Abstract: Natural fiber composites are inexpensive and renewable alternatives to traditional fiber reinforced polymers(FRPs). However, existing natural fiber composites primarily rely on petrochemical based thermosetting matrices, which are difficult to recycle due to their stable crosslinked network structures. To address this challenge, it is desirable to develop natural fiber composites with inherently recyclable biobased matrices. In this study, we developed a dual dynamic network vitrimer matrix from hempseed oil and limonene derivatives and demonstrated its application in hemp fiber reinforced composites. To improve the weak interface between hemp fiber and the polymer matrix, a common challenge in the realm of natural fiber composites, we directly incorporated amino silane into the vitrimer matrix. The amino silane participated in the polymer network, increasing the crosslink density and toughening the matrix, as evidenced by the significant improvement of impact strength from 3.5 kJ/m2 to 10.3 kJ/m2. Moreover, the incorporation of amino silane resulted in a lower water absorption by 11 % in a 7-day soaking for the composites, demonstrating improved fiber/matrix interfacial interaction. Furthermore, our biobased vitrimer matrix exhibits both imine and hydroxy-ester dynamic bonds, which enable the recycling of the biocomposite through a mild and cost-effective aminolysis process (100℃, 3 h, ambient pressure). The decomposed polymer matrix was successfully reused as a polyol for polyurethane adhesives, and the surface morphology of recovered hemp fibers was analyzed and compared with that of the original fibers. These findings will help broaden the use of vitrimers for practical natural fiber composite applications, raise awareness of the problem of recycling natural fiber composite waste, and shed light on the interfacial challenge of natural fiber reinforced vitrimer composites.
* 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.
Reference：
[1] Synthesis, 2009, # 14, p. 2329 - 2332
2
[ 626-19-7 ]
[ 141-43-5 ]
[ 34052-90-9 ]
Reference：
[1] Synlett, 2006, # 10, p. 1479 - 1484
3
[ 626-19-7 ]
[ 95-54-5 ]
[ 29914-81-6 ]
Reference：
[1] Tetrahedron Letters, 2008, vol. 49, # 43, p. 6237 - 6240
[2] Farmaco (Societa chimica italiana : 1989), 2002, vol. 57, # 7, p. 543 - 548
4
[ 626-19-7 ]
[ 626-18-6 ]
Yield
Reaction Conditions
Operation in experiment
84%
With Poly(n-butyl-4-vinylpyridinium)borohydride In ethanol at 20℃; for 2.5 h;
General procedure: To a solution of the substrate (1 mmol) in ethanol as asolvent (5 mL) in a round-bottomed flask (25 mL) equippedwith a magnetic stirrer, P(BVP)BH4 (100 mg) was addedand stirred at room temperature. The progress of thereaction was monitored by TLC. On completion of thereaction, the mixture was filtered and the used reagent waswashed successively with HCl (1.0 M, 2 10 mL) andethanol (2 5 mL). The combined filtrates were evaporatedand the pure product was obtained in moderate to excellent yields. In a few cases in which the reaction wasnot complete, the crude product was purified on silica gelwith an appropriate eluent (Scheme 1).
99 %Chromat.
With formic acid; iron(II) tetrafluoroborate hexahydrate; tris(2-diphenylphosphinoethyl)phosphine In tetrahydrofuran at 60℃; for 2 h; Schlenk technique; Inert atmosphere
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.
Reference：
[1] Chemistry - A European Journal, 2013, vol. 19, # 24, p. 7701 - 7707
[2] Journal of Organic Chemistry, 2018, vol. 83, # 4, p. 2274 - 2281
[3] Comptes Rendus Chimie, 2013, vol. 16, # 8, p. 721 - 727
[4] Comptes Rendus Chimie, 2014, vol. 17, # 1, p. 23 - 29
[5] Indian Journal of Chemistry - Section A Inorganic, Physical, Theoretical and Analytical Chemistry, 2003, vol. 42, # 4, p. 744 - 750
[6] Molecules, 2006, vol. 11, # 5, p. 365 - 369
[7] Journal of Organometallic Chemistry, 2013, vol. 744, p. 156 - 159
[8] Organic and Biomolecular Chemistry, 2014, vol. 12, # 30, p. 5781 - 5788
[9] Dalton Transactions, 2018, vol. 47, # 28, p. 9231 - 9236
Reference：
[1] Journal of the Chemical Society, Chemical Communications, 1985, # 23, p. 1668 - 1669
[2] Journal of the American Chemical Society, 1988, vol. 110, # 13, p. 4221 - 4227
13
[ 626-19-7 ]
[ 52010-98-7 ]
Yield
Reaction Conditions
Operation in experiment
80.2%
With sodium tetrahydroborate In tetrahydrofuran; ethanol for 6 h; Cooling with ice
NaBH4 (1.7 g) was added to a solution of terephthalaldehyde (1a, 20.0 g) or isophthalaldehyde(1b, 20.0 g) in ethanol (100 mL) and tetrahydrofuran (150 mL). The reaction was stirred in an ice-bathfor 6 h. After reaction completion, the solution was quenched with 2Mhydrochloric acid to the pH 5–6.The solvent was evaporated, then water and ethyl acetate were added to the residue. The organicphase was washed with a saturated NaCl and dried with Na2SO4 for 8 h. The mixture was purifiedby silica gel chromatography with petroleum ether-ethyl acetate = 5:1 as eluent to give compound 2a17.6 g (86.1percent yield) and 2b 16.4 g (80.2percent yield), respectively.
80.2%
With sodium tetrahydroborate In tetrahydrofuran; ethanol for 6 h; Cooling with ice
Take a 500mL eggplant-shaped flask, 20g of isophthalaldehyde (0.15mol; 4.0equiv),100ml of ethanol and 150ml of tetrahydrofuran were added to the bottle, stirring to dissolve evenly. Then in the ice bath conditions,One-time slowly added to the bottle 1.7g sodium borohydride solid (9.3mmol; 1.0equiv), the reaction 6h or more,TLC TLC plate, UV analyzer (254nm) to monitor the progress of the reaction. To be terephthalic formaldehyde material completely disappeared, the reaction was stopped by dropping 2mol / L hydrochloric acid solution prepared before quenching, adjusting the pH to 4 to 5,The reaction mixture was then swirled to dryness. The resulting residue was re-dissolved in water and ethyl acetate and added to a separatory funnel.The aqueous phase is extracted with an equal volume of ethyl acetate 2 to 3 times, the combined ethyl acetate layers are washed with saturated aqueous sodium chloride solution.Subsequently, the organic phase is dried overnight over anhydrous sodium sulfate or anhydrous magnesium sulfate. Filter out the desiccant,Weigh about 60-100 mesh size silica gel powder about 30g added to the filtrate, and steam-dried to dry sand, silica gel column chromatography, the choice of elution system for petroleum ether: ethyl acetate = 3: 1, the resulting monomeric Based reduction reaction products, a total of 16.4g II-2 white solid was obtained in a yield of 80.2percent.
80.2%
With sodium tetrahydroborate In tetrahydrofuran; ethanol for 6 h; Cooling with ice
Take a 500mL eggplant-shaped bottle,20 g of meta-benzenedialdehyde (0.15 mol; 4.0 equiv),100ml of ethanol and 150ml of tetrahydrofuran are added to the bottle in order.Stir and dissolve evenly.Then in an ice bath,Slowly add 1.7 g of sodium borohydride solid (9.3 mmol; 1.0 equiv) slowly into the bottle.Reaction more than 6h,Thin layer TLC board,An ultraviolet analyzer (254 nm) monitors the progress of the reaction. After the raw material point of m-benzenedialdehyde is completely disappeared,Stop the reaction,Pre-prepared 2mol/L hydrochloric acid solution was added for quenching.Adjust the pH to 4 to 5,Then the reaction solution was evaporated to dryness.The residue obtained with water,The ethyl acetate was re-dissolved and added to a separatory funnel.The aqueous phase is extracted 2 to 3 times with an equal volume of ethyl acetate.Combine the ethyl acetate layers,Add saturated aqueous sodium chloride solution.Then,The organic phase was dried over anhydrous sodium sulfate or anhydrous magnesium sulfate overnight.Filter out the desiccant,Weigh about 30g of 60-100 mesh silica gel powder into the filtrate.Rotary to dry sand,Silica gel column chromatography separation,The elution system selected was petroleum ether:ethyl acetate = 3:1,The resulting monoaldehyde-based reduction reaction product is collected,A total of 16.4 g of white solid II-2 was obtained.Yield: 80.2percent.
64%
With sodium tetrahydroborate In ethanol at 0℃; for 1 h;
Example 45; 5-Cyano-1 -(3-oxazol-5-yl-benzyl)-1 H-indole-2-carboxylic acid (3-hydroxy-2,2- dimethylpropyDamide EPO <DP n="38"/>To a solution of isophthalaldehyde (1.77g, 13.0mmol) in EtOH (30ml) at 00C, was added sodium borohydride (135mg, 3.5mmol). The reaction was stirred at 0°C for 1 h. The solvent was evaporated and the residue purified by silica chromatography using DCM followed by DCM:MeOH (19:1) to yield 3-hydroxymethyl-benzaldehyde (1.14g, 64percent) as a yellow oil.
54%
With sodium tetrahydroborate; ethanol In tetrahydrofuran at -5 - 0℃; for 10 h; Inert atmosphere
The m-THMPC was synthesized as follows. First, NaBH4 (0.425 g, 9.25 mmol) was added at —5°C with continuous stirring for 30 minutes to a solution of dialdehyde 1 (5 g, 37 mmol) in a mixture of dry EtOH (75 ml) and THF (100 ml). The mixture was then stirred for 10 hours, and the temperature was maintained atabout 0 to -5°C while stirring. The reaction mixture was then neutralized with 2M HCI to pH 5 before the solvents were evaporated. Thereafter, water (200 mL) was added to the residue which was then extracted with AcOEt. The combined organic extracts were dried with MgSO4, and the solvent was evaporated. The product was purified by column chromatography using an AcOEt—hexane (30/70)mixture of solvents. Hydroxymethyl aldehyde was obtained as a colorless liquid and the yield was 2.7 g (54percent).
Reference：
[1] Organic and Biomolecular Chemistry, 2016, vol. 14, # 45, p. 10688 - 10694
[2] Journal of Organometallic Chemistry, 2010, vol. 695, # 1, p. 82 - 89
[3] Dalton Transactions, 2015, vol. 44, # 9, p. 4054 - 4062
[4] Molecules, 2016, vol. 21, # 7,
[5] Patent: CN107522647, 2017, A, . Location in patent: Paragraph 0082; 0083
[6] Patent: CN107522654, 2017, A, . Location in patent: Paragraph 0067; 0068
[7] Patent: WO2006/100208, 2006, A1, . Location in patent: Page/Page column 35-36
[8] Patent: WO2014/189796, 2014, A1, . Location in patent: Paragraph 0120; 0121
[9] Heterocycles, 1989, vol. 28, # 2, p. 967 - 978
[10] Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, 1983, vol. 37, # 8, p. 693 - 698
[11] Tetrahedron Letters, 1999, vol. 40, # 36, p. 6681 - 6684
[12] Molecules, 2006, vol. 11, # 5, p. 365 - 369
[13] Patent: US5438141, 1995, A,
[14] Organic and Biomolecular Chemistry, 2010, vol. 8, # 5, p. 1181 - 1187
[15] Journal of Organometallic Chemistry, 2011, vol. 696, # 15-16, p. 2857 - 2862
[16] Catalysis Letters, 2012, vol. 142, # 7, p. 907 - 913
[17] Organic and Biomolecular Chemistry, 2013, vol. 11, # 18, p. 3046 - 3056
[18] Journal of Natural Products, 2018, vol. 81, # 3, p. 524 - 533
14
[ 626-18-6 ]
[ 626-19-7 ]
[ 52010-98-7 ]
Reference：
[1] Canadian Journal of Chemistry, 2008, vol. 86, # 8, p. 782 - 790
[2] Chinese Journal of Chemistry, 2015, vol. 33, # 5, p. 545 - 549
[3] Journal of Organic Chemistry, 1992, vol. 57, # 22, p. 6063 - 6067
15
[ 626-19-7 ]
[ 52010-98-7 ]
Reference：
[1] Patent: US5350760, 1994, A,
[2] Patent: US5472964, 1995, A,
[3] Patent: US5506227, 1996, A,
Stage #1: 1,3-di(aminomethyl)benzene With hexamethylenetetramine In water at 20℃; for 3h;
Stage #2: With hydrogenchloride for 3h; Reflux;
1
A mixture of 378 g of urotropine and 350 g of water was placed in a reaction kettle and stirred to completely dissolve the urotropine and cooled to 20° C; then add 122 g of m-xylylenediamine to stir, after which 32% hydrochloric acid is added to adjust the pH to 3.6-4.5 and the control temperature does not exceed 20 ° C. The temperature is below 20 ° C, and the control temperature does not exceed 20 ° C, that is, at 0 ° C to 20 ° C, and 20 ° C in this example.B, concentrated hydrochloric acid after adding, heating reflux reaction 3 hours, in the reaction process with concentrated hydrochloric acid to control the reaction solution pH range of 3.5-4.5. After completion of the reaction, the mixture was cooled to 0-5 ° C and filtered. The resulting solid was isophthalaldehyde and dried at 35-40 ° C for 4 hours. The resulting mother liquor was recyled.
With hydrogenchloride; hexamethylenetetramine; acetic acid
1,3-bis-(<i>trans</i>-2-[2]quinolyl-vinyl)-benzene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
97%
With tert-butylammonium hexafluorophosphate(V); calcium(II) trifluoromethanesulfonate In neat (no solvent) at 130℃; for 8h; Green chemistry;
B. General experimental procedure for the synthesis of stryryl azaarenes:
General procedure: A mixture of 2-methyl quinoline (1 mmol), aryl aldehyde (1 mmol), Ca (OTf)2 (5 mol%) andBu4NPF6 (2 mol%) were heated at 130 oC under neat condition for 4-5 h. After completion of the reaction (monitored by TLC), reaction mixture was brought to roomtemperature, diluted with dichloromethane, absorbed on silica gel and purified by column chromatography using petroleum ether/ethyl acetate to give the desired product.
5,5′-(1,3-phenylenebis(methanylylidene))bis(pyrimidine-2,4,6(1H,3H,5H)-trione)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
92%
With sulfuric acid In acetic acid Heating;
92%
With 1,4-disulfo-1,4-diazabicyclo[2.2.2]octane-1,4-diium chloride In water at 70℃; for 0.0333333h; Green chemistry;
General procedure for the preparation of 5-arylmethylene-pyrimidine-2,4,6-trione derivatives
General procedure: A mixture of the aldehyde (1 mmol), barbituric acid (1 mmol) and [DABCO](SO3H)2Cl2 (0.025 mmol, 0.009 g) in water (4 ml) was heated in an oil bath (70 °C). After completion of the reaction, as monitored by TLC, using n-hexane:EtOAc (1:4) as the eluent, the crude product was filtered off, washed with water, and recrystallized from ethanol to give a pure compound.
87%
With verjuice at 60℃; for 0.116667h; Green chemistry;
General procedure for the preparationof 5-arylmethylene-pyrimidine2,4,6-trionederivatives
General procedure: A mixture of aldehyde (1 mmoL), (thio)barbituric acid(1 mmoL) and verjuice (10 mL) was heated in an oil bath(60 °C). After completion of the reaction, as monitored byTLC, using n-hexane:EtOAc (7:3) as the eluent, the reactionmixture was filtered and the precipitated product was washedwith water (3 × 10 mL) to afford the pure compound.
With pyridine
In ethanol at 140℃; for 0.166667h; Microwave irradiation; Inert atmosphere;
With sulfuric acid-modified polyethyleneglycol-6000 In neat (no solvent) at 70℃; for 0.0666667h; Green chemistry;
General procedure for the synthesis of bis-Knoevenagel products under solvent-free conditions
General procedure: A mixture of terephthaldehyde/isophthalaldehyde1a-b (1.00mmol, 0.134 g), acyclic and cyclic active methylene compounds 2a-n (2.00 mmol) and PEG-OSO3H (0.013 mmol, 0.08 g) were mixed thoroughly using a mortar and pestle. The reaction mixture was then transferred to an open Pyrex 100 mL beaker and heated at 70 °C for the given time (Table 5).After completion of the reaction (monitored by TLC), the reaction mixture was cooled to room temperature,added H2O (5 mL) and shaken for 3 min to dissolve PEG-OSO3H. The crude product (insoluble in water) was filtered and recrystallized from hot ethanol (3 mL) to afford the pure product (3a-r). Inorder to recover the catalyst, the filtrate was evaporated under reduced pressure and recovered catalyst was washed with diethyl ether twice (2 mL) andreused after drying under reduced pressure.
3
2 ℓ 4-neck flask in, isophthalaldehyde [H] (50.00 g, 373 ), pyridine (78 g), piperidine (9.5 g) was added and, while stirring the reaction solution was heated to 100 . There was added dropwise the malonate [B] pyridine solution (600 g) in (169.5 g, 1.68 ). After completion of the reaction was confirmed by HPLC, the reaction solution was cooled to 40 and poured the reaction mixture in distilled water (1ℓ). Then, after the addition of concentrated hydrochloric acid until the reaction solution becomes acidic, the solid was filtered off, and washed with water to give the crude of the compound [I]. The crude ethyl acetate / methanol 1: 1 mixed solution to room temperature, stirred for 30 minutes and, after filtration, washing with ethyl acetate, and by drying under reduced pressure, to give the compound [I] (quantity: 80.2 g, yield: 99% ). It shows the 1H-NMR measurement results of the resulting compound [I] below.
91%
With piperidine; pyridine for 24h; Heating;
With pyridine at 50℃;
With sodium acetate; acetic anhydride at 140 - 150℃;
With piperidine; pyridine for 24h; Reflux;
2.2.1. Synthesisof H2mpdam
Phenylenediacrylate acid (H2mpda) was prepared according to the literature [20]. A suspension of1,3-benzenedicarboxaldehyde(500mg, 3.7mmol), malonic acid (1.72g,16.5mmol), and pyridine-piperidine (70:1v/v,7mL) was heated at reflux for 24h. After cooling, the mixture was adjusted to pH1 by the addition of 1N HCl solution. The resulting precipitates were collected by filtration, washed with water, and then dried in vacuo to give a white powder.
2.3. General procedure for the deprotection of 1,1-diacetates
General procedure: A mixture of the 1,1-diacetate of the aldehyde (5 mmol) andP(4-VPH)ClO4 (20 mg) in ethanol (5 mL) was stirred at 50-60°C. Upon completion of the reaction (as determined by TLC),the mixture was filtered to remove the catalyst. The filtrate wascollected and distilled to dryness to give a residue, which waspartitioned between water (10 mL) and Et2O (5 mL). The etherlayer was collected and the aqueous layer was back-extractedwith Et2O (2 × 5 mL). The combined ether layers were washedwith a saturated solution of NaHCO3 (5 mL) and dried overanhydrous Na2SO4. The solvent was removed under vacuum togive the crude product as a residue, which was purified by silicagel column chromatography (n-hexane:ethyl acetate = 85:15(v/v)) to afford the pure aldehyde.
90%
With rice husk supported FeCl3 nanoparticles In ethanol at 70℃; for 0.583333h;
2.9 General procedure for deprotection of 1,1-diacetates
General procedure: A solution of the substrate (1 mmol) in EtOH (3 mL) was stirred as FeCl3-rice husk (0.08 g) was added. The mixture was stirred and heated at 70 °C. The progress of the reaction was monitored by TLC. After completion of the reaction, the mixture was filtered to separate the solid catalyst. The combined filtrates were concentrated on a rotary evaporator to remove EtOH. Water (5 mL) was added and the product was extracted with Et2O (3-5 mL). The organic layer was washed with a saturated solution of NaHCO3 and dried over MgSO4. The solvent was evaporated under reduced pressure. The resultant product was passed through a short column of silica gel (n-hexan-EtOAc, 9:1) to afford pure aldehyde.
87%
With N-sulfonic acid poly(4-vinylpyridinium) chloride In methanol at 20℃; for 0.583333h;
82%
With poly(4-vinylpyridinium) hydrogen sulfate solid acid In methanol at 20℃; for 0.2h; Irradiation;
2.3 General procedure for the deprotection of 1,1-diacetates
General procedure: A mixture of 1,1-diacetate (1 mmol), PVPHS (5 mg ∼ 0.01 mmol) in methanol (2 mL) was irradiated under ultrasonic irradiation at ambient temperature for specified time in Table 1. After completion of the reaction (monitored by TLC), the reaction mixture was diluted by Et2O (20 mL) and filtered to separate the catalyst. The filtrate was washed successively with 10% aq. NaHCO3 (3 × 10 mL) to remove excess of Ac2O and dried over MgSO4. The solvent was evaporated under reduced pressure. The resultant product was passed through short column of silica gel (n-hexane-EtOAc, 9:1) to afford pure aldehyde.
With sulfuric acid-modified polyethyleneglycol-6000 In neat (no solvent) at 70℃; for 0.05h; Green chemistry;
General procedure for the synthesis of bis-Knoevenagel products under solvent-free conditions
General procedure: A mixture of terephthaldehyde/isophthalaldehyde1a-b (1.00mmol, 0.134 g), acyclic and cyclic active methylene compounds 2a-n (2.00 mmol) and PEG-OSO3H (0.013 mmol, 0.08 g) were mixed thoroughly using a mortar and pestle. The reaction mixture was then transferred to an open Pyrex 100 mL beaker and heated at 70 °C for the given time (Table 5).After completion of the reaction (monitored by TLC), the reaction mixture was cooled to room temperature,added H2O (5 mL) and shaken for 3 min to dissolve PEG-OSO3H. The crude product (insoluble in water) was filtered and recrystallized from hot ethanol (3 mL) to afford the pure product (3a-r). Inorder to recover the catalyst, the filtrate was evaporated under reduced pressure and recovered catalyst was washed with diethyl ether twice (2 mL) andreused after drying under reduced pressure.
97.1%
With pyrrole; benzoic acid In ethanol at 40℃; for 3h;
3 Example 3
In a 250 mL three-neck vial,13.4 g (0.1 mol) of m-phthalaldehyde were added in sequence,33.0 g (0.206 mol) of diethyl malonate,Pyrrole 0.3g,Benzoic acid 0.5g,60g of ethanol,Heated to 40 ° C,Reaction for 3 hours,Cooled to 25 ° C,filter,Gives a white solid,After washing with a little ethanol,dry,40.6 g of product was obtained,Yield 97.1%,HPLC content was 99.82%.
Add 170 ml of toluene to 1 liter of the flask,And then added 3,4 grams of isophthalaldehyde,229 grams of malonic acid and 4 grams of pyridine,Stir evenly,Heating up to 80 degrees,Reaction for 3 hours,The liquid phase is traced until the peak area of the m-xylylene is less than 0.5%.After cooling to 25 degrees,filter,Dried to give 210 g of a white powdery solid,Purity 98.2%Yield 96%;
90%
With pyridine at 50 - 100℃; for 4.5h;
IV 3-(3-(2-carboxyvinyl)phenyl)prop-2-enoic acid
A mixture of malonic acid (2.8 g, 27 mmol) and benzene-1,3-dicarboxaldehyde (1.2 g, 9 mmol) in pyridine (3.3 mL) was stirred at 50° C. for 2 h and 100° C. for 2.5 h. After cooling the mixture was poured into aqueous sulfuric acid (17 mL, 1 M) and the white precipitate filtered and dried to give as a white powder (90%). 1H NMR (CDCl3, 400 MHz) δ 6.61 (d, J=16 Hz, 2H), 7.41 (t, J=7.6 Hz, 1H), 7.56 (d, J=16 Hz, 2H), 7.66 (dd, J=8, 1.6 Hz, 2H), 8.01 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ 120.8, 128.3, 130.1, 130.5, 135.6, 143.9, 168.1; lit. mp: 280-282° C.
(i) Py, (ii) (decarboxylation); Multistep reaction;
With sodium tetrahydroborate; In tetrahydrofuran; ethanol; for 6h;Cooling with ice;
NaBH4 (1.7 g) was added to a solution of terephthalaldehyde (1a, 20.0 g) or isophthalaldehyde(1b, 20.0 g) in ethanol (100 mL) and tetrahydrofuran (150 mL). The reaction was stirred in an ice-bathfor 6 h. After reaction completion, the solution was quenched with 2Mhydrochloric acid to the pH 5-6.The solvent was evaporated, then water and ethyl acetate were added to the residue. The organicphase was washed with a saturated NaCl and dried with Na2SO4 for 8 h. The mixture was purifiedby silica gel chromatography with petroleum ether-ethyl acetate = 5:1 as eluent to give compound 2a17.6 g (86.1% yield) and 2b 16.4 g (80.2% yield), respectively.
80.2%
With sodium tetrahydroborate; In tetrahydrofuran; ethanol; for 6h;Cooling with ice;
Take a 500mL eggplant-shaped flask, 20g of isophthalaldehyde (0.15mol; 4.0equiv),100ml of ethanol and 150ml of tetrahydrofuran were added to the bottle, stirring to dissolve evenly. Then in the ice bath conditions,One-time slowly added to the bottle 1.7g sodium borohydride solid (9.3mmol; 1.0equiv), the reaction 6h or more,TLC TLC plate, UV analyzer (254nm) to monitor the progress of the reaction. To be terephthalic formaldehyde material completely disappeared, the reaction was stopped by dropping 2mol / L hydrochloric acid solution prepared before quenching, adjusting the pH to 4 to 5,The reaction mixture was then swirled to dryness. The resulting residue was re-dissolved in water and ethyl acetate and added to a separatory funnel.The aqueous phase is extracted with an equal volume of ethyl acetate 2 to 3 times, the combined ethyl acetate layers are washed with saturated aqueous sodium chloride solution.Subsequently, the organic phase is dried overnight over anhydrous sodium sulfate or anhydrous magnesium sulfate. Filter out the desiccant,Weigh about 60-100 mesh size silica gel powder about 30g added to the filtrate, and steam-dried to dry sand, silica gel column chromatography, the choice of elution system for petroleum ether: ethyl acetate = 3: 1, the resulting monomeric Based reduction reaction products, a total of 16.4g II-2 white solid was obtained in a yield of 80.2%.
80.2%
With sodium tetrahydroborate; In tetrahydrofuran; ethanol; for 6h;Cooling with ice;
Take a 500mL eggplant-shaped bottle,20 g of meta-benzenedialdehyde (0.15 mol; 4.0 equiv),100ml of ethanol and 150ml of tetrahydrofuran are added to the bottle in order.Stir and dissolve evenly.Then in an ice bath,Slowly add 1.7 g of sodium borohydride solid (9.3 mmol; 1.0 equiv) slowly into the bottle.Reaction more than 6h,Thin layer TLC board,An ultraviolet analyzer (254 nm) monitors the progress of the reaction. After the raw material point of m-benzenedialdehyde is completely disappeared,Stop the reaction,Pre-prepared 2mol/L hydrochloric acid solution was added for quenching.Adjust the pH to 4 to 5,Then the reaction solution was evaporated to dryness.The residue obtained with water,The ethyl acetate was re-dissolved and added to a separatory funnel.The aqueous phase is extracted 2 to 3 times with an equal volume of ethyl acetate.Combine the ethyl acetate layers,Add saturated aqueous sodium chloride solution.Then,The organic phase was dried over anhydrous sodium sulfate or anhydrous magnesium sulfate overnight.Filter out the desiccant,Weigh about 30g of 60-100 mesh silica gel powder into the filtrate.Rotary to dry sand,Silica gel column chromatography separation,The elution system selected was petroleum ether:ethyl acetate = 3:1,The resulting monoaldehyde-based reduction reaction product is collected,A total of 16.4 g of white solid II-2 was obtained.Yield: 80.2%.
64%
With sodium tetrahydroborate; In ethanol; at 0℃; for 1h;
Example 45; 5-Cyano-1 -(3-oxazol-5-yl-benzyl)-1 H-indole-2-carboxylic acid (3-hydroxy-2,2- dimethylpropyDamide EPO <DP n="38"/>To a solution of isophthalaldehyde (1.77g, 13.0mmol) in EtOH (30ml) at 00C, was added sodium borohydride (135mg, 3.5mmol). The reaction was stirred at 0C for 1 h. The solvent was evaporated and the residue purified by silica chromatography using DCM followed by DCM:MeOH (19:1) to yield 3-hydroxymethyl-benzaldehyde (1.14g, 64%) as a yellow oil.
54%
With sodium tetrahydroborate; ethanol; In tetrahydrofuran; at -5 - 0℃; for 10h;Inert atmosphere;
The m-THMPC was synthesized as follows. First, NaBH4 (0.425 g, 9.25 mmol) was added at -5C with continuous stirring for 30 minutes to a solution of dialdehyde 1 (5 g, 37 mmol) in a mixture of dry EtOH (75 ml) and THF (100 ml). The mixture was then stirred for 10 hours, and the temperature was maintained atabout 0 to -5C while stirring. The reaction mixture was then neutralized with 2M HCI to pH 5 before the solvents were evaporated. Thereafter, water (200 mL) was added to the residue which was then extracted with AcOEt. The combined organic extracts were dried with MgSO4, and the solvent was evaporated. The product was purified by column chromatography using an AcOEt-hexane (30/70)mixture of solvents. Hydroxymethyl aldehyde was obtained as a colorless liquid and the yield was 2.7 g (54%).
36.57%
With sodium tetrahydroborate; ethanol; In tetrahydrofuran; at 0℃; for 0.166667h;
To a solution of isophthalaldehyde (7.0 g, 52.19 mmol) in THF (35 mL) and EtOH (70 mL) at 0C was added NaBfL (789.75 mg, 20.87 mmol) portion wise, the resulting solution was stirred at 0 C for 10 min, then 10 % HC1 (aq. 50 mL) was added, the mixture was extracted with EtOAc (50 mL x 3). The combined organic layer was washed with brine (25 mL x 2), dried over Na2S04, and concentrated in vacuo. The crude residue was purified via silica chromatography and a gradient of 0%- 100% EtOAc in Hexane to afford 3-(hydroxymethyl)benzaldehyde as a yellow oil (2.6 g, 36.57 %).
With sodium tetrahydroborate; In ethanol;
Step 1 3-(Hydroxymethyl)benzaldehyde To isophthalaldehyde (200 g) in absolute ethanol (3 L) at 0 C. was added NaBH4 (15.6 g). After 1 hour at O C. the reaction mixture was poured onto 25% aqueous ammonium acetate (2 L). The ethanol was evaporated and the product was extracted with EtOAc. The resulting mixture was purified by flash chromatography (30% EtOAc/Hexane) to provide 94 g of the title product.
3,3′,3′′,3′′′-[1,3-phenylenedi(methanetriyl)]tetrakis(4-hydroxy-2H-chromen-2-one)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80%
With alkanedisulfamic acid-functionalized silica-coated magnetic nanoparticles In ethanol; water at 60℃; for 1h; Sonication;
3,3′,3′′,3′′′-[1,3-Phenylenedi(methanetriyl)]tetrakis(4-hydroxy-2H-chromen-2-one) (3g)
General procedure: A mixture of monoaldehyde 2a-e, dialdehyde 2f-g, or trialdehyde2h-j (1 mmol), 4-hydroxy-2H-coumarin-2-one 1 (2.2 mmol for 2a-e,5 mmol for 2f and 2g, or 7 mmol for 2h-j) and ADSA-MNPs (0.1g for 2a-e, 0.12 g for 2f or 2g, or 0.15 g for 2h-j) in 4:1 EtOH-H2O(10 mL) was exposed to ultrasound irradiation at 60 °C for the appropriatetime (see Table 2). When the reaction was complete(TLC), the ADSA-MNPs were removed by using an applied externalmagnetic field. The solution was concentrated then left to evaporateslowly. An EtOH-H2O (5:1) mixture was added, and theresulting solid product was collected by filtration and washed withEtOH-H2O (5:1) to remove excess coumarin 1.
With potassium carbonate In 1,4-dioxane; water for 15h; Heating;
64%
With potassium <i>tert</i>-butylate In tetrahydrofuran at 0 - 25℃; Inert atmosphere;
39%
Stage #1: Methyltriphenylphosphonium bromide With potassium <i>tert</i>-butylate In tetrahydrofuran at 20℃; for 0.333333h; Inert atmosphere; Schlenk technique;
Stage #2: Isophthalaldehyde In tetrahydrofuran at 20 - 40℃; for 1h; Inert atmosphere; Schlenk technique;
With aluminum oxide; hydroxylamine hydrochloride; methanesulfonyl chloride at 100℃; for 0.5h;
94%
With hydroxylamine hydrochloride; pyrographite; methanesulfonyl chloride at 100℃; for 1h;
78%
With hydroxylamine hydrochloride; 2,4,6-triphenylpyrylium tetrafluoroborate In acetonitrile at 40℃; for 24h; Molecular sieve; Irradiation; Inert atmosphere;
50%
With ammonium acetate; acetic acid; 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate at 70℃; for 12h; Inert atmosphere;
General procedures for 4-AcNH-TEMPO+BF4- mediated nitriles synthesis
General procedure: A 15 mm flame-dried test tube, which was equipped with a magnetic stir bar and charged with aldehyde (0.3 mmol, in case of solid), 4-AcNH-TEMPO+BF4- (2.0 equiv, 0.6 mmol), and NH4OAc (4.0 equiv, 1.2 mmol), was evacuated and backfilled with nitrogen (this process was repeated 3 times). After 0.3 mL of AcOH was added, aldehyde (0.3 mmol, in case of liquid), and AcOH (0.3 mL) were added in sequence. The reaction mixture was stirred for 12 h at 70 oC under N2 balloon, and then cooled to room temperature. The reaction was diluted by adding EtOAc and washed 4 M HCl aqueous solution. Two layers were separated, and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with Na2CO3 aqueous solution. The organic layer was dried over MgSO4, filtered, and concentrated to a volume of approximately 20 mL by evaporator. To eliminate remaining aldehyde, aqueous 2 M Na2S2O5 aqueous solution (20 mL) was added to the organic layer and stirred for 2 hours. Two layers were separated, and the organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography to give nitrile products.
80 % Chromat.
With formic acid; hydroxylamine hydrochloride; silica gel for 0.0333333h; Irradiation;
With 4-acetylamino-2,2,6,6-tetramethyl-1-piperidinoxy; ammonium acetate; oxygen; nitric acid; acetic acid; sodium nitrite at 50℃; for 12h;
68 %Spectr.
With 4-acetylamino-2,2,6,6-tetramethyl-1-piperidinoxy; ammonium acetate; oxygen; nitric acid; acetic acid; sodium nitrite at 50℃; for 12h; Green chemistry;
With C35H28Cl2N5PRu; potassium tert-butylate; In toluene; at 50℃; for 6h;
General procedure: using the complex 1 as catalyst in presence of a base following a general procedure. In a round-bottom flask, 1 mmol of substrate, 0.005mmol of catalyst (3.6mg) and 0.010 mmol of tBuOK (1.1mg) were mixed in 10mL toluene. The reaction mixture was heated at 50C in aerobic condition with continuous stirring for 6h and then the solvent was evaporated with a rotary evaporator under reduced pressure. The crude product, thus obtained, was purified on preparative silica gel GF-254 TLC plate using ethyl acetate: hexane (1:10) solvent mixture as eluent. The oxidized products were characterized by NMR spectroscopy (See Figs. S4-S32).
5,5'-(1,3-phenylenebis(methanylylidene))bis(1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
98%
With sulfuric acid-modified polyethyleneglycol-6000 In neat (no solvent) at 70℃; for 0.0333333h; Green chemistry;
General procedure for the synthesis of bis-Knoevenagel products under solvent-free conditions
General procedure: A mixture of terephthaldehyde/isophthalaldehyde1a-b (1.00mmol, 0.134 g), acyclic and cyclic active methylene compounds 2a-n (2.00 mmol) and PEG-OSO3H (0.013 mmol, 0.08 g) were mixed thoroughly using a mortar and pestle. The reaction mixture was then transferred to an open Pyrex 100 mL beaker and heated at 70 °C for the given time (Table 5).After completion of the reaction (monitored by TLC), the reaction mixture was cooled to room temperature,added H2O (5 mL) and shaken for 3 min to dissolve PEG-OSO3H. The crude product (insoluble in water) was filtered and recrystallized from hot ethanol (3 mL) to afford the pure product (3a-r). Inorder to recover the catalyst, the filtrate was evaporated under reduced pressure and recovered catalyst was washed with diethyl ether twice (2 mL) andreused after drying under reduced pressure.
With Poly(n-butyl-4-vinylpyridinium)borohydride; In ethanol; at 20℃; for 2.5h;
General procedure: To a solution of the substrate (1 mmol) in ethanol as asolvent (5 mL) in a round-bottomed flask (25 mL) equippedwith a magnetic stirrer, P(BVP)BH4 (100 mg) was addedand stirred at room temperature. The progress of thereaction was monitored by TLC. On completion of thereaction, the mixture was filtered and the used reagent waswashed successively with HCl (1.0 M, 2 10 mL) andethanol (2 5 mL). The combined filtrates were evaporatedand the pure product was obtained in moderate to excellent yields. In a few cases in which the reaction wasnot complete, the crude product was purified on silica gelwith an appropriate eluent (Scheme 1).
99%Chromat.
With formic acid; iron(II) tetrafluoroborate hexahydrate; tris(2-diphenylphosphinoethyl)phosphine; In tetrahydrofuran; at 60℃; for 2h;Schlenk technique; Inert atmosphere;
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 muL; 0.5 mmol) and 100 muL 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 muL; 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.
ethyl 4-(3-(5-(ethoxycarbonyl)-1,2,3,4-tetrahydro-6-methyl-2-oxopyrimidine-4-yl)-phenyl)-1,2,3,4-tetrahydro-6-methyl-2-oxopyrimidine-5-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
96%
With potassium hydrogensulfate In ethylene glycol at 100℃;
90%
With cobalt(II) nitrate hexahydrate In neat (no solvent) at 80℃; for 0.4h; Green chemistry;
General procedure for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones(thiones)
General procedure: A mixture of aldehyde (1.0 mmol), β-dicarbonyl (1.0 mmol), Co(NO3)2*6H2O (0.15 mmol) and urea or thiourea (1.5 mmol) was magnetically stirred at 80 °C in solvent-free condition. After completion of the reaction, as indicated by TLC (EtOAc/n-hexane, 1:4), the reaction mixture was filtered and the residue recrystallized from ethanol to afford the pure product. All products were characterized by mp, IR and 1H NMR spectra. The physical and spectroscopic data of new compounds is given bellow.
82%
With magnesium sulfate heptahydrate In water at 90℃; for 11h;
82%
With nanosilica at 100℃; for 0.05h; Microwave irradiation; Neat (no solvent);
1 Example 1 Synthesis of Bipolar Bidentate Ligands
In 250mL round bottom flask was added 0.12mol / L dilute hydrochloric acid 100mL,Add 60mmol pyrrole, 5mmol isophthalaldehyde, magnetic stirring at room temperature dark reaction,The reaction system was TLC real-time monitoring. Control the appropriate reaction time,The reaction was stopped by TLC after almost complete consumption of isophthalaldehyde as substrate;The reaction solution was neutralized with ammonia to pH = 8-9, filtered,And wash the filter cake with petroleum ether to the filtrate colorless. The resulting solid was filtered to give a little HPLCThe content of each component is monitored. The remaining solid can be recrystallized from ethyl acetate-petroleum etherPurification by column chromatography (silica, petroleum ether: ethyl acetate = 100: 1 to 1: 1)Vacuum drying bipolar bidentate ligand. The yield was 1.31 g and the yield was 71.3%.
46%
With indium(III) chloride at 20℃; for 2h; Inert atmosphere;
With dihydrogen peroxide In acetonitrile at 85℃; for 4h;
4
To the reaction flask was added compound II (10 mmol) in acetonitrile (60 ml), 13% V-MCM-41 molecular sieve (0. 08 g), 30% hydrogen peroxide (40 ml) was added and the temperature was raised to 85 ° C,After 4 hours of reaction, the product was filtered and the filtrate was poured into a vacuum distillation unit. The acetonitrile and water were recovered under reduced pressure at 60 to 65 ° C and the temperature was raised to 100 to 105 ° CHigh vacuum collection of dibenzaldehyde 9. 4 mmol, yield 94%.
72%
With C15H11ClN4SZn; p-benzoquinone In <i>tert</i>-butyl alcohol for 8h;
2.5. Photo-oxidation of methyl arenes
25 mg of photo-catalyst was placed in 10 mmol of methyl arene in a10 mL cylindrical quartz glass reactor. Then 25 mg of superoxide orhydroxyl radical scavengers(benzoquinone (BQ) / t-butyl alcohol (TB))was added [22]. The photo-oxidation experiments were carried outunder visible light (300 Watts Tungsten lamp) for 8 h [13]. The reactionmixture was monitored with TLC. After completion of reaction, thephoto-catalyst was filtered and washed with distilled water andextracted by using ethyl acetate. The crude products were purified bysimple filter column to yield pure aldehydes (Scheme 2) with 70 to 85%yields.
62%
With tert.-butylhydroperoxide; C29H25Cl2N4Ru(1+)*F6P(1-) In acetonitrile at 60℃; for 3h; Schlenk technique; Inert atmosphere;
47%
Stage #1: m-xylene With chlorine at 20 - 70℃; for 1h;
Stage #2: With hexamethylenetetramine In water at 10 - 100℃; for 8h;
Stage #3: In ethanol at 5℃; for 1h; Reflux;
4 Four specific embodiments:
(1) takeMeta-xylene (1200 g, 11.3 mol) was added to a 2 L chlorination kettle,Heating to 70 (not more than 80 degrees)Slowly access to chlorineChlorine gas (4000 g, 56.3 mol)Continue stirring for 1 hour,Cool to room temperature,Benzyl chloride to obtain more than 2,100.(2) Stage a,The resulting multi-chlorobenzyl take the above (2100g) was added 3L reaction flask,Add oxidizerUrotropine (2100 g, 15 mol),Add solvent water 2L;Stage b,Slowly warming to 100 ,Reaction for 8 hours,Cooled to 10 ,First centrifuge,Get 1200g wet product;Stage c,The product obtained after the first centrifugation was added with ethanol (1 L)Heated to reflux for 1 hour,Cool to 5 ° C,Centrifuge againStage d,The above c re-centrifugation of the resulting product was dried,Drying temperature is 60 ,The product is isophthalaldehyde (720 g, yield 47%).
Multi-step reaction with 2 steps
1: glacial acetic acid; H2SO4; CrO3 / 5 - 10 °C
2: diluted hydrochloric acid
Multi-step reaction with 2 steps
1: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / tetrachloromethane / 15 h / 85 °C
2: sodium methylate; 2-nitropropane / methanol; ethyl acetate / 6 h / 30 °C
1.b
10 parts of previously obtained compound are mixed with 2.8 parts of isophthalaldehyde in 50 parts of ethanol and 1 part of piperidine. The whole mixture is heated to reflux and stirred for 12 hours. Reaction mixture is then cooled to 25°C, filtered and washed with 30 parts of methanol. The yellowish presscake is then dried and the following bis-styryl dye is obtained: [] Yield: 98%; UV-Vis (EtOH) λmax: 348 nm; ε (λmax): 39000 l.mol-1.cm-1 MS (positive mode): 314.5 (M+), 315.5 (M+1), 316.5 (M+2)
With sodium tetrahydroborate; In tetrahydrofuran; ethanol; ethyl acetate;
Step 9 3-(((2-Tetrahydropyranyl)oxy)methyl)benzaldehyde Isophthalaldehyde (150 g, 1.1 mole) was dissolved in THF (1 L) and EtOH (1 L) at 0 C. NaBH4 (11.0 g, 291 mmol) was added portionwise and the mixture stirred 1 hour at 0 C. Addition of 25% aq. NH4 OAc and extraction with EtOAc (2*) followed by purification by flash chromatography (20% to 40% EtOAc in hexanes) yielded 60 g of 3-(hydroxymethyl)benzaldehyde.
With sodium tetrahydroborate; In tetrahydrofuran; ethanol; ethyl acetate;
Step 10 3-(((2-Tetrahydropyranyl)oxy)methyl)benzaldehyde Isophthalaldehyde (150 g, 1.1 mole) was dissolved in THF (1 L) and EtOH (1 L) at 0 C. NaBH4 (11.0 g, 291 mmol) was added portionwise and the mixture stirred 1 hr at 0 C. Addition of 25% aq. NH4 OAc and extraction with EtOAc (2*) followed by purification by flash chromatography (20%?40% EtOAc in hexanes) yielded 60 g of 3-(hydroxymethyl)-benzaldehyde.
With sodium borohydrid; In tetrahydrofuran; ethanol; ethyl acetate;
Step 11 3-((2-Tetrahydropyranyl)oxymethyl) benzaldehyde Isophthalaldehyde (150 g, 1.1 mole) was dissolved in THF (1 L) and EtOH (1 L) at 0 C. Sodium borohydride (11.0 g, 291 mmol) was added portionwise and the mixture stirred 1 hour at 0 C. Addition of 25% aq. NH4 OAc and extraction with EtOAc (2*) gave after evaporation the crude product. Purification by flash chromatography (20% to 40% EtOAc in hexanes) yielded 60 g of m-hydroxymethylbenzaldehyde.
3-(2-(6-phenylpyridin-2-yl)ethenyl)benzaldehyde[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Zinc chloride;
Step 3 Preparation of 3-(2-(6-phenylpyridin-2-yl)ethenyl)benzaldehyde A mixture of <strong>[46181-30-0]2-methyl-6-phenylpyridine</strong> (525 mg) (step 2), isophthalaldehyde (630 mg) and dry zinc chloride (40 mg) was heated at 160 C. under N2 for 3 hours. The resulting mixture was partitioned between 25% aqueous NH40 Ac (20 cc) and ethyl acetate (20 cc) The organic layer was washed with H2 O (10 cc), brine and solvent as removed in vacuo. The residue was purified by chromatography to afford the title compound.
Zinc chloride;
Step 3 Preparation of 3-(2-(6-phenylpyridin-2-yl)ethenyl)benzaldehyde A mixture of <strong>[46181-30-0]2-methyl-6-phenylpyridine</strong> (525 mg) (step 2), isophthalaldehyde (630 mg) and dry zinc chloride (40 mg) was heated at 160C under N2 for 3 hours. The resulting mixture was partitioned between 25% aqueous NH4OAc (20 cc) and ethyl acetate (20 cc). The organic layer was washed with H2O (10 cc), brine and solvent as removed in vacuo . The residue was purified by chromatography to afford the title compound.
With sodium hydroxide; In dichloromethane; water; at 3℃; for 1h;
100 ml of dichloromethane, 25 g of t-butoxy carbonyl methyl triphenyl phosphonium bromide and 10.2 g of isophthalaldehyde were taken into a clean and dry round bottom flask and the resultant reaction mass was stirred for 20 minutes for homogenous solution. The reaction mass was then cooled to 3° C. followed by addition of a mixture of 13.2 g of sodium hydroxide and 20 ml of water in 40 minutes. The organic layer was separated and dried on 5 g of anhydrous sodium sulphate. The organic layer was then distilled off completely at about 40° C. 50 ml of n-heptane was added to the resultant residue and was stirred at 28° C. for 1 hour followed by filtration of separated solid and the solid was washed with 25 ml of n-heptane. The filtrate was taken into a clean and dry round bottom flask and the solvent was distilled off completely at about 62° C. to afford 12 g of intermediate residue.
With poly(4-vinylpyridinium) hydrogen sulfate solid acid In neat (no solvent) at 20℃; for 0.0666667h; Irradiation; Green chemistry;
2.2 General procedure for the preparation of acylals
General procedure: A mixture of aldehyde (1 mmol), acetic anhydride (1.1-3.3 mmol) and PVPHS (5 mg ∼ 0.01 mmol) was irradiated under ultrasonic irradiation at ambient temperature for appropriate time for the time mentioned in the Table 1. After completion of the reaction (monitored by TLC), ethyl acetate (3 × 5 ml) was added to the reaction mixture and the catalyst was recovered by filtration and washed with ethyl acetate (5 mL) and acetone (5 mL). The organic layer was successively washed with a saturated solution of NaHCO3 (10 mL), brine (2 × 10 mL) and water (2 × 10 mL). The organic phase was dried over anhydrous MgSO4, filtered and the solvent was evaporated to give the pure desired compound. The solid crude product thus obtained was purified by recrystallization from cyclohexane, or by column chromatography on a silica gel column. The recovered catalyst, after drying, was reused for four more consecutive acetylation reactions of 4-chlorobenzylaldehyde (1.0 mmol) affording 96%, 96%, 96%, and 95% yields, respectively, in 4, 4, 5, and 5 min (Scheme 2).
93%
With rice husk supported FeCl3 nanoparticles In neat (no solvent) at 20℃; for 0.666667h; chemoselective reaction;
2.8 General procedure for the acetylation of aldehydes
General procedure: Aldehyde (1 mmol), acetic anhydride (2.5 mmol), and FeCl3-rice husk (0.02 g) were mixed at room temperature. The reaction was monitored by TLC. After completion of the reaction ethylacetate (15 mL) was added to the reaction mixture and the catalyst was recovered by filtration, and washed with ethylacetate (5 mL). The organic layer was washed with a saturated solution of NaHCO3 (3 × 15 mL) and water (2 × 10 mL). The organic phase was dried over anhydrous MgSO4, filtered and the solvent was evaporated to give the pure desired compounds. The solid crude product that obtained was purified by recrystallization from cyclohexane, or by column chromatography on a silica gel column.
92%
With Silica bonded propyl-diethylene-triamine-N-sulfamic acid at 20℃; for 0.05h; neat (no solvent); chemoselective reaction;
92%
With poly(4-vinylpyridinium) perchlorate In neat (no solvent) at 20℃; for 0.0833333h; Green chemistry; chemoselective reaction;
2.2. General procedure for the acetylation of aldehydes
General procedure: P(4-VPH)ClO4 was prepared according to literatures[56,57]. Briefly, the aldehyde (5 mmol), Ac2O (5-7.5 mmol) and P(4-VPH)ClO4 (20 mg, 0.016 mmol) were added to a 25-mLbatch reactor equipped with a distillation condenser, and theresulting mixture was stirred at room temperature for a specifiedtime (Table 1). The amount of AC2O used in the reaction was varied in the range of 1.0-1.5 equivalents to assist in the dissolution of the aldehyde and the stirring of the reaction mixture. Upon completion of the reaction (as determine byTLC), the mixture was diluted with diethyl ether (Et2O, 2 × 10mL) and filtered to allow for the recovery of the catalyst. The ether layer was collected and washed sequentially with a saturated solution of NaHCO3 (5 mL) and water (3 × 5 mL) before being dried over anhydrous Na2SO4. The solvent was then removed in vacuo to give the pure acylal product as a residue,which was recrystallized from n-hexane or cyclohexane. There covered catalyst was dried in an oven under vacuum at 50 °C and reused.
88%
With N-sulfonic acid poly(4-vinylpyridinium) chloride at 20℃; for 0.0833333h; Neat (no solvent); chemoselective reaction;
87%
With succinimide-N-sulfonic acid In neat (no solvent) at 20℃; for 0.0833333h;
2.3. Acetylation of alcohols, phenols, thiols, and amines with different substrates
General procedure: A mixture of 1 mmol substrate, 2-3 mmol acetic anhydride, and 5 mg SuSA (0.028 mmol) was stirred at room temperature in the absence of a solvent. The progress of the reaction was monitored by TLC. After completion of the reaction, the mixture was diluted with 15 ml ethyl acetate and filtered. Then the solid residue was washed with 5 ml ethyl acetate, then 5 ml acetone and then dried. The recovered catalyst could be used for three more reaction runs. The organic layer was washed with 5 ml of a saturated solution of NaHCO3, 20 ml brine and 20 ml water, and dried over MgSO4. Evaporation of the solvent followed by column chromatography on silica gel followed by evaporation of the solvent gave the desired product in good to high yields.
80%
With silica-bonded S-sulfonic acid at 20℃; for 0.05h;
In ethanol at 20 - 120℃; for 0.283333h; Microwave irradiation;
General procedure for ligands L1-L4
Thiosemicarbazide (2.19 mmol, 2 equiv) and isophtalaldehyde (1.10 mmol, 1 equiv) were suspended in 4 mL of ethanol in a 10 mL-microwave reactor. The reactor was placed in the microwave oven.The reactor was heated from room temperature to 120 °C (OF) on 2 min by monomode microwaves irradiation (power: 150 W, stirring: 50%, ventilation: 1/3), maintained at 120 °C for 15 min (power: 50 W, stirring: 50%, ventilation: 1/3) and let cooled down to room temperature (power: 0 W, stirring: 50%, ventilation: 3/3). The mixture was filtered and washed with ethanol to give 6. Compound 6 (0.71 mmol, 1 equiv) and DMF-DMA (1.78 mmol, 2.5 equiv) were dissolved in 4 mL of DMF in a 10 mL-microwave reactor. After total solubilisation, the reactor was placed in the microwave oven. The reactor was heated from room temperature to 50 °C (OF) over 1 min by monomode microwaves irradiation (power: 80 W, stirring: 30%, ventilation: 1/3), maintained at 50 °C for 8 min (power: 50 W, stirring: 30%, ventilation: 1/3) and let cooled down to room temperature (power: 0 W, stirring: 30%, ventilation: 3/3). The appropriate α-bromoketone (1.42 mmol, 2 equiv) was added in the previous reactor. The solution turned to orange. After 2 min of stirring, distilled triethylamine (2.13 mmol, 3 equiv) was added. The solution turned to dark red. The reactor was heated from room temperature to 50 °C (OF) over 1 min by monomode microwaves irradiation (power: 70 W, stirring: 30%, ventilation: 1/3), maintained at 50 °C for 8 min (power: 30 W, stirring: 50%, ventilation: 1/3) and let cooled down to room temperature (power: 0 W, stirring: 50%, ventilation: 3/3). The solution was concentrated under reduced pressure. The residue was suspended in 20 mL of dichloromethane, washed five times with 30 mL of water. The organic layer was evaporated under reduced pressure. The residue was suspended in dichloromethane, filtered and washed with dichloromethane.
65%
With hydrogenchloride In ethanol at 20℃; for 3h;
5 Synthesis of compounds (1-10). Example for compound (1)
General procedure: In a round bottom flask for 100 mL, 4-fluorobenzaldehyde (2.5 mmol) was dissolved in ethanol (15 mL), then HCl (03 drops) were added to the reaction at room temperature. Semicarbazide hydrochloride (2.5 mmol) was added and the mixture was maintained under magnetic stirring for 3 h at room temperature. After this time, the mixture was cooled at 0 °C and the precipitate was filtered in a Büchner funnel with a sintered disc filter, washed with cold water, n-hexane and then dried over SiO2. Compounds were recrystallized in hot ethanol, to provide compounds with acceptable purity.
With acetic acid In methanol Reflux;
4.2. General procedure for the synthesis of compounds (1-30)
General procedure: 4.2. General procedure for the synthesis of compounds (1-30)Different acetophenone/benzaldehyde (1 mmol) were reactedand refluxed with thiosemicarbazide (1 mmol) in methanol inthe presence of catalytic glacial acetic acid for 3-5 h. After completionof reaction the mixture were filtered and washed with hexaneto yield pure product. The obtained products (1 mmol) was thenreacted and refluxed with (1 mmol) of methoxy or chloro substitutedphenacyl bromide for 3-5 h. After reaction completion themixture was filter and wash with hexane to yield pure products(1-30) [26,27]. Different spectroscopic techniques, such as EI-MS,1H NMR and 13C NMR were used to determine the structure ofall analogs.
With 3-(2-(piperidin-1-yl)ethylthio)propyl-modified silica In ethanol; water at 20℃; for 0.216667h;
96%
With immobilized Ni-Zn-Fe layered double hydroxide (LDH) on silica-coated magnetite nanoparticles In water for 0.0833333h; Reflux; Green chemistry;
93%
With Fe3O4(at)SiO2(at)CuO-Fe2O3 (binary copper and iron oxides immobilized on silicalayeredmagnetite) In water for 0.0833333h; Reflux;
General procedure for the Knoevenagel condensation of benzaldehyde and malononitrile
General procedure: In a round-bottom flask (10 mL) equipped with a magnetic stirrer, a mixture of benzaldehyde (0.106 g, 1 mmol), malononitrile (0.073 g, 1.1 mmol) and H2O (2 mL) was well mixed at room temperature. Fe3O4(at)SiO2(at)CuO-Fe2O3 (30 mg) was then added and the resulting mixture was stirred for 4 min at reflux. The progress of the reaction was monitored by TLC (eluent: EtOAc/n-hexane: 2/4). After completion of the reaction, the catalyst was separated by an external magnet and the reaction mixture was extracted with EtOAc (2 x 5 mL). The organic solution was then dried over anhydrous Na2SO4. Evaporation of the solvent afforded the pure benzylidenemalononitrile in 90% yield (0.139 g, Table 3, entry 1).
90%
With biguanide-functionalized hierarchical porous covalent organic framework In water at 20℃; for 0.166667h;
2.4. Catalytic performance
General procedure: Knoevenagel condensation reaction: Benzaldehyde (106 mg, 1mmol), malononitrile (73 mg, 1.1 mmol), DG-COF (2 mol%, 7 mg) and H2O (5 mL) were added to a reaction tube. The mixture was stirred atroom temperature for an appropriate time (monitored by TLC). Aftercompletion of the reaction, ethyl acetate was added to the reaction tube.DG-COF was separated by filtration, washed with ethyl acetate, driedunder in vacuum to be recycled and directly reused in the next reaction.The combined organic solvent was concentrated under reduced pressure.The resulting crude product was purified using flash columnchromatography to afford the desired product. The recycle experimentswere performed for 8 times, and the yield of each reaction is calculated.
80%
With mesoporous Al-MCM-41 functionalized by layered double hydroxide nanosheets and (3-aminopropyl)triethoxysilane In ethanol at 80℃; for 2h; Schlenk technique;
General procedure: The catalytic model reaction was carried out as follows:In a Schlenk flask equipped with a magnetic stirrer, septum and condenser, 4-chlorobenzaldehyde (1.0 mmol), (phenylsulfonyl)acetonitrile (1.0 mmol), 70% ALAM (5 mol%) and95% EtOH (5 mL) were added. The flask was immersed ina heating oil bath and the reaction mixture was stirred at80 °C. Upon complete consumption of starting materials asanalysed by TLC (hexane : ethyl acetate, 8 : 2), then the catalystwas separated by centrifuge, washed with water, ethanoland acetone. Resulting reaction mixture was extracted withdiethyl ether (3 × 10 mL). The combined organic layer wasdried over anhydrous Na2SO4and concentrated to affordcrude products, which were purified by column chromatography.It was observed that on MCM-41 surfaces there isalways some residual adsorbed water left behind, even afterheating under vacuum as it was done here. Nevertheless,that does not seem to affect the model reaction, which has infact been reported to take place even in aqueous media [72,73]. Moreover, our final product, 2-amino-4H-chromenes,requires a subsequent cascade type Knoevenagel-Michaeladdition, and that also appears to be promoted readily by ouroptimized catalytic protocol.
Stage #1: Isophthalaldehyde With zinc(II) perchlorate In methanol at 20℃; for 0.5h;
Stage #2: toluene-4-sulfonic acid hydrazide In methanol at 20℃; for 2h;
Synthesis of compound 1
A solution of isophthalaldehyde (179 mg, 1.34 mmol) and a catalytic amount of Zn(ClO4)2 in MeOH (10 mL) were stirred for 30 min at room temperature. A solution of p-toluenesulfonylhydrazide (500 mg, 2.68 mmol) in MeOH (10 mL) was slowly added to the solution above. The reaction mixture was stirred for 2 h at room temperature. After evaporation of the solvent, the residue was recrystallized in acetone/CH2Cl2 (1:3, v/v), resulting in a solid with 93% yield (586 mg). Mp 119-120 °C; IR (KBr) 3200, 1054 cm-1; 1H NMR (400 MHz, DMSO-d6): δ 2.35 (s, 6H, -CH3), 7.40 (m, 5H, Ar), 7.55 (m, 2H, Ar), 7.76 (m, 5H, Ar), 7.92 (s, 2H, -NC-H), 11.53 (s, 2H, -NH); 13C NMR (100 MHz, DMSO-d6): δ 20.9, 124.5, 127.1, 128.2, 129.2, 129.6, 134.2, 136.1, 143.4, 146.2. Anal Calcd for C22H22N4O4S2: C, 56.15; H, 4.71; N, 11.91. Found C, 56.31; H, 4.78; N, 12.22.
In methanol at 20℃; Schlenk technique; Inert atmosphere;
With silica-bonded 5-n-propyl-octahydro-pyrimido[1,2-a]azepinium chloride In ethanol for 6.33333h;
17 General procedure for the preparation of 4H-benzo[b]pyran derivatives
Carbonyl compound (1.0 mmol), malononitrile (1.0 mmol) and aromatic aldehyde (1.0 mmol) were added in a 25.0 mL round-bottomed flask contained (SB-DBU)Cl (0.11 g, 5.0 mol%) and EtOH (5.0 mL). The resulting mixture was stirred at room temperature (method A) [in order of alkyl cyanoacetates, the reaction was carried out in EtOH/H2O (1:1) under reflux conditions (method B)]. After completion of the reaction, as monitored by TLC, ethanol (5 mL) was added to the reaction mixture and heated at 60 °C for ∼5 min to dissolve the product followed by centrifugation for 10 min to separate the (SB-DBU)Cl. The EtOH was evaporated under reduced pressure to give the crude product. The crude product was dissolved in warm EtOH or aqueous EtOH (6.0 mL) and was allowed to stand at room temperature for 3-5 h. The crystalline solids were collected, washed with ethanol and dried. The same procedure was applied for the preparation of spiro-pyran derivatives and complex compounds; however, in the case of the preparation of complex compounds, 2.0 mmol of carbonyl compound, 2.0 mmol of alkylmalonate and 1.0 mmol of dialdehyde were used. The recovered (SB-DBU)Cl was reused for another time without loss of its activity. 3.17 ;4,4'-(1,3-Phenylene)bis(6-amino-3-methyl-1-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile) (8c) ;M.p. = 198 °C (dec.) 1H NMR (DMSO-d6, 500 MHz): δ 1.78 (s, 6H), 4.7 (s, 2H), 7.14-7.18 (m, 6H), 7.29-7.35 (m, 4H), 7.48 (t, J = 8.0 Hz, 4H), 7.76 (d, J = 7.5 Hz, 4H). 13C NMR (DMSO-d6, 125 MHz): δ 13.4, 37.5, 58.9, 99.5, 120.7, 120.8, 127.0, 127.4, 128.1, 130.1, 138.4, 144.6, 146.2, 160.3. Anal. Calcd. for C34H26N8O2: C, 70.58; H, 4.53; N, 19.37; found C, 70.65; H, 4.51; N, 19.39.
94%
With perchloric acid modified cellulose In neat (no solvent) at 70℃; for 0.166667h; Green chemistry;
80%
With sodium bromide In ethanol at 25℃; for 0.333333h; Electrolysis; Green chemistry;
Typical experimental procedure for electrocatalytic synthesis of 1,4-dihydropyrano[2,3-c]pyrazole derivatives
General procedure: A mixture of aryl aldehyde (2 mmol), malononitrile (3 mmol), 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (2 mmol), and NaBr (0.05 g, 0.5 mmol) in EtOH (20 mL) was electrolyzed in an undivided cell equipped with a magnetic stirrer, a graphite anode, and an iron cathode at 25 °C under a constant current density of 10 mA/cm2 [electrodes square 5 cm2] until the catalytic quantity of 0.62 F/mol of electricity was passed. After the electrolysis was finished, the precipitated products were separated by filtration which was then twice rinsed with an ice-cold ethanol/water solution (9:1, 5 mL), and dried under reduced pressure.
With sulfonated rice husk ash In neat (no solvent) at 20℃; for 0.0416667h; chemoselective reaction;
2.4 General procedure for the preparation of 1,1-diacetate
General procedure: Aldehyde (1 mmol) was added to a mixture of RHA-SO3H (10 mg) and acetic anhydride (1.5 mmol) and the resulting mixture was stirred at room temperature. After completion of the reaction (monitored by TLC), dichloromethane (20 mL) was added and the catalyst was separated by filtration. The organic phase was washed with 10% aqueous solution of sodium bicarbonate (2 × 20 mL) and dried over Na2SO4. The solvent was removed under reduced pressure to afford the desired product. The solid crude product was purified by recrystallization from cyclohexane. The spectral (IR, 1H and 13C NMR) data of fluorene-3-carbaldehyde as a new compound is presented below:
With sulfonated rice husk ash In acetonitrile at 60℃; for 0.166667h;
2.5 General procedure for the deprotection of 1,1-diacetates
General procedure: A mixture of 1,1-diacetate (1 mmol), RHA-SO3H (30 mg) in acetonitrile (2 mL) was stirred vigorously at 60 °C. After completion of the reaction (monitored by TLC), the organic solvent was evaporated. Then the reaction mixture was diluted by ethyl acetate (20 mL) and filtered to separate the catalyst. The organic phase was washed with 10% aqueous solution of sodium bicarbonate (2 × 10 mL) to remove excess of Ac2O and dried over Na2SO4. The solvent was evaporated under reduced pressure. The resultant product was passed through a short column of silica gel (n-hexane-EtOAc, 9:1) to afford the pure aldehyde.
With sulfuric acid-modified polyethyleneglycol-6000 In neat (no solvent) at 70℃; for 0.0666667h; Green chemistry;
General procedure for the synthesis of bis-Knoevenagel products under solvent-free conditions
General procedure: A mixture of terephthaldehyde/isophthalaldehyde1a-b (1.00mmol, 0.134 g), acyclic and cyclic active methylene compounds 2a-n (2.00 mmol) and PEG-OSO3H (0.013 mmol, 0.08 g) were mixed thoroughly using a mortar and pestle. The reaction mixture was then transferred to an open Pyrex 100 mL beaker and heated at 70 °C for the given time (Table 5).After completion of the reaction (monitored by TLC), the reaction mixture was cooled to room temperature,added H2O (5 mL) and shaken for 3 min to dissolve PEG-OSO3H. The crude product (insoluble in water) was filtered and recrystallized from hot ethanol (3 mL) to afford the pure product (3a-r). Inorder to recover the catalyst, the filtrate was evaporated under reduced pressure and recovered catalyst was washed with diethyl ether twice (2 mL) andreused after drying under reduced pressure.
91%
With immobilized Ni-Zn-Fe layered double hydroxide (LDH) on silica-coated magnetite nanoparticles In water for 0.666667h; Reflux; Green chemistry;
General Procedure for the Synthesis of Bisthiazolidinones
General procedure: A mixture of dialdehyde (1 mmol), N,N'-diarylthiourea(2 mmol) and choloroacetyl chloride (2.2 mmol) inChCl.2urea (0.3 mL) was added into a test tube with a magnetic stirring bar. The test tube was heated in an oil bath at80 °C for 60-120 minutes and then was cooled to room temperature slowly and ethanol, in some cases MTBE (10 mL)was added slowly and filtered off to extract the product from the deep eutectic solvent. All compounds were characterized on the basis of their spectroscopic data (IR, NMR) and elemental analyses.
With magnetite-sulfuric acid magnetic nanoparticles In neat (no solvent) at 100℃; for 0.25h;
14H-Dibenzo[a,j]xanthene-14-ylarenes 5a-g, 6a, 6b, 7a, and 7b; General Procedure
General procedure: Monoaldehyde 2a-g, dialdehyde 3a or 3b, or trialdehyde 4a or 4b (1 mmol), 2-naphthol (1 mmol for 2a-g, 5 mmol for 3a and 3b and7 mmol for 4a and 3b), and MSA-MNP (0.1 g) were mixed by thorough grinding in a glass mortar then transferred to a suitable apparatus,and heated carefully in an oil bath at 100 °C for the appropriate time (see Table 2) while the progress of the reaction was monitored by TLC. The mixture was cooled to r.t. and hot EtOH (20mL) was added. The MSA-MNP were collected by means of an applied external magnetic field, and the crude solid product was crystallized (EtOH).
(5R,10aS)-5-{3-[(5R,10aS)-3-oxo-1,5,10,10a-tetrahydro[1,3]oxazolo[3,4-b]isoquinolin-5-yl]phenyl}-1,5,10,10a-tetrahydro[1,3]oxazolo[3,4-b]isoquinolin-3-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
98%
With sulfuric acid In chloroform at 20℃; for 12h; diastereoselective reaction;
(5R,10aS)-5-{3-[(5R,10aS)-3-Oxo-1,5,10,10a-tetrahydro[1,3]oxazolo[3,4-b]isoquinolin-5-yl]phenyl}-1,5,10,10a-tetrahydro[1,3]oxazolo[3,4-b]isoquinolin-3-one (8b)
(5R,10aS)-5-{3-[(5R,10aS)-3-Oxo-1,5,10,10a-tetrahydro[1,3]oxazolo[3,4-b]isoquinolin-5-yl]phenyl}-1,5,10,10a-tetrahydro[1,3]oxazolo[3,4-b]isoquinolin-3-one (8b) Concd H2SO4 (98%, 11.28 mmol, 2 equiv) was added dropwise to astirred solution of (S)-4-benzyloxazolidin-2-one (7a, 1 g, 5.64mmol) and isophthalaldehyde (12b, 378 mg, 0.5 equiv) in CHCl3(10 mL) at r.t. After completion of the reaction (TLC), the mixturewas diluted with excess H2O (30 mL), the organic layer was separated,and the aqueous layer was further extracted with CH2Cl2 (3 ×10 mL). The combined organic layers were washed with brine,dried (MgSO4), and concentrated under reduced pressure. Bisoxazoline8b was purified by column chromatography (CH2Cl2-EtOAc,This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.2786 K. D. Thinh, Z. M. Judeh PAPERSynthesis 2014, 46, 2780-2788 Georg Thieme Verlag Stuttgart · New York99:1) and recrystallized (slow addition of hexane into hot saturatedsolution of 8b in CH2Cl2) to give white crystals; yield: 1.24 g (98%).[α]D20 -298 (c 1.00, CH2Cl2).FT-IR (KBr): 2905, 1751, 1413, 1268, 1060, 1019, 741, 715, 622cm-1.1H NMR: δ = 2.80-3.10 (m, 4 H), 3.99-4.08 (m, 4 H), 4.33-4.39 (m,2 H), 5.83 (s, 2 H), 6.84 (d, JH,H = 7.5 Hz, 2 H), 7.05-7.19 (m, 10 H).13C NMR: δ = 34.5, 48.2, 56.4, 68.7, 127.0, 127.4, 128.2, 128.7,128.9, 129.3, 132.4, 134.0, 142.6, 156.6.HRMS (ESI, +): m/z [M + Na]+ calcd for C28H24N2O4: 452.1736;found: 475.1628.
5,5′-(1,3-phenylenebis(methanylylidene))bis(pyrimidine-2,4,6(1H,3H,5H)-trione)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
98%
With butane-1-sulfonic acid immobilized on magnetic silica-coated Fe3O4 nanoparticles In water at 20℃; for 0.166667h;
93%
With 1,4-disulfo-1,4-diazabicyclo[2.2.2]octane-1,4-diium dihydrogen sulfate In water at 20℃; for 0.0166667h; Green chemistry;
90%
With 4-(4-propylpiperazine-1-yl)butane-1-sulfonic acid-modified silica-coated magnetic nanoparticles In water at 60℃; for 0.75h;
88%
With succinimidinium hydrogensulfate In water at 50℃; for 0.25h;
preparation of 5-arylidenepyrimidine-2,4,6(1H,3H,5H)-trione
General procedure: A mixture of an aldehyde (1 mmol), barbituric acid(1 mmol) and [H-Suc]HSO4 (0.009 g) in water (4 mL) washeated in an oil bath (50 °C). After completion of the reaction,as monitored by TLC [eluent: n-hexane:EtOAc (1:4)]the crude product was filtered off, washed with water andrecrystallized from ethanol to offered the pure compound.
General procedure: Isophthalaldehyde (3.00 g, 22.37 mmol) in dry EtOH (50 mL) was slowly added to the solution of N-methylethylenediamine (3.32 g, 44.73 mmol) in boiling dry EtOH (100 mL). The mixture was refluxed for 8 h with stirring. The solution was cooled to roomtemperature and added to an excess of sodium borohydride (NaBH4; 5.08 g, 134.22 mmol). After reduction, the solvent was filteredand evaporated in reduced pressure. The oily residue was extracted with chloroform, and then the product was crystallized from methanol (3.64 g, 65%).
1,3-bis(1-(trimethylsilyloxy)but-3-enyl)benzene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
98%
Stage #1: Isophthalaldehyde With Al-MCM-41 In dichloromethane at 35℃; for 0.0833333h; Inert atmosphere;
Stage #2: allyl-trimethyl-silane In dichloromethane at 35℃; for 0.75h; Inert atmosphere;
2.3.2. In the presence of Al-MCM-41
General procedure: In a two-necked, round-bottomed flask equipped with a mag-netic stirring bar, under an atmosphere of argon was charged with aldehyde (0.106 g, 1.0 mmol, 1 equiv.) and Al-MCM-41(25 mol%, dried prior to use at 300C for 1 h under vacuum)in dichloromethane (2 mL),the mixture was stirred at 35C. After 5 min of stirring, the allyltrimethylsilane (0.228 g, 2 mmol,2 equiv.) in CH2Cl2(0.5 mL) was slowly added, the reaction mixture was stirred at 35C. Upon completion of the reac-tion (TLC; 25 min-24 h), the catalyst was removed by filtration.After the filtrate was concentrated under reduced pressure, onlypure homoallyl silyl ether was obtained, thus further purification by silica-gel column chromatography (petroleum ether thenpetroleum ether-ether 28:1) was necessary. The product gave a satisfactory1H NMR and13C NMR spectra.
3,5-O-(3-formylbenzylidene)-1,2-O-isopropylidene-α-D-xylofuranose[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
43%
Stage #1: Isophthalaldehyde; 1,2-O-isopropylidene-α-D-xylose With toluene-4-sulfonic acid In toluene for 5h; Inert atmosphere; Dean-Stark; Reflux;
Stage #2: With triethylamine In toluene Inert atmosphere; Dean-Stark; Reflux;
3,5-O-(3-formylbenzylidene)-1,2-O-isopropylidene-α-D-xylofuranose (8e)
To a toluene (30 mL) solution of 1,2-O-isopropylidene-α-D-xylofuranose 1 (0.57 g, 3 mmol), isophthalaldehyde (0.41 g, 3 mmol) was added p-toluene sulfonic acid monohydrate, pTSA (9 mg) and the solution was refluxed for 5 h using a Dean-Stark condenser. After this time, Et3N (0.15 mL) was added and the reaction mixture was cooled and extracted with EtOAc. The extract was washed with water; combined extracts were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (10%EtOAc/hexane) to afford a white crystalline solid of corresponding 3,5-O-(3-formylbenzylidene)-1,2-O-isopropylidene-α-D-xylofuranose 8e. Yield: 0.39 g (43%). M.p. 92-94 °C. 1H NMR (500 MHz, CDCl3): δ 10.03 (s, 1H), 8.01 (t, J = 1.6 Hz, 1H), 7.88 (dt, J = 7.6, 1.4 Hz, 1H), 7.77 - 7.74 (m, 1H), 7.54 (dd, J = 9.5, 5.9 Hz, 1H), 6.08 (d, J = 3.7 Hz, 1H), 5.55 (s, 1H), 4.67 (d, J = 3.7 Hz, 1H), 4.49 (t, J = 7.6 Hz, 1H), 4.46 (d, J = 1.6 Hz, 1H), 4.21 - 4.16 (m, 2H), 1.53 (s, 3H), 1.35 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 191.98, 138.63, 136.39, 132.19, 130.08, 129.02, 127.78, 111.95, 105.68, 98.33, 83.81, 79.12, 72.12, 66.82, 26.73, 26.18. IR (KBr): ν 3031(w), 2976 (w), 2924 (m), 2898 (m), 2725 (m), 1701 (s), 1590 (m), 1445 (m), 1408 (m), 1380 (m), 1335 (w), 1268(m), 1211 (m), 1152 (m), 1104 (s), 1069 (m), 1002 (m), 927 (w), 900 (w), 879 (m), 807 (m), 699 (w) cm-1. Anal. Calc. for C16H18O6 (306.30): C 62.74, H 5.92%. Found: C 62.67, H 5.98%.
1-(3-formylbenzyl)azetidine-3-carboxylic acid methyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
330 mg
With sodium tris(acetoxy)borohydride; triethylamine; In tetrahydrofuran; at 20℃; for 3h;
Step 1 (0402) To a mixture of <strong>[100202-39-9]azetidine-3-carboxylic acid methyl ester hydrochloride</strong> (400 mg), benzene-1,3-dicarbaldehyde (708 mg), triethylamine (0.37 mL) and tetrahydrofuran (10 mL) was added sodium blacetoxyborohydride (1.12 g), and the mixture was stirred at room temperature for 3 hours. After the mixture was diluted with ethyl acetate, the resulting mixture was washed with saturated sodium hydrogen carbonate aqueous solution and brine successively, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: 20%-100% ethyl acetate/hexane, gradient elution) to give 1-(3-formylbenzyl) azetidine-3-carboxylic acid methyl ester (330 mg). (0403) MS (ESI, m/z): 234M+H)+
Stage #1: Isophthalaldehyde With ammonium sulfate; oxygen; sodium hydroxide In butan-1-ol at 70℃; for 20h; Autoclave;
Stage #2: isopropylamine In butan-1-ol at 70℃; for 20h; Autoclave;
4
The isophthalaldehyde 0.5mmol, 0.10mmol OMS-2,0.10mmol NaOH, 8mmol ammonium sulfate, n-butanol was added to 2mL stainless steel autoclave with a Teflon liner of 20mL, charged 1.6MPa O2 heated to 70°C , the temperature of the reaction at 20h. 8mmol isopropylamine was added and heated to 70°C , reacted at this temperature for 20h. The catalyst was removed by suction, the solvent was removed by rotary evaporation, was added 5mL H2O, and extracted with n-hexane to give isopropyl N-isopropylcyanobenzamidine crude product from methanol and recrystallized to obtain high purity product, isolated in an yield of 88%.
With triethylsilane; palladium diacetate; sodium hydrogencarbonate; sodium carbonate; at 20℃; under 760.051 Torr; for 48h;
General procedure: A flask was charged with aryl iodide 1 (0.5 mmol), Pd(OAc)2 (2.4 mg, 0.01mmol), Na2CO3 (53.1 mg. 0.5 mmol), NaHCO3 (42.0 mg, 0.5 mmol), and PEG-400 (2 g) beforestandard cycles evacuation and backfilling with dry and pure carbon monoxide. Triethylsilane(162.8 mul, 1.0 mmol) was added successively. Then, the mixture was stirred at room temperaturefor the indicated time. At the end of the reaction, the reaction mixture was extracted with diethylether (3 × 10 mL). The organic phases were combined, and the volatile components wereevaporated under reduced pressure. The crude product was purified by column chromatography onsilica gel (petroleum ether / diethyl ether).
Stage #1: acetophenone With potassium hydroxide In ethanol; water for 0.166667h;
Stage #2: Isophthalaldehyde In ethanol; water at 20℃; for 4h;
General procedures for the preparation of bischalcone
General procedure: Acetophenone (0.360 g, 3.0 mmol for compound 5) and 2-hydroxyacetophenone (0.408 g, 3.0 mmol for compound 6) wasdissolved in 20 mL of ethanol, respectively. 10 mL of 10% aqueousKOHwas added gently into the solution and the mixturewas stirredfor about 10 min. Iso-terephthaldehyde (0.200 g, 1.5 mmol) wasadded into the mixture and stirred vigorously at room temperaturefor 4 h. After that, the reaction flaskwas immersed into ice bath and3MHCl was added until the solutionwas neutralized. The obtainedprecipitate was filtered, rinsed with distilled water and ethanol.The washed precipitate was allowed to air dried. The precipitatewas purified using recrystallization via slow evaporation in tetrahydrofuran(THF).
5,5'-((1,3-phenylenebis(methanylylidene))bis(azanylylidene))bis(1,3,4-thiadiazole-2-sulfonamide)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
38%
With formic acid In ethanol Reflux;
General procedure for preparation of bis-sulfonamide imine compounds (9-24)
General procedure: The bis-sulfonamide imine compounds were synthesized according to literature procedure with some modifications. 9,10 The bis-aldehydes (1.0 equiv) in dry ethanol were added dropwise to the appropriate sulfonamide derivatives (2.0 equiv) which was previously dissolved in ethanol. A catalytic amount of HCOOH (3-4 drops) was then added and the mixture was refluxed for 4-6 h. The completion of the reaction was monitored by TLC and FT-IR. The obtained precipitate was washed with ice-cold methanol/ethanol and collected by filtration. The final desired products(9-24) were dried under vacuum and fully characterized by spectroscopic methods.
(3-formylphenyl)(bis(1H-indol-3-yl))methane[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
94%
In neat (no solvent) for 0.133333h; Microwave irradiation;
(Formylphenyl)diindolylmethanes derivatives 3a-3l
General procedure: In a microwave tube indole (5.7141 mmol) and the dialdehyde (2.8570 mmol) were added; this mixture was mixed well and irradiated with microwave energy (195 °C at 850 W) for 8 min. Then, once the mixture reaction cooled at room temperature, the corresponding reaction products were extracted with acetone and the solvent was removed at reduced pressure. All products were purified by recrystallization with a mixture of ethanol/water.
87%
With toluene-4-sulfonic acid In ethanol at 90℃; for 0.75h; Irradiation;
General procedure for preparation of 12a-12l
General procedure: In a 25-cm3 flask charged with a stirring bar were added4 mmol of corresponding indole 11a-11d, 2 mmol of aldehyde10a-10c, 10 cm3of EtOH, and a small amount ofp-toluenesulfonic acid. This mixture was exposed to IR irradiationat 90 °C for 45 min. After cooling the crude of reaction,it was poured onto ice-water and the precipitated solidwas collected. The dry powder was dissolved in acetone andpurified by preparative chromatography using an eluting systemconsisting of hexane/ethyl acetate (7:3). The scrapingspot was extracted with warm acetone, and after evaporatingthe solvent the spectroscopically pure compounds werecollected.
In neat (no solvent) at 195℃; for 0.133333h; Microwave irradiation;
(3-formylphenyl)(bis(1-methyl-1H-indol-3-yl))methane[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
94%
In neat (no solvent) for 0.133333h; Microwave irradiation;
(Formylphenyl)diindolylmethanes derivatives 3a-3l
General procedure: In a microwave tube indole (5.7141 mmol) and the dialdehyde (2.8570 mmol) were added; this mixture was mixed well and irradiated with microwave energy (195 °C at 850 W) for 8 min. Then, once the mixture reaction cooled at room temperature, the corresponding reaction products were extracted with acetone and the solvent was removed at reduced pressure. All products were purified by recrystallization with a mixture of ethanol/water.
91%
With toluene-4-sulfonic acid In ethanol at 90℃; for 0.75h; Irradiation;
General procedure for preparation of 12a-12l
General procedure: In a 25-cm3 flask charged with a stirring bar were added4 mmol of corresponding indole 11a-11d, 2 mmol of aldehyde10a-10c, 10 cm3of EtOH, and a small amount ofp-toluenesulfonic acid. This mixture was exposed to IR irradiationat 90 °C for 45 min. After cooling the crude of reaction,it was poured onto ice-water and the precipitated solidwas collected. The dry powder was dissolved in acetone andpurified by preparative chromatography using an eluting systemconsisting of hexane/ethyl acetate (7:3). The scrapingspot was extracted with warm acetone, and after evaporatingthe solvent the spectroscopically pure compounds werecollected.
In neat (no solvent) at 195℃; for 0.133333h; Microwave irradiation;
(3-formylphenyl)(bis(2-methyl-1H-indol-3-yl))methane[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
94%
In neat (no solvent) for 0.133333h; Microwave irradiation;
(Formylphenyl)diindolylmethanes derivatives 3a-3l
General procedure: In a microwave tube indole (5.7141 mmol) and the dialdehyde (2.8570 mmol) were added; this mixture was mixed well and irradiated with microwave energy (195 °C at 850 W) for 8 min. Then, once the mixture reaction cooled at room temperature, the corresponding reaction products were extracted with acetone and the solvent was removed at reduced pressure. All products were purified by recrystallization with a mixture of ethanol/water.
86%
With toluene-4-sulfonic acid In ethanol at 90℃; for 0.75h; Irradiation;
General procedure for preparation of 12a-12l
General procedure: In a 25-cm3 flask charged with a stirring bar were added4 mmol of corresponding indole 11a-11d, 2 mmol of aldehyde10a-10c, 10 cm3of EtOH, and a small amount ofp-toluenesulfonic acid. This mixture was exposed to IR irradiationat 90 °C for 45 min. After cooling the crude of reaction,it was poured onto ice-water and the precipitated solidwas collected. The dry powder was dissolved in acetone andpurified by preparative chromatography using an eluting systemconsisting of hexane/ethyl acetate (7:3). The scrapingspot was extracted with warm acetone, and after evaporatingthe solvent the spectroscopically pure compounds werecollected.
In neat (no solvent) at 195℃; for 0.133333h; Microwave irradiation;
(3-formylphenyl)(bis(2-phenyl-1H-indol-3-yl))methane[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
93%
In neat (no solvent) for 0.133333h; Microwave irradiation;
(Formylphenyl)diindolylmethanes derivatives 3a-3l
General procedure: In a microwave tube indole (5.7141 mmol) and the dialdehyde (2.8570 mmol) were added; this mixture was mixed well and irradiated with microwave energy (195 °C at 850 W) for 8 min. Then, once the mixture reaction cooled at room temperature, the corresponding reaction products were extracted with acetone and the solvent was removed at reduced pressure. All products were purified by recrystallization with a mixture of ethanol/water.
89%
With toluene-4-sulfonic acid In ethanol at 90℃; for 0.75h; Irradiation;
General procedure for preparation of 12a-12l
General procedure: In a 25-cm3 flask charged with a stirring bar were added4 mmol of corresponding indole 11a-11d, 2 mmol of aldehyde10a-10c, 10 cm3of EtOH, and a small amount ofp-toluenesulfonic acid. This mixture was exposed to IR irradiationat 90 °C for 45 min. After cooling the crude of reaction,it was poured onto ice-water and the precipitated solidwas collected. The dry powder was dissolved in acetone andpurified by preparative chromatography using an eluting systemconsisting of hexane/ethyl acetate (7:3). The scrapingspot was extracted with warm acetone, and after evaporatingthe solvent the spectroscopically pure compounds werecollected.
In neat (no solvent) at 195℃; for 0.133333h; Microwave irradiation;
Stage #1: Isophthalaldehyde; C20H28N2O3; 1,3-bis[3,5-bis(trifluoromethyl)phenyl]urea With potassium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate In chloroform at 50℃; for 48h; Inert atmosphere;
Stage #2: With sodium tetrahydroborate In methanol Inert atmosphere;
With iodine; triethylamine; triphenylphosphine In toluene at 80℃; for 4h; Sealed tube;
75%
With iodine; triethylamine; triphenylphosphine In toluene at 80℃; for 6h; Sealed tube; Inert atmosphere;
Compounds 4a-c; General Procedure
General procedure: A dried 20 mL reaction tube was charged with I2 (304 mg, 2.4 mmol), PPh3 (630 mg, 2.4 mmol), and toluene (6 mL) under argon. The mixture was stirred at r.t. for 10 min. Then aryl diiodide 3 (1 mmol), 2P-Fe3O4SiO2-Pd(OAc)2 (158 mg, 6 mol%), and Et3N (1.2 g, 12 mmol)were added to this solution. After the addition of HCOOH (368 mg, 8mmol), the reaction tube was immediately sealed and the reaction mixture was stirred at 80 °C for 6 h. After cooling to r.t., the Pd catalyst was magnetically separated and the reaction mixture was then filtered and concentrated under vacuum. The residue was purified bysilica gel column chromatography (light PE/EtOAc 10:1) to give the desired product 4.
With [(Me3Si)2N]2Th[κ2-(N,C)-CH2Si(CH3)2N(SiMe3)] In benzene-d6 at 70℃; for 48h; Sealed tube;
2.15 General procedures for coupling aldehyde and ketones
General procedure: In a typical experiment, a J. Young Teflon sealed NMR tube was charged with the aldehyde (50 equiv) and trifluoromethylketone (150 equiv), followed by adding the desired amount of the catalyst in C6D6. Samples were then sealed and placed in an oil bath preheated to 70°C. The progress of the reaction was monitored at regular intervals using 1H NMR spectroscopy for up to 48h. The yield was calculated from the ratio of aldehyde and corresponding ester from the crude 1H NMR spectra. After completion of the reaction, the pure product was obtained by flash column chromatography on silica gel (15:1 EtOAc: Hexane) and compared with the literature.
With toluene-4-sulfonic acid; In ethanol;Inert atmosphere; Reflux;
Add <strong>[15018-66-3]4-aminoquinazoline</strong> (2.9 g, 20 mmol) to a dry, nitrogen-protected reactor.30mL of ethanol, isophthalic acid (1.34g, 10mmol),Further, a catalyst TsOH (0.1 g) was added, and after stirring, the reaction was refluxed.The reaction was monitored by TLC dot plate, the reaction was completed, cooled to room temperature, and the solvent was distilled off under reduced pressure.The obtained solid was recrystallized from ethanol/toluene and dried in vacuo.Obtained 3.38g of compound 1,The yield was 87.1%.
General procedure: First, 100 mL of H2O-2-MeTHF mixture (70-30) were added to DYTEKA (17.3 g, 149 mmol, 10equivalents) in a 250 mL two-neck round-bottom flask. Then, isophthalaldehyde (2 g, 14.9 mmol, 1equivalent) was solubilized in 30 mL of 2-MeTHF and then added dropwise using a dropping funnel.The reaction crude was stirred and heated until complete aldehyde conversion, at 110 °C. Thesolution was then cooled down to room temperature.
With sodium hydroxide In water; isopropyl alcohol at 75℃; for 10h; Inert atmosphere;
1.1 Example 1: Preparation of Compound Y-1:
Step (1): Take (1.379 g, 8.2 mmol) of substituted acetophenone F-1 and (0.536 g, 4 mmol) of m-xylylene formaldehyde in 10 mL of propanol, and add sodium hydroxide dropwise under nitrogen protection and ice-water bath The solution (7.2 g in 8 mL of water) was heated to 75 ° C, and the reaction was maintained at this temperature for 10 hours. 10% hydrochloric acid was added to neutralize it to about pH 7, and extraction was performed with dichloromethane, followed by silica gel column chromatography (eluent: ethyl acetate: petroleum ether (60-90 ° C) = 20: 1) to obtain 1.01 g Chalcone M-1 with a yield of 58%
ethyl 2-(2,4-diformylphenyl)-2,2-difluoroacetate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
76.2%
With potassium carbonate; eosin y; 4,4'-di-tert-butyl-2,2'-bipyridine In dichloromethane at 25℃; for 30h; Irradiation;
7 Example 7 2- (2,4-diformylphenyl) -2,2-difluoroethyl acetate(I-g)
In a 50 mL round bottom flask equipped with a magnetic stir bar, add isophthalaldehyde (53.6 mg, 0.4 mmol) and eosin Y (13.9 mg, 0.02 mmol),4,4'-di-tert-butyl-2,2'-dipyridine (53.6 mg, 0.2 mmol),Potassium carbonate (165.6 mg, 1.2 mmol) and ethyl bromodifluoroacetate (162.4 mg, 0.8 mmol) were added to the mixture, and dichloromethane (5 mL) was added.The mixture was irradiated with 3W blue light and stirred at 25 ° C for 30 hours.The reaction mixture was washed with saturated brine. The mixture was extracted with ethyl acetate,The combined organic layers were dried over anhydrous Mg2SO4 and concentrated under reduced pressure.The crude product was purified on a silica gel column using n-hexane / ethyl acetate,78.2 mg of product was obtained with a yield of 76.2%,HPLC purity was 98.1%.
52%
With tris[2-phenylpyridinato-C2,N]iridium(III); 1,10-Phenanthroline; sodium acetate In acetonitrile at 20℃; for 24h; Schlenk technique; Inert atmosphere; Irradiation;
38%
With fac-tris[2-phenylpyridinato-C2,N]iridium(III); potassium carbonate In acetone; <i>tert</i>-butyl alcohol at 20℃; for 40h; Inert atmosphere; Schlenk technique; Irradiation; regioselective reaction;
Stage #1: Isophthalaldehyde; 1,1-dimethylprop-3-ynylamine In tetrahydrofuran at 35℃; for 13h;
Stage #2: With sodium tetrahydroborate In tetrahydrofuran; methanol at 0℃; for 1h;
Synthesis of 24
Compound 23 (0.35 mL, 3.4 mmol) was added to a solution of 22 (0.15 g, 1.1 mmol) in dry THF (0.2 mL, 3.0 M) at room temperature. And then the reaction mixture was stirred at 35 °C for 13 h. When starting material was disappeared, the reaction mixture was diluted with MeOH (0.3 M). And then 0.26g of NaBH4 (6.7 mmol) was added to a reaction mixture at 0 °C. After 1 h reaction at room temperature, aq. NH4Cl was drop to the reaction mixture. And then evaporated with reduced pressure. The residue was diluted with CHCl3 (100 mL) and washed with aq. NaHCO3 (2 times, 50 mL). The organic layer was dried over MgSO4, concentrated under reduced pressure. The residue was purified by column chromatography with CHCl3 to give the compound 24 (0.26 g, 85%).
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
