CN104525253B - Application of triethylene diamine as catalyst in catalyzing reaction of aromatic aldehyde and nitro-hydrocarbon to generate nitryl aromatic alcohol - Google Patents

Abstract

The invention discloses new application of triethylene diamine, potassium tert-butoxide, triethylamine, diethylamine or sodium ethoxide, specifically application as a catalyst in catalyzing reaction of aromatic aldehyde and nitro-hydrocarbon to generate nitryl aromatic alcohol. The catalyst involved in the invention is significantly different from the catalysts for preparation of nitryl aromatic alcohol in the prior art, and has the advantages of simple structure, convenience and easy availability, low price, and high product yield. Particularly, when triethylene diamine is adopted as the catalyst, the yield of nitryl aromatic alcohol preparation with triethylene diamine as the catalyst can reach more than 95%. The triethylene diamine catalyst has the advantages of simple operation, low cost and the like, and has good industrial application prospects.

Description

Triethylene diamine is generated in nitryl aromatic alcohol in catalysis aromatic aldehyde with nitro hydrocarbon reaction Catalyst applications

Technical field

The present invention relates to triethylene diamine, potassium tert-butoxide, triethylamine, diethylamine or caustic alcohol are in catalysis aromatic aldehyde and nitro Hydrocarbon reaction generates the catalyst applications in nitryl aromatic alcohol.

Background technology

Nitryl aromatic alcohol is the important source material for preparing medicine intermediate amides compound, mainly by aromatic aldehyde and nitro Hydrocarbon is prepared in the presence of catalyst.

The preparation method to nitryl aromatic alcohol such as Claudio Palomo (Eur.J.Org.Chem.2007,2561-2574) It is reviewed, according to the difference of catalyst, its preparation method mainly has following several：

(1) with oxynitrilase (Hydroxynitrile lyase) as catalyst, catalysis RCHO is reacted with nitro hydrocarbon, instead Answer condition：PH=7, room temperature, 48 hours, yield be 25～77%；

(2) with (mol ratio)：La(OTf)₃(1)/L-2 (3) (L-2 structural formulas are shown below) is catalyst, is catalyzed RCHO is reacted with nitro hydrocarbon, reaction condition：Solvent be acetonitrile, -40 DEG C, 24～96 hours, yield be 65～98%；

(3) catalyst with structural formula as indicated by 10, catalysis RCHO is reacted with nitro hydrocarbon, reaction condition：Solvent is THF, -35 DEG C, 24 hours, yield be 56～90%；

(4) with (mol ratio)：ZnEt₂(2)/L-5 (1) (L-5 structural formulas are shown below) is catalyst, is catalyzed RCHO Reacted with nitro hydrocarbon, reaction condition：Solvent be THF, -25 DEG C, 8～42 hours, yield be 40～90%；

(5) catalyst with structural formula as shown in 12, catalysis PhCHO is reacted with nitro hydrocarbon, reaction condition：Solvent is THF, -20 DEG C, 48 hours, yield is 68%；

(6) with (mol ratio)：Zn(OTf)₂(1), iPr2EtN (1), (+)-NME (1.5) (its structural formula is shown below) For catalyst, it is catalyzed RCHO and is reacted with nitro hydrocarbon, reaction condition：- 40/-60 DEG C, 16～60 hours, yield be 71～ 92%；

(7) catalyst with structural formula as shown in 16, catalysis RCHO is reacted with nitro hydrocarbon, reaction condition：Solvent is Ethanol, room temperature, 4～96 hours, yield be 66～95%；

(8) with (mol ratio)：CuCl₂(1), (-)-sparteine (1) (its structural formula is shown below) is catalyst, Catalysis RCHO is reacted with nitro hydrocarbon, reaction condition：Solvent be methyl alcohol, 0 DEG C, 7～24 hours, yield be 60～＞ 95%；

(9) with (mol ratio)：CuCl (1)/L-8 (1) (L-8 structural formulas are shown below) be catalyst, catalysis RCHO with Nitro hydrocarbon is reacted, reaction condition：Solvent be nPrOH, room temperature, 16～120 hours, yield be 66～＞ 99%；

(10) catalyst with structural formula as indicated at 21, catalysis RCHO is reacted with nitro hydrocarbon, reaction condition：Solvent is iPr₂EtN、CH₂Cl₂, -78/-40 DEG C, 40～144 hours, yield be 72～＞ 99%；

(11) with NAP-MgO as catalyst, catalysis RCHO is reacted with nitro hydrocarbon, reaction condition：Solvent be THF, -78 DEG C, 12～20 hours, yield be 70～95%；

(12) catalyst with structural formula as shown in 24 or 25, catalysis RCHO is reacted with nitro hydrocarbon, reaction condition：It is molten Agent be THF, room temperature, 9～24 hours, high income is up to 85%；

(13) catalyst with structural formula as indicated at 28, catalysis RCHO is reacted with nitro hydrocarbon, reaction condition：Solvent is THF, -20 DEG C, 4～168 hours, yield be 90～99%；

As shown in the above, prior art prepare the method for nitryl aromatic alcohol mostly using baroque compound or Composition is catalyst, under specific reaction condition, could obtain higher yield, and the catalyst for adopting has preparation and is stranded Difficult, production cost is high, it is expensive the problems such as.

Triethylene diamine (abbreviation TEDA), also referred to as triethylenediamine, ring triethylenediamine, CAS：280-57-9, is a kind of Non- yellowing solid amine, its purposes is primarily used to the gel catalyst of polyurethane foam plastics, also acts as epoxy resin and consolidates Change accelerator, and vinyl polymerization, acrylonitrile polymerization, the catalyst of oxirane polymerized hydrocarbon etc..

There are no triethylene diamine, potassium tert-butoxide etc. as the report for preparing nitryl aromatic alcohol catalyst application.

At present, the preparation method of amides compound mainly adopts nitryl aromatic alcohol and organic nitrile for raw material, for example：China The A of patent CN 103864637 discloses a kind of preparation method of N- (β -4-nitro alkyl) amides compound, and the method is by nitro Alcohol is added in reaction bulb, is subsequently adding nitrile, TFMS and solvent, is stirred and evenly mixed, and in the case where temperature is for 25-40 DEG C, reacts 12h ～48h, after question response terminates, decompression removes solvent, and silica gel column chromatography obtains N- (β -4-nitro alkyl) amides compound.

Also there are no to be directly used in the nitryl aromatic alcohol that triethylene diamine etc. is catalyzed preparation without the need for purifying and prepare amide-type The report of compound.

The content of the invention

It is an object of the invention to provide one kind of triethylene diamine, potassium tert-butoxide, triethylamine, diethylamine or caustic alcohol is new Purposes, specifically generates the catalyst applications in nitryl aromatic alcohol in catalysis aromatic aldehyde with nitro hydrocarbon reaction.

Triethylene diamine, potassium tert-butoxide, triethylamine, diethylamine or caustic alcohol are generated in catalysis aromatic aldehyde and nitro hydrocarbon reaction Catalyst applications in nitryl aromatic alcohol.

Preferably, the catalyst is triethylene diamine.

The synthetic route of the catalysis aromatic aldehyde and nitro hydrocarbon reaction generation nitryl aromatic alcohol is：

Comprise the following steps：

A, by R₁CHO、R₂CH₂NO₂, catalyst and polar organic solvent be well mixed, stirring reaction 6 is little at 0 DEG C～40 DEG C When～48 hours, obtain product；

The catalyst is triethylene diamine, potassium tert-butoxide, triethylamine, diethylamine or caustic alcohol；

B, the product of step a is removed into solvent, Jing silica gel column chromatographies obtain oily product, as nitryl aromatic alcohol；

Wherein, R₁For unsubstituted or substituted aromatic radical, R₂For the alkyl of H, C1～C6, the alkoxyl of C1～C6, phenyl, The alkyl-substituted phenyl of halogenophenyl, benzene alkyl or C1～C6.

In step a, reaction temperature is 0 DEG C～25 DEG C；Reaction time is 24 hours～48 hours；The catalyst is three second Alkene diamines；The polar organic solvent is acetonitrile, benzonitrile, benzene acetonitrile, dichloromethane or chloroform；The R₁CHO、R₂CH₂NO₂、 The mol ratio of catalyst is 1：(2～8)：(0.1～2)；The R₁CHO is 1 with the molal volume ratio of organic solvent：(0.5～2) (mol：L).

In step a, the polar organic solvent is acetonitrile, benzonitrile or benzene acetonitrile.

In step a, the R₁CHO、R₂CH₂NO₂, catalyst mol ratio be 1：(2～8)：(0.5～2)；The R₁CHO It is 1 with the molal volume ratio of organic solvent：2(mol：L).

In step b, the eluant, eluent of the silica gel column chromatography is petrol ether/ethyl acetate mixed solvent；The mixed solvent In, petroleum ether is 10 with the volume ratio of ethyl acetate:1.

Preferably,

R₁For phenyl, thienyl, naphthyl, hydroxyl replace phenyl, hydroxyl replace thienyl, hydroxyl replace naphthyl, Difluorophenyl, chlorophenyl, bromo phenyl, fluoro thienyl, chloro-thienyl, bromo thiophene base, fluoro naphthyl, naphthalene chloride Phenyl, the phenyl of propyl group replacement, phenyl, the methyl of butyl replacement that base, bromo naphthyl, methyl substituted phenyl, ethyl replace Substituted thienyl, the thienyl of ethyl replacement, the thienyl of propyl group replacement, thienyl, the methyl substituted naphthalene of butyl replacement Base, the naphthyl of ethyl replacement, the naphthyl of propyl group replacement, the naphthyl of butyl replacement, the phenyl of methoxy substitution, ethyoxyl replace Phenyl, propoxyl group replace phenyl, butoxy replace phenyl, the thienyl of methoxy substitution, ethyoxyl replace thienyl, Thienyl, the thienyl of butoxy replacement, the naphthyl of methoxy substitution, naphthyl, third oxygen of ethyoxyl replacement that propoxyl group replaces The naphthyl that the naphthyl or butoxy that base replaces replaces；

R₂For H, methyl, ethyl, propyl group, butyl, methoxyl group, ethyoxyl, propoxyl group, butoxy, phenyl, difluorophenyl, Chlorophenyl, bromo phenyl, benzyl, phenethyl, phenylpropyl, benzene butyl, tolyl, ethylbenzene, propyl phenyl or butylbenzene base.

Preferably, the nitryl aromatic alcohol is：

Triethylene diamine of the present invention, potassium tert-butoxide, triethylamine, diethylamine or caustic alcohol are anti-in catalysis aromatic aldehyde and nitro hydrocarbon The catalyst applications in nitryl aromatic alcohol should be generated, is had the advantages that：

(1) present invention prepares nitro using the conduct such as triethylene diamine, potassium tert-butoxide, triethylamine, diethylamine or caustic alcohol There is very big difference, the catalyst tool of the present invention in the catalyst of aromatic alcohol, the catalyst for preparing nitryl aromatic alcohol with prior art Have the advantages that simple structure, be conveniently easy to get, price is low, product yield high；

Particularly, during using triethylene diamine as catalyst, R₁The mol ratio of CHO and triethylene diamine is 1：(0.5～ 2) in the range of, preparing the yield of nitryl aromatic alcohol can reach more than 95%；

(2) present invention is also to when the solvent, raw material proportioning, catalyst amount, reaction temperature, the reaction that prepare nitryl aromatic alcohol Between etc. screened, optimize reaction condition；

A, the present invention, as solvent, prepare nitryl aromatic alcohol using acetonitrile, benzonitrile, benzene acetonitrile, dichloromethane or chloroform High income；Particularly, during using acetonitrile, benzonitrile, benzene acetonitrile etc. as solvent, the yield of nitryl aromatic alcohol 75% with On；

B, R of the present invention₁CHO and R₂CH₂NO₂Mol ratio 1：In the range of (2～8), the yield of nitryl aromatic alcohol is prepared It is high；Preferably, R₁CHO and R₂CH₂NO₂Mol ratio be 1：(4～8)；

C, reaction temperature of the present invention prepare the high income of nitryl aromatic alcohol in the range of 0 DEG C～40 DEG C；Particularly, react When temperature is 0 DEG C, the yield of nitryl aromatic alcohol reaches 90%；

D, reaction time of the invention, in more than 12h, prepare the high income of nitryl aromatic alcohol；Particularly, the reaction time is in 24h During the above, the yield of nitryl aromatic alcohol is more than 90%.

(3) nitryl aromatic alcohol prepared by the present invention is used directly for preparing amides compound without the need for purifying, simplifies The preparation process of amides compound, with easy to operate, low cost and other advantages.

The catalyst that catalyst of the present invention prepares nitryl aromatic alcohol with prior art is significantly different, with simple structure, side The advantages of easy, low price, product yield high；Particularly, during using triethylene diamine as catalyst, the present invention prepares nitre The yield of base aromatic alcohol can reach more than 95%, and with easy to operate, low cost and other advantages, prospects for commercial application is good；Together When, nitryl aromatic alcohol prepared by the present invention is used directly for preparing amides compound without the need for purifying, simplifies amide-type The preparation process of compound.

Present invention also offers a kind of preparation method of amides compound.

A kind of preparation method of amides compound, its synthetic route is：

Comprise the following steps：

I, take R₁CHO and R₂CH₂NO₂, add catalyst and R₃CN, stirring reaction 24 hours～48 hours at 0 DEG C～40 DEG C, Obtain the reactant liquor of nitryl aromatic alcohol；

The catalyst is triethylene diamine, potassium tert-butoxide, triethylamine, diethylamine or caustic alcohol；

Ii, in the reactant liquor of step i, add organic acid and halohydrocarbon solvent, stirring reaction 12 at 25 DEG C～40 DEG C Hour～after 48 hours, add sodium acid carbonate to adjust pH=7～8, and solvent is removed, Jing silica gel column chromatographies obtain final product amide-type chemical combination Thing；

Wherein, R₁For unsubstituted or substituted aromatic radical；R₂For the alkyl of H, C1～C6, the alkoxyl of C1～C6, phenyl, Halogenophenyl, the alkyl-substituted phenyl of C1～C6 or benzene alkyl；R₃For the alkyl of H, C1～C6, phenyl, halogenophenyl, benzene alkane The alkyl-substituted phenyl of base or C1～C6.

Preferably,

R₁For phenyl, thienyl, naphthyl, hydroxyl replace phenyl, hydroxyl replace thienyl, hydroxyl replace naphthyl, Difluorophenyl, chlorophenyl, bromo phenyl, fluoro thienyl, chloro-thienyl, bromo thiophene base, fluoro naphthyl, naphthalene chloride Phenyl, the phenyl of propyl group replacement, phenyl, the methyl of butyl replacement that base, bromo naphthyl, methyl substituted phenyl, ethyl replace Substituted thienyl, the thienyl of ethyl replacement, the thienyl of propyl group replacement, thienyl, the methyl substituted naphthalene of butyl replacement Base, the naphthyl of ethyl replacement, the naphthyl of propyl group replacement, the naphthyl of butyl replacement, the phenyl of methoxy substitution, ethyoxyl replace Phenyl, propoxyl group replace phenyl, butoxy replace phenyl, the thienyl of methoxy substitution, ethyoxyl replace thienyl, Thienyl, the thienyl of butoxy replacement, the naphthyl of methoxy substitution, naphthyl, third oxygen of ethyoxyl replacement that propoxyl group replaces The naphthyl that the naphthyl or butoxy that base replaces replaces；

R₂For H, methyl, ethyl, propyl group, butyl, methoxyl group, ethyoxyl, propoxyl group, butoxy, phenyl, difluorophenyl, Chlorophenyl, bromo phenyl, benzyl, phenethyl, phenylpropyl benzene butyl, tolyl, ethylbenzene, propyl phenyl or butylbenzene base；

R₃For H, methyl, ethyl, propyl group, butyl, phenyl, difluorophenyl, chlorophenyl, bromo phenyl, benzyl, benzene second Base, phenylpropyl benzene butyl, tolyl, ethylbenzene, propyl phenyl or butylbenzene base.

Preferably, the amides compound is：

Preferably, in step i, reaction temperature is 0 DEG C；Reaction time is 24 hours.

Preferably, in step i, the catalyst is triethylene diamine.

Preferably, in step ii, reaction temperature is 40 DEG C；Reaction time is 24 hours.

In step ii, the organic acid is TFMS；The halohydrocarbon solvent is dichloromethane or chloroform.

In step ii, the eluant, eluent of the silica gel column chromatography is petrol ether/ethyl acetate mixed solvent；The mixed solvent In, petroleum ether is (1～5) with the volume ratio of ethyl acetate:1.

The R₁CHO、R₂CH₂NO₂, catalyst, organic acid mol ratio be 1：(2～8)：(0.1～2)：(2～4)； The R₁CHO、R₃CN, the molal volume ratio of halohydrocarbon solvent are 1：(0.5～2)：(0.5～4) (mol：L：L).

Preferably, the R₁CHO、R₂CH₂NO₂, catalyst, organic acid mol ratio be 1：(2～8)：(0.5～2)： (3～4)；The R₁CHO、R₃CN, the molal volume ratio of halohydrocarbon solvent are 1：0.5：(1.5～2) (mol：L：L).

The preparation method of amides compound of the present invention, has the advantages that：

(1) present invention using simple structure, be conveniently easy to get, the catalyst such as low-cost triethylene diamine；

(2) present invention is dexterously combined together two-step reaction very much, the organic nitrile such as acetonitrile, benzonitrile, benzene acetonitrile Solvent is both the solvent of first step reaction, is also the raw material of second step reaction；The nitryl aromatic alcohol of preparation is without the need for purifying, Ke Yizhi Connect for preparing amides compound, simplify the preparation process of amides compound, it is low excellent with easy to operate, cost Point；

(3) raw material proportioning, reaction condition etc. of the present invention also to preparing amides compound is optimized；In optimization Under the conditions of, prepare the high income of amides compound.

Obviously, the above of the invention, according to the ordinary technical knowledge and customary means of this area, without departing from Under the premise of the above-mentioned basic fundamental thought of the present invention, the modification of other various ways can also be made, is replaced or is changed.

By the following examples the specific embodiment of form, remakes further specifically to the above of the present invention It is bright.But this scope for being interpreted as above-mentioned theme of the invention should not be only limitted to Examples below.It is all based on the above of the present invention The technology realized belongs to the scope of the present invention.

Specific embodiment

Raw material, equipment used in the specific embodiment of the invention is known product, is obtained by buying commercially available prod.

In the present invention, the Chinese for representing of abridging is as described below：

PE：Petroleum ether；EA：Ethyl acetate.

The inventive method of embodiment 1 prepares nitryl aromatic alcohol

Synthetic route is as follows：

By 4-Fluorobenzaldehyde (126mg, 1mmol), nitromethane (214 μ L, 4mmol) and triethylene diamine (110mg, 0.5mmol) add in reaction bulb, and add acetonitrile 2mL to stir, react 24 hours at 0 DEG C, vacuum distillation removes solvent, silicon Plastic column chromatography (PE:EA=10:1) yellow oily product 177.7mg, yield 95%, are obtained.

¹H NMR(400MHz,CDCl₃),δ：7.37-7.42(m,2H),7.09-7.06(m,2H),5.43-5.40(m, 1H), 4.51-4.58 (dd, J=13.2,9.8Hz, 2H), 3.17 (d, J=3.8Hz, 1H).High resolution mass spectrum, molecular formula is： C₈H₈FNO₃+H⁺, theoretical molecular：186.0488, detection molecules amount：186.0489.

The inventive method of embodiment 2 prepares nitryl aromatic alcohol

Synthetic route is as follows：

By 2 thiophene carboxaldehyde (112mg, 1mmol), nitromethane (214 μ L, 4mmol) and triethylene diamine (110mg, 0.5mmol) add in reaction bulb, and add acetonitrile 2mL to stir, react 24 hours at 0 DEG C, vacuum distillation removes solvent, silicon Plastic column chromatography (PE:EA=10:1) yellow oily product 136.7mg, is obtained, its yield 79%.

¹H-NMR(300MHz,CDCl₃,d ppm)δ：3.10 (br s, 1H), 4.34 (dd, J=3.6,13.2Hz, 1H), 4.56 (dd, J=9.6,13.2Hz, 1H), 5.48 (dd, J=9.6,3.6Hz, 1H), 7.02 (t, J=8.1Hz, 1H), 7.48 (d, J=8.4Hz, 1H), 7.88 (d, J=8.4Hz, 1H).High resolution mass spectrum, molecular formula is：C₆H₇NO₃S+H⁺, Theoretical molecular Amount：174.0225, detection molecules amount：174.0230.

The inventive method of embodiment 3 prepares nitryl aromatic alcohol

Synthetic route is as follows：

By p-tolualdehyde (120mg, 1mmol), nitromethane (214 μ L, 4mmol) and triethylene diamine (110mg, 0.5mmol) add in reaction bulb, and add acetonitrile 2mL to stir, react 24 hours at 0 DEG C, vacuum distillation removes solvent, silicon Plastic column chromatography (PE:EA=10:1) yellow oily product 161.1mg, yield 89%, are obtained.

¹H-NMR(300MHz,CDCl₃,d ppm)δ：2.37 (s, 3H), 3.41 (brs, 1H), 4.39 (dd, J=3.9, 13.2Hz, 1H), 4.63 (dd, J=9.0,13.2Hz, 1H), 5.29 (dd, J=9.0,3.9Hz, 1H), 7.29 (d, J= 9.0Hz, 2H), 7.45 (d, J=9.0Hz, 2H).High resolution mass spectrum, molecular formula is：C₉H₁₁NO₃+H⁺, theoretical molecular： 182.0817, detection molecules amount：182.0821.

The inventive method of embodiment 4 prepares nitryl aromatic alcohol

Synthetic route is as follows：

By benzaldehyde (106mg, 1mmol), nitroethane (285 μ L, 4mmol) and triethylene diamine (110mg, 0.5mmol) add in heart bottle, and add benzonitrile 2mL to stir, react 24 hours at 0 DEG C, vacuum distillation removes solvent, Silica gel column chromatography (PE:EA=10:1) faint yellow oily product 166.5mg, yield 92%, are obtained.

¹H NMR(300MHz,CDCl₃)δ:1.50 (d, J=6.8Hz, 3H), 2.70 (d, J=3.7Hz, 1H), 4.69 (dq, J=3.4Hz, 6.8Hz, 1H), 5.40 (dd, J=3.4Hz, 3.7Hz, 1H), 7.35-7.42 (m, 5H).

The inventive method of embodiment 5 prepares amides compound

Synthetic route is as follows：

Benzaldehyde (106mg, 1mmol) and nitromethane (214 μ L, 4mmol) are added in reaction bulb, three second are subsequently adding Alkene diamines (110mg, 0.5mmol) and benzonitrile 0.5ml, stirring reaction 24 hours at 0 DEG C, addition TFMS (267 μ L, 3mmol) with dichloromethane 1.5mL, react 24 hours at 40 DEG C after stirring.After question response terminates, sodium acid carbonate is added PH is adjusted to be neutrality, vacuum distillation removes solvent, silica gel column chromatography (PE:EA=5:1) white solid product 213.3mg, yield, are obtained 79%, 123.5-124.1 DEG C of fusing point.

Structural characterization：¹H NMR (300MHz, CDCl3) δ=4.84 (dd, J=5.28,12.99Hz, 1H), 5.04 (dd, J =6.30,12.99Hz, 1H), 7.09 (d, J=7.32Hz, 1H), 7.26-7.54 (m, 7H), 7.80 (d, J=7.14Hz, 2H) ；¹³C NMR (200MHz, CDCl₃)：51.6,78.3,126.4,127.1,128.8,128.9,129.3,132.2,133.4, 136.3,167.0.High resolution mass spectrum, molecular formula is:C₁₅H₁₄N₂O₃+H⁺, theoretical molecular：271.1082, detection molecules amount: 271.1080。

The inventive method of embodiment 6 prepares amides compound

Synthetic route is as follows：

4-Fluorobenzaldehyde (126mg, 1mmol) and nitromethane (214 μ L, 4mmol) are added in reaction bulb, is subsequently adding Triethylene diamine (110mg, 0.5mmol) and acetonitrile 0.5mL, stirring reaction 24 hours at 0 DEG C add TFMS (267 μ L, 3mmol) and dichloromethane 1.5mL, react 24 hours at 40 DEG C after stirring.After question response terminates, bicarbonate is added It is neutrality that sodium adjusts pH, and vacuum distillation removes solvent, silica gel column chromatography (PE:EA=1:1) white solid product 189.0mg, is obtained, Yield 83%, 137.8-138.7 DEG C of fusing point.

Structural characterization：¹H NMR(300MHz,CDCl₃) δ=4.70 (dd, J=5.43,12.99Hz, 1H), 4.90 (dd, J =6.54,12.99Hz, 1H), 5.66 (dd, J=6.09,12.87Hz, 1H), 6.46 (bs, 1H), 7.05-7.10 (m, 2H), 7.27-7.32(m,2H)；¹³C NMR(200MHz,CDCl₃):23.2,50.7,78.2,116.1,116.4,128.2,128.3, 161.5,169.8. high resolution mass spectrums, molecular formula is：C₁₀H₁₁FN₂O₃+H⁺, theoretical molecular：227.0826, detection molecules amount： 227.0828。

The inventive method of embodiment 7 prepares amides compound

Synthetic route is as follows：

4-Fluorobenzaldehyde (124mg, 1mmol) and nitromethane (214 μ L, 4mmol) are added in reaction bulb, is subsequently adding Triethylene diamine (110mg, 0.5mmol) and benzonitrile 0.5mL, stirring reaction 24 hours at 0 DEG C add TFMS (267 μ L, 3mmol) and dichloromethane 1.5mL, react 24 hours at 40 DEG C after stirring.After question response terminates, bicarbonate is added It is neutrality that sodium adjusts pH, and vacuum distillation removes solvent, silica gel column chromatography (PE:EA=5:1) white solid product 234.9mg, is obtained, is received Rate 81%, 131.2-131.9 DEG C of fusing point.

Structural characterization：¹H NMR(300MHz,CDCl₃) δ=4.83 (dd, J=5.19,13.05Hz, 1H), 5.04 (dd, J =6.30,13.08Hz, 1H), 5.86 (q, J=6.09Hz, 1H), 7.32-7.39 (m, 2H), 7.46 (t, J=7.54Hz, 2H), 7.56 (t, J=7.32Hz, 1H), 7.80 (d, J=7.44Hz, 2H)；¹³C NMR (200MHz, CDCl₃)：51.0,78.3, 116.2,116.4,127.1,128.2,128.3,128.8,132.3,133.3,167.0.High resolution mass spectrum, molecular formula is： C₁₅H₁₃FN₂O₃+H⁺, theoretical molecular：289.0983, detection molecules amount：289.0979.The inventive method of embodiment 8 prepares acyl Aminated compounds

Synthetic route is as follows：

4-chloro-benzaldehyde (140mg, 1mmol) and nitromethane (214 μ L, 4mmol) are added in reaction bulb, is subsequently adding Triethylene diamine (110mg, 0.5mmol) and acetonitrile 0.5mL, stirring reaction 24 hours at 0 DEG C add TFMS (267 μ L, 3mmol) and dichloromethane 1.5mL, react 24 hours at 40 DEG C after stirring.After question response terminates, bicarbonate is added It is neutrality that sodium adjusts pH, and vacuum distillation removes solvent, silica gel column chromatography (PE:EA=2:1) white solid product 188.8mg, is obtained, is received Rate 78%, 117.6-118.4 DEG C of fusing point.

Structural characterization：¹H NMR (400MHz, CDCl₃) δ=2.08 (s, 3H), 4.73 (dd, J=5.28,13.12Hz, 1H), 4.92 (dd, J=6.48,13.12Hz, 1H), 5.68 (q, J=6.04Hz, 1H), 6.47 (d, J=7.52Hz, 1H), 7.27 (d, J=8.48Hz, 2H), 7.38 (d, J=8.52Hz, 2H)；¹³C NMR (200MHz, CDCl₃) 23.1,50.7, 78.0,127.9,129.4,134.7,135.0,170.0.High resolution mass spectrum, molecular formula is：C₁₀H₁₁ClN₂O₃+H⁺Theoretical molecular Amount：243.0531, detection molecules amount：243.0533.

The inventive method of embodiment 9 prepares amides compound

Synthetic route is as follows：

4-chloro-benzaldehyde (140mg, 1mmol) and nitromethane (214 μ L, 4mmol) are added in reaction bulb, is subsequently adding Triethylene diamine (110mg, 0.5mmol) and benzonitrile 0.5mL, stirring reaction 24 hours at 0 DEG C add TFMS (267 μ L, 3mmol) and dichloromethane 1.5mL, react 24 hours at 40 DEG C after stirring.After question response terminates, bicarbonate is added It is neutrality that sodium adjusts pH, and vacuum distillation removes solvent, silica gel column chromatography (PE:EA=5:1) white solid product 218.8mg, is obtained, is received Rate 72%, 138.4-139.2 DEG C of fusing point.

Structural characterization：¹H NMR(400MHz,CDCl₃):δ=4.86 (dd, J=5.04,13.16Hz, 1H), 5.04 (dd, J =6.24,13.16Hz, 1H), 5.87 (q, J=5.72Hz, 1H), 7.16 (d, J=7.72Hz, 1H), 7.33-7.35 (m, 2H), 7.38-7.40 (m, 2H), 7.49 (t, J=7.80Hz, 2H), 7.54-7.60 (m, 1H), 7.82 (d, J=8.56Hz, 2H)；¹³CNMR(100MHz,CDCl₃):51.0,78.2,127.1,127.8,128.8,129.5,132.3,133.2,134.8, 134.9,167.0.High resolution mass spectrum, molecular formula is：C₁₅H₁₃ClN₂O₃+H⁺, theoretical molecular：305.0687, detection molecules amount： 305.0688.

The inventive method of embodiment 10 prepares amides compound

Synthetic route is as follows：

4-chloro-benzaldehyde (140mg, 1mmol) and nitromethane (214 μ L, 4mmol) are added in reaction bulb, is subsequently adding Triethylene diamine (110mg, 0.5mmol) and benzonitrile 0.5mL, stirring reaction 24 hours at 0 DEG C add TFMS (267 μ L, 3mmol) and dichloromethane 1.5mL, react 24 hours at 40 DEG C after stirring.After question response terminates, bicarbonate is added It is neutrality that sodium adjusts pH, and vacuum distillation removes solvent, silica gel column chromatography (PE:EA=5:1) white solid product 238.5mg, is obtained, is received Rate 75%, 119.9-120.7 DEG C of fusing point.

Structural characterization：¹H NMR (400MHz, CDCl₃) δ=3.66 (s, 2H), 4.66 (dd, J=5.00,13.04Hz, 1H), 4.80 (dd, J=6.48,13.00Hz, 1H), 5.62 (q, J=6.20Hz, 1H), 6.33 (d, J=7.60Hz, 1H), 7.10 (d, J=8.48Hz, 2H), 7.28-7.44 (m, 7H)；¹³C NMR (200MHz, CDCl₃)：43.5,50.6,78.0, 127.6,127.7,129.2,129.3,129.4,134.1,134.6,134.8,170.9；High resolution mass spectrum, molecular formula is： C₁₆H₁₅ClN₂O₃+Na⁺, theoretical molecular：341.0663, detection molecules amount：341.0674.It is prepared by the inventive method of embodiment 11 Amides compound

Synthetic route is as follows：

P-bromobenzaldehyde (185mg, 1mmol) and nitromethane (214 μ L, 4mmol) are added in reaction bulb, is subsequently adding Triethylene diamine (110mg, 0.5mmol) and benzonitrile 0.5mL, stirring reaction 24 hours at 0 DEG C add TFMS (267 μ L, 3mmol) and dichloromethane 1.5mL, react 24 hours at 40 DEG C after stirring.After question response terminates, bicarbonate is added It is neutrality that sodium adjusts pH, and vacuum distillation removes solvent, silica gel column chromatography (PE:EA=5:1) white solid product 266.6mg, is obtained, is received Rate 81%, fusing point：160.1-161.1℃.

Structural characterization：¹H NMR (400MHz, CDC_l3) δ=4.84 (dd, J=4.80,13.04Hz, 1H), 7.43-7.58 (m, 5H), 7.82 (d, J=7.44Hz, 2H)；¹³C NMR (200MHz, CDC_l3)：51.0,77.8,122.9,127.1,128.1, 132.3,133.2,135.4,167.0.High resolution mass spectrum, molecular formula is：C₁₅H₁₃BrN₂O₃+H⁺, theoretical molecular： 349.0182, detection molecules amount：349.0183.

The inventive method of embodiment 12 prepares amides compound

Synthetic route is as follows：

P-tolyl aldehyde (120mg, 1mmol) and nitromethane (214 μ L, 4mmol) are added in reaction bulb, Ran Houjia Enter triethylene diamine (110mg, 0.5mmol) and acetonitrile 0.5mL, stirring reaction 24 hours at 0 DEG C add TFMS (267 μ L, 3mmol) and dichloromethane 1.5mL, react 24 hours at 40 DEG C after stirring.After question response terminates, bicarbonate is added It is neutrality that sodium adjusts pH, and vacuum distillation removes solvent, silica gel column chromatography (PE:EA=1:1) white solid product 173.2mg, is obtained, is received Rate 78%, 116.4-117.2 DEG C of fusing point.

Structural characterization：¹H NMR(300MHz,CDCl₃):δ=2.03 (s, 3H), 2.33 (s, 3H), 4.71 (dd, J= 5.28,12.84Hz, 1H), 4.87 (dd, J=6.48,13.11Hz, 1H), 5.63 (q, J=6.54Hz, 1H), 6.60 (bs, 1H),7.18-7.26(m,4H)；¹³CNMR(200MHz,CDCl³):21.1,23.1,51.3,78.3,126.5,129.8, 133.6,138.6,170.2.High resolution mass spectrum, molecular formula is：C₁₁H₁₄N₂O₃+H⁺, theoretical molecular：223.1077, detection point Son amount：223.1085.

The inventive method of embodiment 13 prepares amides compound

Synthetic route is as follows：

O-bromobenzaldehye (185mg, 1mmol) and nitromethane (214 μ L, 4mmol) are added in reaction bulb, is subsequently adding Triethylene diamine (110mg, 0.5mmol) and acetonitrile 0.5mL, stirring reaction 24 hours at 0 DEG C add TFMS (267 μ L, 3mmol) and dichloromethane 1.5mL, react 24 hours at 40 DEG C after stirring.After question response terminates, bicarbonate is added It is neutrality that sodium adjusts pH, and vacuum distillation removes solvent, silica gel column chromatography (PE:EA=2:1) white solid product 203.3mg, is obtained, is received Rate 71%, 139.6-140.1 DEG C of fusing point.

Structural characterization：¹H NMR(400MHz,CDCl₃):δ=2.10 (s, 3H), 4.81 (dd, J=4.72,13.08Hz, 1H), 4.97 (dd, J=7.08,13.08Hz, 1H), 5.99-6.03 (m, 1H), 6.91 (d, J=7.60Hz, 1H), 7.20- 7.27 (m, 1H), 7.28-7.54 (m, 2H), 7.62 (d, J=7.84Hz, 1H)；¹³C NMR(100MHz,CDCl₃):23.3, 55.3,86.4,126.5,128.6,129.1,136.9,169.9.High resolution mass spectrum, molecular formula is：C₁₀H₁₁BrN₂O3+H⁺, reason By molecular weight：287.0029, detection molecules amount：287.0028.

The inventive method of embodiment 14 prepares amides compound

Synthetic route is as follows：

1- naphthaldehydes (156mg, 1mmol) and nitromethane (214 μ L, 4mmol) are added in reaction bulb, three are subsequently adding Ethylene diamine (110mg, 0.5mmol) and acetonitrile 0.5mL, stirring reaction 24 hours at 0 DEG C, addition TFMS (267 μ L, 3mmol) with dichloromethane 1.5mL, react 24 hours at 40 DEG C after stirring.After question response terminates, sodium acid carbonate is added PH is adjusted to be neutrality, vacuum distillation removes solvent, silica gel column chromatography (PE:EA=2:1) white solid product 180.6mg, yield, are obtained 70%, 162.1-163.0 DEG C of fusing point.

Structural characterization：¹H NMR(400MHz,CDCl₃):δ=2.05 (s, 3H), 4.92-5.02 (m, 2H), 6.33 (d, J= 7.44Hz, 1H), 6.57 (q, J=6.88Hz, 1H), 7.46-7.48 (m, 2H), 7.57-7.64 (m, 2H), 7.87-7.93 (m, 2H), 8.12 (d, J=8.44Hz, 1H)；¹³C NMR(100MHz,CDCl₃):23.1,47.6,77.4,122.3,123.2, 125.1,126.4,127.4,129.2,129.7,130.4,132.1,134.1,169.7.High resolution mass spectrum, molecular formula is： C₁₄H₁₄N₂O₃+H⁺, theoretical molecular：259.1077, detection molecules amount：259.1080.

The inventive method of embodiment 15 prepares amides compound

Synthetic route is as follows：

Benzaldehyde (106mg, 1mmol) and nitroethane (286 μ L, 4mmol) are added in reaction bulb, three second are subsequently adding Alkene diamines (110mg, 0.5mmol) and acetonitrile 0.5mL, stirring reaction 24 hours at 0 DEG C are determined after reaction completely with TLC, are added TFMS (267 μ L, 3mmol) and dichloromethane 1.5mL, react 24 hours after stirring at 40 DEG C.Question response is tied Shu Hou, it is neutrality to add sodium acid carbonate to adjust pH, and vacuum distillation removes solvent, silica gel column chromatography (PE:EA=2:1) white, is obtained solid Body product 164.2mg, yield 74%, 185.5-186.0 DEG C of fusing point.

Structural characterization：¹H NMR(400MHz,CDCl₃):δ=1.58 (d, J=6.76Hz, 3H), 2.09 (s, 3H), 4.98- 5.05 (m, 1H), 5.46-5.52 (m, 1H), 6.70 (d, J=9.20Hz, 1H), 7.27-7.41 (m, 5H)；¹³C NMR (100MHz,CDCl₃):23.2,29.7,51.2,122.9,128.1,128.2,130.3,133.8,135.2,169.6.High score Mass spectrum is distinguished, molecular formula is：C₁₁H₁₄N₂O₃+H⁺, theoretical molecular：223.1026, detection molecules amount：223.1030.

In order to illustrate beneficial effects of the present invention, the present invention provides tests below example：

Test example 1 prepares the catalyst screening of 2- nitro -1- phenylethanols

Synthetic route is as follows：

By benzaldehyde (106mg, 1mmol), nitromethane (214 μ L, 4mmol), catalyst different in table 1 are selected respectively (1mmol) add in reaction bulb with 2mL dichloromethane, stirring reaction 24 hours under room temperature, vacuum distillation removes solvent, silica gel column layer Analysis (PE:EA=10:1) yellow oily product, is obtained, its yield is as shown in table 1.

¹H-NMR(300MHz,CDCl₃,d ppm):δ:3.41 (br s, 1H), 4.38 (dd, J=3.3,13.2Hz, 1H), 4.54 (dd, J=9.6,13.2Hz, 1H), 5.29 (dd, J=9.6,3.3Hz, 1H), 7.53 (m, 5H).

The selection result of the different catalysts of table 1

Sequence number	Catalyst	Temperature (DEG C)	Yield (%)
				1	Triethylamine	Room temperature	25
2	Diethylamine	Room temperature	20
				3	Potassium tert-butoxide	Room temperature	44
4	Caustic alcohol	Room temperature	20
				5	The water of triethylene diamine six	Room temperature	67

As shown in Table 1, triethylene diamine, potassium tert-butoxide, triethylamine, diethylamine or caustic alcohol can serve as system of the present invention The catalyst of standby 2- nitro -1- phenylethanols；Particularly, during using triethylene diamine or potassium tert-butoxide as catalyst, 2- nitre The high income of base -1- phenylethanols.

Test example 2 prepares the solvent screening of 2- nitro -1- phenylethanols

Synthetic route is as follows：

By benzaldehyde (106mg, 1mmol), nitromethane (214 μ L, 4mmol), triethylene diamine (220mg, 1mmol) and Select solvents different in 2mL tables 2 to add respectively to stir in reaction bulb, react 24 hours at room temperature, vacuum distillation is removed Solvent, silica gel column chromatography (PE:EA=10:1) yellow oily product, is obtained, its yield is as shown in table 2.

The selection result of the different solvents of table 2

Sequence number volume	Solvent	Yield (%)
			1	Dichloromethane	67
2	Chloroform	65
			3	Toluene	10
4	Acetonitrile	83
			5	Benzonitrile	80
6	Benzene acetonitrile	75

As shown in Table 2, acetonitrile, benzonitrile, benzene acetonitrile, dichloromethane or chloroform prepare 2- nitro -1- benzene as the present invention The solvent of base ethanol, the high income of 2- nitro -1- phenylethanols；Particularly, using acetonitrile, benzonitrile, benzene acetonitrile etc. as molten During agent, the yield of 2- nitro -1- phenylethanols is more than 75%.

Test example 3 prepares the reaction temperature screening of 2- nitro -1- phenylethanols

Synthetic route is as follows：

By benzaldehyde (106mg, 1mmol), nitromethane (214 μ L, 4mmol), triethylene diamine (220mg, 1mmol) and 2mL acetonitriles are added and stirred in reaction bulb, are reacted 24 hours under the different temperatures being placed in table 3, and vacuum distillation removes solvent, silicon Plastic column chromatography (PE:EA=10:1) yellow oily product, is obtained, its yield is as shown in table 3.

The selection result of the differential responses temperature of table 3

Sequence number	Temperature (DEG C)	Yield (%)
			1	Room temperature	83
2	0	90
			3	40	71

As shown in Table 3, reaction temperature of the present invention prepares the yield of 2- nitro -1- phenylethanols in the range of 0 DEG C～40 DEG C It is high；Particularly, reaction temperature is 0 DEG C, and the yield of 2- nitro -1- phenylethanols reaches 90%.

Test example 4 prepares the raw material proportioning screening of 2- nitro -1- phenylethanols

Synthetic route is as follows：

Select benzaldehyde (106mg, 1mmol), triethylene diamine (220mg, 1mmol) and respectively different moles in table 4 The nitromethane of ratio is added in reaction bulb, and adds acetonitrile 2mL to stir, and is reacted 24 hours at 0 DEG C, and vacuum distillation is except molten Agent, silica gel column chromatography (PE:EA=10:1) yellow oily product, is obtained, its yield is as shown in table 4.

The selection result of the different benzaldehydes of table 4 and nitromethane mol ratio

Sequence number	Benzaldehyde and nitromethane mol ratio	Yield (%)
			1	1:2	82
2	1:4	90
			3	1:8	91

As shown in Table 4, the mol ratio of benzaldehyde and nitromethane is 1：In the range of (2～8), 2- nitro -1- phenyl is prepared The high income of ethanol；Preferably, benzaldehyde and the mol ratio of nitromethane are 1：(4～8).

Test example 5 prepares the catalyst amount screening of 2- nitro -1- phenylethanols

Synthetic route is as follows：

By benzaldehyde (106mg, 1mmol), nitromethane (214 μ L, 4mmol) and respectively select table 5 in different mol ratio Triethylene diamine add in reaction bulb, and add acetonitrile 2mL to stir, react 24 hours at 0 DEG C, vacuum distillation is except molten Agent, silica gel column chromatography (PE:EA=10:1) yellow oily product, is obtained, its yield is as shown in table 5.

The selection result of the benzaldehyde of table 5 and triethylene diamine different mol ratio

Sequence number	Benzaldehyde and triethylene diamine mol ratio	Yield (%)
			1	1：0.1	30
2	1：0.2	45
			3	1：0.5	95
5	1：2	96

As shown in Table 5, the mol ratio of benzaldehyde and triethylene diamine is 1：In the range of (0.1～2), catalysis is may be incorporated for Prepare 2- nitro -1- phenylethanols；Particularly, the mol ratio of benzaldehyde and triethylene diamine is 1：In the range of (0.5～2), 2- The high income of nitro -1- phenylethanols.

Test example 6 prepares the reaction time screening of 2- nitro -1- phenylethanols

Synthetic route is as follows：

By benzaldehyde (106mg, 1mmol), nitromethane (214 μ L, 4mmol) and triethylene diamine (110mg, 0.5mmol) add in reaction bulb, and add acetonitrile 2mL to stir, carry out 6h, 12h, 24h and 48h reaction at 0 DEG C respectively, Vacuum distillation removes solvent, silica gel column chromatography (PE:EA=10:1) yellow oily product, is obtained, its yield is as shown in table 6.

The screening of the differential responses time of table 6

Sequence number	Reaction time (h)	Yield (%)
			1	6	50
2	12	70
			3	24	95
5	48	95

As shown in Table 6, when the reaction time is 6h, the yield of 2- nitro -1- phenylethanols is 50%；With the reaction time Extend, yield is also with raising；When reaction time is 24h, the yield of 2- nitro -1- phenylethanols has reached 95%, then prolongs In the long reaction time, yield is without significant change.

The preparation method of nitryl aromatic alcohol of the present invention, has the advantages that：

(1) present invention prepares nitro using the conduct such as triethylene diamine, potassium tert-butoxide, triethylamine, diethylamine or caustic alcohol There is very big difference, the catalyst tool of the present invention in the catalyst of aromatic alcohol, the catalyst for preparing nitryl aromatic alcohol with prior art Have the advantages that simple structure, be conveniently easy to get, price is low, product yield high；

Particularly, during using triethylene diamine as catalyst, R₁The mol ratio of CHO and triethylene diamine is 1：(0.5～ 2) in the range of, preparing the yield of nitryl aromatic alcohol can reach more than 95%；

(2) present invention is also to when the solvent, raw material proportioning, catalyst amount, reaction temperature, the reaction that prepare nitryl aromatic alcohol Between etc. screened, optimize reaction condition；

A, the present invention, as solvent, prepare nitryl aromatic alcohol using acetonitrile, benzonitrile, benzene acetonitrile, dichloromethane or chloroform High income；Particularly, during using acetonitrile, benzonitrile, benzene acetonitrile etc. as solvent, the yield of nitryl aromatic alcohol 75% with On；

B, R of the present invention₁CHO and R₂CH₂NO₂Mol ratio 1：In the range of (2～8), the yield of nitryl aromatic alcohol is prepared It is high；Preferably, R₁CHO and R₂CH₂NO₂Mol ratio be 1：(4～8)；

C, reaction temperature of the present invention prepare the high income of nitryl aromatic alcohol in the range of 0 DEG C～40 DEG C；Particularly, react When temperature is 0 DEG C, the yield of nitryl aromatic alcohol reaches 90%；

D, reaction time of the invention, in more than 12h, prepare the high income of nitryl aromatic alcohol；Particularly, the reaction time is in 24h During the above, the yield of nitryl aromatic alcohol is more than 90%.

In sum, the catalyst that the present invention is adopted is significantly different with the catalyst that prior art prepares nitryl aromatic alcohol, Have the advantages that simple structure, be conveniently easy to get, price is low, product yield high；Particularly, using triethylene diamine as catalyst When, the present invention prepares the yield of nitryl aromatic alcohol can reach more than 95%, with easy to operate, low cost and other advantages, industry Application prospect is good.

Test example 7 prepares the methylene chloride screening of amides compound

Synthetic route is as follows：

By benzaldehyde (106mg, 1mmol), nitromethane (214 μ L, 4mmol) and triethylene diamine (110mg, 0.5mmol) add in reaction bulb, be separately added into the acetonitrile of different volumes in table 7, stirring reaction 24 hours at 0 DEG C add trifluoro The dichloromethane of correspondence different volumes in methanesulfonic acid (263 μ L, 3mmol) and table 7, reaction 24 is little at 40 DEG C after stirring When.After question response terminates, it is neutrality to add sodium acid carbonate to adjust pH, and vacuum distillation removes solvent, silica gel column chromatography (PE:EA=2:1), White solid product is obtained, yield is as shown in table 7.

Structural characterization：¹H NMR (400MHz, CDCl₃) δ=2.02 (s, 3H), 4.70 (dd, J=5.52,12.90Hz, 1H), 4.87 (dd, J=6.90,12.93Hz, 1H), 5.66 (q, J=7.23Hz, 1H), 6.62 (d, J=7.23Hz, 1H), 7.26-7.39 (m, 5H)；High resolution mass spectrum, molecular formula is：C₁₀H₁₂N₂O₃+H⁺, theoretical molecular：209.0921, detection molecules Amount：209.0918.

The selection result of the acetonitrile of table 7 and dichloromethane proportioning

Sequence number	Acetonitrile	Dichloromethane	Yield (%)
				1	2ml	0ml	Trace
2	1ml	1ml	35
				3	0.5ml	1.5ml	82
4	0.5ml	2ml	78
				5	0.5ml	4ml	50
6	0.5ml	6ml	20
				7	0.5ml	1ml	55
8	0.5ml	0.5ml	40

As shown in Table 7, the molal volume ratio of benzaldehyde, acetonitrile, dichloromethane is 1：(0.5～1)：(0.5～6) (mol： L：L in the range of), the amides compound of the present invention can be prepared；Particularly, mole body of benzaldehyde, acetonitrile, dichloromethane Product ratio is 1：0.5：(1.5～2) (mol：L：L in the range of), the high income of amides compound is prepared.

Test example 8 prepares the reaction temperature screening of amides compound

Synthetic route is as follows：

Benzaldehyde (106mg, 1mmol) and nitromethane (214 μ L, 4mmol) are added in reaction bulb, is then respectively adding The acetonitrile of triethylene diamine (110mg, 0.5mmol) and 0.5mL, stirring reaction 24 hours, are subsequently adding TFMS at 0 DEG C (263 μ L, 3mmol) and 2mL dichloromethane, after stirring respectively at 0 DEG C, rt, 40 DEG C react 24 hours.Question response is tied Shu Hou, it is neutrality to add sodium acid carbonate to adjust pH, and vacuum distillation removes solvent, silica gel column chromatography (PE:EA=2:1) white, is obtained solid Body product, yield is as shown in table 8.

The selection result of the differential responses temperature of table 8

Sequence number	Temperature/DEG C	Yield
			1	0	35
2	rt	60
			3	40	82

As shown in Table 8, reaction temperature can prepare the amides compound of the present invention in the range of 0 DEG C～40 DEG C,；It is special It is not that when reaction temperature is 40 DEG C, the yield of product reaches 82%.

Test example 9 prepares the TFMS consumption screening of amides compound

Synthetic route is as follows：

Benzaldehyde (106mg, 1mmol) and nitromethane (214 μ L, 4mmol) are added in reaction bulb, is then respectively adding The acetonitrile of triethylene diamine (110mg, 0.5mmol) and 0.5mL, stirring reaction 24 hours at 0 DEG C are separately added in table 9 different The TFMS and 2mL dichloromethane of mole, reacts 24 hours after stirring at 40 DEG C.After question response terminates, plus Enter sodium acid carbonate to adjust pH is neutrality, and vacuum distillation removes solvent, silica gel column chromatography

(PE:EA=2:1) white solid product, is obtained, yield is as shown in table 9.

The selection result of the different benzaldehydes of table 9 and three fluosulfonic acid mol ratios

Sequence number	TFMS consumption/mmol	Yield
			1	2	47
2	3	82
			3	4	80

As shown in Table 9, benzaldehyde, nitromethane, the mol ratio of triethylene diamine, TFMS is 1：4：0.5：(2 ～4) in the range of, can prepare the present invention amides compound；Particularly, benzaldehyde, nitromethane, triethylene diamine, The mol ratio of TFMS is 1：4：0.5：(3～4), the high income of product.

The preparation method of amides compound of the present invention, has the advantages that：

(1) present invention using simple structure, be conveniently easy to get, the catalyst such as low-cost triethylene diamine；

(2) present invention is dexterously combined together two-step reaction very much, the organic nitrile such as acetonitrile, benzonitrile, benzene acetonitrile Solvent is both the solvent of first step reaction, is also the raw material of second step reaction；The nitryl aromatic alcohol of preparation is without the need for purifying, Ke Yizhi Connect for preparing amides compound, simplify the preparation process of amides compound, it is low excellent with easy to operate, cost Point；

(3) raw material proportioning, reaction condition etc. of the present invention also to preparing amides compound is optimized；In optimization Under the conditions of, prepare the high income of amides compound.

In sum, the present invention using simple structure, be conveniently easy to get, the catalyst such as low-cost triethylene diamine, very Dexterously two-step reaction is combined together, the organic nitrile solvent such as acetonitrile, benzonitrile, benzene acetonitrile is both the molten of first step reaction Agent, is also the raw material of second step reaction；The nitryl aromatic alcohol of preparation is used directly for preparing amide-type chemical combination without the need for purifying Thing, simplifies the preparation process of amides compound, has the advantages that easy to operate, low cost, high income, prospects for commercial application Well.

Claims (2)

1. triethylene diamine generates the catalyst applications in nitryl aromatic alcohol, the catalysis in catalysis aromatic aldehyde with nitro hydrocarbon reaction Aromatic aldehyde and nitro hydrocarbon reaction generate the synthetic route of nitryl aromatic alcohol：

Comprise the following steps：

A, by R₁CHO、R₂CH₂NO₂, catalyst and polar organic solvent be well mixed, stirring reaction 24 hours～48 is little at 0 DEG C When, obtain product；

The R₁CHO、R₂CH₂NO₂, catalyst mol ratio be 1：(4～8)：(0.5～2)；

The catalyst is triethylene diamine；

The polar organic solvent is acetonitrile, benzonitrile, benzene acetonitrile, dichloromethane or chloroform；

The R₁CHO is 1mol with the molal volume ratio of organic solvent：(0.5～2) L；

B, the product of step a is removed into solvent, Jing silica gel column chromatographies obtain oily product, as nitryl aromatic alcohol；

Wherein, R₁For phenyl, R₂For H.

2. purposes according to claim 1, it is characterised in that：In step b, the eluant, eluent of the silica gel column chromatography is oil Ether/ethyl acetate mixed solvent；In the mixed solvent, petroleum ether is 10 with the volume ratio of ethyl acetate:1.