CN110003047A - A kind of acetone cyanohydrin reacts the method for preparing nitrile with alkyl halide - Google Patents
A kind of acetone cyanohydrin reacts the method for preparing nitrile with alkyl halide Download PDFInfo
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- C07C253/00—Preparation of carboxylic acid nitriles
Abstract
The present invention provides a kind of acetone cyanohydrin and reacts the method for preparing nitrile with alkyl halide.The problems such as present invention is to use acetone cyanohydrin as cyanating reagent, solves in existing preparation method and makees cyanogen source using Cymag, potassium cyanide or the expensive third level natural division of severe toxicity, and the reaction time is long, and yield is lower, and reaction condition is stringent.Method: acetone cyanohydrin is dissolved in the in the mixed solvent being made of aprotic higher boiling dipole solvent and aprotic low boiling point solvent, catalyst lithium hydroxide is added, alkyl halide is added after stirring one hour at 25-50 DEG C, the reaction was continued 2-3 hours, saturated salt solution is added to wash twice, organic layer is separated, after dry, solvent is evaporated off, nitrile compounds can be obtained.The method reaction toxicity that the present invention prepares nitrile compounds is smaller, and simple process is easy to operate, and production cost is low, and yield is up to 95% or more.
Description
Technical field
The invention belongs to technical field of organic synthesis, it is related to a kind of acetone cyanohydrin and reacts the method for preparing nitrile with alkyl halide.
Background technique
Nitrile is the organic matter of a kind of cyano-containing, it is important industrial chemicals, has important answer in fields such as medicine, new materials
With wherein it is a variety of medicine of production, in pesticides that representative compound such as adiponitrile, which are the raw material for preparing nylon66 fiber, benzene acetonitrile,
Mesosome；Acrylonitrile can produce synthetic rubber and engineering plastics etc. with other monomers combined polymerization.
The existing method for preparing nitrile is more, but most common method is that fatty halogenated hydrocarbons and metal cyanides carry out nucleophilic
Substitution reaction prepares nitrile.The limitation of this method mainly has Cymag, potassium cyanide of (1) metal cyanides for severe toxicity, thus band
The problems such as serious environmental pollution and personal safety for coming；(2) Cymag/potassium cyanide belongs to inorganic salts, several in organic solvent
It is insoluble, it needs to be added phase transfer catalyst, such as tetrabutylammonium bromide, cetyltrimethyl ammonium, 18 6 ethers of hat, increases life
Produce cost；(3) when reactant is tertiary alkyl halide, reaction causes the yield of substitution product lower to eliminate based on product；(4)
When reactant is the weaker alkyl halide of the reactivities such as alkyl chloride or bromoalkane, needs to be added potassium iodide or sodium iodide is helped and urged
Agent.In order to overcome this to react existing drawbacks described above, laboratory is mostly using third level natural division as cyanating reagent at present, but is somebody's turn to do
Substance is expensive, and atom utilization is low, and reaction need to carry out under the conditions of stringent anhydrous and oxygen-free, therefore is not able to satisfy industrialization life
It produces and requires.
It is this comparatively safe using acetone cyanohydrin, substitution hydrogen cyanide (mankind's lethal dose is 0.57mg/kg), Cymag, cyanogen
Thus the cyanating reagent for changing the severe toxicity such as potassium (LD50 of acetone cyanohydrin is 52mg/kg, and the LD50 of Cymag is 6mg/kg), avoids
The problems such as bring environmental pollution and personal safety；Acetone cyanohydrin is the by-product for producing acrylonitrile, cheap, uses acetone
The cyanating reagent of cyanalcohol fictitious hosts valuableness, will substantially reduce production cost, more has practical value.Existing acetone cyanohydrin is made
The method for preparing cyanide by the nucleophilic substitution of alkyl halide for cyanogen source is less, and the catalyst used in existing report is
Uncommon organic alkali tetramethylguanidine or afraid of water, inflammable lithium hydride etc..
Summary of the invention
The present invention is to solve Cymag, the potassium cyanide when the existing method for preparing nitrile with alkyl halide using severe toxicity to be catalyzed
Agent or Atom economy are poor, expensive third level natural division makees cyanogen source and the reaction time is longer, and yield is lower, reaction condition
The problems such as stringent.The new method that a kind of nucleophilic substitution using alkyl halide and acetone cyanohydrin prepares nitrile is provided.
The method that the present invention prepares nitrile using the nucleophilic substitution of acetone cyanohydrin and alkyl halide, the specific steps are as follows:
Acetone cyanohydrin is dissolved in and is mixed by what aprotic higher boiling dipole solvent and aprotic low boiling point solvent formed
In bonding solvent, it being added catalyst lithium hydroxide, 25-50 DEG C is added alkyl halide after stirring one hour, and TLC is monitored after raw material disappears,
Add water washing, ethyl acetate extraction, ethyl acetate layer uses water and saturated common salt water washing respectively again, uses anhydrous Na2SO4After drying
Filtering and concentrating obtains nitrile.
The further cyanating reagent is acetone cyanohydrin.
The molar ratio of the further acetone cyanohydrin and alkyl halide is 1.1-1.5:1.
The further catalyst is monohydrate lithium hydroxide, and the molar ratio of monohydrate lithium hydroxide and alkyl halide is
1.1-1.5:1。
The further alkyl halide is primary alkyl halide and secondary alkyl halide.
The further alkyl halide is alkyl chloride, bromoalkane and idoalkane, and wherein alkyl halide can be, but not limited to,
Following compounds: benzyl chloride, chloro-normal butane, chloro-chung butane, 1,4- dichloroetane, 1- chloro-octane, 3- chloropropionate, 1-
Chloro- 2- vinylbenzene, 3- chloroethyl nitrile, 1,2- dichloroethanes, chlorinated dodecane；Bromination of n-butane, chung-bromo butane, 1,4- dibromo fourth
The bromo- 3- phenyl-propane of alkane, 1-, 3- bromopropionitrile, cylite, the bromo- methyl propionate of 3-, 1- bromo ethyl phenenyl, 4- bromo butyric acid methyl ester, bromo
Normal octane, bromo-octadecane, diphenyl-bromomethane, 2 bromo pentane, 7- bromine cognac oil, glycol dibromide；Iodo-n-butane, iodine
For normal octane, iododecane.
The further reaction temperature is 25-50 DEG C, preferably 50 DEG C.
The further reaction dissolvent is that aprotic higher boiling dipole solvent and aprotic low boiling point solvent form
Mixed solvent, wherein aprotic higher boiling dipole solvent is 1,3- dimethyl-imidazolinone, N-Methyl pyrrolidone, pregnancy
Base phosphoric triamide；Low boiling point solvent is methylene chloride, chloroform, acetone, acetonitrile, tetrahydrofuran, ether.
The ratio of the further mixed solvent is that aprotic higher boiling dipole solvent and aprotic low boiling point are molten
The volume ratio of agent is 1:2-1:7, preferably 1:3.
Reaction principle of the invention are as follows: with alkyl halide parent can occur for acetone cyanohydrin under the catalysis of monohydrate lithium hydroxide
Core substitution reaction prepares nitrile.
Beneficial effects of the present invention:
The present invention uses acetone cyanohydrin as cyanogen source, instead of toxic articles Cymag, potassium cyanide；Instead of expensive
The cyanating reagents such as trimethylsilyl cyanide.
Reaction condition of the invention is mild, and the reaction time is short, and reaction yield reaches 95% or more.
The present invention does catalyst, simple process, lower production costs using cheap monohydrate lithium hydroxide.
Detailed description of the invention
Fig. 1 is the nuclear magnetic resonance spectroscopy of benzene acetonitrile in embodiment one；
Fig. 2 is the carbon-13 nmr spectra of benzene acetonitrile in embodiment one；
Fig. 3 is the infrared spectroscopy of benzene acetonitrile in embodiment one.
Fig. 4 is the nuclear magnetic resonance spectroscopy of succinonitrile in embodiment ten；
Fig. 5 is the carbon-13 nmr spectra of succinonitrile in embodiment ten；
Fig. 6 is the infrared spectroscopy of succinonitrile in embodiment ten.
Specific embodiment
The technical solution of the present invention is not limited to the following list, further includes between each specific embodiment
Any combination.
Specific embodiment 1: present embodiment reacts the method for preparing nitrile using acetone cyanohydrin with alkyl halide, it is specific to walk
It is rapid as follows:
Acetone cyanohydrin is dissolved in and is mixed by what aprotic higher boiling dipole solvent and aprotic low boiling point solvent formed
In bonding solvent, it being added catalyst lithium hydroxide, 25-50 DEG C is added alkyl halide after stirring one hour, and TLC is monitored after raw material disappears,
Add water washing, ethyl acetate extraction, ethyl acetate layer uses water and saturated common salt water washing respectively again, uses anhydrous Na2SO4After drying
Filtering and concentrating obtains nitrile.
Specific embodiment 2: the present embodiment is different from the first embodiment in that: reaction dissolvent is 1,3- diformazan
The mixed solvent of base imidazolone and tetrahydrofuran composition.It is other same as the specific embodiment one.
Specific embodiment 3: the present embodiment is different from the first embodiment in that: reaction dissolvent is 1,3- diformazan
The mixed solvent of base imidazolone and methylene chloride composition.It is other same as the specific embodiment one.
Specific embodiment 4: the present embodiment is different from the first embodiment in that: reaction dissolvent is N- methyl pyrrole
The mixed solvent of pyrrolidone and acetone composition: other same as the specific embodiment one.
Specific embodiment 5: the present embodiment is different from the first embodiment in that: 1,3- dimethyl-imidazolinone
Volume ratio with the mixed solvent of tetrahydrofuran composition is 1:2.It is other same as the specific embodiment one.
Specific embodiment 6: the present embodiment is different from the first embodiment in that: 1,3- dimethyl-imidazolinone
Volume ratio with the mixed solvent of tetrahydrofuran composition is 1:5.It is other same as the specific embodiment one.
Specific embodiment 7: the present embodiment is different from the first embodiment in that: 1,3- dimethyl-imidazolinone
Volume ratio with the mixed solvent of tetrahydrofuran composition is 1:7.It is other same as the specific embodiment one.
Specific embodiment 8: the present embodiment is different from the first embodiment in that: catalyst monohydrate hydroxide
The molar ratio of lithium and alkyl halide is 1.3:1.It is other same as the specific embodiment one.
Specific embodiment 9: the present embodiment is different from the first embodiment in that: catalyst monohydrate hydroxide
The molar ratio of lithium and alkyl halide is 1.5:1.It is other same as the specific embodiment one.
Specific embodiment 10: the present embodiment is different from the first embodiment in that: acetone cyanohydrin and alkyl halide
Molar ratio is 1.2:1.It is other same as the specific embodiment one.
Specific embodiment 11: the present embodiment is different from the first embodiment in that: acetone cyanohydrin and alkyl halide
Molar ratio be 1.5:1.It is other same as the specific embodiment one.
Specific embodiment 12: the present embodiment is different from the first embodiment in that: reaction temperature is 50 DEG C.Its
It is same as the specific embodiment one.
Specific embodiment 13: present embodiment is unlike specific embodiment one to one of 12: alkyl halide
For benzyl chloride, chloro-normal butane, chloro-chung butane, 1,4- dichloroetane, 1- chloro-octane, 3- chloropropionate, the chloro- 2- benzene second of 1-
Alkane, 3- chloroethyl nitrile, 1,2- dichloroethanes, chlorinated dodecane；Bromination of n-butane, chung-bromo butane, 1,4- dibromobutane, 1- are bromo-
3- phenyl-propane, 3- bromopropionitrile, cylite, the bromo- methyl propionate of 3-, 1- bromo ethyl phenenyl, 4- bromo butyric acid methyl ester, n-octane bromide,
Bromo-octadecane, diphenyl-bromomethane, 2 bromo pentane, 7- bromine cognac oil, glycol dibromide；Iodo-n-butane, iodo are just pungent
Alkane, iododecane.It is other identical as specific embodiment one to one of 12.
Elaborate below to the embodiment of the present invention, following embodiment under the premise of the technical scheme of the present invention into
Row is implemented, and gives detailed embodiment and specific operating process, but protection scope of the present invention is not limited to following realities
Apply example.
Embodiment 1:
The method for preparing nitrile is reacted with alkyl halide with acetone cyanohydrin, it is characterised in that specific step is as follows for this method:
1.5mol acetone cyanohydrin is dissolved in the in the mixed solvent of 1,3- dimethyl-imidazolinone and tetrahydrofuran composition,
(volume ratio 1:3), be added 1.5mol catalyst monohydrate lithium hydroxide, 50 DEG C stirring one hour after be added 1mol cylite,
After TLC monitors raw material disappearance, after adding water washing, ethyl acetate extraction, ethyl acetate layer is washed with water and saturated common salt respectively again
It washs, uses anhydrous Na2SO4Filtering and concentrating obtains benzene acetonitrile product after drying.Reaction time 2.5h, yield 97%.
Nuclear magnetic resonance spectroscopy (the 300MH of benzene acetonitrileZ, CDCl3, unit ppm) and 7.39-7.32 (m, 5H) as shown in Figure 1:,
3.75(s,2H)。
Carbon-13 nmr spectra (the 75MH of benzene acetonitrileZ, CDCl3, unit ppm) as shown in Figure 2: 129.9,128.9,127.8,
127.7,117.8,23.3
Infrared spectroscopy (KBr coating method, the unit: cm of benzene acetonitrile-1) as shown in Figure 3: 3068,3034,2251,1603,
1497,1454,1417,1078,1030,740
It is correct that hydrogen spectrum, carbon spectrum and the infrared spectroscopy of binding compounds, which can be seen that synthesized compound structure,.
Embodiment 2: all experiment conditions of the present embodiment and processing method are same as Example 1, are only changed to cylite
Benzyl chloride, reaction time 4.5h, yield 95.6%.
Embodiment 3: all experiment conditions of the present embodiment and processing method are same as Example 1, only will be by 1,3- diformazan
The mixed solvent of base imidazolone and tetrahydrofuran composition is changed to the mixing of 1,3- dimethyl-imidazolinone and methylene chloride composition
Solvent, reaction time 5.5h, yield 95.7%.
Embodiment 4: all experiment conditions of the present embodiment and processing method are same as Example 1, only by 1,3- dimethyl
The mixed solvent of imidazolone and tetrahydrofuran composition is changed to the mixed solvent of N-Methyl pyrrolidone and acetone composition, when reaction
Between be 3.5h, yield 96.3%.
Embodiment 5: all experiment conditions of the present embodiment and processing method are same as Example 1, only by 1,3- dimethyl
The mixed solvent of imidazolone and tetrahydrofuran composition is changed to the mixed solvent of hexamethylphosphoramide and ether composition, when reaction
Between be 5h, yield 95.2%.
Embodiment 6: all experiment conditions of the present embodiment and processing method are same as Example 1, only by 1,3- dimethyl
The volume ratio of the mixed solvent of imidazolone and tetrahydrofuran composition is that 1:3 is changed to 1:5, reaction time 3.5h, and yield is
96.7%.
Embodiment 7: all experiment conditions of the present embodiment and processing method are same as Example 1, only by catalyst list water
The molar ratio 1.5:1 for closing lithium hydroxide and cylite is changed to 1.3:1, reaction time 4.5h, yield 96.2%.
Embodiment 8: all experiment conditions of the present embodiment and processing method are same as Example 1, only by acetone cyanohydrin with
The molar ratio of cylite is that 1.5:1 is changed to 1.2:1, reaction time 4h, yield 95.9%.
Embodiment 9: all experiment conditions of the present embodiment and processing method are same as Example 1, only by temperature by 50 DEG C
25 DEG C, reaction time 5h are changed to, yield 95.3%.
Embodiment 10: all experiment conditions of the present embodiment and processing method are same as Example 1, are only changed to cylite
3- chloroethyl nitrile, reaction time 3.5h, yield 98%.Nuclear magnetic resonance spectroscopy (the 300MH of product succinonitrileZ, CDCl3, unit
Ppm) as shown in Figure 4: 2.76 (s, 4H)；Carbon-13 nmr spectra (the 75MH of succinonitrileZ, CDCl3, unit ppm) as shown in Figure 5:
116.2,14.7；Infrared spectroscopy (KBr coating method, the unit: cm of succinonitrile-1) as shown in Figure 6: 3465,2989,2955,2254,
1427,1003,964,822,762,605。
Embodiment 11: all experiment conditions of the present embodiment and processing method are same as Example 1, are only changed to cylite
The chloro- 2- vinylbenzene of 1-, reaction time 2.5h, yield 97.9%.The hydrogen nuclear magnetic resonance modal data of product benzenepropanenitrile
(300MHZ, CDCl3, unit ppm): 7.36-7.24 (m, 5H), 2.97 (t, J=7.36Hz, 2H), 2.63 (t, J=7.40Hz,
2H)；Carbon-13 nmr spectra data (the 75MH of benzenepropanenitrileZ, CDCl3, unit ppm): 138.1,128.9,128.2,127.2,
119.1,31.5,19.3；Ir data (KBr coating method, the unit: cm of benzenepropanenitrile-1): 3087,3069,3030,2868,
2246,1604,1496,1454,1425,1079,1340,749。
Embodiment 12: all experiment conditions of the present embodiment and processing method are same as Example 1, are only changed to cylite
3- chloropropionate, reaction time 3.5h, yield 95.9%.The hydrogen nuclear magnetic resonance modal data of product 3- cyanopropionate
(300MHz, CDCl3, unit ppm): 4.19 (q, J=7.09Hz, 2H), 2.65 (s, 4H), 1.27 (t, J=7.13Hz, 3H)；
Carbon-13 nmr spectra data (the 75MH of 3- cyanopropionateZ, CDCl3, unit ppm): 170.0,118.5,61.5,30.0,
14.1,12.6；Ir data (KBr coating method, the unit: cm of 3- cyanopropionate-1): 2927,2854,2251,
1736,1691,1422,1377,1199,1114,1018,854,617。
Embodiment 13: all experiment conditions of the present embodiment and processing method are same as Example 1, are only changed to cylite
Chlorooctadecane, reaction time 4.5h, yield 95.1%.The hydrogen nuclear magnetic resonance modal data of product N- nonadecyl nitrile
(300MHz, CDCl3, unit ppm): 2.33 (t, J=7.03,2H), 1.68-1.63 (m2H), 1.49-1.44 (m, 2H), 1.26
(s, 28H), 0.88 (t, J=5.54Hz, 3H)；Carbon-13 nmr spectra data (the 75MH of N- nonadecyl nitrileZ, CDCl3, unit
Ppm): 119.9,32.0,29.7,29.6,29.4,28.8,28.7,25.4,22.7,17.2,14.2；N- nonadecyl nitrile it is red
External spectrum data (KBr coating method, unit: cm-1): 3064,3032,2987,2938,2877,2242,1958,1896,1669,
1385,752,570。
Embodiment 14: all experiment conditions of the present embodiment and processing method are same as Example 1, are only changed to cylite
Diphenyl-bromomethane, reaction time 4.5h, yield 95.2%.Hydrogen nuclear magnetic resonance modal data (the 300MH of product diphenatrilZ,
CDCl3, unit ppm): 7.35 (m, 10H), 5.14 (s, 1H)；Carbon-13 nmr spectra data (the 75MH of diphenatrilZ, CDCl3,
Unit ppm): 135.9,129.2,128.3,127.8,42.8；Diphenatril ir data (KBr pressed disc method, unit:
cm-1)3027,2933,2852,2243,1658,1597,1492,1118,1079,744,697,540。
Embodiment 15: all experiment conditions of the present embodiment and processing method are same as Example 1, are only changed to cylite
The bromo- 3- phenyl-propane of 1-, reaction time 3h, yield 96%.The hydrogen nuclear magnetic resonance modal data of product 4- phenylbutyronitrile
(300MHZ, CDCl3, unit ppm): 7.36-7.17 (m, 5H), 2.80-2.75 (t, J=7.40Hz, 2H), 2.34-2.29 (t, J
=7.09Hz, 2H), 2.00-1.95 (m, 2H),；4- phenylbutyronitrile carbon-13 nmr spectra data (75MHZ, CDCl3, unit ppm):
139.7,128.6,128.4,126.5,119.5,34.3,26.9,16.3；4- phenylbutyronitrile ir data (KBr film
Method, unit: cm-1): 3085,3069,3029,2928,2867,2246,1603,1497,1455,1425,1082,1 030,748,
701。
Embodiment 16: all experiment conditions of the present embodiment and processing method are same as Example 1, are only changed to cylite
7- bromine cognac oil, reaction time 4h, yield 96.8%.Product 7- cyano cognac oil: hydrogen nuclear magnetic resonance modal data
(300MHZ, CDCl3, unit ppm): 4.15-4.11 (q, J=7.02Hz, 2H), 2.34-2.27 (t, J=11.72Hz, 4H),
1.66-1.61 (m, 4H), 1.47-1.40 (t, J=5.39Hz 2H), 1.38-1.35 (m, 2H), 1.27-1.22 (t, J=
7.04Hz,3H)；Carbon-13 nmr spectra data (the 75MH of 7- cyano cognac oilZ, CDCl3, unit ppm): 173.4,119.6,
132.4,60.1,34.0,28.2,28.1,25.0,24.4,16.9,14.1；The ir data of 7- cyano cognac oil
(KBr coating method, unit: cm-1): 2936,2863,2245,1732,1464,1373,1252,1187,1096,1033.
Embodiment 17: all experiment conditions of the present embodiment and processing method are same as Example 1, are only changed to cylite
Isosorbide-5-Nitrae-dibromobutane, reaction time 3h, yield 97.9%.Nuclear magnetic resonance spectroscopy (the 300MH of product adiponitrileZ, CDCl3,
Unit ppm): 2.44-2.41 (m, 4H)；1.83-1.81(m,4H)；Carbon-13 nmr spectra (the 75MH of adiponitrileZ, CDCl3, unit
Ppm): 118.72,24.21,16.59；Infrared spectroscopy (KBr coating method, the unit: cm of adiponitrile-1): 2949,2881,2249,
1697,1462,1427,1335,898,766。
Embodiment 18: all experiment conditions of the present embodiment and processing method are identical as embodiment 13, only by Isosorbide-5-Nitrae-dibromo
Butane is changed to Isosorbide-5-Nitrae-dichloroetane, reaction time 4.5h, yield 95.3%.
Embodiment 19: all experiment conditions of the present embodiment and processing method are same as Example 1, are only changed to cylite
3- methyl bromide c, reaction time 3.5h, yield 98.2%.The nuclear magnetic resonance spectroscopy of product 3- cyanopropanoic acid methyl ester
(300MHZ, CDCl3, unit ppm): 3.73 (s, 3H), 2.70-2.61 (m, 4H)；The carbon-13 nmr spectra of 3- cyanopropanoic acid methyl ester
(75MHZ, CDCl3, unit ppm): 170.4,118.4,52.3,29.8,13.0；Infrared spectroscopy (the KBr of 3- cyanopropanoic acid methyl ester
Coating method, unit: cm-1): 3328,2959,2251,1667,1576,1506,1387,1279,1181,950,883,682.
Embodiment 20: all experiment conditions of the present embodiment and processing method are same as Example 1, are only changed to cylite
Iodo-n-butane, reaction time 3.5h, yield 95.5%.Hydrogen nuclear magnetic resonance modal data (the 300MH of product valeronitrileZ,
CDCl3, unit ppm): 2.34 (t, J=7.02Hz, 2H), 1.67-1.59 (m, 2H), 1.52-1.44 (m, 2H), 0.92 (t, J
=7.20Hz, 3H)；Carbon-13 nmr spectra data (the 75MH of valeronitrileZ, CDCl3, unit ppm): 119.8,27.4,21.8,16.8,
13.2；Ir data (KBr coating method, the unit: cm of valeronitrile-1): 2992,2941,2243,1460,1382,1190,
1141,976,876,696,596,475。
Embodiment 21: all experiment conditions of the present embodiment and processing method are same as Example 1, are only changed to cylite
Iodo normal octane, reaction time 3.5h, yield 97.2%.Hydrogen nuclear magnetic resonance modal data (the 300MH of product pelargonitrileZ,
CDCl3, unit ppm): 2.35-2.30 (t, J=7.06Hz, 2H), 1.69-1.60 (m, 2H), 1.43-1.41 (m, 2H),
1.30-1.27 (m, 8H), 0.87-0.85 (t, J=6.62Hz, 3H)；Carbon-13 nmr spectra data (the 75MH of product pelargonitrileZ,
CDCl3, unit ppm): 119.9,31.7,29.0,28.7,22.6,17.1,14.1；Ir data (the KBr of product pelargonitrile
Coating method, unit: cm-1): 2927,2856,2246,1466,1427,1377,723.
Embodiment 22: all experiment conditions of the present embodiment and processing method are same as Example 1, are only changed to cylite
Iododecane, reaction time 3h, yield 96.6%.Hydrogen nuclear magnetic resonance modal data (the 300MH of product pentadecane nitrileZ,
CDCl3, unit ppm):: 2.33 (t, J=7.09Hz, 2H), 1.68-1.63 (m, 2H), 1.44-1.41 (m, 2H), 1.25 (s,
20H), 0.88 (t, J=6.17Hz, 3H)；Carbon-13 nmr spectra data (the 75MH of pentadecane nitrileZ, CDCl3, unit ppm):
119.8,31.9,29.7,29.6,29.5,29.4,29.3,28.7,25.4,22.7,17.1,14.1；The infrared light of pentadecane nitrile
Modal data (KBr coating method, unit: cm-1): 2926,2854,2247,1686,1466,1427,1378,1297,722.
By the product structure of embodiment 10-22, statistics indicate that, synthesized compound structure is correct.
Claims (9)
1. a kind of acetone cyanohydrin reacts the method for preparing nitrile with alkyl halide, it is characterised in that specific step is as follows for this method:
It is molten that acetone cyanohydrin is dissolved in the mixing being made of aprotic higher boiling dipole solvent and aprotic low boiling point solvent
In agent, it is added catalyst lithium hydroxide, 25-50 DEG C is added alkyl halide after stirring one hour, and TLC is monitored after raw material disappears, and adds water
Washing, ethyl acetate extraction, ethyl acetate layer use water and saturated common salt water washing respectively again, use anhydrous Na2SO4It is filtered after drying
It is concentrated to get nitrile.
2. synthetic method according to claim 1, it is characterised in that the cyanating reagent is acetone cyanohydrin.
3. synthetic method according to claim 1, it is characterised in that the molar ratio of acetone cyanohydrin and alkyl halide is 1.1-
1.5:1。
4. synthetic method according to claim 1, it is characterised in that the catalyst is monohydrate lithium hydroxide, monohydrate
The molar ratio of lithium hydroxide and alkyl halide is 1.1-1.5:1.
5. synthetic method according to claim 1, it is characterised in that the alkyl halide is primary alkyl halide and secondary alkyl halide.
6. according to claim 1 with synthetic method described in 5, it is characterised in that the alkyl halide be alkyl chloride, bromoalkane and iodine
For alkane, wherein alkyl halide can be, but not limited to, following compounds: benzyl chloride, chloro-normal butane, chloro-chung butane, Isosorbide-5-Nitrae-two
The chloro- 2- vinylbenzene of chlorobutane, 1- chloro-octane, 3- chloropropionate, 1-, 3- chloroethyl nitrile, 1,2- dichloroethanes, chlorinated dodecane；
The bromo- 3- phenyl-propane of bromination of n-butane, chung-bromo butane, 1,4- dibromobutane, 1-, 3- bromopropionitrile, cylite, the bromo- propionic acid of 3-
Methyl esters, 1- bromo ethyl phenenyl, 4- bromo butyric acid methyl ester, n-octane bromide, bromo-octadecane, diphenyl-bromomethane, 2 bromo pentane, 7- bromine heptan
Acetoacetic ester, glycol dibromide；Iodo-n-butane, iodo normal octane, iododecane.
7. synthetic method according to claim 1, it is characterised in that reaction temperature is 25-50 DEG C, preferably 50 DEG C.
8. synthetic method according to claim 1, it is characterised in that the reaction dissolvent is aprotic higher boiling dipole
The mixed solvent of solvent and aprotic low boiling point solvent, wherein aprotic higher boiling dipole solvent is 1,3- methylimidazole
Quinoline ketone, N-Methyl pyrrolidone, hexamethylphosphoramide；Low boiling point solvent is methylene chloride, chloroform, acetone, acetonitrile, four
Hydrogen furans, ether.
9. according to claim 1 and synthetic method described in 6,7, it is characterised in that the ratio of the mixed solvent is aprotic
The volume ratio of higher boiling dipole solvent and aprotic low boiling point solvent is 1:2-1:7, preferably 1:3.
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| CN113461509A (en) * | 2021-07-13 | 2021-10-01 | 无锡贝塔医药科技有限公司 | Preparation method of naphthalene ring C-marked alpha-naphthylacetic acid |
| CN114456086A (en) * | 2021-12-28 | 2022-05-10 | 哈尔滨理工大学 | Synthesis method of beta-cyano ketone |
| CN116987004A (en) * | 2023-09-27 | 2023-11-03 | 新华制药（寿光）有限公司 | Synthesis method of 3- (3, 4-dimethoxy phenyl) -2-amino-2-methylpropanenitrile |
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| CN113461509A (en) * | 2021-07-13 | 2021-10-01 | 无锡贝塔医药科技有限公司 | Preparation method of naphthalene ring C-marked alpha-naphthylacetic acid |
| CN114456086A (en) * | 2021-12-28 | 2022-05-10 | 哈尔滨理工大学 | Synthesis method of beta-cyano ketone |
| CN116987004A (en) * | 2023-09-27 | 2023-11-03 | 新华制药（寿光）有限公司 | Synthesis method of 3- (3, 4-dimethoxy phenyl) -2-amino-2-methylpropanenitrile |
| CN116987004B (en) * | 2023-09-27 | 2023-12-12 | 新华制药（寿光）有限公司 | Synthesis method of 3- (3, 4-dimethoxy phenyl) -2-amino-2-methylpropanenitrile |
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