CN1931897A - Polyglycol modifier for benzoic acid/nitrobenzoic acid and its synthesis process - Google Patents
Polyglycol modifier for benzoic acid/nitrobenzoic acid and its synthesis process Download PDFInfo
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Abstract
The present invention relates to one kind of medicine intermediate, and is especially polyglycol modified benzoic acid/ nitrobenzoic acid and its synthesis process. The synthesis process includes the first step of reaction of polyglycol, benzoic acid/ nitrobenzoic acid and chloroformylating material to obtain crude polyglycol modified benzoic acid/ nitrobenzoic acid product, and the second step of purifying the crude product to obtain refined white modified benzoic acid powder product or yellow nitrobenzoic acid powder product. The present invention has rich material source, low cost, simple synthesis path, high production efficiency and other advantages, and the polyglycol modified benzoic acid/ nitrobenzoic acid has high medicine carrying amount, slow release effect and raised water solubility.
Description
Technical field
The carbowax modifier of phenylformic acid/nitrobenzoic acid and synthetic method thereof relate to a kind of pharmaceutical intermediate and synthesis technical field thereof, belong to chemistry and pharmaceutical chemistry synthetic technology.
Background of invention
Phenylformic acid/nitrobenzoic acid is the pharmaceutical intermediate of using always.The medicine of a lot of clinical applications all has the molecular structure similar to it, and this class material is slightly soluble in water.For example nicotinic acid is significant clinically small-molecule drug, needs long term administration, and the transformation period is short, for keeping certain Plasma Concentration, the palpus frequent drug administration; Nicotinic acid acidity is stronger in addition, and during oral administration, often gi tract being produced stimulates.In order to address the above problem, need carry out modification to this class medicine, these medicines are very expensive usually, need carry out the exploration of the experiment condition of modification with other molecular model, and phenylformic acid and nitrobenzoic acid can be used as model drug.
Nontoxic, the no teratogenecity of polyoxyethylene glycol (PEG), non-immunogenicity, inexpensive, the source is abundant, has extraordinary water-soluble and biocompatibility, when coupling drug divides the period of the day from 11 p.m. to 1 a.m, its premium properties can be given the medicine after the modification, change its biology in the aqueous solution and distribute behavior and solvability.PEG produces the space barrier around the medicine of its modification, reduce the enzymolysis of medicine, avoids very fast elimination in renal metabolism, the prolong drug transformation period, and medicine can be discerned by immune system cell, help bringing into play drug effect.This field of macromole modified medicaments is a hot research in recent years.Although phenylformic acid and nitrobenzoic acid are used for exploring the experiment condition of PEG modified medicaments.But the report that the PEG that up to the present, yet there are no phenylformic acid and nitrobenzoic acid modifies.
(thesis topic is big monomeric synthetic for containing medicine end group PEG for document.Shen Liangjun, Li Qinghai.Anhui Normal University's journal.2002.25:154) relate to the synthetic method of the polyethyleneglycol modified nicotinic acid of monohydroxy, this synthetic method is that the monohydroxy polyoxyethylene glycol mixes with nicotinic acid, adopt dicyclohexylcarbodiimide (DCC) dehydration, with under the condition of Dimethylamino pyridine (DMAP) as catalyzer, synthesized monohydroxy polyoxyethylene glycol/nicotinic acid modifier.But raw material DCC in this method and DMAP are relatively more expensive, and cost is higher; And the productive rate of the polyoxyethylene glycol of the monohydroxy in this method/nicotinic acid modifier is very low, is 40%～50%.
Summary of the invention
The objective of the invention is to disclose a kind of carbowax modifier of phenylformic acid/nitrobenzoic acid, another object of the present invention provides a kind of method of synthetic above-mentioned modifier.
In order to achieve the above object, the invention discloses benzoic carbowax modifier, its structural formula is as follows:
N represents 45～450 integer.
The carbowax modifier of nitrobenzoic acid has following structure,
N represents 45～450 integer.
Phenylformic acid among the present invention and nitrobenzoic acid carbowax modifier are at room temperature all soluble in water, also be dissolved in methylene dichloride, trichloromethane, tetrahydrofuran (THF), acetone, ethanol, N, most organic solvents such as dinethylformamide, but be insoluble to ether, sherwood oil is respectively white, deep yellow pressed powder.
Second technical problem that the present invention will solve provides the synthetic method of the carbowax modifier of above-mentioned phenylformic acid/nitrobenzoic acid.The technical scheme that addresses this problem is to adopt following synthetic route:
The first step polyoxyethylene glycol and phenylformic acid/nitrobenzoic acid-chlorine formylation thing reacts, and makes the raw product of the carbowax modifier of phenylformic acid/nitrobenzoic acid.
Second goes on foot the raw product of the carbowax modifier of purification phenylformic acid/nitrobenzoic acid, makes the highly finished product of the carbowax modifier of phenylformic acid/nitrobenzoic acid.
Wherein phenylformic acid/nitrobenzoic acid-chlorine formylation thing adopts following method synthetic:
A. phenylformic acid/nitrobenzoic acid and thionyl chloride react, and make the raw product of phenylformic acid/nitrobenzoic acid-chlorine formylation thing;
B. the purify raw product of phenylformic acid/nitrobenzoic acid-chlorine formylation thing obtains highly finished product.
Now describe concrete steps of the present invention in detail:
The preparation of benzoic carbowax modifier:
The preparation of the raw product of the benzoic carbowax modifier of the first step
With the polyoxyethylene glycol is raw material, adds the highly finished product of phenylformic acid-chlorine formylation thing, adds solvent, adds triethylamine.Solvent is benzene, toluene.By polyoxyethylene glycol: the highly finished product of phenylformic acid-chlorine formylation thing: solvent: triethylamine=1: (0.05～0.16): (2.5～4.5): (0.1～0.2) weight ratio is measured; under nitrogen atmosphere and the magnetic agitation; refluxed 24 hours down in 60～90 ℃ of oil baths, make the raw product of benzoic carbowax modifier.The structural formula of benzoic carbowax modifier is
In the formula, n represents 45～450 integer;
The purification of benzoic carbowax modifier raw product of second step
The product that the first step is made filters, filtrate decompression is boiled off most of solvent, get concentrated solution,, dissolve with benzene then with the anhydrous diethyl ether precipitation, placement is spent the night, repeat above-mentioned filtration, underpressure distillation, anhydrous diethyl ether precipitation, with ether washing three times, vacuum-drying is to constant weight, make benzoic carbowax modifier highly finished product, product is the white solid powder.
Benzoic carbowax modifier water soluble, ethanol, benzene, tetrahydrofuran (THF), toluene, chloroform, dichloromethane solvent are insoluble to ether, sherwood oil.
The preparation of the carbowax modifier of nitrobenzoic acid:
The preparation of the raw product of the carbowax modifier of the first step nitrobenzoic acid
With the polyoxyethylene glycol is raw material, adds the highly finished product of nitrobenzoic acid-chlorine formylation thing, adds solvent, adds triethylamine.Solvent is benzene, toluene.By polyoxyethylene glycol: the highly finished product of phenylformic acid/nitrobenzoic acid-chlorine formylation thing: solvent: triethylamine=1: (0.06～0.21): (2.5～4.5): (0.1～0.2) weight ratio is measured; under nitrogen atmosphere and the magnetic agitation; refluxed 24 hours down in 60～90 ℃ of oil baths, make the raw product of the carbowax modifier of nitrobenzoic acid.The structural formula of the carbowax modifier of nitrobenzoic acid is
In the formula, n represents 45～450 integer;
The purification of the carbowax modifier raw product of the second step nitrobenzoic acid
The product that the first step is made filters, filtrate decompression is boiled off most of solvent, get concentrated solution,, dissolve with benzene then with the anhydrous diethyl ether precipitation, placement is spent the night, repeat above-mentioned filtration, underpressure distillation, anhydrous diethyl ether precipitation, with ether washing three times, vacuum-drying is to constant weight, make the carbowax modifier highly finished product of nitrobenzoic acid, product is the deep yellow pressed powder.
The carbowax modifier water soluble of nitrobenzoic acid, ethanol, benzene, tetrahydrofuran (THF), toluene, chloroform, dichloromethane solvent are insoluble to ether, sherwood oil.
Benzene feedstock formic acid-chlorine formylation thing in the aforesaid method was undertaken by following two steps:
A. the raw product of phenylformic acid-chlorine formylation thing
With the phenylformic acid is raw material, drips the purified thionyl chloride.By phenylformic acid: thionyl chloride=(1～1.2): the weight ratio of (1.7～2) is measured, and under 70～90 ℃ of stirrings, reacts 3～7 hours, and in the question response system when no solid and the generation of no bubble, stopped reaction makes the raw product of phenylformic acid-chlorine formylation thing.
B. the purification of phenylformic acid-chlorine formylation thing
The thionyl chloride that pressure reducing and steaming is excessive adds benzene, removes benzene under reduced pressure, makes the highly finished product of phenylformic acid-chlorine formylation thing, is white solid.
The synthetic method of the raw material nitrobenzoic acid-chlorine formylation thing in the aforesaid method sees that (thesis topic is the new way of synthetic 4-nitro-4-chlorobenzophenone to document.Huang Xianghong.Chemical reagent, 2002,24 (3): 171).
Beneficial effect of the present invention is:
1. raw material polyoxyethylene glycol among the present invention and thionyl chloride source is abundant, and cost is low.
2. the raw material polyoxyethylene glycol among the present invention contains two hydroxyls, so each macromolecular drug loading height.
3. synthetic route is simple.Route of the present invention is received it on polyoxyethylene glycol by activating phenylformic acid and nitrobenzoic acid earlier, and the reaction times is short, the production efficiency height.
4. because synthesis material thionyl chloride of the present invention easily distills,, be easy to purifying so the purification of products method is simple.
5. product productive rate height.Product productive rate of the present invention is 80～85%.
Description of drawings
Fig. 1 is Fourier transform infrared spectroscopy (IR) figure of benzoic carbowax modifier among the embodiment 1.
Fig. 2 is Fourier transform infrared spectroscopy (IR) figure of the carbowax modifier of nitrobenzoic acid among the embodiment 1.
Can illustrate that from Fig. 1 the synthetic product is the highly finished product of benzoic carbowax modifier.Fig. 2 illustrates that the synthetic product is the highly finished product of the carbowax modifier of nitrobenzoic acid.
Embodiment
Embodiment 1
The preparation of the raw product of the benzoic carbowax modifier of the first step
With the polyoxyethylene glycol is raw material, adds the highly finished product of phenylformic acid-chlorine formylation thing, adds solvent, adds triethylamine.Solvent is a benzene.The add-on of highly finished product, solvent and the triethylamine of polyoxyethylene glycol, phenylformic acid-chlorine formylation thing is respectively 10.6g (2.4mmol), 1.4g (10mmol), 30ml and 3.5ml.The weight ratio of highly finished product, solvent and the triethylamine of polyoxyethylene glycol, phenylformic acid-chlorine formylation thing is 1: (0.05～0.16): (2.5～4.5): (0.1～0.2).Under nitrogen atmosphere and the magnetic agitation, 80 ℃ of oil baths refluxed 24 hours down, made the raw product of benzoic carbowax modifier.The structural formula of benzoic carbowax modifier is
In the formula, n represents 90;
The purification of benzoic carbowax modifier raw product of second step
The product that the first step is made filters, filtrate decompression is boiled off most of solvent, get concentrated solution, precipitate with anhydrous diethyl ether, dissolve with benzene then, placement is spent the night, and repeats above-mentioned filtration, underpressure distillation, anhydrous diethyl ether precipitation, with ether washing three times, vacuum-drying is to constant weight, make benzoic carbowax modifier highly finished product, product is white solid powder 10.2g, productive rate 85%.
The solvent benzol of embodiment 1 can change toluene into.
Benzene feedstock formic acid-chlorine formylation thing in the aforesaid method was undertaken by following two steps:
A. the raw product of phenylformic acid-chlorine formylation thing
With the phenylformic acid is raw material, drips the purified thionyl chloride.The add-on of phenylformic acid and thionyl chloride is respectively 1.22g (10mmol) and 3ml (40mmol); by phenylformic acid: the weight ratio of thionyl chloride=1: 2.45 is measured; under 70 ℃ of stirrings; reacted 3 hours; when no solid and no bubble produce in the question response system; stopped reaction makes the raw product of phenylformic acid-chlorine formylation thing.
B. the purification of phenylformic acid-chlorine formylation thing
The thionyl chloride that pressure reducing and steaming is excessive adds benzene, removes benzene under reduced pressure, makes the highly finished product of phenylformic acid-chlorine formylation thing, is white solid.
Embodiment 2
The preparation of the raw product of the benzoic carbowax modifier of the first step
With the polyoxyethylene glycol is raw material, adds the highly finished product of phenylformic acid-chlorine formylation thing, adds solvent, adds triethylamine.Solvent is a benzene.The add-on of highly finished product, solvent and the triethylamine of polyoxyethylene glycol, phenylformic acid-chlorine formylation thing is respectively 5.3g (2.4mmol), 1.4g, 30ml and 3.5ml.The weight ratio of highly finished product, solvent and the triethylamine of polyoxyethylene glycol, phenylformic acid-chlorine formylation thing is 1: (0.1～0.3): (5.0～9.0): (0.2～0.4).Under nitrogen atmosphere and the magnetic agitation, 60 ℃ of oil baths refluxed 24 hours down, made the raw product of benzoic carbowax modifier.The structural formula of benzoic carbowax modifier is
In the formula, n represents 45;
The purification of benzoic carbowax modifier raw product of second step
The product that the first step is made filters, filtrate decompression is boiled off most of solvent, get concentrated solution, precipitate with anhydrous diethyl ether, dissolve with benzene then, placement is spent the night, and repeats above-mentioned filtration, underpressure distillation, anhydrous diethyl ether precipitation, with ether washing three times, vacuum-drying is to constant weight, make benzoic carbowax modifier highly finished product, product is white solid powder 5.7g, productive rate 85%.
The preparation of the benzene feedstock formic acid-chlorine formylation thing in the aforesaid method and embodiment 1 are together.
Embodiment 3
The preparation of the raw product of the benzoic carbowax modifier of the first step
With the polyoxyethylene glycol is raw material, adds the highly finished product of phenylformic acid-chlorine formylation thing, adds solvent, adds triethylamine.Solvent is a benzene.The add-on of highly finished product, solvent and the triethylamine of polyoxyethylene glycol, phenylformic acid-chlorine formylation thing is respectively 14.8g (2.4mmol), 1.4g, 30ml and 3.5ml.The weight ratio of highly finished product, solvent and the triethylamine of polyoxyethylene glycol, phenylformic acid-chlorine formylation thing is 1: (0.03～0.11): (1.8～3.2): (0.07～0.14).Under nitrogen atmosphere and the magnetic agitation, 90 ℃ of oil baths refluxed 24 hours down, made the raw product of benzoic carbowax modifier.The structural formula of benzoic carbowax modifier is
In the formula, n represents 136;
The purification of benzoic carbowax modifier raw product of second step
The product that the first step is made filters, filtrate decompression is boiled off most of solvent, get concentrated solution, precipitate with anhydrous diethyl ether, dissolve with benzene then, placement is spent the night, and repeats above-mentioned filtration, underpressure distillation, anhydrous diethyl ether precipitation, with ether washing three times, vacuum-drying is to constant weight, make benzoic carbowax modifier highly finished product, product is white solid powder 12.96g, productive rate 80%.
The preparation of the benzene feedstock formic acid-chlorine formylation thing in the aforesaid method and embodiment 1 are together.
Embodiment 4
The preparation of the raw product of the carbowax modifier of the first step nitrobenzoic acid
With the polyoxyethylene glycol is raw material, adds the highly finished product of nitrobenzoic acid-chlorine formylation thing, adds solvent, adds triethylamine.Solvent is a benzene.The add-on of highly finished product, solvent and the triethylamine of polyoxyethylene glycol, nitrobenzoic acid-chlorine formylation thing is respectively 10.6g (2.4mmol), 1.9g (10mmol), 30ml and 3.5ml.The weight ratio of highly finished product, solvent and the triethylamine of polyoxyethylene glycol, nitrobenzoic acid-chlorine formylation thing is 1: (0.06～0.21): (2.5～4.5): (0.1～0.2).Under nitrogen atmosphere and the magnetic agitation, 80 ℃ of oil baths refluxed 24 hours down, made the raw product of the carbowax modifier of nitrobenzoic acid.The structural formula of the carbowax modifier of nitrobenzoic acid is
In the formula, n represents 90;
The purification of the carbowax modifier raw product of the second step nitrobenzoic acid
The product that the first step is made filters, filtrate decompression is boiled off most of solvent, get concentrated solution,, dissolve with benzene then with the anhydrous diethyl ether precipitation, placement is spent the night, repeat above-mentioned filtration, underpressure distillation, anhydrous diethyl ether precipitation, with ether washing three times, vacuum-drying is to constant weight, make the carbowax modifier highly finished product of nitrobenzoic acid, product is a brown solid powder 10.6g productive rate 85%.
The solvent benzol of embodiment 4 can change toluene into.
Raw material p-nitrobenzoic acid-chlorine formylation thing in the aforesaid method was undertaken by following two steps:
A. the raw product of p-nitrobenzoic acid-chlorine formylation thing
With the p-nitrobenzoic acid is raw material, drips the purified thionyl chloride.The add-on of p-nitrobenzoic acid and thionyl chloride is respectively 1.67g (10mmol) and 3ml (40mmol); by p-nitrobenzoic acid: the weight ratio of thionyl chloride=1: 2.45 is measured; under 70 ℃ of stirrings; reacted 6 hours; when no solid and no bubble produce in the question response system; stopped reaction makes the raw product of p-nitrobenzoic acid-chlorine formylation thing.
B. the purification of p-nitrobenzoic acid-chlorine formylation thing
The thionyl chloride that pressure reducing and steaming is excessive adds benzene, removes benzene under reduced pressure, makes the highly finished product of p-nitrobenzoic acid-chlorine formylation thing, is faint yellow solid.
Embodiment 5
The preparation of the raw product of the carbowax modifier of the first step nitrobenzoic acid
With the polyoxyethylene glycol is raw material, adds the highly finished product of nitrobenzoic acid-chlorine formylation thing, adds solvent, adds triethylamine.Solvent is a benzene.The add-on of highly finished product, solvent and the triethylamine of polyoxyethylene glycol, nitrobenzoic acid-chlorine formylation thing is respectively 5.3g (2.4mmol), 1.9g, 30ml and 3.5ml.The weight ratio of highly finished product, solvent and the triethylamine of polyoxyethylene glycol, nitrobenzoic acid-chlorine formylation thing is 1: (0.1～0.3)/(0.13～0.42): (5.0～9.0): (0.2～0.4).Under nitrogen atmosphere and the magnetic agitation, 60 ℃ of oil baths refluxed 24 hours down, made the raw product of the carbowax modifier of nitrobenzoic acid.The structural formula of the carbowax modifier of nitrobenzoic acid is
In the formula, n represents 45;
The purification of the carbowax modifier raw product of the second step nitrobenzoic acid
The product that the first step is made filters, filtrate decompression is boiled off most of solvent, get concentrated solution, precipitate with anhydrous diethyl ether, dissolve with benzene then, placement is spent the night, and repeats above-mentioned filtration, underpressure distillation, anhydrous diethyl ether precipitation, with ether washing three times, vacuum-drying is to constant weight, make the carbowax modifier highly finished product of nitrobenzoic acid, product is brown solid powder 6.1g, productive rate 85%.
The preparation of the raw material nitrobenzoic acid-chlorine formylation thing in the aforesaid method and embodiment 4 are together.
Embodiment 6
The preparation of the raw product of the carbowax modifier of the first step nitrobenzoic acid
With the polyoxyethylene glycol is raw material, adds the highly finished product of nitrobenzoic acid-chlorine formylation thing, adds solvent, adds triethylamine.Solvent is a benzene.The add-on of highly finished product, solvent and the triethylamine of polyoxyethylene glycol, nitrobenzoic acid-chlorine formylation thing is respectively 14.8g (2.4mmol), 1.9g, 30ml and 3.5ml.The weight ratio of highly finished product, solvent and the triethylamine of polyoxyethylene glycol, nitrobenzoic acid-chlorine formylation thing is 1: (0.05～0.15): (1.8～3.2): (0.07～0.14).Under nitrogen atmosphere and the magnetic agitation, 90 ℃ of oil baths refluxed 24 hours down, made the raw product of the carbowax modifier of nitrobenzoic acid.The structural formula of the carbowax modifier of nitrobenzoic acid is,
In the formula, n represents 136;
The purification of the carbowax modifier raw product of the second step nitrobenzoic acid
The product that the first step is made filters, filtrate decompression is boiled off most of solvent, get concentrated solution, precipitate with anhydrous diethyl ether, dissolve with benzene then, placement is spent the night, and repeats above-mentioned filtration, underpressure distillation, anhydrous diethyl ether precipitation, with ether washing three times, vacuum-drying is to constant weight, make the carbowax modifier highly finished product of nitrobenzoic acid, product is deep yellow pressed powder 13.36g, productive rate 80%.
The preparation of the raw material nitrobenzoic acid-chlorine formylation thing in the aforesaid method and embodiment 4 are together.
Method of the present invention is applicable to that the PEG of the chemicals that contains carboxyl modifies.
Claims (7)
1. the carbowax modifier of a phenylformic acid/nitrobenzoic acid is characterized in that, benzoic carbowax modifier has following structure,
N represents 45～450 integer.
The carbowax modifier of nitrobenzoic acid has following structure,
N represents 45～450 integer.
2. the synthetic method of the described benzoic carbowax modifier of claim 1 is characterized in that:
The preparation of the raw product of the benzoic carbowax modifier of the first step
Earlier by polyoxyethylene glycol: the highly finished product of phenylformic acid-chlorine formylation thing: solvent: triethylamine=1: 0.05～0.16: 2.5～4.5: 0.1～0.2 weight ratio is measured, be raw material then with the polyoxyethylene glycol, the highly finished product that add phenylformic acid-chlorine formylation thing, add solvent, add triethylamine, under nitrogen atmosphere and the magnetic agitation, refluxed 24 hours down, make the raw product of benzoic carbowax modifier in 60～90 ℃ of oil baths;
The purification of benzoic carbowax modifier raw product of second step
The product that the first step is made filters, filtrate decompression is boiled off most of solvent, get concentrated solution,, dissolve with benzene then with the anhydrous diethyl ether precipitation, placement is spent the night, repeat above-mentioned filtration, underpressure distillation, anhydrous diethyl ether precipitation, with ether washing three times, vacuum-drying is to constant weight again, make benzoic carbowax modifier highly finished product, product is a white powder.
3. the synthetic method of the carbowax modifier of the described nitrobenzoic acid of claim 1 is characterized in that:
The preparation of the raw product of the carbowax modifier of the first step nitrobenzoic acid
Earlier by polyoxyethylene glycol: the highly finished product of nitrobenzoic acid-chlorine formylation thing: solvent: triethylamine=1: 0.06～0.21: 2.5～4.5: 0.1～0.2 weight ratio is measured, be raw material then with the polyoxyethylene glycol, the highly finished product that add nitrobenzoic acid-chlorine formylation thing, add solvent, add triethylamine, under nitrogen atmosphere and magnetic agitation, refluxed 24 hours down in 60～90 ℃ of oil baths, make the raw product of the carbowax modifier of nitrobenzoic acid;
The purification of the carbowax modifier raw product of the second step nitrobenzoic acid
The product that the first step is made filters, filtrate decompression is boiled off most of solvent, get concentrated solution,, dissolve with benzene then with the anhydrous diethyl ether precipitation, placement is spent the night, repeat above-mentioned filtration, underpressure distillation, anhydrous diethyl ether precipitation, with ether washing three times, vacuum-drying is to constant weight again, make the carbowax modifier highly finished product of nitrobenzoic acid, product deep yellow powder.
4. the synthetic method of a kind of benzoic carbowax modifier according to claim 2, it is characterized in that: solvent is benzene or toluene.
5. the synthetic method of the carbowax modifier of a kind of nitrobenzoic acid according to claim 3, it is characterized in that: solvent is benzene or toluene.
6. synthetic method according to claim 2 is characterized in that: the synthetic method of phenylformic acid-chlorine formylation thing that the first step is used, undertaken by following two steps:
The raw product of A, phenylformic acid-chlorine formylation thing, with the phenylformic acid is raw material, drip the purified thionyl chloride, the amount that adds is by phenylformic acid: thionyl chloride=1～1.2: 1.7～2 weight ratio is measured, under 70～90 ℃ of stirrings, reacted 3～7 hours, when no solid and no bubble produce in the question response system, stopped reaction makes the raw product of phenylformic acid-chlorine formylation thing;
The purification of B, phenylformic acid-chlorine formylation thing, the thionyl chloride that pressure reducing and steaming is excessive adds benzene, removes benzene under reduced pressure, makes the highly finished product of phenylformic acid-chlorine formylation thing, is white solid.
7. synthetic method according to claim 3 is characterized in that: the synthetic method of nitrobenzoic acid-chlorine formylation thing that the first step is used, undertaken by following two steps:
The raw product of A, nitrobenzoic acid-chlorine formylation thing, with the nitrobenzoic acid is raw material, drip the purified thionyl chloride, add-on is by nitrobenzoic acid: thionyl chloride=1～1.2: 1.7～2 weight ratio is measured, under 70～90 ℃ of stirrings, reacted 3～7 hours, the stopped reaction during generation of no solid and no bubble in the question response system makes the raw product of nitrobenzoic acid-chlorine formylation thing;
The purification of B, nitrobenzoic acid chlorine formylation thing, the thionyl chloride that pressure reducing and steaming is excessive adds benzene, removes benzene under reduced pressure, makes the highly finished product of nitrobenzoic acid-chlorine formylation thing, is the deep yellow solid.
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