CN1007811B - Process for preparing carbamic acid derivatives - Google Patents

Abstract

The present invention relates to a preparation method of a carbamic acid derivative represented by the formula (1). The meanings of symbols in the formula are described in a specification. According to the method, carbamic acid ester, thiocarbamate or urea can be obtained by reacting a compound with a halogenated derivative in the temperature of-5 to 150 DEG C and in the existence of a halogen acid receptor, wherein the molecular formula of the compound is NH, and the formula of the halogenated derivative is disclosed in the specification. The carbamic acid derivative is a very useful compound, particularly an effective pesticide.

Description

Process for preparing carbamic acid derivatives

The present invention relates to a kind of novel process for preparing carbamic acid derivative, more particularly, it relates to a class formula and is:

The preparation technology of derivative, in the formula, Y represents alcohol radical, thiol group or amido.Therefore, such derivative is carbamate, thiocarbamate or urea.

For example, usually the method for preparing carbamate and thiocarbamates compound is chloro-formic ester or sulfo-chloro-formic ester and amine reaction, as " chemistry comment " the 64th phase in 1964 the 656th～663 page of (Chemical Keview, 1964,64, Pages 656～663) paper narrate like that.Or with urea chloride or isocyanic ester and alcohol, phenol or thiol reactant.(Ge Liya: " organic chemistry monograph " X IV volume, the 20th～31 page).

As for urea, normally obtain with isocyanic ester or urea chloride and amine reaction.When they when being symmetric, also can prepare (Ge Liniya: XI V volume, the 85th page, 30 pages) with phosgene and amine reaction.

Yet, more than various technologies be not can both prepare to wish the compound obtain, perhaps these technologies are difficult to carry out sometimes.

Some starting material is:

-unsettled.Many chloro-formic esters (for example chloroformic acid chaff ester, the chloroformic acid tert-butyl ester and chloroformic acid are to the anisole methyl esters) are exactly this situation.

-poisonous.For example, isocyanic ester, phosgene.Especially the lightweight formyl is a carcinogenic substance.

-or pollutent.Lightweight sulfo-chloro-formic ester class for example.

People have carried out seeking the research of variation route.

In the presence of catalyzer (for example uranyl nitrate),, made a few compounds by methylcarbonate or ethyl-carbonate and aniline reaction.But output is all very low, and has to obtain a large amount of by products simultaneously at high temperature (100 ℃, United States Patent (USP) 3,763,217) reacting by heating mixture.

Unless in the presence of catalyzer (for example 2 hydroxy pyrimidine), diphenyl carbonate can not generate carbamate (the rugged liter in mountain with the amine reaction, Yi Kou fortune Tian Xiong and Dong Fu two: " polymer science " the 17th volume, the 835th～841 page of (1979)-Noborn yamazaki and Todao Igudi, Fuknji Higashi, Journal of Poiymer Sciencll, Vol, 17 Pages 835～841(1979).

Also the someone has proposed other carboxylamine reagent.For example:

-folded oxygen compound, the synthetic of triazo-compound undertaken by several stages, is inapplicable.These chemical combination image BCC triazo-compound is the same, can carry out volatile decomposition, (" applied chemistry " is English international, the second phase in 1977 the 16th page of Angew, and Chem, Int, Ed, Engl, 16,1977No2).

-having carried out some tests with special carbonic ether (for example mixture p-nitrophenyl carbonate ester), the by product that obtains is difficult to remove.

-carbonic acid hydrogen ester.This class is synthetic very inapplicable and expensive.With the hydrogen-carbonate tert-butyl ester especially like this.Moreover also lost protecting group.

-fluoro manthanoate.This class manthanoate preparation difficulty, and need to use starting material that be difficult to process, noncommodityization, for example ClCOF or BrCOF.

After deliberation the reaction of some carbamate and amine.Urea only is being heated to after about 150～230 ℃, under the condition of using catalyzer, just can obtain (Phillippe Ah nurse and Fu Langke A Blang, " chemistry comment ", 1965, the 574 pages of Chemical Review, 1965, Page574).

In these different technologies, always there are alcohol or phenol to generate, these things are difficult to remove usually, and reaction is a reversible.

In some cases, the preparation urea is absolutely not.For example, when TMSIM N imidazole urethanum and ethamine reaction, what obtain is N-ethyl carbamic acid ethyl ester and imidazoles, and can not get urea.

More than this simple evaluation, the limitation of traditional technology has been described, also undesirable by the result of variation route gained.

Therefore, wish to have a universal method that is suitable for preparing various carbamic acid derivatives.This method is not only used with regard to the dangerous initial compounds with regard to less, and with regard to working conditions and removing of by product and Yan Douying realizes easily.

According to technology of the present invention, be suitable for preparing a large amount of carbamic acid derivatives, be particularly suited for preparing the carbamic acid derivative that other route can not prepare.

The formula of the present invention relates to is:

The preparation technology of carbamic acid derivative.R wherein ¹And R ²(they can be identical groups, also can be different groups) representative:

-hydrogen atom;

-replace or non-replacement, the fat group or the aromatic yl aliphat group of saturated or unsaturated, straight chain or side chain;

-replace or non-replacement, saturated or unsaturated alicyclic group;

-that replace or non-replacement, saturated or unsaturated heterocyclic group.

Perhaps the nitrogen-atoms that connects with their institutes keys forms ring together, and that this ring can form is saturated or unsaturated, the part of loop systems that replace or non-replacement, also can comprise one or several other heteroatoms

Y represent OR,

Deng group.Wherein R represents the aliphatic group or the aryl group on behalf of aliphatic of that replace or non-replacement, saturated or unsaturated, straight chain or side chain, that replace or non-replacement, saturated or unsaturated alicyclic group, aromatic group perhaps that replace or non-replacement.R ³And R ⁴(they can be identical, also can be different) represent hydrogen atom, that replace or non-replacement, saturated or unsaturated aliphatic group, aryl group on behalf of aliphatic, alicyclic group or heterocyclic group, or aromatic group that replace or non-replacement, perhaps the nitrogen-atoms that is linked with them forms a heterocycle saturated or unsaturated, that replace or non-replacement together, and this heterocycle can comprise one or several other heteroatoms.R ⁶And R ⁷(they can be identical, also can be different) representative saturated or unsaturated, that replace or non-replacement, straight chain or side chain fat group or alicyclic group, perhaps representative (but not being the two while) hydrogen atom, alkylthio or alkoxyl group.

This technology is that when the haloid acid acceptor existed, under the temperature between-5 °～150 ℃, formula was:

Hydrogenous aminocompound and formula be:

Alpha-halogen carbonic acid derivatives reaction.R wherein ¹And R ²Same as described above with the connotation of Y.X represents fluorine, chlorine or bromine atom.R ⁵Represent hydrogen atom, replace or non-replacement, saturated or unsaturated aliphatic group, aryl group on behalf of aliphatic or alicyclic group, perhaps representative aromatic group that replace or non-replacement.

This reaction can be finished in the presence of solvent, also can finish in the presence of solvent-free.

This reaction can be represented with following synoptic diagram:

Can be surprisingly found out that by reaction formula HX is by cancellation, but, follow amino takes place not as desired usually

Be connected on the halogen-containing carbon atom, thereby form:

For example, in the reaction of alpha-chlorinated carbonates and acid, come to this:

(the Aktiebolaget Astra patent France patent No. 2,201,870)

（ASTRA-Patent????FR2，201，870）

On the contrary, according to our technology, the division of alpha-halogen derivative takes place in the reaction,

Group is connected on the group of aminocompound, and aldehyde R is arranged ⁵CHO generates.

Formula is Initial hydrogeneous aminocompound can use ammonia and most of known primary amine or secondary amine.

Work as R ¹Or R ²When representing fatty group, it preferably comprises 1 to 20 carbon atom.R ¹And R ²Also can represent and contain the nearly alicyclic group or the aryl group on behalf of aliphatic of 50 carbon atoms, for example phenmethyl.They also can form a heterocycle together, for example piperidines subring, morpholine ring or imidazole ring.

Substituent R ¹And R ²Can be various groups, for example alkyl be by acid, alcohol, ester, ether, sulfydryl or amino the replacement.

As effective amine, methylamine, diethylamine, Di-n-Butyl Amine, isobutylamine, n-octyl amine, thanomin, benzene methanamine, N-methyl N-phenmethyl amine, piperidines, imidazoles, hexamethylene imine, morpholine and diethanolamine arranged what this can mention.

The natural amino acid or synthesizing amino acid, optical amino-acid, non-optical amino-acid or the DL-Amino Acid that use in peptide is synthetic are also very suitable.

For example, what this can mention L-phenylalanine, L-proline(Pro), glycine, L-tyrosine, L-Serine, L-aspartic acid, proline(Pro), glycine ethyl ester and phenylglycocoll arranged.

Second initial compounds that uses can be alpha-halogen carbonic ether, thiocarbonic ester or carbamate, preferably the alpha-chloro thing.

Preparing this compound can carry out with various known methods.For example, the preparation chlorinated derivative, by as shown in the formula alpha-chloro chloro-formic ester and oxy-compound or thiol reactant.

As M Ma Ciluo (MMatzner), like that " " chemistry comment " the 64th volume; the 651st～654 page of (1964)-Chem, Pew, 64Pages651～654(1964) " that R Ku Erkeji (RKurkjy) and the spy of RJ section (RJCotter) are narrated in paper, or with amine by means of " European patent application " (European Patent Application) № .45,234 or 331401766,7, in the method preparation narrated.

The preparation of alpha-chloro chloro-formic ester itself is very simple, and the method with being proposed among " European patent application " № .40153 prepares on the contrary with phosgene and aldehyde.

Radicals R ⁵Little group preferably is for example by 1 to 4 aliphatic group that carbon atom is formed.It can be a substituted radical, preferably with the substituted radical of halogen atom (particularly chlorine atom).Methyl and trichloromethyl are the groups of particularly important.

Radicals R in carbonic ether or the thiocarbonic ester can be various groups, and this group can be

-aliphatic group preferably comprises 1 to 12 carbon atom.For example, methyl, ethyl or the tertiary butyl.These groups also can be substituting groups, for example have the heterocyclic group, as furyl.

-aryl group on behalf of aliphatic is phenmethyl for example.

The aromatic nucleus of-replacement or non-replacement, it can form the part that also can not form member ring systems.Phenyl or 2 for example, 3-dihydro-2,2-dimethyl-7-benzofuryl.

No matter this radicals R is to belong to any, can use one or several

Or

Group replaces.

Especially when initial amine was an amino acid, it was in order to protect one of amino group commonly used in peptide is synthetic.The for example tertiary butyl, phenmethyl, p-nitrophenyl methyl, 9-fluorene methyl, 2,2,2-three chloroethyls, three silicomethane ethyl or furfuryl groups.In this case, the alpha-chlorinated carbonates and the carbonic acid tert-butyl ester are the compounds of particularly important.

For example, the R in the initial alpha-chloro carbamate ³And R ⁴Represent hydrogen atom or methyl, perhaps the nitrogen-atoms with their links forms an imidazole ring together.Therefore, alpha-chloro ethoxycarbonyl imidazoles and N-methylamino-formic acid 1,2,2,2, the tetrachloro ethyl ester is the compound of particularly important.

R ⁶And R ⁷Especially represent hydrogen atom, methylthio group, C ₁₁～C ₁₂Aliphatic group or comprise the alicyclic group of 30 carbon atoms.R ⁶And R ⁷Substituting group can be alkyl or the group that contains heteroatoms (particularly sulphur atom).

Owing to discharge haloid acid HX in the reaction, therefore, must have the acceptor of acid to exist for removing haloid acid.

The acceptor of acid can be organic bases or mineral alkali.

In the alkali of preferentially selecting for use, (for example triethylamine, pyridine, N, accelerine and formula are at this have sodium hydroxide, potassium hydroxide, yellow soda ash, sodium bicarbonate, salt of wormwood and saleratus, magnesium oxide and S-WAT (these alkali usually all use with the form of the aqueous solution) and the tertiary amine that can mention Raw material self).

The amount that adds the alkaline matter in the medium should be all acid that is enough to discharge in the neutralization reaction, cans be compared to stoichiometrical number most just over some.

Be that the reaction of foundation is preferably in the solvent medium and carries out with the present invention.Usually using one or more is the inert solvent to reactant.These solvents are preferably selected from chloro fat family solvent.For example, methylene dichloride, 1,2-ethylene dichloride, cyclic ethers or acyclic ether (resembling tetrahydrofuran (THF)), acetone, pyridine, acetonitrile, dimethyl formamide or alcohols (for example ethanol or the trimethyl carbinol) with diox.Can contain a certain amount of water in the reaction medium, for example,, water must be arranged for making the mineral alkali dissolving.

Temperature of reaction depends on the character of solvent and the anti-activity of starting compound, generally between-5 ° to 150 ℃.The reaction of carbonic ether or thiocarbonic ester and amine, temperature of reaction usually between 0 ° to 30 ℃, the reaction of amino formate, temperature of reaction is between 30 ° to 100 ℃.

Starting material compound uses by stoichiometrical amount usually.There preferably have in two kinds of reactants to be a kind of more excessive a little.

When raw material amine uses as sour acceptor again, transformed corresponding to each equivalent

Group will use two normal amine at least.

The order that reactant adds not is a principal feature of the present invention.But,, preferably add other starting compound earlier, and then add amine when amine is primary amine when using as the acceptor, alkali of acid again.

Can easily obtain chemical compound lot with technology of the present invention, some of them compound usual method is to be difficult to preparation.These compounds are of great use as medicine.For example, the amino formate of used as pesticides has: carbofuran, N-methyl carbamic acid 3,4 dimethyl phenyl esters, aldicarb and SevinCarbaryl; Thiocarbamates has: butylate, EPTC and Hydram; Ureas has: chlorotoluron and monuron.In peptide is synthetic, make intermediate, as, the amino amino formate ester.For example in this synthetic (" tetrahedron " the 39th volume, the 24th phase that aspartame (Aspartartame) is arranged that can mention, the 4121st～4126 page, people Tetra hedron Volume39 such as nineteen eighty-three, B moral, 24 phases, 4121～4126, B, Ycl et al).

The present invention can illustrate by following example.

Example 1, N, the preparation of N-di-n-butyl aethylis carbamas

Anhydrous tetrahydro furan (the 20 milliliters of tetrahydrofuran (THF)s) drips of solution of 26 gram (0.2 mole) Di-n-Butyl Amines is added to 15.2 gram (0.1 mole) carbonic acid α-chloroethyl ethyl esters

80 milliliters of tetrahydrofuran solutions in.

The adding of reactant is at 20 ℃, under agitation carries out.Reaction is the reaction of slight exotherm, and observes the sedimentary generation of hydrochloric acid Di-n-Butyl Amine.Under 20 ℃, mixture was stirred 2 hours, remove by filter throw out, steam tetrahydrofuran (THF).

Residuum is dissolved in 200 milliliters of methylene dichloride.Solution is earlier with 50 milliliters of saturated KHCO ₃Solution washing, and then, use dried over mgso with the washing of 50 ml waters, evaporation removes and desolvates, at last with remaining mixture underpressure distillation.

Like this, 15.1 gram N have just been obtained, N-di-n-butyl urethanum (productive rate 75%).Boiling point 78～80 ℃/40 handkerchiefs (0.3 mmhg).

IR: γ c=1700 centimetre ^-1

¹H NMR：

0.9～1.7ppm(17H) complex spike

3.2ppm(4H) triplet

4.1ppm(2H) quartet

O-CH ₂。

The preparation of example 2.N n-octyl urethanum.

7.6 gram (0.05 mole) carbonic acid α-chloroethyl ethyl esters are dissolved in 10 milliliters of solution in the tetrahydrofuran (THF) and are cooled to 5～10 ℃, join 12.9 gram (0.1 mole) n-octyl amine that also have been cooled to 5～10 ℃ then and be dissolved in 40 milliliters of solution in the tetrahydrofuran (THF).

After under agitation adding, mixture is raised to room temperature, and keeps this temperature, stirred two hours.

Remove by filter throw out, evaporate solvent, residuum is dissolved in 50 milliliters of ether then, solution is refiltered once, ether washs with 50 ml waters mutually.

With the solution dried over mgso, evaporation removes and desolvates, then with the remaining mixture underpressure distillation.Like this, just obtain the carbamate of 8.64 gram expections.Productive rate 86%.

Product boiling point: 110 ℃/40 handkerchiefs (0.3 mmhg).

IR: 1700 centimetres of γ c=0 ^-1;

3300 centimetres of VH-H ^-1

¹H NMR：

0.1～1.7ppm (18H) complex spike (CH ₂) _nCH ₃;

3.2ppm (2H) quartet N-CH ₂;

4.1ppm (2H) quartet O-CH ₂;

5.2ppm (1H) complex spike

The preparation of example 3.N-n-octyl urethanum

In reactor, add 6.5 gram (0.05 mole) n-octyl amine, 30 milliliters of tetrahydrofuran (THF)s, 10 ml waters and 10 gram salt of wormwood K ₂CO ₃The temperature of maintenance system is at 5～10 ℃, and under agitation dropwise adding is dissolved in the gram of 7.6 in 5 milliliters of tetrahydrofuran (THF)s (0.05 mole) carbonic acid α-chloroethene ethyl ester.

Mixture is gone back up to room temperature, and remain under this temperature and to stir one hour.Add 50 milliliters of saturated aqueous common salts then.Mixture merges twice extractive ether mutually with 40 milliliters of ether extractings twice, uses dried over mgso.

After evaporation removes and desolvates,, obtain 7.4 gram N-n-octyl urethanum with the residuum underpressure distillation.Productive rate 74%.Boiling point: 110～112 ℃/40 handkerchiefs (0.3 mmhg).

Example 4.N, the preparation of N-di-n-butyl urethanum

Stirring and maintaining the temperature under 5～10 ℃, 8.4 grams (0.055 mole) are being dissolved in 10 milliliters of carbonic acid α-chloroethyl ethyl ester solution in the tetrahydrofuran (THF) dropwise join 6.5 gram (0.05 mole) Di-n-Butyl Amines and 5.56 gram (0.055 mole) triethylamines are dissolved in the solution of 40 milliliters of tetrahydrofuran (THF)s.

Mixture is gone back up to room temperature, and keep this temperature to stir two hours.

The elimination throw out evaporates solvent, and underpressure distillation is then collected the carbamate of 6.3 gram expections, productive rate 63%.Product boiling point 76 ℃/26.6 handkerchiefs (0.2 mmhg).

The preparation of example 5.N-n-octyl t-butyl carbamate

A) carbonic acid α-chloroethene ester tert-butyl ester is synthetic

A reactor cooling that fills 600 milliliters of methylene dichloride, 43.7 gram (0.59 mole) trimethyl carbinols and 94.7 gram (0.66 mole) chloroformic acid α-chloroethene esters is arrived+5 ℃, under agitation dropwise add 57 gram (0.72 mole) pyridines then, the temperature that keeps system simultaneously is between 10～20 ℃.At room temperature mixture was stirred 4 hours then.

Reaction mixture with 100 milliliter of 1 centinormal 1 aqueous hydrochloric acid washing, is used 200 milliliters of saturated Na earlier again ₂CO ₃Solution washing is used 100 milliliters of frozen water washed twice at last.Collect organic phase, use dried over mgso.

Steam after the solvent, underpressure distillation obtains 91.5 gram carbonic acid α-ethyl tert-butyl esters.Productive rate 86%.

Product boiling point: 88 ℃/2.7 kPas (20 mmhg).

IR: 1750 centimetres of γ c=0 ^-1

¹H NMR：

1.5pmm (9H) (CH ₃) ₃-C-is unimodal;

1.8ppm (3H) CH ₃-C is bimodal;

6.4ppm (1H)

Quartet;

B) reaction of carbonic acid α-chloroethyl tert-butyl ester and n-octyl amine

52 grams (0.4 mole) are dissolved in 60 milliliters of n-octyl amine in the anhydrous tetrahydro furan dropwise to join in 36.2 gram (0.2 mole) carbonic acid α-chloroethyl tert-butyl ester solution that are dissolved in 120 milliliters of tetrahydrofuran (THF)s.Stir while dripping down at 10 ℃.

Mixture was at room temperature stirred about 15 hours, remove by filter insoluble compound then, evaporate tetrahydrofuran (THF).Residuum is dissolved in 400 milliliters of methylene dichloride.Solution is successively used 100 milliliter of 1 centinormal 1 HCl aqueous solution, 200 ml waters, 100 milliliters of saturated KHCO ₃The aqueous solution and the washing of 100 ml waters.

With the solution dried over mgso, evaporation removes and to desolvate, then with remaining mixture underpressure distillation.

Like this, obtain the carbamate of 36.52 gram expections.Productive rate 80%.

Product boiling point: 142 ℃/200 handkerchiefs (1.5 mmhg).

IR: 1690 centimetres of γ c=0 ^-1;

3340 centimetres of γ H-H ^-1;

¹H NMR：

0.1～1.3ppm (15H) complex spike

1.4ppm it is (9H) unimodal

3.0ppm (2H) quartet

4.7ppm (1H) complex spike

C) preparation of the carbonic acid chloromethyl tert-butyl ester

Its preparation method and routine 5a) in the same.Reactant restrains chloromethylchloroformate and 8.1 milliliters of pyridines with 7.4 gram (0.1 mole) trimethyl carbinols, 15.48.Obtain 9.2 gram carbonic acid tert-butyl ester chloromethyl esters.Productive rate 55%.Product boiling point: 82 ℃/2 kPas (15 mmhg).

¹H NMR：

1.4ppm (CH ₃) ₃-C is unimodal

5.8ppm CH ₂-Cl is unimodal

IR: 1750 centimetres of γ c=0 ^-1

D) reaction of the carbonic acid chloromethyl tert-butyl ester and n-octyl amine

Its method and routine 5b) in the same.But replace the carbonic acid 1-chloroethene ester tert-butyl ester with the carbonic acid chloromethyl tert-butyl ester.Begin with the 6.5 gram n-octyl amine and the 8.5 gram carbonic acid chloromethyl tert-butyl esters.Obtain 4.3 gram and above-mentioned routine 5b) the identical N-n-octyl t-butyl carbamate that obtains.Productive rate 38%.

The preparation of example 6.N-n-octyl carboxylamine chaff ester

A) carbonic acid α-chloroethyl chaff ester is synthetic

Its method and routine 5a) in the same.But 0.22 mole of chloroformic acid α-chloroethene ester is dropwise joined 0.2 mole of furfuryl alcohol and 0.24 mole of pyridine is dissolved in the solution of 200 milliliters of methylene dichloride.

Collect 35.55 gram carbonic acid α-chloroethyl chaff esters.Productive rate is 87%.Product boiling point 94～98 ℃/13.3 handkerchiefs (0.1 milliliter of mercury column).

IR: 1750 centimetres of γ c=0 ^-1

¹H NMR：

1.8ppm (3H) bimodal CH ₃-C;

5.2ppm (2H) unimodal CH ₂O;

6.3～6.6ppm (3H) complex spike

H-C=O and

Complex spike

7.5ppm (1H) complex spike

B) reaction of carbonic acid α-chloroethyl chaff ester and n-octyl amine

Its method and routine 5b) the same, but carbonic ether 10.2 grams (0.05 mole) that will obtain above are dissolved in 30 milliliters of tetrahydrofuran (THF)s, and 12.9 gram (0.1 mole) n-octyl amine are dissolved in 15 milliliters of tetrahydrofuran (THF)s.

Carbamate 11.05 grams that obtain expecting, productive rate 87%.Product boiling point 162 ℃/66.6 handkerchiefs (0.5 mmhg), fusing point: 29 ℃.

IR: 1700 centimetres of ν c=0 ^-1;

3340 centimetres of ν NH ^-1

¹H NMR：

0.7～1.5ppm (15H) complex spike (CH ₂) _nCH ₃;

3.1ppm (2H) quartet CH ₂N;

4.9ppm (1H) wide complex spike NH;

5.0ppm (2H) unimodal CH ₂O;

6.4ppm (2H) complex spike H-C=;

7.4ppm (1H) complex spike

The preparation of example 7.N-n-octyl carboxylamine chaff ester

In reactor, add the K of 6.5 gram (0.05 mole) n-octyl amine, 30 milliliters of tetrahydrofuran (THF)s and 20 milliliters 5 moles ₂CO ₃The aqueous solution.Temperature is remained on 5～10 ℃, under agitation dropwise be added dropwise to 11.25 gram (0.55 mole) carbonic acid α-chloroethyl chaff esters.

Mixture is gone back up to room temperature, and remain under this temperature and to stir 18 hours, add 50 milliliters of saturated aqueous common salts then.With mixture with twice of 40 milliliters of ether extracting.Ether is merged mutually, use dried over mgso.

Remove after the also underpressure distillation of desolvating, collect the carbamate of 9.5 gram expections, productive rate 75%.Product boiling point: 142 ℃/26.6 handkerchiefs (0.2 mmhg).

The preparation of example 8.N-n-octyl benzyl carbamate

A) carbonic acid α-chloroethyl benzene methyl is synthetic

Its synthetic method and routine 5a) in the same.But with 200 milliliters of methylene dichloride, 21.6 gram (0.2 mole) phenylcarbinols, 31.6 gram (0.22 mole) chloroformic acid α-chloroethene ester and 0.2 mole of pyridine.

Therefore, collect 40.5 gram carbonic acid α-chloroethyl benzyl esters, productive rate 94%.Product boiling point 100 ℃/66.6 handkerchiefs.

IR: 1760 centimetres of γ c=0 ^-1;

¹H NMR：

1.8ppm (3H) doublet CH ₃-;

5.2ppm (2H) unimodal CH ₂;

6.4ppm (1H) quartet O-CH-Cl;

7.3ppm (5H) proton of unimodal aryl.

B) reaction of carbonic acid α-chloroethyl benzyl ester and n-octyl amine

Its method and routine 5b) the same.But, be that 19.4 gram (0.15 mole) n-octyl amine are dissolved in 30 milliliters of tetrahydrofuran (THF)s, 16.2 gram (0.075 mole) above-mentioned carbonic ethers are dissolved in 40 milliliters of tetrahydrofuran (THF)s.

Obtain the carbamate of 17.7 gram expections.Productive rate 90%.Product boiling point: 180 ℃/66.6 handkerchiefs (0.5 mmhg).

Fusing point: 33～34 ℃.

IR: 1680 centimetres of γ c=0 ^-1;

3380 centimetres of γ NH ^-1;

¹H NMR：

0.7～1.5ppm (15H) complex spike (CH ₂) _nCH ₃;

3.1ppm (2H) quartet CH ₂N;

4.8ppm (1H) unimodal NH;

5.1ppm it is (2H) unimodal

;

7.3ppm (5H) unimodal aryl proton.

The preparation of example 9.N-isobutylamino phenyl formate

A) carbonic acid α-chloroethyl phenyl ester is synthetic

Its method and routine 5a) in the same.But with 500 milliliters of methylene dichloride, 47 gram (0.5 mole) phenol, 79 gram (0.55 mole) chloroformic acid α-chloroethene ester and 0.5 mole of pyridine.

Therefore, collect 94.23 gram carbonic acid α-chloroethyl phenyl esters.

Productive rate 94%.Product boiling point 110 ℃/66.6 handkerchiefs (0.5 mmhg)

IR: 1770 centimetres of γ c=0 ^-1

¹H NMR：

1.7ppm (3H) doublet CH ₃;

6.35ppm (1H) quartet CH-Cl;

7.0～7.3ppm (5H) complex spike aryl proton.

B) reaction of carbonic acid α-chloroethyl phenyl ester and isobutylamine

The same in its method and the example 7.But with 7.3 gram (0.1 mole) isobutylamines, 35 milliliters 5 moles K ₂CO ₃Carbonic acid α-chloroethyl the phenyl ester of the aqueous solution and 20.1 grams (0.1 mole).

Except that desolvating and in sherwood oil, after the recrystallization, obtaining the product of 12.5 gram expections.Productive rate 65%.

Product fusing point: 66～67 ℃.

IR: 1710 centimetres of γ c=0 ^-1;

3400 centimetres of γ NH ^-1;

¹H NMR：

0.9ppm (6H) doublet CH ₃;

1.8ppm (1H) multiplet ;

3.1ppm (2H) triplet CH ₂-N;

5.3ppm (1H) wide unimodal NH;

7.0～7.3ppm (5H) complex spike aryl proton.

The preparation of example 10. tertiary butyloxycarbonyl phenylpiperidines

Its method is the same with example 7, but restrains (0.1 mole) piperidines, 60 milliliters of tetrahydrofuran (THF)s, 20 milliliters of unsaturated carbonate aqueous solutions of potassium and 0.11 mole of carbonic acid α-chloroethyl tert-butyl ester with 8.5.

Mixture only need stir two hours.Collect 14.8 gram tertiary butyloxycarbonyl phenylpiperidines.Productive rate 80%.

Product boiling point: 96～98 ℃/2 kPas (15 mmhg)

IR: 1690 centimetres of γ c=0 ^-1;

¹H NMR：

1.3～1.6ppm （15H） -CH ₂-，CH ₃-

3.3ppm （4H） CH ₂-N

The preparation of example 11. sulphur-ethyl n-n-octyl thiocarbamate

A) thiocarbonic acid SOH α-chloroethene S-ethyl ester is synthetic

Its method and routine 5a) in the same.But it is that 31.5 gram (0.22 mole) chloroformic acid α-chloroethene esters are joined the 12.4(0.2 mole) sulfur alcohol and 15.8 gram (0.2 mole) pyridines are dissolved in the solution of 200 milliliters of methylene dichloride.

Obtain 21.1 gram sulphur-ethylenebis dithiocarbamate carbonic acid α-chloroethene esters.Productive rate 62.5%.

Product boiling point: 110 ℃/5.86 kPas (44 mmhg).

IR: 1720 centimetres of γ c=0 ^-1

¹H NMR：

1.3ppm triplet CH ₃;

1.75ppm doublet CH ₃;

2.8ppm quartet CH ₂-S;

6.5ppm quartet O-CHCl.

B) reaction of sulphur-ethylenebis dithiocarbamate carbonic acid α-chloroethene ester and n-octyl amine

Its method is the same with example 7, but 6.5 gram (0.05 mole) n-octyl amine in the raw material of usefulness, 30 milliliters of tetrahydrofuran (THF)s, 20 milliliters 5 moles K ₂CO ₃The aqueous solution and 8.43 gram (0.05 mole) above-mentioned thiocarbonic esters.

Therefore, collect 5.3 gram sulphur-ethyl n-n-octyl thiocarbamates, productive rate 49%.

Product boiling point: 146～152 ℃/66.6 handkerchiefs (0.5 mmhg).

IR: 1650 centimetres of γ c=0 ^-1;

3300 centimetres of γ NH ^-1

¹H NMR：

0.7～1.6ppm (18H) complex spike (CH ₂) _nCH ₃;

2.8ppm (2H) quartet CH ₂S;

3.1ppm (2H) false triplet CH ₂N;

3.2ppm (1H) wide unimodal NH.

The preparation of example 12 to 19 various benzyl carbamates

In these examples, according to the method for example 7, with carbonic acid α-chloroethyl benzene methyl and various primary amine and secondary amine reaction.

The temperature condition of reaction, the physicals and the productive rate of reaction times, products therefrom are as shown in table 1.(table 1 is seen below)

Example 20.N, the preparation of N-hexa-methylene thiourethane (Hydram)

The preparation method is the same with example 11, with thiocarbonic acid SOH α-chloroethene S-ethyl ester and hexamethylene imine reaction.

Productive rate with 70% obtains distillatory " Hydram " product.

Boiling point: 141 ℃/1.7 kPas (13 mmhg).

The preparation of example 21.N-phenmethyl t-butyl carbamate

A) carbonic acid 1,2,2, the 2-tetrachloro ethyl tert-butyl ester synthetic

9.9 gram (0.04 mole) chloroformic acids, 1,2,2,2 tetrachloro ethyl esters are joined the trimethyl carbinol (3 grams aly; 0.04 in methylene dichloride (50 milliliters) solution mole).Mixture is cooled to 0 ℃, dropwise adds 3.2 gram (0.04 mole) pyridines.Again mixture was at room temperature stirred 4 hours.Add 20 milliliters of frozen water then.Isolate organic phase,, use dried over mgso, evaporate solvent with 20 milliliters of frozen water washings.Obtain 11.3 gram white solids (productive rate 99%).White solid is put into the sherwood oil recrystallization, obtain the carbonic ether that 9.9 gram purifying are crossed.Productive rate 87%, product fusing point: 70 ℃.

Boiling point: 96 ℃/866 handkerchiefs (6.5 mmhg).

IR: 1770 centimetres of γ c=0 ^-1

¹H NMR:(CDCl ₃, tetramethylsilane);

1.5(unimodal, CH ₃); 6.7(unimodal, CH).

B) reaction of above-mentioned carbonic ether and benzene methanamine

1.1 gram (0.01 mole) benzene methanamines are dissolved in 20 milliliters of tetrahydrofuran (THF)s, add 3 milliliters 5 moles wet chemical.

2.9 gram (0.01 mole) carbonic acid tetrachloro ethyl tert-butyl esters are dissolved in 5 milliliters of tetrahydrofuran (THF)s, and under 5 ℃, it are joined in the benzene methanamine solution.Mixture was stirred one hour down at 20 ℃.Decant goes out organic phase, with 10 milliliters of saturated NaCl solution washings and dry, evaporates solvent.With remaining mixture distillation, obtain the carbamate of 2.0 gram expections then.Productive rate 96%.

Product boiling point: 103 ℃/6.7 handkerchiefs (0.05 mmhg).

Product is put into the sherwood oil recrystallization, obtain the carbamate of 1.84 gram expections, yield 89%.Product fusing point: 54 ℃ (in the document being 53～54 ℃).

The preparation of example 22. tertbutyloxycarbonyl imidazoles

Under 0 ℃, and in the presence of 5 milliliters 5 moles wet chemical, with 5 gram (17.5 moles) carbonic acid 1,2, the tetrahydrofuran (THF) of 2, the 2 tetrachloro ethyl tert-butyl esters (10 milliliters) solution joins in tetrahydrofuran (THF) (20 milliliters) solution of imidazoles (1.2 grams, 17.6 gram moles).Mixture was stirred one hour down at 20 ℃.Then the organic phase decant is gone out, with 10 milliliters of saturated NaCl solution washings.

After the organic phase drying, evaporate solvent.With resulting residuum distillation, obtain 2.55 gram products, productive rate 86%, product boiling point: 64 ℃/133.3 handkerchiefs (1 mmhg), fusing point: 43 ℃ then.

Example 23.N-methyl carbamic acid 2,3-dihydro 2, the preparation of 2-dimethyl 7-benzofuranyl ester (carbofuran)

A) carbonic acid 1-chloroethyl 2,3-dihydro 2,2-dimethyl 7-benzofuranyl ester synthetic-

21.5 gram (0.15 mole) chloroformic acid 1-chloroethene esters are joined 2 aly, 3-dihydro 2,2-dimethyl 7-cumarone alcohol (24.6 grams; 0.15 in methylene dichloride (150 milliliters) solution mole).Mixture is cooled between 0～5 ℃, dropwise adds 12 gram (0.15 mole) pyridines.Mixture was stirred 3 hours down at 20 ℃.Use 2 * 50 milliliters of frozen water washing organic phases then, and use dried over mgso, steam solvent then, obtain a kind of yellow oil.Redistillation obtains the carbonic ether that 34.1 grams are expected.Productive rate 84%.Product boiling point 127 ℃/66.6 handkerchiefs (0.5 mmhg).

B) reaction of above-mentioned carbonic ether and methylamine

5.4 gram (0.02 mole) above-mentioned carbonic ethers are dissolved in 20 milliliters of tetrahydrofuran (THF)s.Add 10 milliliters of about K of 5 moles then ₂CO ₃The aqueous solution, then adding 1.7 milliliters of (0.02 mole) concentration is 40% aqueous methylamine solution.Under 20 ℃, mixture was stirred 15 hours.With the organic phase decant,, evaporate solvent then with saturated NaCl solution washing, and with product crystallization in the methyl cyclohexane.Obtain 3.5 gram N-methyl carbamic acids 2,3-dihydro 2,2-dimethyl 7-benzofuranyl ester.Productive rate 79%.

Product fusing point: 148 ℃.

C) its method with above-mentioned a), b) the same, but use N, accelerine replacement pyridine, the intermediate product carbonic ether need not distill.Begin with 16.4 grams 2,3-dihydro 2,2-dimethyl 7-cumarone alcohol obtains 16.8 gram carbofuran, productive rate 76% then.Product fusing point: 147 ℃.

Example 24.N-methyl N '-preparation of piperidyl urea

A) the N-methyl carbamic acid 1,2,2,2-tetrahydrochysene ethyl ester synthetic

With 34.7 milliliters of (0.4 mmole) concentration is that 40% aqueous methylamine solution dropwise joins 49.4 gram (0.2 mole) chloroformic acids 1,2,2 that remain on 0 ℃, in the methylene dichloride of 2-tetrachloro ethyl ester (150 milliliters) solution.At room temperature, mixture was stirred two hours.Then organic phase is washed with 2 * 100 ml waters, use dried over mgso.

Evaporation is desolvated, and makes the product crystallization.Obtain the carbamate of 42.6 gram expections, productive rate 88%.

Product fusing point: 105～106 ℃.

¹H NMR：2.75 （CH ₂-N）;

5.2????（NH）;

6.7????（CH-Cl）。

IR: 1760 centimetres of ν c=0 ^-1

B) the N-methyl N '-piperidyl urea synthetic

The carboxylamine alcohol that 4.83 grams (0.02 mole) are obtained above is dissolved in 30 milliliters of tetrahydrofuran (THF)s and 5 milliliters of K ₂CO ₃In the saturated aqueous solution.Solution is remained on 10 ℃, add 1.7 gram (0.02 mole) piperidines.At room temperature, mixture was stirred 4 hours.Then the organic phase decant is gone out, with 50 milliliters of saturated common salt water washings, use dried over mgso, evaporation is desolvated, and residuum is distilled.Obtain 1.8 gram N-methyl N '-piperidyl urea.Productive rate 63%.Product boiling point 110 ℃/6.7 handkerchiefs (0.05 mmhg).

The preparation of example 25. imidazoles carbonyl piperidines

A) alpha-chloro ethoxycarbonyl imidazoles is synthetic

28.6 gram (0.2 mole) ethyl chloroformates drop by drop are added in water-soluble middle refrigerative 27.2 gram (0.4 mole) imidazoles to be dissolved in the solution of 200 milliliters of methylene dichloride.At room temperature mixture was stirred 4 hours, add 50 milliliters of frozen water then.Organic phase is washed with 2 * 50 ml waters, uses dried over mgso again.Steam solvent, distillation then obtains 38.1 gram alpha-chloro ethoxycarbonyl imidazoles.

Productive rate 73%.Product boiling point: 80 ℃/66.6 handkerchiefs (0.5 mmhg).Product is a colourless liquid, at room temperature spontaneously crystallization.50 ℃ of fusing points.

¹H NMR:(60MHz, CDCl ₃Tetramethylsilane)

δ: 1.9(doublet, CH ₃);

6.7(quartet, OCH-Cl);

7.05; 7.4; 8.2(3 individual vacation is unimodal, imidazoles).

IR: 1770 centimetres of ν c=0 ^-1

B) reaction of alpha-chloro ethoxycarbonyl imidazoles and piperidines

Tetrahydrofuran (THF) (10 milliliters) solution of 8.5 gram (0.1 mole) piperidines is dropwise added alpha-chloro ethoxycarbonyl imidazoles (8.75 grams; 0.05 in tetrahydrofuran (THF) (50 milliliters) solution mole).During dropping solution to be cooled to+5 ℃, at room temperature stir then.

Remove by filter piperidine hydrochlorate, then organic phase is washed with water once, use dried over mgso, and evaporation is desolvated.With remaining mixture distillation, collect the product of 6.2 gram expections.Productive rate 70%.Product boiling point 134 ℃/26.6 handkerchiefs (0.2 mmhg).

In refrigerator, the automatic crystallization of the liquid that obtains above.Fusing point: 33 ℃.

¹H NMR:1.5ppm multiplet (CH ₂) ₃;

3.5ppm multiplet ;

Imidazolyl

IR: 1690 centimetres of ν c=0 ^-1

Example 26.N, the preparation of N-diethyl Orazamide

Its method and routine 25b) the same, but replace piperidines with diethylamine, obtain the desirable urea of 6.5 grams.Productive rate 78%.

Product boiling point: 106 ℃/26.6 handkerchiefs (0.2 mmhg).

Fusing point: 41 ℃ (literature value is 38～43 ℃).

¹H NMR:1.2ppm (triplet, CH ₃);

3.4ppm (quartet, CH ₂N);

Imidazoles.

IR: 1690 centimetres of ν c=0 ^-1

Example 27.2-methyl-2-(first sulphur) preparation of propionic aldehyde base oxygen-((methylamino-) carbonyl) oxime (aldicarb)

With 50 milliliters of toluene and 6.65 gram (0.05 mole) 2-methyl 2-(methylthio groups) propionaldoxime adds in 5 milliliter of 10 centinormal 1 caustic soda successively.At room temperature, mixture is stirred several minutes,, remove and anhydrate then by component distillation.Mixture is with the ice-water bath cooling and dropwise add 7.15 gram (0.05 mole) chloroformic acid 1-chloroethene esters.Under about 10～15 ℃, mixture was stirred one hour.The aqueous methylamine solution that dropwise adds 10 milliliters of (about 0.13 mole) concentration 40% then.Under same temperature, with mixture restir one hour.With the organic phase decant, with the washing of 10 milliliters of frozen water, use dried over mgso, be evaporated to driedly, obtain 8.7 and restrain hazel solid.90 ℃ of fusing points.

Synthesizing of example 28. tertiary butyl oxidation carbonyl L-aspartic acids

1.33 gram (10 mmole) L-aspartic acids are dissolved in the mixture of 30 milliliters of diox/water (1: 1), add 4.2 milliliters of (30 mmole) triethylamines.Stir this mixture to dissolving (about 10 minutes) fully, add 2.85 gram (10 mmole) carbonic acid tert-butyl esters 1,2,2 then, 2-tetrachloro ethyl ester.Under 20 ℃, mixture was stirred 6 hours.Add 50 ml waters again.Mixture is with 2 * 20ml ethyl acetate extraction.With water 6NHCl acidifying (PH ₃-3), use 3 * 30 milliliters of ethyl acetate extractings then.Extract desolvates with dried over mgso and evaporation with saturated NaCl solution washing.The product that obtains is put in crystallization in ethyl acetate and the sherwood oil, obtains the acid of 1.4 gram expections.Productive rate 60%.

The product fusing point: 116～118 ℃, fusing point is 114～116 ℃ on the document

(α) ²⁰ _D=-5(C 1.0 methyl alcohol)

(α) ²⁰ _D(literature value)=-6.2(C 1.0 methyl alcohol)

The preparation of example 29. chaff oxygen carbonyl glycine ethyl esters

2.05 gram (10 mmole) carbonic acid α-chloroethyl chaff esters are joined remain on the gram of 1.03 between 5～10 ℃ (10 mmole) glycine ethyl ester and be dissolved in the mixing solutions of solution of potassium carbonate of 6 milliliters of tetrahydrofuran (THF)s and 4 milliliters 0.5 mole.Mixture is risen to room temperature, stirred 18 hours.Add 50 milliliters of saturated aqueous common salts then.Mixture is with 3 * 40 milliliters of extracted with diethyl ether.Organic phase is merged, use dried over mgso.Remove the back distillation of desolvating, collect the product of 1.5 gram expections.Productive rate 66%.

Product boiling point: 144 ℃/40 handkerchiefs (0.3 mmhg).

IR: 1680 centimetres of ν c=0 ^-1;

3280 centimetres of ν NH ^-1

¹H NMR:(CDCl ₃, tetramethylsilane)

1.3ppm triplet, CH ₃;

3.95ppm doublet,

;

4.2ppm quartet CH ₂(CH ₃);

5.1ppm it is unimodal

;

5.2ppm wide unimodal NH;

6.4ppm complex spike H-C=;

7.4ppm complex spike

The preparation of example 30. benzene methoxycarbonyl L-proline(Pro)

Under 50 ℃, at 1.15 gram (10 mmole) L-proline(Pro), 10 ml methanol and 3 milliliters of saturated K ₂CO ₃Add 2.36 gram (11 mmole) carbonic acid phenmethyl α-chloroethene esters in the solution that the aqueous solution is formed.React after four hours, add 5 ml waters.Mixture is with 10 milliliters of ether washed twice, and to be acidified to pH with 6NHCl be 2～3, uses ethyl acetate extraction then.

After solvent steamed, product crystallization in the mixture of ethyl acetate/petroleum ether.Obtain 2.2 gram benzene methoxycarbonyl L-proline(Pro).Productive rate 88%.

75～76 ℃ of product fusing points (76～78 ℃ of literature values)

Example 31. carbonic acid 1,2,2, the preparation of 2-tetrachloro ethyl 2-front three (base) silylation ethyl ester

Preparation method and routine 21a) the same.Begin with 5.91 gram three silyl ethanol and 12.35 gram chloroformic acid tetrachloro ethyl esters.Obtain the product of 13.6 gram expections.Productive rate 83%.

Product boiling point: 92～94 ℃/6.6 handkerchiefs.

IR: 1750 centimetres of ν c=0 ^-1

¹H NMR:(CDCl ₃, the external standard tetramethylsilane);

0.1 (unimodal, CH ₃-Si);

1.1 (triplet, CH ₂-Si);

4.35 (triplet, CH ₂-O);

6.7 (unimodal, CH-Cl);

The preparation of example 32. 3 silyl ethoxycarbonyl L-phenylalanines

0.83 gram (5 mmole) L-phenylalanine is dissolved in the mixture (12 milliliters) that contains 1.4 milliliters of (10 mmole) triethylamine De diox/water (1: 2).Mixture is cooled to 0 ℃.Once add 1.8 grams (5.5 mmole) and be dissolved in above-mentioned carbonic ether in 4 milliliters of dioxs.Keep 0 ℃ after two hours, add 20 ml waters.Mixture is at every turn with twice of 20 milliliters of extracted with diethyl ether.Water is acidified to pH2～3 with 6NHCl, and then uses 50 milliliters of ethyl acetate extractions 3 times at every turn.Extraction liquid also evaporates with dried over mgso.Obtain 1.4 gram buttery expection products.Productive rate 100%.

¹H NMR:(CDCl ₃, tetramethylsilane);

0 (unimodal, CH ₃-Si);

0.9 (triplet, CH ₂-Si);

3.0 （OCH ₂- ）;

4.0 (triplet, O-CH ₂-C-Si);

4.5(multiplet, ), 5.2(is unimodal, NH);

7.2(unimodal, phenyl);

8.7（

）

The oily product is dissolved in 5 milliliters of ether, adds 2 milliliter of two ring ethylamine.After the crystallization, collect 1.93 grams, three silyl ethoxycarbonyl L-phenylalanine dicyclohexyl amine salt.Productive rate 78%.111～112 ℃ of fusing points.

Claims (8)

1, the preparation method of the carbamic acid derivative shown in the following formula,

R in the formula ¹And R ²(they can identical also can be inequality) representative:

Hydrogen atom;

The straight or branched aliphatic group that contains 1～8 carbon atom;

The arylated alkyl that contains 7～8 carbon atoms;

Perhaps R ¹And R ²Constitute the ring that contains 4～6 carbon atoms with the nitrogen-atoms that links, this ring can contain an oxygen heteroatom, or forms the morpholine ring, perhaps imidazole ring, R ¹And R ²Group can be by acid, alcohol, ester, ether, sulfydryl or amino the replacement;

Wherein R representative:

Contain 1～4 carbon atom straight chain or straight chain aliphatic group, 2,2,2-three chloroethyls, three silicomethane ethyls; Perhaps,

Phenmethyl, the oil of mirbane methyl, phenyl, benzofuryl, fluorene methyl, these groups can be by methyl substituted;

R wherein ³And R ⁴Can be identical, also can be different, they represent hydrogen atom or methyl, perhaps form imidazole ring together with nitrogen-atoms; R wherein ⁶And R ⁷Also can represent hydrogen atom, first

The method is characterized in that when the haloid acid acceptor was deposited, between-5 °～150 ℃ and under the condition that inert solvent exists, molecular formula was

Aminocompound and molecular formula in

Alpha-halogen carbonic acid derivatives reaction,

In the formula, R ¹, R ²Identical with above-mentioned connotation with Y, X represents fluorine, chlorine or bromine atoms, R ⁵Represent hydrogen atom or by halogen or the fat base that contains 1～4 carbon atom that do not replaced by halogen.

2, the described method of claim 1, wherein X represents the chlorine atom.

3, claim 1 or 2 described methods, alpha-halogen derivative wherein are carbonic acid α-chloroethene ethyl esters, the carbonic acid α-chloroethene tert-butyl ester, carbonic acid α-chloroethene sugar ester, carbonic acid α-chloroethene ester benzene methyl, carbonic acid α-chloroethene ester phenyl ester, carbonic acid α-chloroethene ester 2,3-dihydro-2,2-dimethyl-7-benzofuranyl ester, carbonic acid 1,2,2, the 2-tetrachloro second tert-butyl ester, thiocarbonic acid SOH α-chloroethene ester S-ethyl ester, alpha-chloro oxyethyl group imidazoles, N-methyl carbamic acid 1,2,2,2-tetrachloro ethyl ester, sulfuric acid 1,2,2,2-tetrachloro ethyl ester 2-three silicomethane ethyl esters, or 2-methyl 2-(first sulphur) propionic aldehyde base oxygen-(alpha-chloro ethoxycarbonyl) oxime.

4, claim 1 or 2 described methods, amine wherein is methylamine, diethylamine, Di-n-Butyl Amine, isobutylamine, n-octyl amine, thanomin, benzene methanamine, imidazoles, hexamethylene imine, morpholine, diethanolamine, N-methyl-N-phenmethyl amine, piperidines, L-phenylalanine, L ₁-proline(Pro), glycine, L ₁-tyrosine, L ₁-Serine, L ₁-aspartic acid, glycine ethyl ester, phenylglycocoll or proline(Pro).

5, claim 1 or 2 described methods, wherein said inert solvent is from chloro fat family solvent, ring or acyclic ethers, alcohols, acetone, pyridine is chosen in acetonitrile and the dimethyl formamide.

6, claim 1 or 2 described methods, wherein said acid acceptor refers to organic or inorganic alkali.

7, the described method of claim 6, wherein said organic or inorganic alkali is sodium hydroxide, potassium hydroxide, S-WAT, yellow soda ash, sodium bicarbonate, salt of wormwood, saleratus, magnesium oxide, tertiary amine or molecular formula are

Raw material amine, R wherein ¹And R ²Connotation same as above.

8, the described method of claim 7, tertiary amine wherein is a triethylamine, pyridine or N, N-xylidene(s).