue was added DI water (10 mL). The water was distilled out to leave about 4 mL of solution which was allowed to gradually cool to room temperature with the stirring off. Upon cooling, white crystals were evident. The solid was isolated by filtration and washed with DI water (4 mL). The solids were dried at 100 °C to yield 0.41 g of white crystalline product. A sample of the product was dissolved in acetone for GC analysis and results are shown in Table 7. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 5 h; | Octanedioic acid (1.00 g, 5.75 mmol), 2-methyl-2-propanol (6.9 mL, 71.8 mmol), EDCI (1.1 g, 5.74 mmol) and DMAP (0.7 g, 5.74 mmol) were dissolved in DCM (6.8 mL). The reaction was stirred at room temperature for 5 hours. The reaction mixture was diluted with diethyl ether (60 mL) and washed with 0.01 N HCI (50 mL) and water (50 mL). The organic phase was then dried over MgS04 and the solvent was removed in vacuo. The crude product was purified by flash column chromatography with 1 : 1 EtOAc: Petrol to give 8-(fe f-butoxy)-8- oxooctanoic acid (0.41 g, 1.77 mmol, 31percent) as colourless oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.94 (br s, 1 H), 2.18 (dd, J = 14.6, 7.3 Hz, 4H), 1.54-1.42 (m, 4H), 1.40 (s, 9H), 1.34-1.20 (m, 4H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With sulfuric acid;Reflux; | To a solution of suberic acid (5.0 g, 0.028 mol) in CH3OH (20 mL) was added H2SO4 (0.5 mL), and the mixture was refluxed overnight. The solution was concentrated under vacuum. The resulting precipitate was extracted three times with ethyl ether 50 ml. The combined organic extracts were washed with 10% aq. NaHCO3 solution and brine, and dried using MgSO4. Evaporation under reduced pressure gave dimethyl suberate as an oil (5.5g, 95%). 1H NMR (CDCl3, 400 MHz) 3.65 (s, 6H, OCH3), 2.20 (t, 4H, J = 7.0 Hz, H-2 and 7), 1.56 (m, 4H, H-3 and 6), 1.24 (m, 4H, H-4 and 5). Hydroxylamine hydrochloride (17 g, 0.25 mol) in CH3OH (100 mL) was mixed with KOH (14g, 0.25 mol) at 40 C in CH3OH (150 mL), cooled to 0 C, and filtered. The dimethyl suberate (5.5 g, 0.027mol) was then added to the filtrate followed by addition of KOH. The mixture was stirred at room temperature for 1 h. The mixture was added to stirring cold water (500 mL), and the pH was adjusted to 7 by adding acetic acid. The precipitate was filtered off, and the resulting product was dried in a vacuum oven to yield suberohydroxamic acid (5.0 g, 90%). 1H NMR (DMSO-d6, 400 MHz) 9.47 (br s, OH), 1.92 (t, 4H, J = 7.0 Hz, H-2 and 7), 1.46 (m, 4H, H-3 and 6), 1.21 (m, 4H, H-4 and 5); MS (ESI+) m/z 205 [M+H]+ FontWeight="Bold" FontSize="10" |
85% | With sulfuric acid; In methanol; for 12h; | To a solution of octanedioic acid (100 g, 0.58 mol) in methanol (450 mL), H2SO4 (10 mL) was added and the mixture was heated to reflux for 12 h. After cooling to room temperature, the solvent was removed under reduced pressure. The residue was poured to ice water (200 mL) and extracted with ethyl ether (3 400 mL), the combined organic phase was washed with 10% sodium bicarbonate (200 mL) and brine (200 mL), dried with MgSO4 and concentrated under reduced pressure to give 12 (98 g, 85%) as colorless oil. 1H NMR (300 MHz, CDCl3) d: 1.24-1.39 (m, 4H, -CH2), 1.56-1.69 (m, 4H, -CH2), 2.26-2.35 (m, 4H, 2CH2CO2), 3.67 (s, 6H, 2CO2CH3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With acetic anhydride at 150℃; for 1.5h; Inert atmosphere; | |
100% | With acetic anhydride | |
99% | With acetic anhydride at 160℃; for 2h; |
98% | With acetic anhydride at 140℃; for 1h; Inert atmosphere; | |
98% | With acetic anhydride at 140℃; for 3h; | |
98% | With acetic anhydride for 4h; Reflux; | Dicarboxylic Acid Anhydrides-General Procedure (1b,c) General procedure: First, 19 mmol of a dicarboxylic acid was dissolved in 50 mL of acetic anhydride and refluxedfor 4 h. The solvents were removed under reduced pressure, obtaining 18 mmol ofa cyclic anhydride. |
97% | With acetic anhydride at 150℃; for 1h; Inert atmosphere; | |
97% | With acetic anhydride for 1.5h; Reflux; | |
96% | With acetic anhydride for 1h; Heating; | |
50.4% | With acetic anhydride for 1h; Heating / reflux; | A solution of suberic acid (5.0 g, 28.7 mmol) in acetic anhydride (10 mL) was heated at reflux for 1 h. After cooling to RT, the solvent was removed in vacuo. The pale yellow residue was recrystallized from acetonitrile. After filtration and drying to the vacuum pump, the oxonane-2,9-dione was obtained as a white solid (2.26 g, 50.4 % yield).MW = 156.18; Yield: 50.4%; White Solid; Mp (°C) = 51-52 (Litt. 69.4) |
45% | With acetic anhydride; glacial acetic acid for 1h; Reflux; | |
With acetyl chloride | ||
With acetic anhydride | ||
With acetic anhydride for 1h; Heating / reflux; | 2 Compound 3c: 8-Oxo-8-(phenylamino)octanoic acid A solution of suberic acid (5.00 g, 28.7 mmol) in acetic anhydride (10 mL) was heated under reflux for 1 hour. After cooling to r.t., the solvent was removed in vacuo. The crude yellow oil was used without any further purification for the next step. Aniline (3.00 mL, 28.7 mmol) was added to a stirred solution of the produced anhydride in anhydrous THF (10 mL). After stirring at r.t. for 30 minutes, the reaction mixture was diluted with water until a colorless solid precipitated, which was collected by filtration. Recrystallisation from water/acetonitrile gave the pure compound as a colorless solid.The reaction yielded 2.74 g (11.0 mmol, 39 %) of 3c as a colorless solid: TLC: R/= 0.52 (DCM/MeOH 9:1); MS (MALDI-ToF, CHCA): m/z (%) = 250.2 (100, [M+H]+, calc. 250.1), 272.3 (26, [M+Naf, calc. 272.1); 1H-NMR (500 MHz, DMSO-D6): δ = 1.27-1.32 (m, 4H), 1.46-1.50 (m, 2H), 1.55-1.58 (m, 2H), 2.18 (t, 3J=7.5 Hz, 2H), 2.28 (t, 3J=7.5 Hz, 2H), 6.99 (m, 3J=7.5 Hz, IH), 7.25-7.28 (m, 3J=7.5 Hz, 2H), 7.56-7.58 (m, 3J=7.5 Hz, 2H), 9.82 (m, IH), 11.9 (s, IH). | |
With acetic anhydride Reflux; | ||
In acetic anhydride for 1h; Reflux; | A solution of suberic acid (5.00 g, 28.70 mmol) in acetic anhydride (10 mL) was heated under reflux for 1 h. After cooling to rt, the solvent was removed in vacuo. The crude yellow oil was used without any further purification for the next step. Appropriate o-phenylendiamine 3 (28.70 mmol) was added to the produced anhydride. After stirring at 120 °C for 30 minutes, the reaction mixture was diluted with water until a colorless solid precipitated, which was collected by filtration. Recrystallisation from water/acetonitrile gave the pure compound 4a-d as a colorless solid. | |
With acetic anhydride for 2h; Reflux; | ||
With acetic anhydride Reflux; | 1 Example 1 General procedure: General procedure for the preparation of the cyclic carboxylic anhydrides: A solution of carboxylic diacid in acetic anhydride (ca. 3 M) was heated at reflux overnight. After cooling to room temperature, acetic anhydride was removed under reduced pressure (ca. 10 mmHg) to give the desired cyclic carboxylic anhydrides. Suberic anhydride: XH NMR (300 MHz, DMSO-i) δ 2.41 (m, 4H), 1.62 (m, 4H), 1.34 (m, 4H). | |
With acetic anhydride Heating; | ||
With acetic anhydride at 150℃; for 1h; | ||
With acetic anhydride for 1h; Reflux; | Synthesis of Compound 15 A mixture of suberic acid (5 g, 28.7 mmol) in a 10 mL single-necked flask,5 mL of acetic anhydride was added, heated to reflux for 1 hour, then cooled to room temperature, solvent stripping under reduced pressure gave 4.26 g of crude product 2 (95.1%). | |
4.2 g | With acetic anhydride for 3h; Reflux; | 1.1 1) To a 100 mL single-necked flask was added 5.0 g of suberic acid and 10 mL of acetic anhydride, refluxed for 3 h and then cooled to room temperature. The remaining acetic anhydride and by-product acetic acid were distilled off under reduced pressure. The resulting solid was recrystallized from acetonitrile to give a white solid suberic anhydride 4.2 g. |
With acetic anhydride for 1h; Heating; | Synthesis of compound 15 Weigh the suberic acid (5 g, 28.7 mmol) in a 10 mL single-necked flask,Add 5 mL of acetic anhydride,After heating for 1 h, the mixture was cooled to room temperature and decompressed under reduced pressure to give 4.26 g of crude product 2 (95.1%). | |
With acetic anhydride at 140℃; for 1h; | Suberanilic acid (6)1 A suspension of suberic acid (4, 3.08 g, 17.7 mmol, 1.0 eq) in acetic anhydride (6 mL) was heated under reflux for 1 h then cooled to rt and concentrated in vacuo. The crude material was crystallised from boiling acetonitrile to yield crude suberic anhydride (5, 2.47 g, 88%)which was used without further purification. Aniline (2.80 mL, 31.8 mmol, 2.0 eq) was addedto a solution of crude suberic anhydride (5, 2.47 g, 15.6 mmol, 1.0 eq) in tetrahydrofuran(15 mL) and stirred at rt for 4 h. Water (30 mL) was added to the reaction and the precipitate was removed by filtration. The remaining solution was acidified with aqueous hydrochloric acid(1 M, 50 mL) and extracted with ethyl acetate (2 × 100 mL). The combined organiccomponents were washed with water (100 mL), and brine (100 mL), dried (Na2SO4), filtered,and concentrated in vacuo. The resulting residue was then crystallised from boiling water toyield suberanilic acid (6, 1.20 g, 27%) as a colourless solid. | |
With acetic anhydride at 150℃; for 2h; Inert atmosphere; | ||
With acetic anhydride for 12h; Reflux; | ||
With acetic anhydride Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With oxygen; trifluoroacetic acid; sodium nitrite at 0 - 20℃; for 5.25h; | 22 An operation was conducted in the same manner as in Example 2 except that cyclohexanol was replaced by an alicyclic secondary alcohol compound or an alicyclic ketone compound, both shown in Table 2 as a raw material compound. The results are shown in Table 2. |
92% | With dihydrogen peroxide In water; acetonitrile at 90℃; for 11h; Green chemistry; | |
85% | With dihydrogen peroxide In water at 90℃; for 20h; | 8 H2WO4 (25.0 mg, 0.100 mmol), 30% aqueous hydrogen peroxide (3.7 ml, 33 mmol) and cyclooctanone (1.3 ml, 10 mmol) were mixed and stirred at 90 °C for 20 hours. When determination by GLC was carried out in the same manner as in Example 1, the yield of suberic acid was 85%. |
82% | With oxygen; copper dichloride In acetic acid at 80℃; for 6h; | |
81% | Stage #1: cycloactanone With Oxone; ruthenium(III) chloride monohydrate In water at 70℃; for 6h; Stage #2: In ethanol Cooling; | |
With sulfuric acid; chromic acid | ||
With chromium(III) oxide; sulfuric acid | ||
With nitric acid | ||
With diperiodatonickelate(IV) ion; hydroxide In water at 293 - 313℃; activation parameters <E, ΔH(excit.), ΔG(excit.), ΔS(excit.)> were investigated; | ||
With acetic acid; 1,3-dichloro-[1,3,5]triazinane-2,4,6-trione In water at 35℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 2h; | Organic synthesisGeneral procedure for the synthesis of linker molecules (compound 1 and 2)To a solution of the di-acid (suberic acid or 3,3?-dithiodipropionic acid) (500 mg, 2.4 mmol) indry DCM (10 mL)was added EDC?HCI (1.37 g, 7.1 mmol) and N-hydroxysuccinimide (656.8mg, 5.7 mmol). The mixture was stirred for 2 hours at rt. The organic phase was washed witha 2.5% aqueous solution of NaHSO4 (2 x 10 mL) and brine (10 mL), dried over anhydrous Na2504, filtered and concentrated in vacuo. No further purification was performed. Both compounds 1 and 2 were isolated as white solids with full conversion. DSS linker (Disuccinimidyl suberate) (compound 1) 1H NMR (400 MHz, CDCI3) 62.82 (s, 8H), 2.60 (dt, J = 2.5, 7.4 Hz, 4H), 1.80-i .71 (m, 4H),1.48-1.42 (m, 4H). 13C NMR (100 MHz, CDCI3) 6 169.3, 168.6, 30.9, 28.2, 25.7, 24.4. | |
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In acetone; at 25℃; for 24h; | General procedure: NHS-Cn was prepared as described by Chen et al. (2011) with a small modification; end-bit binary acid (15 mmol each; C2, C3, C4, C5, C6, C8, C10, C14) and NHS (40 mmol) were dissolved in acetone (25 mL), and then EDC (30 mmol) was added to the solution. The clear mixture was gently stirred at 25C for 24 h. After the acetone was removed by rotary evaporation under reduced pressure, the residue was washed several times with deionised water and then dried under vacuum at 50C. The crosslinker thus prepared was characterised by the 1H NMR and FT-IR spectra. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36% | With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 23℃; for 0.75h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With zirconium tetrachloride bis(tetrahydrofuran) complex; hydrogen; C24H20B(1-)*C36H55ClIrN2P2(1+); sodium hydride; butan-1-ol In toluene at 180 - 190℃; for 28h; | |
23% | With potassium hydroxide; samarium diiodide In tetrahydrofuran; water for 0.01h; Ambient temperature; | |
94.8 %Chromat. | With cobalt(II) oxide; hydrogen In 1,4-dioxane at 189.84℃; for 10h; Autoclave; | 2.3 Catalytic evaluation and product analysis General procedure: The hydrogenation of carboxylic acids or other substrates was performed in a high-pressure stainless-steel autoclave (Xinyuan Chemical Machinery, Series CJK, 300 mL) with a maximum stirring rate of 1500 r/min. In a typical experiment, 0.2 g of catalyst (or without catalyst for the control experiment), 3 mmol of the substrate, and 100 mL alkane solvent (n-hexane, n-heptane, i-octane, or n-dodecane) were well mixed in the autoclave and purged with pure nitrogen at room temperature. The gas supply and discharge were carried out manually through needle valves. The autoclave was rapidly heated to the desired temperature and hydrogen was introduced at 2 MPa to initiate the reaction. The reaction pressure was kept at 2 MPa with a small negative deviation (∼0.2 MPa) owing to the consumption of hydrogen. Samples of the liquid phase were continuously taken through a sampling tube with a filter at certain intervals. The stirring rate was kept at 750 r/min during the reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic anhydride at 250℃; Yield given; | ||
With formate dehydrogenase; 1200 U catalase; OleT in combination with the putidaredoxin electron-transfer system CamAB; P450 monooxygenase OleT; ammonium formate; β-nicotinamide adenine dinucleotide, disodium salt, reduced form In ethanol Enzymatic reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With C24H33IrN4O3; water; sodium hydroxide for 18h; Reflux; | |
91% | With sodium bromate; sodium hydrogensulfite In acetonitrile for 2h; Heating; | |
86% | With Iron(III) nitrate nonahydrate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium chloride; oxygen In 1,2-dichloro-ethane at 25℃; for 48h; |
86% | With Iron(III) nitrate nonahydrate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium chloride; oxygen In 1,2-dichloro-ethane at 20℃; for 48h; Schlenk technique; | 16 Example 15: Synthesis of cyclohex-3-ene-1-carboxylic acid General procedure: Other operations Reference Example 1 was carried out using cyclohexane-3-ene-1-methanol (114.7 mg, 98% purity,1.0 mmol) for 48 hours to give cyclohex-3-ene-1-carboxylic acid 102.5 mg, 81%) (petroleum ether: ethyl acetate= 5: 1).In the oxygen atmosphere (oxygen balloon)Fe (NO3) 3 · 9H2O (40.4 mg, 0.10 mmol),2,2,6,6-tetramethylpiperidine nitrogen oxide (TEMPO, 15.5 mg, 0.10 mmol)KCl (7.5 mg, 0.10 mmol),Dodecanol (189.0 mg, 98% purity, 1.0 mmol) and1,2-dichloroethane (DCE, 4 mL)Was added to a 50 mL Schlenk tube.Stir at room temperature for 12 h, TLC monitoring until completion of the reaction.The reaction solution was filtered through a short column of silica gel, eluted with ether (75 mL) and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5: 1)The corresponding dodecanoic acid (199.2 mg, 100%) was obtained. |
62% | With potassium permanganate; acetic acid In water at 75℃; for 5.16667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 24 % Chromat. 2: 7% 3: 2.6% 4: 4% | With dihydrogen peroxide In water at 85℃; for 7h; Further byproducts given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 5.0h; | Octanedioic acid (1.00 g, 5.75 mmol), 2-methyl-2-propanol (6.9 mL, 71.8 mmol), EDCI (1.1 g, 5.74 mmol) and DMAP (0.7 g, 5.74 mmol) were dissolved in DCM (6.8 mL). The reaction was stirred at room temperature for 5 hours. The reaction mixture was diluted with diethyl ether (60 mL) and washed with 0.01 N HCI (50 mL) and water (50 mL). The organic phase was then dried over MgS04 and the solvent was removed in vacuo. The crude product was purified by flash column chromatography with 1 : 1 EtOAc: Petrol to give 8-(fe f-butoxy)-8- oxooctanoic acid (0.41 g, 1.77 mmol, 31%) as colourless oil. 1H NMR (400 MHz, DMSO-d6) delta ppm 11.94 (br s, 1 H), 2.18 (dd, J = 14.6, 7.3 Hz, 4H), 1.54-1.42 (m, 4H), 1.40 (s, 9H), 1.34-1.20 (m, 4H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With hydrogenchloride; sodium sulfate In ethyl acetate; N,N-dimethyl-formamide; <i>tert</i>-butyl alcohol | 15 EXAMPLE 15 EXAMPLE 15 This example shows the oxidation of cyclooctene using Condition A. Cyclooctene (100 mg) was dissolved in DMF (10 mL), and OsO4 (0.11 mL, 2.5% in tBuOH) was added and stirred for 5 min. OXONE (2.23 g) was added in one portion and the reaction had a final volume (14 mL). The reaction was stirred at room temperature for 3 hours or until the solution becomes colorless. This usually marks the completion of the reaction which was verified by TLC or GC. Na2SO3 (600 mg) was added, to reduce the remaining Os(VIII), and stirred for an additional hour or until solution became dark brown/black. EtOAc was added to extract the products and 1N HCl was used to dissolve the salts. The organic extract was washed with 1N HCl (50 mL*3) and brine (50 mL), dried over Na2SO4, and the solvent was removed under reduced pressure to obtain the crude product. Suberic acid was obtained in 82% yield, 92% yield by GC, after purification by silica gel column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With HCl In ethanol 0.5 equiv. of dicarboxylic acid was added to EtOH soln. of Ru-complex, few drops of concd. HCl was added, mixt. was refluxed for 30 h; soln. was evapd. to dryness, residue was dissolved in dry MeOH, chromy. on silica gel/petroleum ether(60-80 °C)-ethyl acetate mixt. (30:70), solid was recrystd. from CHCl3/petroleum ether (60-80 °C) (1:3), dried in vac., elem. anal.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With sodium periodate; RuCl3*2.9H2O In water at 20℃; for 0.5h; Sonication; | |
87% | With (tetra-n-butyl-ammonium)3(tetra(oxodiperoxotungstato)phosphate); dihydrogen peroxide In water at 90℃; for 3h; | |
70% | Stage #1: 1,2-cyclooctene With oxygen; ozone In tetrahydrofuran at 0℃; Stage #2: With hydroxylamine hydrochloride In tetrahydrofuran at 0 - 20℃; Inert atmosphere; |
47% | With dihydrogen peroxide; 2,6-dichlorobenzoic acid In water; acetonitrile at 20 - 60℃; for 23.1h; | 8 Experiment 8: Cyclooctene -> suberic acidTo a mixture of [Mn203 (Me3-TACN) 2] (PF6)2.H20 (8.1 mg, 10 μϖιο, 0.1 mol%) and 2 , 6 -dichlorobenzoic acid (57.3 mg, 0.30 mmol, 3.0 mol%) in CH3CN (7 ml) was added H202 (30 μ of a 50% aq. solution, 0.53 mmol) at room temperature and the resulting mixture was stirred for 20 min. Subsequently cyclooctene (1.16 g, 10 mmol) was added together with CH3CN (2 ml) and water (1 ml) . H202 (2.83 ml of a 50% aq. solution, 50 mmol, 5.0 equiv.) was then added at room temperature using a syringe pump (0.07 ml/h) . New batches of [Mn203 (Me3- TACN)2] (PF6)2.H20 (8.1 mg, 10 μϖιο, 0.1 mol% per batch) were added to the reaction mixture 17, 25 and 40.5 hours after the addition of H202 had commenced. When the addition of H202 was completed, the mixture was stirred for additional 1 hour. Water (10 ml) and Et20 (10 ml) were added and the pH of the aqueous layer was set to pH > 9 by adding some saturated NaHC03 (aq.) . The organic layer was separated and the aqueous layer was washed with Et20 (3x15 ml) . The pH of the aqueous layer was subsequently set to pH < 2 with some 10% HC1 (aq.) and was extracted with Et20 (3x20 ml) . The combined organic extracts were dried over anhydrous Na2S04. The solvents were removed in vacuo yielding 868 mg of a solid with a purity of circa 95% (determined by XH MR) , 47% yield of suberic acid. XH NMR (400 MHz, acetone-d6) δ 1.34-1.39 (m, 4H) , 1.56-1.63 (m, 4H) , 2.28 (t, J = 7.4, 4H) . N.B. NMR showed other compounds as well, including 2 , 6-dichlorobenzoic acid. |
23% | Stage #1: 1,2-cyclooctene With dihydrogen peroxide In water; acetonitrile at 20℃; for 25.33h; Stage #2: With sodium hydroxide In diethyl ether; water; acetonitrile Stage #3: With hydrogenchloride In water | 1 cyclooctene -> suberic acid To a mixture of [Mn2O3(Me3-TACN)2](PF6)2.H2O (16.2 mg, 20 μmol) and 2,6-dichlorobenzoic acid (114.6 mg, 0.60 mmol) in CH3CN (14 ml) was added H2O2 (60 μl of a 50 % aq. solution, 1.06 mmol) at room temperature and the resulting mixture was stirred for 20 min. Subsequently cyclooctene (20 mmol) was added together with CH3CN (4 ml) and water (2 ml). H2O2 (4.53 ml of a 50 % aq. solution, 80 mmol) was then added at room temperature using a syringe pump (0.14 ml/hr). A second amount of [Mn2O3(Me3-TACN)2](PF6)2.H2O (16.2 mg, 20 μmol) was added to the reaction mixture 24 hours after the addition of hydrogen peroxide had commenced. When the addition of hydrogen peroxide was completed, the mixture was stirred for an additional hour. Water (10 ml) and diethyl ether (10 ml) were added and the pH of the aqueous layer was set to pH > 10 by adding some 4 M NaOH (aq.). The organic layer was separated and the aqueous layer was washed with diethyl ether (3x15 ml). The pH of the aqueous layer was subsequently set to pH < 1.5 with some 10% HCl (aq.) and was extracted with diethyl ether (5x10 ml). The combined extracts were washed with brine (15 ml) and subsequently dried over anhydrous Na2SO4. The solvents were evaporated in vacuo yielding 0.95 g of a solid with a purity of circa 84% (determined by 1H NMR). Suberic acid was thus obtained in about 23% yield. 1H NMR (400 MHz, acetone-d6): δ 1.39-1.43 (m, 4H), 1.61-1.66 (m, 4H), 2.34 (t, J = 7.5 Hz, 4H), 10.5 (br s, 2H). N.B. NMR showed other compounds as well, including 2,6-dichlorobenzoic acid |
60 %Spectr. | With carbon dioxide; oxygen In acetic acid at 100℃; for 1h; | 19 Example 19; Oxidation of Cyclooctene Using CAT and NHSI; This reaction was performed with a solution of 0.1191 g (1.03 mmol) of N-hydroxysuccinimide, 2.0357 g (18.5 mmol) of cyclohexene and 0.1330 g (0.53 mmol) of cobalt acetate tetrahydrate in 40 ml of acetic acid was heated to 100° C. in a Parr Hastelloy reactor with temperature and pressure transducer. After the temperature reached 100° C., 745 psi of CO2 was introduced into the reactor, then 120 psi of O2 was added slowly to the reactor. The mixture was stirred under pressure for one hour at 100° C., then the pressure was released, and the mixture was cooled to room temperature. The mixture solution was extracted with ethyl acetate then washed with a saturated NaCl solution in water and, dried over Na2SO4 to give 1,8-ocatane dioic 60% yield analyzed by NMR. |
With ammonium cerium (IV) nitrate; sodium trimethylsilylpropionate-d4; C18H22N4O2Ru(2+)*2F6P(1-); water at 60℃; for 4.5h; | ||
With dihydrogen peroxide; chloroacetic acid In water at 90℃; for 8h; | Reaction conditions:Typical experimental procedure for the oxidative cleavage of cyclohexene:0 . 33 g of Na2WO4 • 2H2O ( 0 . 5 mol% ) and 0 . 25 g of H2WO4 ( 0 . 5 mol%) are stirred for 2 minutes in 5 mL of distilled water. Next, 113.2 g 30 % of dihydrogen peroxide are added, followed by 0.19 g of chloroacetic acid (2 mol%) . The resultant mixture is stirred for 5 minutes, and 16.4 g of cyclohexene and 0.40 g of Aliquat 336 (1 mol%) are subsequently added. The reaction mixture is then stirred at the applied temperature (see Table below) for 4 hours. Isolated yield of adipic acid: 26.3 g (yield = 90%) . These amounts of reactants correspond to the following ratios: olefin : H2O2 : tungstate : PTC ratio = 100 : 500 : 1 : 1Noyori's system for comparison (Sato, K.; Aoki, M.; Noyori, R., Science 1998, 281, 1646-1647) . 4.01 g Na2WO4 (1 mol%) / 5.67 g (CH3 (ϖ-C8H17) 3N] HSO4 (1 mol%)/ 100 g cyclohexene / 607 g dihydrogen peroxide 30%. The reaction mixture is heated at 75-90 0C for 8 hours. Isolated yield of adipic acid: 138 g (yield = 78%) . olefin : H2O2 : tungstate : PTC ratio = 100 : 440 : 1: 1Summary of the oxidative cleavages of cycloalkenes to the corresponding dicarboxylic acidsSubstrate Product RT 40 60 90 Noyori' s 0C 0C 0C system cyclohexene adipic acidLaJ 99% 99% 99% 99% 93%; 4h4 -eyelohexene- meso-1, 2,3,4- 90% 90% 97% 99% 92%; 8h 1,2 -dicarbbutanetetra oxylic acid carboxylic acid[a] cyclopentene glutaric acidLaJ 62% 84% 92% 99% 90%; 13h cyclooctene Suberic acidLbJ 20% 67% 94% 97% 9%; 13h phenanthrene 2,2' biphenyl 12% 69% 73% 92% 41%; 13h carboxylic acidtbl1-octene Heptanoic acid[bJ 2% 15% 23% 60% 36%; 17h4 hours reaction time. 8 hours reaction time. All conversions were determined by Gas Chromatography | |
With ammonium cerium (IV) nitrate; [Ru(dmp)2(H2O)2](PF6)2; water-d2 at 20℃; for 3h; Inert atmosphere; | ||
98 %Chromat. | With dihydrogen peroxide In acetonitrile for 4h; Reflux; | |
95 %Chromat. | With dihydrogen peroxide In acetonitrile for 4h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With HCl In water High Pressure; mixt. was placed in digestion bomb, HCl was added to pH=4.7, heated at 150°C for 24 h, cooled slowly in air to 25°C; ppt. was isolated, washed with water and acetone; elem. anal.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydroxylamine; dicyclohexyl-carbodiimide; 1,1'-carbonyldiimidazole; In tetrahydrofuran; at 25 - 30℃; | A mixture of CDI (0.5eq) and DCC (0.8eq) in THF (15 vol) was stirred for 1 hour at 25- 30C. Suberic acid (leq) and hydroxylamine (leq) in THF (1 vol) was added and the mixture stirred for a further 1 hour. Then CDI (0.5eq), DCC (0.8eq) and aniline (leq) were added to the mixture and the mixture was stirred for a further 16-20 hours. The solid byproduct was removed by filtration and the filtrate was concentrated in vacuo at 50C to obtain crude vorinostat. Molar Yield = 55-60% Purity by HPLC > 95.8% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride; at 80℃; for 24h;Reflux; | Octanedioic acid bis-[5-chloro-2-(2,4-dichloro-phenoxy)-phenyl]ester A solution of <strong>[3380-34-5]triclosan</strong> (17.4 grams, 60.09 mmol), suberic acid (5 grams, 28.70 mmol) and thionyl chloride (12.23 grams, 102.77 mmol) was refluxed at 80 C. for 24 hours. Excess thionyl chloride was distilled off and the product was taken in ethyl acetate followed by washing with 5% sodium bicarbonate solution. The ethyl acetate layer was then dried over sodium sulphate. The dried ethyl acetate layer was treated with charcoal. 80% of the ethyl acetate was distilled off and the rest of it was precipitated in hexane. The precipitate was filtered and dried to get 11 grams of 12 as a white powder with the m.p of 81-83 C. Analytical sample was prepared by recrystallisation from a mixture of ethyl acetate:hexane (1:6). m.p: 83-85 C. Mass: M+H2O=735.5. 1H NMR (CDCl3) delta 1.32 (t, 4H, CH2), 1.61 (t, 4H, CH2), 2.44 (t, 4H, CH2), 6.84 (m, 4H, Ar), 7.16 (m, 6H, Ar), 7.43 (s, 2H, Ar). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50.1% | The condensation was similar to that reported earlier by Bakshi and Mathur [11] and Vagg and co-workers [12]. Suberic acid (1.97 g, 0.1136 mmol) and 2-(amino methyl) benzimidazole dihydrochloride (5 g, 0.0227 mmol) were taken in pyridine (20 ml). The mixture was stirred gently for 10 min, during which a white precipitate appeared. The reaction mixture was then heated slowly on a water bath at a temperature of 40 C. A solution of triphenyl phosphite (TPP) (7.07 ml, 22.8 mmol) was added drop wise over a period of 15 min. The mixture was stirred simultaneously. After addition of P(OPh3)3 was complete and the initially formed precipitate had dissolved, the temperature of the reaction was slowly raised to 70 C. The clear solution thus obtained was stirred for about 9-10 h at a temperature of 70-75 C on a water-bath. The resulting brown colored solution was then washed with sodium bicarbonate till all effervescence ceased and then washed twice with distilled water. A yellowish white solid appeared which was washed first with water and then acetone (Scheme 1). This was then recrystallized with methanol and precipitated by water. The product was filtered off, and dried and analyzed for the composition C24H28N6O2*0.5H2O, Yield: 3 g (50.1%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | Stage #1: octane-1,8-dioic acid With benzotriazol-1-ol; dicyclohexyl-carbodiimide In tetrahydrofuran at 0℃; for 0.5h; Stage #2: C115H159N3O74 With 4-methyl-morpholine In tetrahydrofuran at 0 - 20℃; for 38h; Stage #3: With methanol; sodium methylate at 20℃; for 12h; | 4.1.13. N-{2-N-{2-[1,3-di-(O-β-D-galactopyranosyl-(1→4)-β-D-glucopyranosyloxy)]propanyl}pentane-1,5-diamidyl}octane-1,8-diamide (19) Compound 19 was prepared by the same procedure as describedfor the preparation of 14. The yield was 94%;a25D 12:5 (c 1.28 in H2O); 1H NMR (D2O, 400 MHz): d = 4.41(d, J1,2 = 7.7 Hz, 8H; H-1), 4.35 (d, J10,20 = 8.1 Hz, 8H; H-10), 3.90-3.25 (m, 116H; H-2,3,4,5,6a,b, H-20,30,40,50,6a0,b0, CH2O, CHNH2),2.32-2.19 (m, 8H; CH2CO), 2.02-1.51 (m, 8H, CH2), 1.24(m, 4H;CH2); 13C NMR (D2O, 100 MHz): d = 181.2, 177.1, 175.0, 173.5(CO), 103.0 (C-10), 102.7, 102.6 (C-1), 78.5 (C-4), 75.4, 74.8, 74.3,72.9, 72.8, 72.6, 71.0, 68.8, 68.6 (C-2,3,5, C-20,30,40,50, CH2O), 61.1,60.2 (C-6, C-60), 53.4, 49.4, 49.2, 49.0,35.4, 31.9 (CHNH, COCH2), 28.0, 27.2, 25.2, 23.2 (CH2); MALDI-TOF MS: m/z calcd forC126H216N6O94: 3341.2 [M+Na]+; found: 3340.7. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | Stage #1: octane-1,8-dioic acid With benzotriazol-1-ol; dicyclohexyl-carbodiimide In tetrahydrofuran at 0℃; for 0.5h; Stage #2: N-{2-[1-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl-(1→4)-2,3,6-tri-O-acetyl-β-D-glucopyranosyloxy)-3-(2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyloxy)]propanyl}-2-aminopentane-1,5-diamide In tetrahydrofuran at 0 - 20℃; for 38h; Stage #3: With methanol; sodium methylate at 20℃; for 12h; | 4.1.40. N-{2-N-{2-[1-(O-β-D-galactopyranosyl-(1→4)-β-D-glucopyranosyloxy)-3-(O-α-D-mannopyranosyloxy)]propanyl}pentane-1,5-diamidyl}octane-1,8-diamide (46) Compound 46 was prepared by the same procedure as describedfor the preparation of 14. The yield was 93%;a25D 22:6 (c 1.06 in H2O); 1H NMR (400 MHz, D2O): d = 4.78(s, 4H; H-100), 4.41 (d, J1,2 = 7.8 Hz, 4H; H-1), 4.37 (d, J10,20 = 7.8 Hz,4H; H-10), 4.26-2.80 (m, 112H; H-2,3,4,5,6a,b, H-20,30,40,50,6a0,b0 ,H-200,300,400,500,6a00,b00, CH2O, CHNH), 2.23-1.26 (m, 32H; CH2CO,CH2); 13C NMR (100 MHz, D2O): d = 177.1, 174.8, 173.6, 173.5(CO), 102.9, 102.4 (C-1, C-10), 100.2, 100.1, 99.6 (C-100), 78.4 (C-4,C-400), 75.3 (C-3), 74.8 (C-5), 74.2 (C-2), 72.8 (C-300), 72.5 (C-50, C-30), 70.9 (C-200), 70.5, 70.0, 68.5 (CH2O), 66.7, 66.6 (C-20), 66.2 (C-500), 65.9 (C-40), 61.0 (C-60), 60.9 (C-600), 60.1 (C-6), 49.4, 49.2, 48.8(CHNHCO), 35.4, 31.9 (CH2CO), 27.9, 25.1, 20.3 (CH2); HRESI-TOFMS: m/z calcd for C102H176N6O74: 1358.00117 [M+2Na]2+; found:1358.00137. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 1h; | 8-(Benzyloxy)-8-oxooctanoic acid(1) To a solution of octanedioic acid (1 g, 5.7 mmol) and benzylic alcohol (0.31 g, 2.9 mmol) in dichloromethane (25 mL) were added 4-dimethylaminopyridine (0.39 g, 3.2 mmol) andN,N'-dicyclohexylcarbodiimide (0.66 g, 3.2 mmol). The mixture was stirred at room temperature for 1 h and concentratedin vacuo. Water (40 mL) was then added and the mixture was extracted with ethyl acetate (3 x 40 mL). The combined organic layers were washed with water (2 x 75 mL) and concentratedin vacuo. The obtained crude product was purifiedviasilica gelcolumn chromatography (cyclohexane/ethyl acetate, 80/20) affording1as a translucent solid (0.545 g, 71% yield).1H NMR (CDCl3, 300 MHz) δ 7.39-7.30 (m, 5H), 5.11 (s, 2H), 2.38-2.31 (m, 4H), 1.70-1.58 (m, 4H), 1.37-1.31 (m, 4H).13C NMR (CDCl3, 75 MHz) δ 178.9 (Cq), 173.7 (Cq), 136.2 (Cq), 128.7 (2 CH), 128.3 (3 CH), 66.3 (CH2), 34.4 (CH2), 33.9 (CH2), 28.8 (CH2), 28.8 (CH2), 24.9 (CH2), 24.6 (CH2). LR-MS (DCI/NH3) m/z calculated for C15H21O4(M+H+)265.15, found 265.2 (M+H+), 282.2 (M+NH4+). |
47.5% | With toluene-4-sulfonic acid In toluene Dean-Stark; Reflux; | Synthesis of monobenzyl sebacate (Supplementary material, Scheme S1) General procedure: The method of English, Girard, Jasys, Martingano, and Kellogg (1990) was adapted for the synthesis of monobenzyl sebacate. Sebacic acid (0.25mol, 50.56g), toluene (200mL), benzyl alcohol (0.30mol, 1.2equiv., 32.4g, 31.1mL), and p-toluene sulfonic acid (2.5mmol, 0.475g) were combined in a Dean-Stark apparatus and refluxed until the desired volume of H2O (0.30mol, 5.40mL) was collected from the Fischer esterification of the sebacic acid, indicating the end of the reaction. The mixture was allowed to cool to room temperature, then 150mL of DI water was added to the reaction. Using vigorous mixing, this mixture was adjusted to pH 9 with 6M NaOH. The aqueous layer with the di-acid and mono-ester was separated and washed twice with 50mL of diethyl ether; these diethyl ether washes contained primarily the dibenzyl ester by-product, and were discarded. Diethyl ether (200mL) was combined with the aqueous layer which was acidified to pH of 2.0-2.5 with 6M HCl. The ether layer containing the mono-ester was separated. To purify further, the ether layer was washed with 1M NaHCO3. The ether layer then was concentrated under reduced pressure and vacuum-dried for 1.5h to yield the final product as white, needle-like solid. Yield: 29.0% (16.96g, 0.058mol). |
47.5% | With toluene-4-sulfonic acid In toluene Dean-Stark; Reflux; | Synthesis of monobenzyl sebacate (Supplementary material,Scheme S1 ). General procedure: The method of English, Girard, Jasys, Martingano,and Kellogg (1990) was adapted for the synthesis of monobenzylsebacate. Sebacic acid (0.25 mol, 50.56 g), toluene (200 mL), benzylalcohol (0.30 mol, 1.2 equiv., 32.4 g, 31.1 mL), and p-toluene sulfonicacid (2.5 mmol, 0.475 g) were combined in a Dean-Stark apparatusand refluxed until the desired volume of H2O (0.30 mol, 5.40 mL)was collected from the Fischer esterification of the sebacic acid,indicating the end of the reaction. The mixture was allowed to coolto room temperature, then 150 mL of DI water was added to thereaction. Using vigorous mixing, this mixture was adjusted to pH 9with 6 M NaOH. The aqueous layer with the di-acid and mono-esterwas separated and washed twice with 50 mL ofdiethyl ether; thesediethyl ether washes contained primarily the dibenzyl ester byproduct, and were discarded. Diethyl ether (200 mL) was combinedwith the aqueous layer which was acidified to pH of 2.0-2.5 with6 M HCl. The ether layer containing the mono-ester was separated.To purify further, the ether layer was washed with 1 M NaHCO3.The ether layer then was concentrated under reduced pressure andvacuum-dried for 1.5 h to yield the final product as white, needlelike solid. Yield: 29.0% (16.96 g, 0.058 mol). |
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride | 2.3. Synthesis and characterization of hydrophobically modified chitosan General procedure: The functionalized chitosan was synthesized by two-step reaction.At the first step, dithiodipropionic acid or adipic acid was reacted withbenzyl alcohol to yield dithiodipropionic acid mono benzyl ester oradipic acid mono benzyl ester. Taking dithiodipropionic acid as anexample, 4.205 g dithiodipropionic acid (20 mmol) and 0.432 g benzylalcohol (4 mmol) were firstly dissolved in 40 mL dimethylformamide.Then 0.62 g EDC (4 mmol) and 0.049 g DMAP were added and reactedunder room temperature for 12 h. DMF was removed by rotary evaporationand DCM was added to precipitate the unreacted dithiodipropionicacid. The filtrate was washed with saturated sodium chlorideand dried with anhydrous sodium sulphate. The product was purifiedwith column chromatography. The column was firstly washed withDCM:methanol (15:1) and then with DCM:methanol (10:1) to yieldfinal product. | |
With toluene-4-sulfonic acid In toluene for 5h; Inert atmosphere; Reflux; | 2.1 Step 1: 8-(benzyloxy)-8-oxooctanoic acid To a solution of octanedioic acid (4.0g, 22.96mmol) and p-toluenesulfonic acid (200mg, 1.051mmol) in toluene (12mL) was added benzyl alcohol (2.6mL, 25.01mmol). The resultant mixture was heated to reflux, stirred at reflux for 5h, cooled to rt, and concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column (80g), eluting with 0-100% EtOAc in hexanes to give the title compound. UPLC Method B: calculated for C17H24NO4292.17, observed m/e: 293.1 [M+1]; tR=1.22/2.0min. 1H NMR (CDCl3) d 7.38-7.32 (s; 5 H); 5.11 (s; 2 H); 2.35 (dt; J=9.52; 7.48Hz; 4 H); 1.61-1.66 (m; 4 H); 1.33-1.35 (m; 4 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77.7% | In methanol; chloroform; | Salt 1 was prepared by mixing L1 (0.27 g, 1.0 mmol) and AA (0.15 g, 1.0 mmol) in an acetonitrile-methanol mixture (v/v%, 1:4, 10 ml).The resulting solution was stirred for 6 h, and filtered through Celite. The filtrate was evaporated until dryness under vacuum, and the white solid obtained was redissolved in methanol. The same procedure was applied on salt 3 as outlined above for 1 using SUA (0.17 g, 1.0 mmol) with 77.7% (0.35 g, 0.78 mmol)yields. Anal. Calcd. (%) for C24H34N2O6 (446.54): C, 64.55; H, 7.67;N, 6.27. Found: C, 63.87; H, 7.56; N, 6.53. FT-IR (KBr, cm-1):3659, 3337, 2945, 2845, 2759, 2617, 2259, 2049, 1611, 1529,1455, 1377, 1256, 1109, 1057, 931, 841, 791, 529. 1H NMR(DMSO-d6, ppm) δ: 12.21 (s, br, 4H, NH2), 5.99-6.59 (m, 8H, CH,Ar L1), 3.18 (t, 4H, CH2, aliphatic L1), 2.29 (s, 4H, CH2, Benzylic L1), 2.16 (t, 4H, CH2, SUA2-), 1.54 (t, 4H, CH2, SUA2-), 1.28 (m, 4H,CH2, SUA2-). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.34%Chromat.; 88.58%Chromat.; 10.6%Chromat. | With Amberlyst 35; In water; acetic acid; at 95℃; for 20h;Inert atmosphere; | Example 5: Saponification of <strong>[1732-09-8]dimethyl suberate</strong> to yield suberic acid To a 250 mL round bottom flask equipped with a stir bar, heating mantle, temperature probe, and short path distillation head was added crude <strong>[1732-09-8]dimethyl suberate</strong> (1.15 g), Amberlyst 35 (0.2 g, pre-washed with methanol), acetic acid (10 mL), and DI water (2 mL). The reaction was heated to 95 C for 20 hours with a gentle stream of nitrogen (0.05 SCFH) passing through the headspace. GC analysis showed high conversion of <strong>[1732-09-8]dimethyl suberate</strong> to suberic acid as shown in Table 6.Table 6 - GC analysis of crude reaction mixture[0093] The product solution was cooled and filtered to remove catalyst using a syringe filter (0.45 u, polypropylene). The clear product solution was loaded to a 250 mL round bottom flask equipped with a stir bar, heating mantle, temperature probe, and short path distillation head. The acetic acid was distilled out under atmospheric pressure to leave an oily residue. To the residue was added DI water (10 mL). The water was distilled out to leave about 4 mL of solution which was allowed to gradually cool to room temperature with the stirring off. Upon cooling, white crystals were evident. The solid was isolated by filtration and washed with DI water (4 mL). The solids were dried at 100 C to yield 0.41 g of white crystalline product. A sample of the product was dissolved in acetone for GC analysis and results are shown in Table 7. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With oxygen; manganese(II) acetate; In toluene; at 50℃; for 6.0h; | Example 62: A solution of 15.0g 1,8-octanedial in 20.0g toluene is charged into a lOOcc jacketed glass vessel. Mn(OAc)2 catalyst (O.lg) is also added to the solution. Air is sparged into the vessel at 500ml/min for 6 hrs at 50C. GC analysis of the product shows 50% conversion of the 1,8-octanedial to insoluble 1,8-octanedioic acid and 8-oxo-octanoic acid products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a 10 mL glass peptide synthesis vessel was added Rink Amide AM resin (0.60 g, 0.31 mmol)and DMF (4 mL). The mixture was gently agitated with a wrist-action Burrel shaker for 1h andthen filtered. A 20% solution of piperidine in DMF (4 mL) was added and the mixture wasagitated for 30 min. The resin was filtered and then washed with DMF (3 × 4 mL). 7-N-(Fluorenylmethoxycarbonyl)aminocoumarin-4-acetic acid1 (0.40 g, 0.91 mmol), HOBt.H2O (140mg, 0.95 mmol) and DMF (4 mL) was added to the resin followed by DIC (144 muL, 0.93 mmol).The mixture was agitated for 24h, filtered and then washed with DMF (3 × 4mL), THF (3 × 4mL)and MeOH (3 × 4mL) respectively.General Procedure for Coupling the First Fmoc-Amino Acid to the ACC-ResinTo a 10 mL glass peptide synthesis vessel was added ACC-resin (0.31 mmol) and DMF (4 mL).The mixture was gently agitated with a wrist-action Burrel shaker for 1h and then filtered. A 20%solution of piperidine in DMF (4 mL) was added and the mixture was agitated for 30 min. Theresin was filtered and then washed with DMF (3 × 4 mL). In a separate scintillation vial wereadded Fmoc-amino acid (1.32 mmol), HOBt (200 mg, 1.32 mmol), DMF (4 mL) and DIC (200 muL,1.29 mmol). After a preactivation time of 5 min, the mixture was added to the resin and agitatedovernight. The resin was filtered and washed with DMF (3 × 4 mL).Representative Synthesis of a Di-peptide -ACCAs a representative example, the synthesis of N-suc-L-Phe-Gly-ACC is described. To a 10 mLglass peptide synthesis vessel was added Fmoc-Gly-ACC-resin (0.1 mmol) and DMF (3 mL). The mixture was gently agitated for 1h and then filtered. A 20% solution of piperidine in DMF (3mL) was added and the mixture was agitated for 30 min. The resin was filtered and then washedwith DMF (3 × 3 mL). In a separate scintillation vial were added Fmoc-L-Phe-OH (190 mg, 0.5mmol), HOBt (76 mg, 0.5 mmol), DMF (3 mL) and DIC (76 muL, 0.5 mmol). After a preactivationtime of 5 min, the mixture was added to the resin and agitated for 5h. The resin was filtered andwashed with DMF (3 × 4 mL). A 20% solution of piperidine in DMF (3 mL) was added and themixture was agitated for 30 min. The resin was filtered and then washed with DMF (3 × 3 mL).Succinic anhydride (100 mg, 1.0 mmol), DMF (3mL) and DIPEA (150 muL, 0.9 mmol) were addedand the mixture was agitated overnight, filtered and then washed with DMF (3 × 4 mL). Asolution of TFA:iPr3SiH:H2O (95:2.5:2.5, 3 mL) was added and the mixture was agitatedovernight. The resin was filtered and washed with TFA (2 × 3 mL). The combined filtrate wasconcentrated and the residue was washed with ether (3 × 3 mL) to give suc-L-Phe-Gly-ACC aspale yellow solid (32 mg, 62%). Amino terminus of some peptides was capped as the acetylderivative. This was accomplished by premixing AcOH (5 equiv), HOBt (5 equiv) and DIC (5equiv) in DMF and adding the mixture to the resin. The resulting mixture was agitated for 5h,filtered, and then washed with DMF. For ACC-peptides 11-18, the amino terminus was coupledwith the corresponding dicarboxylic acid as follows: In a separate scintillation vial were addeddicarboxylic acid (5 equiv), HOBt (5 equiv), DMF and DIC (5 equiv). After a pre-activation time of5 min, the mixture was added to the resin and agitated overnight. The resin was filtered andwashed with DMF (3 × 4 mL). The purification of all ACC-peptides was performed either bysimply washing the solid thoroughly with ether or by reverse-phase HPLC (ACN/H2O-0.1% TFA,15 - 60% for 20 min, 20 mL/min, 254 nm detection for 22.5 min). Purity check for all ACCpeptideswas completed by analytical reverse-phase HPLC (ACN/H2O-0.1% TFA, 10 - 60% for20 min, 1 mL/min, 254 nm detection for 23 min). Retention times are indicated as tR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | Stage #1: octane-1,8-dioic acid With 4-methyl-morpholine; benzotriazol-1-ol; dicyclohexyl-carbodiimide In tetrahydrofuran at 0℃; for 0.5h; Stage #2: 1-N-{2-[1,3-di-(2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyloxy)]propyl}-amino-5-N-{2-[1,3-di-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl-(1→4)-2,3,6-tri-O-acetyl-β-D-glucopyranosyloxy)]propyl}glutamic diamide In tetrahydrofuran at 0 - 20℃; for 38h; | General procedure: N-Boc-L-glutamic acid-5-benzyl ester (0.51g, 1.52mmol) was dissolved in dry THF (1mL) that was cooled to 0°C followed by the addition of EDC•HCl (0.35g, 1.82mmol), HOBt (0.25g, 1.82mmol) and NMM (50μL). The mixture was stirred at 0°Cfor 0.5h. A solution of compound 2a (1.16g,1.52mmol) in dry THF (2 mL) was added dropwise and the mixture was stirred at 0°C for2 h, followed by stirring at room temperature for 36 h. The mixture was concentrated and the residue was diluted with CH2Cl2. Thesolution was filtered and the filtrate was washed with saturated aqueous sodiumbicarbonate, aqueous citric acid and water, dried (Na2SO4) and evaporated under diminished pressure. The crude product was purified by flash chromatography with PE/EtOAc = 1:1 as eluent to give compound 3a (1.24g) as a colorless syrup in 76% yield |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | This compound was prepared by the Fmoc chemistry-based manual SPPS on Rink Amide MBHAresin. For each amino acid coupling reaction, four equivalents of a Nalpha-Fmoc-protected amino acid,3.8 equivalents of the coupling reagent HBTU and the additive HOBt were used in the presence of 0.4MNMM/DMF, and the coupling reaction was allowed to proceed at room temperature for 1 h. A 20%(v/v) piperidine/DMF solution was used for Fmoc removal. After the completion of the on-resin aminoacid assembling and the N-terminal -amino group acetylation with acetic anhydride in the presenceof 0.4 M NMM/DMF, the side chain Mtt protecting group from two Lys(Mtt) residues were selectivelyremoved with a 1% (v/v) TFA/DMF solution before the two exposed free amino groups were acylatedwith Fmoc-glycine under peptide coupling reaction condition. After the Fmoc removal from thetwo incorporated Fmoc-glycine residues with a 20% (v/v) piperidine/DMF solution, the two newlyexposed free amino groups were then acylated with suberic acid at room temperature for 1 h underpeptide coupling reaction condition. The resulting resin-bound cyclized peptide was then treatedwith a 2% (v/v) solution of hydrazine (NH2NH2) in DMF, the exposed free amino group at the centralposition was then reacted with ethyl 3-isothiocyanatopropionate (2 x 5 h). The subsequent treatmentwith reagent K (83.6% (v/v) TFA, 5.9% (v/v) phenol, 4.2% (v/v) ddH2O, 4.2% (v/v) thioanisole, and2.1% (v/v) ethanedithiol) at room temperature for 4 h cleaved the crude ethyl ester intermediatefrom the resin and removed the side chain Pbf and tBu protecting groups as well. Following the concentration of the cleavage filtrate and the precipitation in cold diethyl ether of the crude ethylester intermediate (34% pure per analysis with RP-HPLC on an analytical C18 column (0.46 x 25 cm,5 mum)), it was purified by RP-HPLC on a semi-preparative C18 column (1 x 25 cm, 5 mum). The columnwas eluted with a gradient of ddH2O containing 0.05% (v/v) TFA (mobile phase A) and acetonitrilecontaining 0.05% (v/v) TFA (mobile phase B) (0%-60% B in 60 min) at 4.5 mL/min and monitored at214 nm. The pooled desired HPLC fractions were concentrated in vacuo to remove acetonitrile, and theremaining aqueous solution was lyophilized to afford the purified ethyl ester intermediate in an overallsynthetic yield of 41% as a puffy white solid whose exact mass was confirmed by a unit-resolution ESI-MS analysis. This purified intermediate was then dissolved in a mixture of MeOH/ddH2O(3/1, v/v), and to the resulting solution was added at 0 C LiOH to a final concentration of ~12.5 M.The reaction mixture was subsequently stirred at 4 C overnight, acidified at 0 C with 6 N HCl to pH~1, and concentrated under reduced pressure. The ethyl ester hydrolysis product 4 was then isolatedas a puffy white solid from the resulting residue by semi-preparative RP-HPLC as described above,using the following gradient of the afore-mentioned mobile phases A and B: 0%-40% B in 60 min. Thepurity of the purified 4 was >95% as verified by RP-HPLC on an analytical C18 column (0.46 x 25 cm,5 mum) eluted with the following gradient of the afore-mentioned mobile phases A and B: 0%-30% B in60 min. The exact mass of the purified compound 4 was confirmed by HRMS analysis (see Table 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | General procedure: This compound was prepared by the Fmoc chemistry-based manual SPPS on Rink Amide MBHAresin. For each amino acid coupling reaction, four equivalents of a Nalpha-Fmoc-protected amino acid,3.8 equivalents of the coupling reagent HBTU and the additive HOBt were used in the presence of 0.4MNMM/DMF, and the coupling reaction was allowed to proceed at room temperature for 1 h. A 20%(v/v) piperidine/DMF solution was used for Fmoc removal. After the completion of the on-resin aminoacid assembling and the N-terminal -amino group acetylation with acetic anhydride in the presenceof 0.4 M NMM/DMF, the side chain Mtt protecting group from two Lys(Mtt) residues were selectivelyremoved with a 1% (v/v) TFA/DMF solution before the two exposed free amino groups were acylatedwith Fmoc-glycine under peptide coupling reaction condition. After the Fmoc removal from thetwo incorporated Fmoc-glycine residues with a 20% (v/v) piperidine/DMF solution, the two newlyexposed free amino groups were then acylated with suberic acid at room temperature for 1 h underpeptide coupling reaction condition. The resulting resin-bound cyclized peptide was then treatedwith a 2% (v/v) solution of hydrazine (NH2NH2) in DMF, the exposed free amino group at the centralposition was then reacted with ethyl 3-isothiocyanatopropionate (2 x 5 h). The subsequent treatmentwith reagent K (83.6% (v/v) TFA, 5.9% (v/v) phenol, 4.2% (v/v) ddH2O, 4.2% (v/v) thioanisole, and2.1% (v/v) ethanedithiol) at room temperature for 4 h cleaved the crude ethyl ester intermediatefrom the resin and removed the side chain Pbf and tBu protecting groups as well. Following the concentration of the cleavage filtrate and the precipitation in cold diethyl ether of the crude ethylester intermediate (34% pure per analysis with RP-HPLC on an analytical C18 column (0.46 x 25 cm,5 mum)), it was purified by RP-HPLC on a semi-preparative C18 column (1 x 25 cm, 5 mum). The columnwas eluted with a gradient of ddH2O containing 0.05% (v/v) TFA (mobile phase A) and acetonitrilecontaining 0.05% (v/v) TFA (mobile phase B) (0%-60% B in 60 min) at 4.5 mL/min and monitored at214 nm. The pooled desired HPLC fractions were concentrated in vacuo to remove acetonitrile, and theremaining aqueous solution was lyophilized to afford the purified ethyl ester intermediate in an overallsynthetic yield of 41% as a puffy white solid whose exact mass was confirmed by a unit-resolution ESI-MS analysis. This purified intermediate was then dissolved in a mixture of MeOH/ddH2O(3/1, v/v), and to the resulting solution was added at 0 C LiOH to a final concentration of ~12.5 M.The reaction mixture was subsequently stirred at 4 C overnight, acidified at 0 C with 6 N HCl to pH~1, and concentrated under reduced pressure. The ethyl ester hydrolysis product 4 was then isolatedas a puffy white solid from the resulting residue by semi-preparative RP-HPLC as described above,using the following gradient of the afore-mentioned mobile phases A and B: 0%-40% B in 60 min. Thepurity of the purified 4 was >95% as verified by RP-HPLC on an analytical C18 column (0.46 x 25 cm,5 mum) eluted with the following gradient of the afore-mentioned mobile phases A and B: 0%-30% B in60 min. The exact mass of the purified compound 4 was confirmed by HRMS analysis (see Table 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With triethylamine; at 160℃; for 5h;Autoclave; Green chemistry; | General procedure: Into a stainless steel pressure microreactor of capacity 17 mL was charged 5 wt % of zeolite NaY-Bf, 100 mmol of carboxylic acid, and 300-400 mmol of dimethyl carbonate, the reactor was hermetically closed, and the reaction mixture was heated at 180-200C for 5 h. On completion of the reaction the reactor was cooled to room temperature, opened, the reaction mixture was filtered through a bed of Al2O3. Unreacted dimethyl carbonate was distilled off, the residue was distilled at atmospheric pressure or in a vacuum, or it was crystallized from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 27.5% 2: 17.5% 3: 6.8% 4: 17.6% 5: 11.4% | With 7CeO2*7Nb2O5*3La2O3*K2O*2Bi2O3; oxygen at 120℃; for 15h; Autoclave; | 5 Example 5. Catalytic oxidation of methyl oleate (>99%) with the mixed oxide 7(CeO2) 7(Nb2O5) 3(La2O3) 1(K2O) 2(Bi2O3) under P02 = 9 bar. In order to improve the stability of the catalyst and its activity, multiple mixed oxides were prepared. The mixed oxide 7(CeO2) 7(Nb2O5) 3(La2O3) 1(K2O) 2(Bi2O3), prepared according to Example 1 , showed excellent stability in catalysis and good reaction rate and selectivity. The catalyst (50 mg) was placed in a glass reactor, kept in vacuo for 30 min to eliminate humidity and added with methyl oleate (1 mL ) under N2. The reactor was placed in a stainless steel autoclave that was closed, evacuated, charged with O2 (9 bar) and heated to T=120 °C for a time variable between t=0,66 and 15h. At the end the catalyst was recovered by centrifugation and the liquid processed as reported in Example 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82.9% | In dichloromethane; at 140℃; for 4h; | The product containing the intermediate M3 obtained in step (1) is first dissolved in 150 ml of methylene chloride with stirring.After the solution is complete, 0.1 mol of suberic acid is added dropwise after heating to 140 C. After 4 hours at this temperature, the solvent is distilled off and dried with calcium oxide at 70 C., and the product is recrystallized three times with acetone solvent. Above, the polymerizable functional monomer D3 was obtained, and the monomer yield was calculated and tested to be 82.9% and the monomer purity was 99.8%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
32% | With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In methanol at 20℃; | 1.0 1,6-di-(N-6-amino-1,2,3,4-tetrahydro-1,3-dimethyl-2,4-dioxo-5-pyrimidyl)-hexanamid (1a-1) 5,6-Diamino-1 ,3-dimethyluracil hydrate (0.20 g, 1.2 mmol) and suberic acid (0.092 g, 0.53 mmol) were added to MeOH (15 ml_). EDC-HCI (2.6 g, 1.4 mmol) was then added in one portion and stirred overnight at room temperature. The pH was adjusted to 8 and a white precipitate formed. The precipitate was filtered and washed with acetone giving (1a- 1). Yield: 0.082 g (32%). 1H NMR (d6-DMSO, 500MHz, 22 "C): δ 8.27 (s, 2H), 6.53 (s, 4H), 3.31 (s, 6H), 3.1 1 (s, 6H), 2.25 (t, 3JHH = 7.4 Hz, 4H), 1.61-1.53 (m, 4H), 1.37-1.32 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | Stage #1: octane-1,8-dioic acid With benzotriazol-1-ol In tetrahydrofuran at 0℃; for 0.166667h; Inert atmosphere; Stage #2: With dicyclohexyl-carbodiimide In tetrahydrofuran for 0.583333h; Inert atmosphere; Stage #3: 2-(3-aminopropyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione In tetrahydrofuran at 20℃; for 24h; Inert atmosphere; | N1,N8-bis(3-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)propyl)octanediamide,(C38H38N4O6), (5); While stirring at 0°C under N2 atmosphere, hydroxybenzotriazole (HOBt) (135 mg, 1 mmol) wasadded to the solution of suberic acid (160 mg, 0.9 mmol) in 100 mL of anhydrous THF, and stirredfor 10 min. Then, N,N'-dicyclohexylcarbodiimide (DCC) (206 mg, 1 mmol) was added to the reactionmixture. After 35 min, compound 1a (508 mg, 2 mmol) was added to the reaction mixture and stirred atroom temperature for 24 h. The formed precipitate of DCU was removed by filtration, and the filtratewas evaporated under vacuum. The residue was dissolved in 50 mL EtOAc. The formed solution waswashed successively with saturated aqueous solution of sodium bicarbonate (NaHCO3) (30 mL x 3),5% aqueous solution of potassium bisulfate (KHSO4) (30 mL x 3), and saturated aqueous solution ofsodium chloride (NaCl) (30 mL 3), and then dried with anhydrous sodium sulfate (Na2SO4) [40].After filtration, the filtrate was evaporated under vacuum to give the title compound. EtOAc/ n-hexane(1/ 20) solvent system was used for the purification (yield 61%). LC-MS: [M + H]+ = 647.1H NMR (500 MHz, CD3Cl),δ ; 1.35 (s, 4H, 2xCH2), 1.71-1.60 (m, 4H, 2xCH2), 1.88 (t, J = 6.2 Hz,4H, 2xCH2), 2.21 (t, J = 7.6 Hz, 4H 2xNCH2), 3.20 (q, J = 6.1 Hz, 4H, 2xNHCH2), 4.18 (t, J = 6.3 Hz, 4H,2xO = CCH2), 6.46 (t, J = 6.2 Hz, 2H, 2xNH), 7.69 (t, J = 8.1 Hz, 4H, ArH), 8.15 (d, J = 8.2 Hz, 4H, ArH),8.52 (d, J = 7.2 Hz, 4H, ArH) ppm. |
Stage #1: octane-1,8-dioic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 4 - 20℃; for 2h; Stage #2: 2-(3-aminopropyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione In dichloromethane at 20℃; for 0.166667h; Stage #3: With triethylamine In dichloromethane at 20℃; for 2h; | 4 Example 4: Synthesis of Ni, N8-bis(3-( 1,3 -dioxo- 1 H-benzo [de] isoquinolin-2 (3H)-yl) propyl)octanediamide (Formula Ia) Suberic acid (0.4 mmol) was dissolved in DCM and oxalyl chloride (1.6 mmol) was added dropwisc to the reaction medium at + 4 0 C. The reaction was brought to room temperature by the addition of 1-2 drops of DMF. The reaction was stirred at room temperature for 2 hours. The product was obtained in pure form. The obtained product was dissolved in DCM and then added to the reaction flask containing Formula ha .After stirring at room temperature for 10 minutes, triethylamine (1.2 mmol) was added and the reaction was stirred at room temperature for 2 hours. For purification by column chromatography, the DCM / MeOH (40/1) solvent system was used.Analysis Data: L LC-MS: calculated = 646 (M), found 645 ([M + 1]). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69.1% | 0.52 g (3 mmol) of suberic acid was dissolved in 15 ml of anhydrous dioxane, and after adding 0.25 g (2.5 mmol) of triethylamine, 0.28 g (2.4 mmol) of thionyl chloride was added dropwise, and vacuum nitrogen was added dropwise. The mixture was refluxed at 110 C for 4 h. 0.78 g (3.2 mmol) of <strong>[95058-81-4]gemcitabine</strong> was added, and 0.19 g (1.5 mmol) of triethylamine was added dropwise thereto at room temperature, and the mixture was subjected to vacuum nitrogen-protection overnight, and the reaction was completed by TLC. The reaction mixture was concentrated under reduced pressure to give a red brown oil. Column chromatography gave a white solid in 69.1% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | General procedure: A mixture of the corresponding dicarboxylic acids (3.4 mmol) and <strong>[1937-19-5]aminoguanidine hydrochloride</strong> (1.88 g, 17 mmol) in water (2 mL) was irradiated in a 10 mL seamless pressure vial using microwave system operating at maximal microwave power up to 300 W at 220 C for 15 min. After cooling to the ambient temperature, 1 mL of 17 M aq. NaOH solution was added to the vial and the reaction mixture was irradiated again at 200 C for 10 min. After cooling to the ambient temperature, the precipitated solid was filtered, washed with cold water and recrystalised from water to give desired products 6, 11-17. The reaction was also replicated in an increase scale of dicarboxylic acids (17 mmol) and <strong>[1937-19-5]aminoguanidine hydrochloride</strong> (9.40 g, 85 mmol) increasing the base and solvent quantities proportionally. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | General procedure: PQdiphosphate(0.349 g, 0.766mmol) and TEA (0.428 mL, 3.211mmol) were stirred in dichloromethane (15 mL) to obtain PQ base.Dicarboxylicacid (succinic,fumaric, maleic,glutaric,adipic,pimelic,suberic, oritaconicacid) (0.333mmol) was activated using HATU (0.279, 0.733mmol) in the presence ofHuenig?sbase (DIEA) (0.255 mL, 1.465mmol) in dichloromethane (10 mL). After 15 min, a solution of PQ base was added to a solution of correspondingdicarboxylicacid and stirred overnight at room temperature. The solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate (30 mL) and extracted with brine (3 × 30 mL), dried over anhydrous sodiumsulfateand evaporated. The crude product was purified by column chromatography (mobile phase cyclohexane/ethyl acetate/methanol 1:1:0.5). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With 4-methyl-morpholine; 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; N,N-dimethyl-formamide; at 0 - 20℃; for 12h;Inert atmosphere; | General procedure: To a stirred solution of succinic acid (680mg, 5.8mmol) in DMF (10mL) was added anhydrous DCM (150mL). Then the mixture was cooled to 0C, NMM (1.16g, 11.5mmol), VHL-1 (1.0g, 2.3mmol), HOAT (63mg, 0.46mmol) and EDCI.HCl (530mg, 2.8mmol) were added sequentially. The solution was purged and refilled with nitrogen. The resulting mixture was stirred at room temperature for 12h. The reaction mixture was quenched with water (1mL). After concentration, the residue was purified reverse phase ISCO (C18) to afford the desired compound s-4a (4-(((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-4-oxobutanoic acid) (s-4a) (0.82g, 65% yield) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | Stage #1: octane-1,8-dioic acid With thionyl chloride In dichloromethane for 4.5h; Reflux; Stage #2: 1,2-dimethoxybenzene With aluminum (III) chloride In dichloromethane at 0℃; for 5h; | 4.1.18. General procedure for the preparation of compounds 1,6-bis(3,4-dimethoxyphenyl)hexane-1,6-dione (18a) and 1,7-bis(3,4-dimethoxyphenyl)heptane-1,7-dione (18b) General procedure: To a solution of 17 (7.20 mmol) in DCM (20 mL) at room temperature was slowly added SOCl2 (5 mL). The mixture was heated a treflux for 4.5 h and the reaction solvents were removed in vacuo.The crude product was re-dissolved in DCM (5 mL), and was added dropwise to a stirring mixture of veratrole (2.00 g, 14.40 mmol) and aluminum trichloride (AlCl3) (2.02 g, 15.12 mmol) in DCM (20 mL). The resulting solution was stirred at 0 C for 5 h before pouring into ice water (50 mL). The mixture was extracted with DCM(3 20 mL), washed with saturated NaHCO3 (20 mL) and brine. Thecombined organic layer was removed in vacuo to afford 18. 18a:white solid, yield 98%, mp: 149e151 C; 18b: white solid, yield 95%,mp: 156e158 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dimethyl sulfoxide; at 20℃; for 1h; | (0452) Compound 18, referred to as Bis(TT), was synthesized using Suberic acid and 2-thiazoline-2-thiol (TT) as starting materials. Briefly, 500 mg of Suberic acid (2.87 mmol, 1 eq), 752.7 mg of TT (6.31 mmol, 2.2 eq) and 1.431 g of EDC (7.46 mmol, 2.6 eq) were dissolved in 17.5 mL of dry DMSO. 70.15 mg of DMAP (0.57 mmol, 0.2 eq) was added and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with DCM and washed twice with 1 M HCl and once with DI water. The organic fractions were dried with sodium sulfate and evaporated under reduced pressure to provide a yellow solid in quantitative yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 4-methyl-morpholine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide In dichloromethane at 20℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86.03% | In methanol | a. (isonicotinamide) 2: (suberic acid) [(L) 2 ·(H 2 sub)] (1) A solution of suberic acid (17.4 mg, 0.1 mmol) in 10 mL methanol was added dropwise to a vigorously stirred solution of isonicotinamide (12.2 mg, 0.1 mmol) in methanol (3 mL) over 5 min. The solution was stirred for a few minutes, filtered into a test tube, and left standing at room temperature for 9 days. Col-orless block crystals were isolated after slow evaporation of the methanol solution in air. The crystals were collected and dried in air to give [(L) 2 ·(H 2 sub)] ( 1 ). (yield: 36 mg, 86.03%, based on L). mp 176-177 °C. Elemental analysis: Calc. for C 20 H 26 N 4 O 6 (418.45): C, 57.35; H, 6.21; N, 13.38. Found: C, 57.25; H, 6.10; N, 13.24. In- frared spectrum (cm -1 ): 3584s( (OH)), 3337s(multiple, as (NH)), 3264s( s (NH)), 3160m, 2994m, 2884m, 2691m, 2502m, 1894m, 1722s( (C = O)), 1670s( as (C = O)), 1624m( (C = C)), 1565m, 1522m, 1477m, 1435m( (C = N)), 1393m, 1348m, 1294s( s (C-O)), 1250m, 1205m, 1161m, 1119m, 1074m, 1032m, 988m, 944m, 901m, 857m, 814m, 765m, 717m, 672m, 631m, 604m. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | In N,N-dimethyl acetamide; water; at 95℃; for 96h; | A mixture containing H2SCA (0.0175 g,0.1 mmol),Cd(NO3)24H2O (0.0309 g, 0.1 mmol), and BIB (0.0144 g,0.05 mmol) were dissolved in a solution containing H2O and N,Ndimethylacetamide(3 mL, v1/v2 1/2) and kept at 95 C for 4 days.Colorless transparent bulk crystals were obtained. Yield: 68% relativelyto Cd. FT-IR data (Fig. S4, KBr, cm1): 3457(β), 3130(w),2933(m), 2743(w), 1579(s), 1435(s), 1244(w), 1072(w), 824(w),766(s), 616(w), 656(w), 512(w). |
Tags: 505-48-6 synthesis path| 505-48-6 SDS| 505-48-6 COA| 505-48-6 purity| 505-48-6 application| 505-48-6 NMR| 505-48-6 COA| 505-48-6 structure
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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