CN104529823B - Benzimidate compound preparation method - Google Patents
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Abstract
The invention discloses a benzimidate compound preparation method. According to the invention, a benzonitrile derivative represented by a formula (III) is subjected to a reaction with alcohol and a catalyst under a temperature of -30 DEG C to 50 DEG C, such that benzimidate derivative hydrochloride represented by a formula (II) is obtained; or alkali is used for neutralizing after the reaction, such that a benzimidate derivative represented by a formula (I) is obtained. According to the invention, a mixed gas is used as the catalyst, such that high-yield high-product-purity benzimidic acid derivative and hydrochloride thereof can be directly obtained. A target production yield is higher than 93%, and the content is higher than 95%. Also, with the method, the hydrogen chloride dose can be greatly reduced, and the amount of agents used for producing hydrogen chloride can be greatly reduced. The conversion efficiency is high, and the reaction process is simple to operate. The method is suitable for industrial production.
Description
Technical field
The invention belongs to field of fine chemical is and in particular to a class can be used as the benzene first of pesticide, medicine and chemical intermediate
Imines acid derivative and its preparation method of hydrochlorate.
Background technology
Imidic acid ester type compound has very extensive purposes in pesticide and pharmaceutically, be prepare amidine compound main in
Mesosome.Find that some amidine salt can treat schistosomicide in one's early years, but toxicity is larger, the benzenecarboximidamide that some long-chain alkoxy bases replace
Salt has the effect of surfactant, is referred to as Spanon.Now, amidine compound be mainly used for synthesize nitrogenous miscellaneous
Cycle compound, such as：Imidazoles, thiazole, pyrimidine ring etc., play an important role in nitrogenous heterocyclic synthesis.Research finds,
Amidine salt is also used as water-soluble azo class initiator, is used widely in aqueous solution polymerization with emulsion polymerization.
The synthetic method of amidine compound is Pinner amidine synthetic method typically using acid catalyzed process, first prepares cyano compound
Become imidoether, then react the corresponding amidine of generation with amine：
Pinner amidine synthesizes：
In the synthesis of antibacterial 2-cyano-3-amino-3-phenylancryic acetate of CN101417962 report, also using to benzimide acid esters：
The synthesis of target compound imidoether, document report is mainly become by acid catalysiss cyano, and acid becomes this reaction
Key.
But, in actual application, but there is serious defect, reactant in single acid catalyzed process synthesizing imine acid esters
Need in system to be passed through large excess of hydrogen chloride gas, both not environmentally, also uneconomical, as old in Xibei Univ. of Agricultural ＆ Forest Science ＆ Technology pacify the good
Thesis for the doctorate《Propamidine Fungicides are studied》In report 4,4- bis--cyano group -1,3- two phenoxypropane alcoholysis system
Standby imidoether, needs the amount of about 15 times of hydrogen chloride, and yield reaches 86.5%；
Yadav, Veejendra K. in European Journal of Organic Chemistry, 2005 (2), report in 452-456
Road, is first obtained hydrogen chloride with 8 times of chloroacetic chloride and excessive ethanol synthesis, adds benzonitrile, catalyzed alcoholysis becomes benzene first sub-
Amino acid ethyl ester, yield 94%.Although the method be pollution-free prepare hydrogen chloride, yield is also higher, chloroacetic chloride consumption
Excessively, increased cost, and in course of reaction, generate a large amount of ethyl acetate, reduce production efficiency.
Meanwhile, use merely the preparation of chlorination hydrogen catalysis benzonitrile derivative, reaction carries out not complete, and purity to be obtained compares
High benzimide acid ester derivant and its hydrochlorate, the benzene first being necessary for obtaining separating out in reactant liquor by the process filtering is sub-
Amino acid ester derivant HCl, solid, this can cause the spilling of a large amount of hydrogen chloride gas on producing, and makes workshop environment special
Not severe, production equipment is very easy to corrosion.
Content of the invention
It is an object of the invention to provide the benzene first of a kind of use chlorination hydrogen amount few transformation efficiency Gao product purity height, high income is sub-
Amino acid ester derivant and its preparation method of hydrochlorate.
The purpose of the present invention can be reached by following measures：
A kind of preparation method of the compound shown in formula I or formula II, the benzonitrile derivative shown in formula III with
Alcohol and catalyst are reacted at -30～50 DEG C, obtain the benzimide acid ester derivant hydrochloric acid shown in formula II after reaction
With alkali neutralization after salt, or reaction, obtain the benzimide acid ester derivant shown in formula I；
Wherein,
Described alcohol is R-OH；
Described catalyst is hydrogen chloride and sulfur dioxide mixture gas, or can produce a kind of gas in hydrogen chloride and sulfur dioxide
The single or multiple compound of body is combined with another kind of gas, or can produce the single of hydrogen chloride and sulfur dioxide simultaneously
Or multiple compound；
Described X is hydrogen, halogen, alkyl, alkoxyl, hydroxyl, amino, aryl, aryloxy group, aralkyl, aralkyl oxygen
Base, aryloxyalkyl group or fragrant oxygen alkoxyl；
Described n is 1～5；
Described R be C1～C6 alkyl, C1～C6 haloalkyl, C3～C6 thiazolinyl, C3～C6 haloalkenyl group, C3～
C6 alkynyl or C3～C6 halo alkynyl.
In a kind of technical scheme, produced by the benzonitrile derivative shown in formula III and catalyst hydrogen chloride or catalyst
The mol ratio of hydrogen chloride is 1：1～1：10, further preferred 1：1～1：4；Benzonitrile derivative and catalyst titanium dioxide
The mol ratio of sulfur dioxide produced by sulfur or catalyst is 1：0.1～1：10, further preferred 1：0.5～1：3.
Catalyst in the present invention selects hydrogen chloride and sulfur dioxide mixture gas, or the change that can produce one of which gas
Compound is combined with another kind of gas, or can produce the compound of two kinds of gases simultaneously.Wherein for hydrogen chloride and dioxy
Change sulfur mixed gas, can directly be prepared during the course of the reaction, it would however also be possible to employ existing gas is passed through, can also adopt
With produce in existing commercial production or other reaction systems contain or not contain the hydrogen chloride of other gases and sulfur dioxide mixes
Close gas.The method of the present invention has no specific requirement for the material that can produce hydrogen chloride or sulfur dioxide gas, as long as
Do not affect or have a strong impact on the process of primary response in reaction.In a kind of scheme, hydrogen chloride can be produced for described
Compound includes not affecting the combining of the acyl chlorides of the reaction process and alcohol lower alcohol of chloroacetic chloride and below C4 (particularly), or
Concentrated hydrochloric acid or the combination of sulphuric acid；The compound that sulfur dioxide can be produced includes combining of sodium sulfite and sulphuric acid；Can be same
When produce the compound of hydrogen chloride and sulfur dioxide and include thionyl chloride and water.
In a kind of scheme, heretofore described add (leading to) enters dry hydrogen chloride and sulfur dioxide mixture gas catalyst
Mode can include but is not limited in the following manner：It is passed through hydrogen chloride gas and the dioxy of set amount respectively to reaction system
Change sulfur gas；Produce after the hydrogen chloride of set amount in reaction system with other raw materials, such as chloroacetic chloride adds methanol, then is passed through
The sulfur dioxide gas of set amount；It is passed through hydrogen chloride and the sulfur dioxide mixture gas of the fixed proportion preparing；It is passed through industry
Upper containing hydrogen chloride and sulfur dioxide mix waste gas, such as acid and thionyl chloride prepare 1 that acyl chlorides forms hydrogen chloride sum：1 mixing
Waste gas；Produce after the sulfur dioxide of set amount in reaction system with other raw materials, such as sodium sulfite adds sulphuric acid, then leads to
Enter the hydrogen chloride gas of set amount；Produce hydrogen chloride and the sulfur dioxide of set amount with other raw materials in reaction system simultaneously,
Etc..
In the reaction of the present invention, directly filter after benzonitrile derivative and alcohol and catalyst reaction, obtain shown in formula II
Benzimide acid ester derivant hydrochlorate；Or it is neutralized to neutrality with alkali liquor after benzonitrile derivative and alcohol and catalyst reaction,
The benzimide acid ester derivant shown in formula I is directly obtained after isolating organic layer precipitation.The target of this law gained is produced
Raw yield is more than 93%, and content is more than 95%.
In a kind of scheme, benzonitrile derivative is -10-30 DEG C with the temperature of alcohol and catalyst reaction；The present invention is in benzonitrile
Solvent in derivant and alcohol and catalyst reaction be selected from dichloromethane, chloroform, carbon tetrachloride, dichloroethanes, petroleum ether,
Normal hexane, hexamethylene, benzene, toluene, chlorobenzene, ethyl acetate, N,N-dimethylformamide, oxolane, acetonitrile,
One or more of dioxane or dimethyl sulfoxide.
In a kind of scheme, the alkali in order to reactant liquor after neutralization reaction is selected from sodium hydroxide, potassium hydroxide, calcium hydroxide, first
Sodium alkoxide, Sodium ethylate, potassium tert-butoxide, pyridine, morpholine, methylamine, dimethylamine, trimethylamine, ethamine, diethylamine, triethylamine,
One or more of ammonia, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, Calcium Carbonate；Alkali can directly add,
The mode that aqueous solution may also be employed adds.In the reaction preparing formula I compound, it is neutralized to neutrality with alkali, i.e. pH
Value 6～8, preferable ph is 7.
In a kind of preferred version, in formula (I) of the present invention, formula (II) and formula (III), X be hydrogen, halogen, C1～
C4 alkyl, C1～C4 alkoxyl, hydroxyl, amino, C6～C14 aryl, C6～C14 aryloxy group, C6～C14 virtue
Alkyl, C6～C14 aralkoxy, C6～C14 aryloxyalkyl group or C6～C14 virtue oxygen alkoxyl.
In a kind of preferred version, in each structural formula of the present invention, X is hydrogen, halogen, C1～C4 alkyl or C1～C4
Alkoxyl.
In a kind of preferred version, in each structural formula of the present invention, X be hydrogen, fluorine, chlorine, bromine, methyl, ethyl, positive third
Base, isopropyl, methoxyl group, ethyoxyl, positive propoxy or isopropoxy.
In a kind of preferred version, in formula (I) of the present invention, formula (II) and formula (III), n is 1～5；Excellent in another kind
Select in scheme, n is 1～2, particularly 1 or 2.
In a kind of preferred version, in each structural formula of the present invention and alcohol, R is C1～C4 alkyl, C1～C4 halo
Alkyl, C3～C6 thiazolinyl, C3～C6 haloalkenyl group, C3～C6 alkynyl or C3～C6 halo alkynyl.
In another kind of preferred version, R is C1～C4 alkyl or C1～C4 haloalkyl.
In a kind of preferred version, R is methyl, ethyl, n-pro-pyl, isopropyl, halogenated methyl, halogenated ethyl, halo
N-pro-pyl or haloisopropyl.
Unless otherwise indicated, the following term using in the specification and in the claims has implication discussed below：
" halogen " represents fluorine, chlorine, bromine or iodine, preferably fluorine or chlorine.
" alkyl " represents the aliphatic group of the saturation of 1-20 carbon atom, (mentions in this specification including straight chain and branched group
Digital scope, such as " 1-20 ", refer to this group, now for alkyl, can contain 1 carbon atom, 2 carbon atoms, 3
Individual carbon atom, 4 carbon atoms, 5 carbon atoms, 6 carbon atoms etc., until include 20 carbon atoms).Containing 1～4
The alkyl of carbon atom is referred to as low alkyl group.
" cycloalkyl " represents the monocyclic of all carbon or the ring that condenses (in each ring that " condensing " ring means in system and system
Other rings share a pair of the carbon atom adjoining) group, wherein one or more rings do not have the pi-electron system being fully connected
System, the example (being not limited to) of cycloalkyl is cyclopropane, Tetramethylene., Pentamethylene., cyclopentenes, hexamethylene, diamantane (obsolete),
Cyclohexadiene, cycloheptane and cycloheptatriene.
" alkoxyl " represents-O- (unsubstituted alkyl) and-O- (unsubstituted cycloalkyl).Representative example include but not
It is limited to methoxyl group, ethyoxyl, propoxyl group, butoxy, ring propoxyl group, cyclobutoxy group, cyclopentyloxy, cyclohexyloxy etc..
" aryl " represent 5 to 12 carbon atoms full carbon is monocyclic or fused polycycle group, there is the pi-electron system of total conjugated
System.The non-limiting examples of aryl have phenyl, naphthyl and anthryl.Aryl can be substituted or unsubstituted.When substituted
When, substituent group is preferably one or more, more preferably one, two or three, and then is more preferably one or two,
Independently selected from by low alkyl group, three alkylhalide groups, halogen, hydroxyl, lower alkoxy, sulfydryl, (low alkyl group) sulfenyl,
Cyano group, acyl group, Thioacyl etc..Preferably, aryl is alternatively replaced by one or two substituent group, and substituent group is independently
Selected from halogen, low alkyl group, three alkylhalide groups, hydroxyl, sulfydryl, cyano group, N- acylamino-, list or dialkyl amino, carboxylic
Base or N- sulfonamido.
" aryloxy group " represents-O- (aryl) group.Representative example includes but is not limited to phenoxy group, naphthoxy and anthracene epoxide
Deng.
" aralkyl " represents-(alkane its)-(aryl) group.Wherein alkyl preferably employs low alkyl group, representative example bag
Include but be not limited to benzyl, phenethyl etc..
" aralkoxy " represents-O- (alkane its)-(aryl) group.Wherein alkyl preferably employs low alkyl group, representative real
Example includes but is not limited to benzyloxy, benzene ethyoxyl etc..
" aryloxyalkyl group " represents-(alkane its)-O- (aryl) group.Wherein alkyl preferably employs low alkyl group, representative real
Example includes but is not limited to Phenoxymethyl, benzene oxygen ethyl etc..
" fragrant oxygen alkoxyl " represents-O- (alkane its)-O- (aryl) group.Wherein alkyl preferably employs low alkyl group, represents
Property example include but is not limited to benzene oxygen methoxyl group, benzene oxygen ethyoxyl etc..
" haloalkyl " represents by the alkyl of one or more halogen substiuted, preferably as defined above by one or more halogens
The low alkyl group replacing, it can be replaced by one or more identical or different halogen atoms, such as-CH2Cl、-CF3、
-CH2CF3、-CH2CCl3Deng.
" thiazolinyl " represents the undersaturated aliphatic group containing at least one C=C of 2-20 carbon atom, including straight chain and side chain
(digital scope mentioned in this specification, such as " 1-20 ", refer to this group to group, now for alkyl, can contain 1
Carbon atom, 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms, 6 carbon atoms etc., until include 20
Individual carbon atom).Thiazolinyl containing 2～6 carbon atoms is referred to as low-grade alkenyl.
" haloalkenyl group " represents by the thiazolinyl of one or more halogen substiuted, preferably by the rudimentary alkene of one or more halogen substiuted
Base.
" alkynyl " represents the undersaturated aliphatic group containing at least one C ≡ C of 2-20 carbon atom, including straight chain and side chain
(digital scope mentioned in this specification, such as " 1-20 ", refer to this group to group, now for alkyl, can contain 1
Carbon atom, 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms, 6 carbon atoms etc., until include 20
Individual carbon atom).Alkynyl containing 2～6 carbon atoms is referred to as low-grade alkynyl.
" halo alkynyl " represents by the alkynyl of one or more halogen substiuted, preferably by the rudimentary alkynes of one or more halogen substiuted
Base.
Beneficial effects of the present invention：
Method of the present invention is used mixed gas as catalyst, can directly obtain the benzene of high yield and high product purities
Azomethine acid derivative and its hydrochlorate, the yield that its target produces is more than 93%, and content is more than 95%.Pass through in this law
Mixed gas are used as catalyst, can greatly reduce the response time, a large amount of usage amounts reducing hydrogen chloride, also can be big
Width reduces the pharmaceutical quantities producing needed for hydrogen chloride, and this law transformation efficiency is high, and course of reaction is simple to operate, beneficial to industrialized production.
Specific embodiment
For the ease of further appreciating that to the present invention, examples provided below has done more detailed description to it.These are real
Apply example only for narration not for limiting the scope of the present invention or implementation principle.
Embodiment 1：The preparation of benzimidic acid ethvl ester
In 1000ml reaction bulb, 103g (1mol) benzonitrile is dissolved in 184g (4mol) ethanol, adds 176g
(2mol) ethyl acetate, ice bath cools to 0 DEG C, is slowly added dropwise people 157g (2mol) chloroacetic chloride, under the conditions of 5 DEG C, leads to
Enter 64g sulfur dioxide, insulation reaction 2 hours, be warmed up to 25 DEG C, be incubated 14 hours, Deca sodium bicarbonate is satisfied in reactant liquor
And solution, until reactant liquor becomes neutral, separate organic layer, water layer is extracted twice with 100ml ethyl acetate, merge organic faciess,
100ml washes once, and organic faciess precipitation, to complete, obtains colourless liquid product 145.9g, efficient liquid phase chromatographic analysis, containing benzene
Formimidic acid ethyl ester 96.2%, benzonitrile 2.3%, yield is 94.2%.
Embodiment 2：Preparation to chlorobenzene formimidic acid ethyl ester
In 500ml reaction bulb, 137.5g (1mol) p-Cyanochlorobenzene is dissolved in 50.6g (1.1mol) ethanol, then plus
Enter 150ml dichloroethanes, ice bath cools to 0 DEG C, be slowly introducing the tail gas preparing acyl chlorides, hydrogen chloride and sulfur dioxide ratio are big
About 1:1, as reactant liquor weightening more than 199g, stop ventilation, insulation reaction 2 hours, be warmed up to 25 DEG C, be incubated 14 hours,
Deca 10% sodium hydroxide solution in reactant liquor, until reactant liquor becomes neutral, separates organic layer, water layer 100ml dichloro
Ethane is extracted twice, and merges organic faciess, and 100ml washes once, and organic faciess precipitation, to complete, obtains colourless liquid product 182.6g,
Efficient liquid phase chromatographic analysis, containing to chlorobenzene formimidic acid ethyl ester 95.5%, p-Cyanochlorobenzene 3.2%, yield is 95%.
Embodiment 3：Preparation to methoxybenzene carboximidic acid methyl ester hydrochlorate
150ml dichloroethanes, 107.1g (0.9mol) thionyl chloride is added in 500ml reaction bulb, and ice bath cools to 0 DEG C,
It is slowly added dropwise 16.2g water, drips off within 1 hour, continue stirring reaction after 30 minutes, add 35.2g (1.1mol) methanol,
134g (1mol) to methoxy benzonitrile, 0-5 DEG C of insulation reaction 2 hours, be warmed up to 25 DEG C, be incubated 12 hours, with
Track to methoxy benzonitrile content be less than 3%, nitrogen blowing 1 hour in reactant liquor, tail gas with sodium hydrate aqueous solution absorb,
Reactant liquor is cooled to 0 DEG C, is incubated 1 hour, filter, obtain white solid 189.5g, yield is 95%, high-efficient liquid phase color
Analysis of spectrum, containing to methoxybenzene formimidic acid ethyl ester 99.3%.
Reference examples 1：The preparation of benzimidic acid ethvl ester
230g (5mol) ethanol is added in 1000ml reaction bulb, ice bath cools to 0 DEG C, is slowly added dropwise people 314g (4mol)
Chloroacetic chloride, under the conditions of 5 DEG C, insulation reaction 2 hours.103g (1mol) benzonitrile is added in reaction bulb, is warmed up to 25 DEG C,
Insulation 72 hours, the Deca saturated solution of sodium bicarbonate in reactant liquor, until reactant liquor becomes neutral, water layer 100ml acetic acid
Ethyl ester is extracted twice, and merges organic faciess, and 100ml washes once, and organic faciess precipitation, to complete, obtains colourless liquid product 139.5g,
Efficient liquid phase chromatographic analysis, containing benzimidic acid ethvl ester 85.2%, benzonitrile 12.4%.
Reference examples 2：The preparation of benzimidic acid ethvl ester
276g (6mol) ethanol is added in 1000ml reaction bulb, ice bath cools to 0 DEG C, is slowly added dropwise people 314g (4mol)
Chloroacetic chloride, under the conditions of 5 DEG C, insulation reaction 2 hours.51.5g (0.5mol) benzonitrile is added in reaction bulb, is warmed up to
25 DEG C, it is incubated 16 hours, the Deca saturated solution of sodium bicarbonate in reactant liquor, until reactant liquor becomes neutral, water layer 100ml
Ethyl acetate is extracted twice, and merges organic faciess, and 100ml washes once, and organic faciess precipitation, to complete, obtains colourless liquid product
139.5g, efficient liquid phase chromatographic analysis, containing benzimidic acid ethvl ester 83.1%, benzonitrile 16.9%.
This reference examples presses Yadav, Veejendra K. in document European Journal of Organic Chemistry, 2005
(2), in 452-456, the process of report is carried out.Result is not reaching to the effect of document, in the presence of 8 times of chloroacetic chlorides, 16
16.9% raw material is still had not react, far from the conversion ratio of reach document report 100% after hour.The method is not only non-
Often uneconomical, and do not reach satisfied Production requirement.
Reference examples 3：The preparation of benzimidic acid ethvl ester
By 103g (1mol) benzonitrile, 50.6g (1.1mol) dehydrated alcohol and 200g dichloroethanes put into 500ml reaction bulb
In, less than 10 DEG C of stirring cooling.The hydrochloric acid of 534g (5.26mol) 36% is slowly dropped in 667g concentrated sulphuric acid, the chlorine of generation
Change hydrogen to be passed through after drying in reaction bulb, holding reaction temperature, control ventilation, Continuous aeration 6-8 hour, then
It is warmed up to 25 DEG C, stirring reaction 72 hours, the Deca saturated solution of sodium bicarbonate in reactant liquor, until reactant liquor becomes neutral,
Water layer is extracted twice with 100ml ethyl acetate, merges organic faciess, and 100ml washes once, and organic faciess precipitation, to complete, obtains no
Color fluid product 141.3g, efficient liquid phase chromatographic analysis, containing benzimidic acid ethvl ester 87.1%, benzonitrile 10.8%, yield is
82.6%.
Claims (9)
1. the preparation method of a kind of formula I or the compound shown in formula II is it is characterised in that the benzene first shown in formula III
Carbonitrile derivatives are reacted at -30～50 DEG C with alcohol and catalyst, obtain the benzimide acid esters shown in formula II after reaction
With alkali neutralization after derivant hydrochloric acid salt, or reaction, obtain the benzimide acid ester derivant shown in formula I；
Wherein,
Described alcohol is R-OH；
Described catalyst is hydrogen chloride and sulfur dioxide mixture gas, or can produce a kind of gas in hydrogen chloride and sulfur dioxide
The single or multiple compound of body is combined with another kind of gas, or can produce the single of hydrogen chloride and sulfur dioxide simultaneously
Or multiple compound；
Described X is hydrogen, halogen, C1～C4 alkyl, C1～C4 alkoxyl, C6～C14 aryl, C6～C14 virtue oxygen
Base, C6～C14 aralkyl, C6～C14 aralkoxy, C6～C14 aryloxyalkyl group or C6～C14 virtue oxygen alkoxyl；
Described n is 1～5；
Described R be C1～C6 alkyl, C1～C6 haloalkyl, C3～C6 thiazolinyl, C3～C6 haloalkenyl group, C3～
C6 alkynyl or C3～C6 halo alkynyl.
2. preparation method according to claim 1 is it is characterised in that the benzonitrile derivative shown in formula III and catalyst
The mol ratio of hydrogen chloride produced by middle hydrogen chloride or catalyst is 1：1～1：10；Two in benzonitrile derivative and catalyst
The mol ratio of sulfur dioxide produced by sulfur oxide or catalyst is 1：0.1～1：10.
3. preparation method according to claim 2 is it is characterised in that the benzonitrile derivative shown in formula III and catalyst
The mol ratio of hydrogen chloride produced by middle hydrogen chloride or catalyst is 1：1～1：4；Two in benzonitrile derivative and catalyst
The mol ratio of sulfur dioxide produced by sulfur oxide or catalyst is 1：0.5～1：3.
4. preparation method according to claim 1 is it is characterised in that reaction temperature is -10-30 DEG C；Reaction dissolvent is selected from two
Chloromethanes, chloroform, carbon tetrachloride, dichloroethanes, petroleum ether, normal hexane, hexamethylene, benzene, toluene, chlorobenzene, acetic acid
One or more of ethyl ester, N,N-dimethylformamide, oxolane, acetonitrile, dioxane or dimethyl sulfoxide.
5. preparation method according to claim 1 is it is characterised in that described alkali is selected from sodium hydroxide, potassium hydroxide, hydrogen-oxygen
Change calcium, Feldalat NM, Sodium ethylate, potassium tert-butoxide, pyridine, morpholine, methylamine, dimethylamine, trimethylamine, ethamine, diethylamine,
One or more of triethylamine, ammonia, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, Calcium Carbonate；In preparation
In the reaction of formula I compound, it is neutralized to neutrality with alkali.
6. preparation method according to claim 1 is it is characterised in that the described compound that can produce hydrogen chloride includes acyl chlorides
With alcohol combine or concentrated hydrochloric acid and concentrated sulphuric acid combination；The compound that sulfur dioxide can be produced includes sodium sulfite and sulphuric acid
Combination；Hydrogen chloride can be produced simultaneously and the compound of sulfur dioxide includes thionyl chloride and water.
7. preparation method according to claim 1 it is characterised in that after benzonitrile derivative and alcohol and catalyst reaction directly
Filter, obtain the benzimide acid ester derivant hydrochlorate shown in formula II；Or benzonitrile derivative and alcohol and catalyst
It is neutralized to neutrality with alkali liquor after reaction, after isolating organic layer precipitation, directly obtain the benzimide acid esters shown in formula I
Derivant.
8. preparation method according to claim 1 it is characterised in that described X be hydrogen, halogen, C1～C4 alkyl or C1～
C4 alkoxyl；Described n is 1～2；Described R is C1～C4 alkyl or C1～C4 haloalkyl.
9. preparation method according to claim 1 it is characterised in that described X be hydrogen, fluorine, chlorine, bromine, methyl, ethyl,
N-pro-pyl, isopropyl, methoxyl group, ethyoxyl, positive propoxy or isopropoxy；Described n is 1 or 2；Described R is first
Base, ethyl, n-pro-pyl, isopropyl, halogenated methyl, halogenated ethyl, halo n-pro-pyl or haloisopropyl.
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| CN101481332A (en) * | 2009-02-26 | 2009-07-15 | 南京中狮化学品有限公司 | Method for synthesizing alkoxy aromatic amidine compounds |
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| CN101481332A (en) * | 2009-02-26 | 2009-07-15 | 南京中狮化学品有限公司 | Method for synthesizing alkoxy aromatic amidine compounds |
Non-Patent Citations (2)
| Title |
|---|
| A Remarkably Efficient Markovnikov Hydrochlorination of Olefins and Transformation of Nitriles into Imidates by Use of AcCl and an Alcohol;Veejendra K. Yadav et al.;《Eur. J. Org. Chem.》;20051231;第452-456页 * |
| 丙烷脒杀菌剂开发研究;陈安良;《中国优秀博硕士学位论文全文数据库 (博士) 工程科技Ⅰ辑（月刊）2006年》;20061115(第11 期);B016-42 * |
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