CN102863305A - Preparation method of amide from nitrile - Google Patents
Preparation method of amide from nitrile Download PDFInfo
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- CN102863305A CN102863305A CN201210357102XA CN201210357102A CN102863305A CN 102863305 A CN102863305 A CN 102863305A CN 201210357102X A CN201210357102X A CN 201210357102XA CN 201210357102 A CN201210357102 A CN 201210357102A CN 102863305 A CN102863305 A CN 102863305A
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- RUSAWEHOGCWOPG-UHFFFAOYSA-N N#Cc1cc([N+]([O-])=O)ccc1 Chemical compound N#Cc1cc([N+]([O-])=O)ccc1 RUSAWEHOGCWOPG-UHFFFAOYSA-N 0.000 description 1
- KWAYEPXDGHYGRW-UHFFFAOYSA-N NC(c1cc([N+]([O-])=O)ccc1)=O Chemical compound NC(c1cc([N+]([O-])=O)ccc1)=O KWAYEPXDGHYGRW-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention discloses a preparation method of amide from nitrile. The method includes reaction of hydrolysis by heating nitrile under air or nitrogen condition and in ammonia water by alkaline catalyst. The method can implement simple, mild and green hydrolysis and synthesize a series of amide compounds. The catalyst is low in price, small in toxicity, low in dosage, mild in reaction condition and easy to operate in air. Organic solvent is not required in reaction, and ammonia water which is cheap and easy to obtain is used as green solvent. Pollution possibly caused by organic solvent to environment, excess hydrolysis caused by using excess alkali and the like can be reduced greatly.
Description
Technical field
The invention belongs to the field of chemical synthesis, be specifically related to a kind of method that is prepared acid amides by the nitrile hydrolysis.
Background technology
Amides is not only important organic synthesis reagent, also be the general intermediates of multi-field middle application such as and material development synthetic at medicine, the amide compound that contains substituent functionalization also can embody the various active such as pharmacology, biochemistry, so amides all has widely application in many-sides such as synthetic applied research and industry medicine.Therefore, the Study of synthesis method of acid amides is one of interest of studying of people always.Compare with additive method, the hydrolysis of nitrile compounds is a kind of direct, the economic and easy method of preparation acid amides.Up to now, report the method for a lot of nitrile hydrolysis on the document, but still had shortcoming separately.
The hydrolysis reaction of traditional nitrile prepares the method for acid amides to use excessive strong acid such as sulfuric acid etc., carries out under severe condition, so functional group's kind of suitable substrates is limited, and acid medium pollutes large, aftertreatment trouble.On the contrary, the method for hydrolysis of nitrile under alkaline condition then easily causes excessively the carrying out of hydrolysis, generates corresponding acid and greatly reduces product yield; Although can suppress excessively hydrolysis by the method that adds hydrogen peroxide, use hydrogen peroxide that very large potential safety hazard is also arranged, thereby the method is difficult to more massive reaction and a large amount of preparation.In addition, the hydrolysis reaction of nitrile under alkaline condition, using the trimethyl carbinol instead is that solvent also can suppress excessively hydrolysis generation, but the method need be used NaOH or the KOH strong alkaline condition of 5-6 times of equivalent, reaction efficiency is low, functional group's poor compatibility, and owing to being not the reaction of catalysis, also be difficult to a large amount of synthetic.Therefore, the method for excessive metalcatalyzing has also been developed in afterwards a lot of researchs.Studies show that, nearly all transition metal can be hydrolyzed into acid amides by the catalysis nitrile.But also there are many shortcomings in the method for excessive metalcatalyzing.Such as; valuable transition metal-catalyzed method effect is often relatively good; but these reactions not only need the condition of protection of inert gas; these metal catalysts are expensive, many times also need to use complicated part or Kaolinite Preparation of Catalyst complex compound in advance, cause also that these noble metal catalysts are difficult to obtain, popularization and application is limited.Heavy-metal residual also is the problem that needs consideration and solve in the product.The reaction of cheap metal catalysis also has many reports, but because these catalyst effect are relatively poor, also often need complicated part, and catalyst levels is larger, and some cheap metal has than high toxicity also.
Therefore, research is used hypotoxicity, nontoxicity catalyzer even be need not the method that catalysis nitrile hydrolysis that transition metal participates in prepare acid amides is worth studying very much.The present invention is intended to develop a kind of nontransition metal catalyzer, realizes that nitrile compounds is hydrolyzed the method for preparing amides under simple, gentle, the green condition.
Summary of the invention
The problem to be solved in the present invention is to provide a kind of catalysis process: from nitrile cheap, that stablize, be easy to get; seek suitable catalyzer; at the hydrolysis reaction of the nitrile that participates in without transition-metal catalyst and need not to carry out under the condition of nitrogen protection, realize that environmental pollution is little, the synthetic method of efficient amides.
Reaction related among the present invention can represent with following general formula:
R can be that various functional groups are substituted in 2-, and 3-, or all kinds of substituted heteroaryls such as the phenyl of 4-or all kinds of substituted aryl, substituted furan, substituted thiophene, substituted pyridines can also be the alkyl of various carbon chain lengths and substitution in side chain.
The solvent of reaction can be water, ammoniacal liquor, is preferably ammoniacal liquor.
Alkaline catalysts involved in the present invention can be LiOH, NaOH, KOH, CsOH, t-BuOK, t-BuONa, Mg (OH)
2, Ca (OH)
2Deng, be preferably CsOH.
In the reaction of the present invention, the preferred 1 ~ 200mol% of the consumption of used alkaline catalysts is preferably 5-30mol%.
In the reaction of the present invention, reaction can be carried out under air or protection of inert gas, and reaction is preferably under the air and reacts without impact under air conditions.
The temperature that reaction is carried out is room temperature ~ 180 ° C, preferred 100～160 ° of C.Reaction times is 1 ~ 24 hour, preferred 1～12 hour.
Employed alkaline catalysts can directly be bought and obtain among the present invention.Other method of reporting in present method and the document is compared, the catalyzer low price, toxicity is little, consumption is lower, reaction conditions is gentle, get final product under air, easy handling, reaction need not organic solvent, uses the ammoniacal liquor that cheaply is easy to get to be the solvent of green, so present method can greatly reduce organic solvent pollution and the use excess base that environment may cause caused the problems such as excessive hydrolysis.
Embodiment
To help to understand the present invention by following embodiment, but be not restricted to content of the present invention.
Embodiment 1
Cyanophenyl prepares benzamide
Add successively CsOHH in the reaction tubes
2O (0.0336g, 10mol%) and PhCN (2mmol), adding ammoniacal liquor (1.0mL) is solvent again, reaction tubes sealing post-heating to 100 ° C reaction 1h.GC-MS records reaction conversion ratio more than 99%, product column chromatography separating-purifying, separation yield 81%.
1H?NMR(500MHz,d
6-DMSO):δ7.98(b,1H),7.89-7.86(m,2H),7.54-7.51(m,1H),7.47-7.44(m,2H),7.36(b,1H).
13C?NMR(125.4MHz,d
6-DMSO):δ167.9,134.2,131.2,128.2,127.4.MS(EI):m/z(%)224(6),223(32),222(14),132(2),131(8),130(4),118(2),106(23),105(100),104(5),103(9),91(5),79(9),78(4),77(11),65(3).
Embodiment 2
The methyl cyanophenyl is prepared methyl benzamide
Add successively CsOHH in the reaction tubes
2O (0.0336g, 10mol%) and to methyl cyanophenyl (2mmol), adding ammoniacal liquor (1.0mL) is solvent again, reaction tubes sealing post-heating to 100 ° C reaction 6h.GC-MS records reaction conversion ratio more than 99%, product column chromatography separating-purifying, separation yield 80%.
1H?NMR(500MHz,CDCl
3):δ7.71(d,J=8.0Hz,2H),7.25(d,J=8.0Hz,2H),6.01(b,2H),2.40(s,3H).
13C?NMR(125.4MHz,CDCl
3):δ169.4,142.5,130.6,129.3,127.4,21.5.MS(EI):m/z(%)136(5),135(60),120(8),119(100),117(3),92(5),91(74),90(8),89(10),65(33),64(4),63(13),51(9),50(6),44(12),41(5),40(9),39(20),38(4).
Embodiment 3
M-tolunitrile prepares m-methyl benzamide
Add successively CsOHH in the reaction tubes
2O (0.0336g, 10mol%) and m-tolunitrile (2mmol), adding ammoniacal liquor (1.0mL) is solvent again, reaction tubes sealing post-heating to 100 ° C reaction 6h.GC-MS records reaction conversion ratio more than 99%, product column chromatography separating-purifying, separation yield 68%.
1H?NMR(500MHz,d
6-DMSO):δ7.91(b,1H),7.71(s,1H),7.68-7.66(m,1H),7.33(d,J=5.0Hz,2H),7.30(b,1H),2.35(s,3H).
13C?NMR(125.4MHz,d
6-DMSO):δ168.0,137.4,134.3,131.7,128.0,124.5,20.9.MS(EI):m/z(%)136(6),135(63),120(9),119(100),117(4),116(2),92(6),91(77),90(5),89(7),65(18),63(6),62(2),51(4),44(3),39(6).
Embodiment 4
Gas chromatography prepares anthranilamide
Add successively CsOHH in the reaction tubes
2O (0.0336g, 10mol%) and Gas chromatography (2mmol), adding ammoniacal liquor (1.0mL) is solvent again, reaction tubes sealing post-heating to 100 ° C reaction 4h.GC-MS records reaction conversion ratio more than 99%, product column chromatography separating-purifying, separation yield 71%.
1HNMR(500MHz,d
6-DMSO):δ7.70(b,1H),7.51(d,J=8.0Hz,1H),7.12(m,1H),7.03(b,1H),6.67(d,J=8.0Hz,1H),6.53(b,2H),6.47(m,1H).
13C?NMR(125.4MHz,d
6-DMSO):δ171.3,150.1,131.8,128.7,116.4,114.4,113.7.MS(EI):m/z(%)137(6),136(74),120(15),119(100),118(6),93(4),92(52),91(15),66(4),65(24),64(9),63(6),52(5),39(9).
Embodiment 5
The m-nitro nitrile prepares the m-nitro methane amide
Add successively CsOHH in the reaction tubes
2O (0.0336g, 10mol%) and m-nitro formonitrile HCN (2mmol), adding ammoniacal liquor (1.0mL) is solvent again, reaction tubes sealing post-heating to 100 ° C reaction 1h.GC-MS records reaction conversion ratio more than 99%, product column chromatography separating-purifying, separation yield 75%.
1HNMR(500MHz,d
6-DMSO):δ8.69(d,J=2.0Hz,1H),8.39(b,1H),8.36(d,J=8.0Hz,2H),8.31(d,J=7.5Hz,1H),7.77(m,1H),7.73(b,1H).
13C?NMR(125.4MHz,d
6-DMSO):δ165.8,147.8,135.7,133.8,130.1,125.9,122.2.MS(EI):m/z(%)167(6),166(67),151(8),150(100),105(3),104(33),103(8),92(17),77(14),76(54),75(32),74(32),73(6),65(26),64(6),63(9),62(5),53(4),52(5),51(26),50(52),46(20),44(50),39(9),38(8),37(5),30(31).
Embodiment 6
Fluorobenzonitrile is prepared fluorobenzamide
Add successively CsOHH in the reaction tubes
2O (0.0336g, 10mol%) and p-Fluorophenyl cyanide (2mmol), adding ammoniacal liquor (1.0mL) is solvent again, reaction tubes sealing post-heating to 100 ° C reaction 2h.GC-MS records reaction conversion ratio more than 99%, product column chromatography separating-purifying, separation yield 85%.
1H?NMR(500MHz,d
6-DMSO):δ7.99(b,1H),7.97-7.94(m,2H),7.38(b,1H),7.29-7.26(m,2H).
13C?NMR(125.4MHz,d
6-DMSO):δ166.8,163.9(d,JC-F=248.3Hz),130.7,130.1,115.1(d,JC-F=22.6Hz).MS(EI):m/z(%)140(6),139(62),124(8),123(100),122(2),121(5),96(10),95(80),94(8),93(3),83(3),76(4),75(35),74(10),70(4),69(8),68(6),63(4),62(3),61(3),57(4),51(7),50(14),44(11),39(3),38(3),37(4),31(3).
Embodiment 7
The p-Cyanochlorobenzene preparation is to chlorobenzamide
Add successively CsOHH in the reaction tubes
2O (0.0672g, 20mol%) and p-Cyanochlorobenzene (2mmol), adding ammoniacal liquor (1.0mL) is solvent again, reaction tubes sealing post-heating to 100 ° C reaction 12h.GC-MS records reaction conversion ratio more than 99%, product column chromatography separating-purifying, separation yield 70%.
1H?NMR?(500MHz,d
6-DMSO):δ8.04(b,1H),7.89(d,J=8.5Hz,2H),7.53(d,J=8.5Hz,2H),7.45(b,1H).
13C?NMR(125.4MHz,d
6-DMSO):δ166.8,136.0,133.0,129.4,128.3.MS(EI):m/z(%)157(16),155(50),141(29),140(8),139(100),137(8),113(16),112(5),111(51),85(4),77(5),76(8),75(35),74(15),73(5),51(10),50(21),44(10),38(5),28(4).
Embodiment 8
Chlorobenzamide between the m-chlorobenzene nitrile preparation
Add successively CsOHH in the reaction tubes
2O (0.0336g, 10mol%) and m-chlorobenzene nitrile (2mmol), adding ammoniacal liquor (1.0mL) is solvent again, reaction tubes sealing post-heating to 100 ° C reaction 3h.GC-MS records reaction conversion ratio more than 99%, product column chromatography separating-purifying, separation yield 75%.
1H?NMR(500MHz,d
6-DMSO):δ8.09(b,1H),7.92-7.91(m,1H),7.86-7.83(m,1H),7.61-7.59(m,1H),7.52(b,1H),7.51-7.48(m,2H).
13C?NMR(125.4MHz,d
6-DMSO):δ166.4,136.3,133.1,131.0,130.2,127.3,126.1.MS(EI):m/z(%)157(16),156(4),155(50),141(29),140(8),139(100),137(8),113(16),112(5),111(51),85(4),77(5),76(8),75(35),74(15),73(5),51(10),50(21),44(10),28(4).
Embodiment 9
O-chloro benzonitrile prepares adjacent chlorobenzamide
Add successively CsOHH in the reaction tubes
2O (0.0336g, 10mol%) and o-chloro benzonitrile (2mmol), adding ammoniacal liquor (1.0mL) is solvent again, reaction tubes sealing post-heating to 100 ° C reaction 3h.GC-MS records reaction conversion ratio more than 99%, product column chromatography separating-purifying, separation yield 75%.
1H?NMR(500MHz,d
6-DMSO):δ7.86(b,1H),7.57(b,1H),7.49-7.47(m,1H),7.46-7.41(m,2H),7.40-7.36(m,1H).
13C?NMR(125.4MHz,d
6-DMSO):δ168.2,137.1,130.5,129.60,129.57,128.6,127.0.MS(EI):m/z(%)157(18),156(4),155(58),142(2),141(32),140(8),139(100),113(12),112(6),111(38),85(3),77(9),76(8),75(26),74(8),51(9),50(16),44(11),38(4),37(3).
Embodiment 10
Bromoxynil is prepared brombenzamide
Add successively CsOHH in the reaction tubes
2O (0.0336g, 10mol%) and to bromoxynil (2mmol), adding ammoniacal liquor (1.0mL) is solvent again, reaction tubes sealing post-heating to 100 ° C reaction 6h.GC-MS records reaction conversion ratio more than 99%, product column chromatography separating-purifying, separation yield 66%.
1H?NMR(500MHz,d
6-DMSO):δ8.05(d,1H),7.83-7.81(m,2H),7.67-7.65(m,2H),7.46(b,1H).
13CNMR(125.4MHz,d
6-DMSO):δ166.9,133.4,131.2,129.6,125.0.MS(EI):m/z(%)201(51),199(53),185(94),184(7),183(100),157(37),155(38),77(20),76(46),75(45),74(26),73(6),65(6),51(22),50(67),49(6),44(25).
Embodiment 11
P-HBN prepares the para hydroxybenzene methane amide
Add successively CsOHH in the reaction tubes
2O (0.3694g, 110mol%) and p-HBN (2mmol), adding ammoniacal liquor (1.0mL) is solvent again, reaction tubes sealing post-heating to 100 ° C reaction 12h.GC-MS records reaction conversion ratio more than 70%, product column chromatography separating-purifying, separation yield 50%.
1H?NMR(500MHz,d
6-DMSO):δ9.94(b,1H),7.73(d,J=8.5Hz,2H),7.71(b,1H),7.05(b,1H),6.77(d,J=9.0Hz,2H).
13C?NMR(125.4MHz,d
6-DMSO):δ167.6,160.1,129.4,125.0,114.6.MS(EI):m/z(%)138(5),137(59),122(8),121(100),93(36),92(6),66(4),65(33),64(6),63(12),62(6),55(4),53(7),50(4),44(7),39(22),38(7),37(3).
Embodiment 12
The 1-naphthyl cyanide prepares naphthalene-1-acid amides
Add successively CsOHH in the reaction tubes
2O (0.0336g, 10mol%) and 1-naphthyl cyanide (2mmol), adding ammoniacal liquor (1.0mL) is solvent again, reaction tubes sealing post-heating to 100 ° C reaction 6h.GC-MS records reaction conversion ratio more than 99%, product column chromatography separating-purifying, separation yield 75%.
1H?NMR?(500MHz,d
6-DMSO):δ8.32-8.30(m,2H),8.01-7.96(m,3H),7.64(d,J=6.5Hz,1H),7.59-7.52(m,4H).
13C?NMR(125.4MHz,d
6-DMSO):δ171.4,135.4,134.0,130.53,130.50,128.9,127.4,126.9,126.4,125.9,125.7.MS(EI):m/z(%)172(9),171(72),170(26),156(9),155(75),154(7),153(4),128(15),127(100),126(28),125.4(3),115(9),101(9),85(4),77(12),76(5),75(10),63(12),51(8),50(6),44(4).
Embodiment 13
The 2-cyanopyridine prepares 2-acid amides pyridine
Add successively CsOHH in the reaction tubes
2O (0.0336g, 10mol%) and 2-cyanopyridine (2mmol), adding ammoniacal liquor (1.0mL) is solvent again, reaction tubes sealing post-heating to 100 ° C reaction 1h.GC-MS records reaction conversion ratio more than 99%, product column chromatography separating-purifying, separation yield 79%.
1H?NMR?(500MHz,CDCl
3):δ8.58(d,J=4.5Hz,1H),8.22(d,J=8.0Hz,1H),7.88-7.85(m,2H),7.47-7.44(m,1H),5.97(b,1H).
13C?NMR(125.4MHz,d
6-DMSO):δ166.5,150.8,149.0,138.2,127.0,122.4.MS(EI):m/z(%)123(2),122(29),80(6),79(100),78(34),76(5),53(7),52(50),51(39),50(20),49(5),44(19),39(8),38(6),37(4),28(7),27(8),26(7),16(5).
Embodiment 14
Nicotinonitrile prepares 3-acid amides pyridine
Add successively CsOHH in the reaction tubes
2O (0.0336g, 10mol%) and nicotinonitrile (2mmol), adding ammoniacal liquor (1.0mL) is solvent again, reaction tubes sealing post-heating to 100 ° C reaction 1h.GC-MS records reaction conversion ratio more than 99%, product column chromatography separating-purifying, separation yield 74%.
1H?NMR?(500MHz,d
6-DMSO):δ9.02(s,1H),8.71(dd,J=1.5,J=5.0Hz,1H),8.20(d,J=7.5Hz,1H),8.14(b,1H),7.58(b,1H),7.48(dd,J=8.0,J=5.0Hz,1H).
13C?NMR(125.4MHz,d
6-DMSO):δ166.4,151.8,148.6,135.1,129.7,123.4.MS(EI):m/z(%)123(8),122(100),106(60),105(6),104(3),94(3),79(8),78(69),77(7),76(3),75(2),53(3),52(12),51(30),50(13),49(2),44(8),39(3),38(2).
Embodiment 15
The 4-cyanopyridine prepares 4-acid amides pyridine
Add successively CsOHH in the reaction tubes
2O (0.0336g, 10mol%) and 4-cyanopyridine (2mmol), adding ammoniacal liquor (1.0mL) is solvent again, reaction tubes sealing post-heating to 100 ° C reaction 1h.GC-MS records reaction conversion ratio more than 99%, product column chromatography separating-purifying, separation yield 73%.
1H?NMR(500MHz,d
6-DMSO):δ8.72(d,J=6.0Hz,2H),8.24(b,1H),7.77(d,J=5.5Hz,2H),7.71(b,1H).
13C?NMR(125.4MHz,d
6-DMSO):δ166.3,150.2,141.3,121.4.MS(EI):m/z(%)123(8),122(100),107(2),106(40),79(12),78(56),77(2),53(2),52(15),51(36),50(14),49(2),44(13),39(3),28(3),26(2).
Embodiment 16
2-chloro-4-cyanopyridine prepares 2-chloropyridine-4-methane amide
Add successively CsOHH in the reaction tubes
2O (0.0336g, 10mol%) and 2-chloro-4-cyanopyridine (2mmol), adding ammoniacal liquor (1.0mL) is solvent again, reaction tubes sealing post-heating to 100 ° C reaction 3h.GC-MS records reaction conversion ratio more than 99%, product column chromatography separating-purifying, separation yield 89%.
1H?NMR(500MHz,d
6-DMSO):δ8.57(d,J=5.0Hz,1H),8.33(b,1H),7.87(b,2H),7.78(dd,J=5.0,J=1.5Hz,1H).
13C?NMR(125.4MHz,d
6-DMSO):δ164.9,150.9,150.7,144.9,122.1,121.0.MS(EI):m/z(%)158(25),157(7),156(78),142(32),141(8),140(100),114(16),112(48),85(14),78(8),76(19),75(4),51(10),50(16),44(13),28(3).
Embodiment 17
2 cyano pyrazine prepares 2-acid amides pyrazine
Add successively CsOHH in the reaction tubes
2O (0.0336g, 10mol%) and 2 cyano pyrazine (2mmol), adding ammoniacal liquor (10mL) is solvent again, reaction tubes sealing post-heating to 100 ° C reaction 1h.GC-MS records reaction conversion ratio more than 99%, product column chromatography separating-purifying, separation yield 50%.
1H?NMR?(500MHz,d
6-DMSO):δ9.19(d,J=1.5Hz,1H),8.85(d,J=2.5Hz,1H),8.71(dd,J=2.5,J=1.5Hz,1H),8.25(b,1H),7.86(b,1H).
13C?NMR(125.4MHz,d
6-DMSO):δ170.3,152.6,150.3,148.9,148.8.MS(EI):m/z(%)124(7),123(100),81(4),80(80),79(18),54(2),53(51),52(32),51(9),44(18),40(2),28(12),26(15).
Embodiment 18
The 2-cyano thiophene prepares 2-acid amides thiophene
Add successively CsOHH in the reaction tubes
2O (0.0336g, 10mol%) and 2-cyano thiophene (2mmol), adding ammoniacal liquor (1.0mL) is solvent again, reaction tubes sealing post-heating to 100 ° C reaction 3h.GC-MS records reaction conversion ratio more than 99%, product column chromatography separating-purifying, separation yield 63%.
1H?NMR(500MHz,d
6-DMSO):δ7.99(b,1H),7.78-7.76(m,2H),7.40(b,1H),7.18-7.16(m,1H).
13CNMR(125.4MHz,d
6-DMSO):δ168.1,145.5,136.2,133.9,133.1.MS(EI):m/z(%)129(4),128(5),127(75),113(6),112(7),111(100),83(13),82(8),81(7),58(13),57(18),54(4),53(4),50(5),45(19),44(18),39(60),38(10).
Embodiment 19
Cyclopropanecarbonitrile preparation ring propionic acid amide
Add successively CsOHH in the reaction tubes
2O (0.0336g, 10mol%) and cyclopropanecarbonitrile (2mmol), adding ammoniacal liquor (1.0mL) is solvent again, reaction tubes sealing post-heating to 100 ° C reaction 3h.GC-MS records reaction conversion ratio more than 99%, product column chromatography separating-purifying, separation yield 80%.
1H?NMR(500MHz,d
6-DMSO):δ7.49(b,1H),6.73(b,1H),1.52-1.47(m,1H),0.65-0.59(m,4H).
13CNMR(125.4MHz,d
6-DMSO):δ175.2,13.8,6.7.MS(EI):m/z(%)85(8),84(61),69(25),68(8),54(5),44(100),43(8),42(41),41(72),40(16),39(90),38(20),37(12),28(26),27(20),26(12),16(10),15(7),14(6).
Embodiment 20
Acetonitrile prepares ethanamide
Add successively CsOHH in the reaction tubes
2O (0.0336g, 10mol%) and acetonitrile (2mmol), adding ammoniacal liquor (1.0mL) is solvent again, reaction tubes sealing post-heating to 100 ° C reaction 12h.GC-MS records reaction conversion ratio more than 80%, product column chromatography separating-purifying, separation yield 60%.
1H?NMR(500MHz,d
6-DMSO):δ7.30(b,1H),6.68(b,1H),1.77(s,3H).
13C?NMR(125.4MHz,d
6-DMSO):δ171.6,22.4.MS(EI):m/z(%)59(M
+).
Embodiment 21
Valeronitrile prepares valeramide
Add successively CsOHH in the reaction tubes
2O (0.0672g, 20mol%) and valeronitrile (2mmol), adding ammoniacal liquor (1.0mL) is solvent again, reaction tubes sealing post-heating to 160 ° C reaction 24h.GC-MS records reaction conversion ratio more than 99%, product column chromatography separating-purifying, separation yield 50%.
1H?NMR(500MHz,d
6-DMSO):δ7.22(b,1H),6.66(b,1H),2.03(t,J=7.5Hz,2H),1.49-1.43(m,2H),1.29-1.24(m,2H),0.89-0.85(m,3H).
13C?NMR(125.4MHz,d
6-DMSO):δ174.3,34.8,27.2,21.8,13.7.MS(EI):m/z(%)86(3),85(2),73(3),72(18),60(3),59(100),57(11),55(5),44(39),43(9),42(4),41(16),39(6),29(19),28(4).
Embodiment 22
Benzyl cyanide prepares phenylacetamide
Add successively CsOHH in the reaction tubes
2O (0.0672g, 20mol%) and benzyl cyanide (2mmol), adding ammoniacal liquor (1.0mL) is solvent again, reaction tubes sealing post-heating to 160 ° C reaction 24h.GC-MS records reaction conversion ratio more than 96%, product column chromatography separating-purifying, separation yield 70%.
1H?NMR?(500MHz,CDCl
3):δ7.38-7.35(m,2H),7.32-7.27(m,3H),5.56(b,1H),5.38(b,1H),3.59(s,2H).
13C?NMR(125.4MHz,CDCl
3):δ173.4,134.9,129.4,129.1,127.5,43.4.MS(EI):m/z(％)135(18),93(7),92(92),91(100),90(5),89(8),65(25),64(3),63(11),51(8),50(4),44(21),41(3),39(16),38(3).
Embodiment 23
The p-chlorobenzyl cyanide preparation is to the chlorobenzene ethanamide
Add successively CsOHH in the reaction tubes
2O (0.0672g, 20mol%) and p-chlorobenzyl cyanide (2mmol), adding ammoniacal liquor (1.0mL) is solvent again, reaction tubes sealing post-heating to 160 ° C reaction 24h.GC-MS records reaction conversion ratio more than 80%, product column chromatography separating-purifying, separation yield 55%.
1H?NMR?(500MHz,d
6-DMSO):δ7.48(b,1H),7.36(d,J=8.5Hz,2H),7.27(d,J=8.5Hz,2H),6.90(b,1H),3.78(s,2H).
13C?NMR(125.4MHz,d
6-DMSO):δ171.8,135.5,130.96,130.91,128.0,41.3.MS(EI):m/z(%)158(14),156(41),128(15),127(24),126(46),125(63),112(4),99(6),92(8),91(100),90(7),89(16),77(5),65(5),63(9),51(6),39(7),31(17).
Embodiment 24
Cinnamyl nitrile prepares cinnamide
Add successively CsOHH in the reaction tubes
2O (0.0672g, 20mol%) and cinnamyl nitrile (2mmol), adding ammoniacal liquor (1.0mL) is solvent again, reaction tubes sealing post-heating to 160 ° C reaction 24h.GC-MS records reaction conversion ratio more than 99%, product column chromatography separating-purifying, separation yield 68%.
1H?NMR?(500MHz,d
6-DMSO):δ7.57-7.54(m,3H),7.44-7.37(m,4H),7.10(b,1H),6.62(d,J=16.0Hz,1H).
13C?NMR(125.4MHz,d
6-DMSO):δ166.6,139.1,134.9,129.4,128.9,127.5,122.3.MS(EI):m/z(%)148(6),147(55),146(100),131(60),130(22),129(61),128(18),104(8),103(80),102(35),78(12),77(49),76(10),63(8),51(32),50(13),44(9),39(7).
Claims (7)
1. method that is prepared acid amides by nitrile is characterized in that its reaction formula is shown below under air or the inert gas conditions, with the hydrolysis reaction of alkaline catalysts catalysis nitrile in water or ammoniacal liquor:
Wherein:
R is alkyl, phenyl, substituted-phenyl, heteroaryl or substituted heteroaryl;
Temperature of reaction is room temperature ~ 180 ° C;
Reaction times is 1 ~ 24 hour.
2. a kind of method that is prepared acid amides by nitrile as claimed in claim 1, it is characterized in that: the heteroaryl among the described R is furans, thiophene or pyridyl.
3. a kind of method that is prepared acid amides by nitrile as claimed in claim 1, it is characterized in that: described alkaline catalysts is LiOH, NaOH, KOH, CsOH, t-BuOK, t-BuONa, Mg (OH)
2Or Ca (OH)
2
4. a kind of method that is prepared acid amides by nitrile as claimed in claim 3, it is characterized in that: described alkaline catalysts is CsOH.
5. a kind of method that is prepared acid amides by nitrile as claimed in claim 3, it is characterized in that: the consumption of described alkaline catalysts is 1 ~ 200mol%.
6. a kind of method that is prepared acid amides by nitrile as claimed in claim 5, it is characterized in that: the consumption of described alkaline catalysts is 5-30mol%.
7. a kind of method that is prepared acid amides by nitrile as claimed in claim 1, it is characterized in that: described temperature of reaction is 100 ~ 160 ° of C, and the reaction times is 1～24 hour.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103232359A (en) * | 2013-05-09 | 2013-08-07 | 温州大学 | Environmental-friendly nitrile hydrolysis method |
| CN103342654A (en) * | 2013-07-02 | 2013-10-09 | 扬州大学 | Novel method for hydrolyzing nitrile group to acylamino |
| CN104341320A (en) * | 2013-08-09 | 2015-02-11 | 苏州景泓生物技术有限公司 | Preparation method of key intermediate VIII of saxagliptin |
| CN104478796A (en) * | 2014-12-18 | 2015-04-01 | 天津汉德威药业有限公司 | Preparation method of isonicotinamide |
| CN106478442A (en) * | 2016-10-14 | 2017-03-08 | 湖北科技学院 | A kind of synthetic method of primary amide compound |
| CN110773144A (en) * | 2019-10-28 | 2020-02-11 | 湖南科技学院 | Catalytic system for preparing amide by hydrolyzing cyano and application thereof |
| CN113620867A (en) * | 2021-09-03 | 2021-11-09 | 内蒙古蓝科生物科技有限公司 | Synthesis method of fluopyram |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110773144A (en) * | 2019-10-28 | 2020-02-11 | 湖南科技学院 | Catalytic system for preparing amide by hydrolyzing cyano and application thereof |
| CN113620867A (en) * | 2021-09-03 | 2021-11-09 | 内蒙古蓝科生物科技有限公司 | Synthesis method of fluopyram |
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