CN1277637A - Method for preparing a substituted benzamide - Google Patents
Method for preparing a substituted benzamide Download PDFInfo
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- CN1277637A CN1277637A CN98810505A CN98810505A CN1277637A CN 1277637 A CN1277637 A CN 1277637A CN 98810505 A CN98810505 A CN 98810505A CN 98810505 A CN98810505 A CN 98810505A CN 1277637 A CN1277637 A CN 1277637A
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- benzonitrile
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12P13/00—Preparation of nitrogen-containing organic compounds
- C12P13/02—Amides, e.g. chloramphenicol or polyamides; Imides or polyimides; Urethanes, i.e. compounds comprising N-C=O structural element or polyurethanes
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Abstract
The invention concerns a method for preparing a substituted benzamide, preferably a halogenated benzamide. More particularly, the invention concerns the preparation of 2,6-difluorobenzamide, by biological hydrolysis. It concerns a method for preparing a substituted benzamide by enzymatic hydrolysis of a substituted benzonitrile, characterised in that it consists in subjecting the substituted benzonitrile to hydrolysis in the presence of a tetrameric enzyme with alpha 2 beta 2 structure having a defined amino acid sequence.
Description
The present invention relates to a kind of substituted benzamide, the preparation method of preferred halobenzamides.The present invention relates more specifically to by biological hydrolysis preparation 2, the method for 6-difluorobenzamide.
2, the 6-difluorobenzamide is a kind of known intermediate (referring to GB-A-1 324 293) that is used to prepare pesticide product, especially diflubenzuron.
By chemosynthesis approach preparation 2, the 6-difluorobenzamide exists problem, and this is because 2, and the hydrolysis of 6-difluoro benzonitrile is in tart medium extremely, and is concrete as carry out in the presence of 60% vitriol oil.In fact not only yield is not very high, is no more than 80%, and this method makes us dissatisfied part and also be because of generating a large amount of salt by-product, thereby pollutes and make purification difficult and cost height.In addition, have found that, cause and to take neutralization procedure owing to use a large amount of sulfuric acid.
In addition, FR-A-2 294 999 discloses a kind of amides method for hydrolysis of finishing by biological hydrolysis.So, can obtain benzamide by hydrolysis benzonitrile under the effect of brevibacterium sp bacterium according to Bergey is described.But the activity that it should be noted that R 312 bacterial strains is specific for the aliphatics nitrile: so it is to the activity lower (60 μ mol/h.mg enzyme) of benzonitrile, because production efficiency is extremely low, makes it can't adapt to suitability for industrialized production.
Unexpectedly, have found that under the effect of enzyme that preferably on the brevibacterium sp bacterium and more preferably under the effect of R312 bacterial strain and mutant strain A4 thereof 2, the 6-difluorobenzamide can be hydrolyzed.
Particularly, theme of the present invention is a kind ofly to replace the method that benzonitrile prepares substituted benzamide by enzymically hydrolyse, it is characterized in that in structure be α
2β
2Tetramer enzyme exist and to replace benzonitrile generation hydrolysis down, described tetramer enzyme has at least 50%, preferably is higher than 80% homology and has following amino acid sequences:
-α chain:
MSVTIDHTTENAAPAQAPVSDRAWALFRALDGKGLVPDGYVEGWKKTFEEDFSPRRGAEL?60
VARAWTDPEFRQLLLTDGTAAVAQYGYLGPQGEYIVAVEDTPTLKNVIVCSLCSCTAWP?119
ILGLPPTWYKSFEYRARVVREPRKVLSEMGTEIASDIEIRVYDTTAETRYMVLPQRPAG?178
TEGWSQEQLQEIVTKDCLIGVAIPQVPTV?207
-β chain:
MDGVHDLAGVQGFGKVPHTVNADIGPTFHAEWEHLPYSLMFAGVAELGAFSVDEVRYV58
VERMEPRHYMMTPYYERYVIGVATLMVEKGILTQDELESLAGGPFP?104
LSRPSESEGRPAPVETTTFEVGQRVRVRDEYVPGHIRMPAYCRGRVGTI?153
SHRTTEKWPFPDAIGHGRNDAGEEPTYHVKFAAEELFGSDTDGGSVVVDLFEGYLEPAA?212
In this application, the habitual implication in amino acid whose abbreviation and present technique field is corresponding, and specifically is disclosed in " biochemical theory " that the people showed (the 2nd edition, F1ammarion medical science press, 113 pages) such as Albert L.Lehinger.
Particularly, they are meant: glycine=G, L-Ala=A, Xie Ansuan=V, leucine=L, Isoleucine=I, proline(Pro)=P, phenylalanine=F, tyrosine=Y, tryptophane=W, Serine=S, Threonine=T, halfcystine=C, methionine(Met)=M, l-asparagine=N, glutamine=Q, Aspartic Acid=D, L-glutamic acid=E, Methionin=K, arginine=R, Histidine=H
Term among the application " replacement " is meant, in benzonitrile class initial reactant, at least one on the aromatic ring in 5 hydrogen atoms replaced by non-hydrogen atom.Specifically can be replaced by halogen, carbon, oxygen or nitrogen-atoms.
According to the present invention, the mode that can be entirely satisfactory by biological hydrolysis prepares 2,6-difluoro benzonitrile.
As if because in the prior art, the enzymically hydrolyse benzonitrile is very difficult, so 2,6-difluoro benzonitrile probably can't be by biological hydrolysis.
People still can't predict can hydrolysis 2,6-difluoro benzonitrile and obtain good hydrolysis effect.
According to the inventive method, replace benzonitrile, preferred 2, the hydrolysis in the presence of enzyme of 6-difluoro benzonitrile with above-mentioned definition aminoacid sequence.
According to the present invention, both can use the microorganism cells that contains described enzyme, also can adopt the preparation of acellular enzyme, but in one situation of back,, cause production cost to increase owing to must carry out the extraction of enzyme.
In this application, the cell and the isolating enzyme of expressing enzyme should be represented in term " enzyme ".
Preferred cell rather than the isolating enzyme of using.
Described enzyme can derive from the brevibacterium sp microorganism, more specifically can derive from tyrothricin R312 bacterial strain or its mutant strain tyrothricin sp A4.
R312 bacterial strain and mutant strain A4 thereof belong to known and especially are disclosed among the FR-A-2294 999 and Nicolas Bernet presents in the paper (on June 30th, 1989) of the state-run high agronomy of Meng Boliye school.R 312 and A4 at Dutch voor Shimmel culture collection center with preserving number CBS 71773 and CBS LMD 792 preservations.
Described mutant strain is characterised in that this bacterial strain has been lost the ability of the most amidess of hydrolysis, but retains and the identical Nitrile hydratase activity of wild-type tyrothricin sp.R 312 bacterial strains simultaneously.
Can obtain the tyrothricin bacterial strain by in the substratum that contains carbon source such as glucose, phosphoric acid salt and ammonia, magnesium and ferrous ion, cultivating.Above-mentioned substratum can be rich in organic nitrogen source such as yeast extract or peptone.
Described enzyme or bacterial strain for example can be fixed on carrier such as the silicon-dioxide or in the gel, this belongs to the scope of the invention equally by assembling.
The carrier technique for fixing it is known to the person skilled in the art that and specifically can be with reference to the works " fixing means of enzyme and cell " of Gordon F.Bickerstaff.
The present invention is preferably applied in hydrolysis 2,6-difluoro benzonitrile, but the inventive method also can adopt more specifically other reactant corresponding to the replacement benzonitrile class of following formula (I):
In the formula (I):
R
1The expression hydrogen atom, halogen atom, preferred fluorine, chlorine or bromine atom, or haloalkyl, preferred perfluoroalkyl, or any other radicals R,
R
2With R
1Identical or different, the expression hydrogen atom, halogen atom, preferred fluorine, chlorine or bromine atom, or haloalkyl, preferred perfluoroalkyl, or any other radicals R,
R
1And R
2In at least one is not a hydrogen atom,
N equals 1-4.
The inventive method preferred and be the reactant of halogenated benzyl nitrile class more specifically suc as formula shown in (Ia):
In the formula (Ia):
R
1The expression halogen atom, preferred fluorine, chlorine or bromine atom; Or haloalkyl, preferred perfluoroalkyl,
R
2With R
1Identical or different, the expression hydrogen atom; Halogen atom, preferred fluorine, chlorine or bromine atom; Or haloalkyl, preferred perfluoroalkyl, or any other radicals R,
N equals 1-4.
In formula (I) with (Ia), have one or more R
1And R
2Group is positioned at ortho position, contraposition or a position of cyano group.
Preferred group R
1And R
2Be positioned at the ortho position of cyano group.
R
1And R
2Represent halogen atom, but also can represent preferably to contain the haloalkyl of 1-12 carbon atom and 1-7 halogen atom.
Preferred group is the whole haloalkyl that contains 1-5 carbon atom and preferably contain 1-7 halogen atom, preferred perfluoroalkyl.
As the more specifically example of haloalkyl, can mention fluoro-alkyl, for example fluoro methyl, difluoromethyl, trifluoromethyl, fluoro ethyl, 1,1,1-trifluoroethyl, pentafluoroethyl group, fluoro propyl group, fluoro butyl or trifluoro amyl group.Preferred trifluoromethyl.
Radicals R in the formula (I)
1And R
2And the radicals R in the formula (Ia)
2Can have other implication shown in the symbol R.
Radicals R can possess any characteristic, and condition is that R does not disturb hydrolysis reaction.
For example, can mention: hydroxyl; Contain 1-6 carbon atom, preferably contain the alkyl or the alkoxyl group of 1-4 carbon atom; Amino or contained 1-6 carbon atom by one or two, the preferred amino that alkyl replaced of 1-4 carbon atom.
Preferred compound is R wherein
1Represent fluorine atom, chlorine atom or trifluoromethyl R simultaneously
2With R
1Represent identical or differently the formula (I) of hydrogen atom, fluorine atom, chlorine atom or trifluoromethyl or (Ia) shown in compound.
As the formula that is applicable to the inventive method (I) or (Ia) example of reactant, can mention :-Salicylnitrile ,-p-HBN,-O-methoxy benzonitrile ,-to HOMOVERATRONITRILE ,-adjacent bromo benzonitrile,-adjacent chloro benzonitrile ,-to the chloro benzonitrile ,-chloro a benzonitrile,-m-trifluoromethyl benzonitrile ,-2, the 6-dichloro-benzonitrile,-2,6-difluoro benzonitrile ,-to the methyl benzonitrile,-to aminobenzonitrile
In the compound, preferred reactant is 2,6-difluoro benzonitrile and m-trifluoromethyl benzonitrile in formula (I) or (Ia).
According to the inventive method, replace benzonitrile, preferred 2,6-difluoro benzonitrile is hydrolyzed in the presence of described enzyme.
This is reflected in the buffered water-bearing media and finishes.
In a preferred embodiment of the inventive method, reaction raw materials contains up to 3mol/l benzonitrile reactant.
In stem cell weight, the concentration that exists of microorganism is 1-50g/l, preferred 2-10g/l.
The reactant medium is cushioned, and preferred pH is in the scope of 6-8 and be more preferably 7.
For the pH that obtains to expect, can be referring to document, concrete as Rex.M.C, " (biochemical research data " (the 3rd edition, Oxford Science Press, 1986, the 432 pages) that the people showed such as Davison.
In the methods of the invention, adopt ordinary method, contain 1-500mmol PO with respect to every liter of solution of especially making particularly by potassium hydrogen phosphate sodium
4 =The ionic phosphate buffer soln.
In order under service temperature, to obtain the pH of expection, pH is transferred to proper level by the sodium hydroxide or the sodium bicarbonate buffer liquid of suitable concentration.
In fact, the inventive method is easy and easy to implement.
Under agitation, enzyme reactant and unpack format or the microorganism cells carrier band is joined in the buffer medium that is transferred to suitable pH.
Heating suits to carry out in preferred 10 ℃-30 ℃ scope at 10 ℃-40 ℃.
Temperature of reaction need be kept for some time, normally 4 hours-20 hours.
When reaction finishes, obtain the substituted benzamide of precipitation forms, preferred halobenzamides.
According to the habitual isolation technique of liquid/solid, preferably reclaim in a usual manner by filtration.
If desired, purify with suitable organic solvent.
The superiority of the inventive method is and can makes benzamide by not generating the high method for hydrolysis of any salt compounds and production efficiency.
The following example illustrates but does not limit the present invention.
In an embodiment, abbreviation has following implication:
-DFBN=2,6-difluoro benzonitrile
-DFBZ=2, the 6-difluorobenzamide
-DC=stem cell embodiment 1
The production of cell
In following substratum, cultivate the microorganism tyrothricin sD.A4 that can produce Nitrile hydratase:
-damping fluid (Na
2HPO
4/ KH
2PO
4) pH 7 50mmol/l
-FeSO
4·7H
2O????????????????????????0.01g/l
-MgSO
4·H
2O?????????????????????????0.5g/l
-thiamine hydrochloride 0.002g/l
-glucose 10g/l
-NH
4Cl???????????????????????????????5g/l
Preparation contains the aqueous solution of different components and utilizes the autoclaving sterilization respectively, but ferrous solution and thiamines solution are by filtration method sterilization (millipore filtration, HA type, 0.45 μ m).
The substratum that makes that is used for the high-density cells cultivation of tyrothricin sp.A4 contains above-mentioned basic medium and replenishes Difco yeast extract and glucose.
Tyrothricin sp.A4 cultivates in Erlenmeyer flask, and culture is filled into 1/5th places of Erlenmeyer flask volume, to guarantee the substratum ventilation.Under 28 ℃, these Erlenmeyer flasks stir (amplitude 5cm) with the 150rpm vibration on worktable.
At first, be present in cell original seed in the liquid nitrogen on inoculating with (Difco) agar ware of Columbia medium preparation.The first pre-culture is to prepare in the 50ml substratum with culture dish.After about 20 hours, inoculate second culture.This cultivation reaches exponential phase of growth after 15 hours.
In order to obtain more many cells, its production is to carry out in 2 liters fermentor tank.Culture parameters is set as follows: the dividing potential drop of-pH7-oxygen is adjusted to: 50%
Continuing to adjust dividing potential drop by opening intake valve under the stirring.The valve maximum is opened to 1.5vvm, so that do not cause overventilation;-stir: 300rpm during beginning (quickening during the fermentation);-temperature: 28 ℃.
The recovery of cell
With cell centrifugation, with physiological saline or contain the physiological saline washing of 20% glycerine, recentrifuge.With two different approaches frozen cells:
-cell is joined in the 0.1mol phosphoric acid buffer, be evenly distributed in the Eppendorf tube, store down at-30 ℃ subsequently;
-be chilled in the cell mass preparation in the liquid nitrogen and be stored in-80 ℃ the refrigerator.
Assessment to dry weight
Obtain a certain amount of cell from the designated volume culture, with distilled water wash and be suspended in the distilled water, the pasteurizing unit internal heating of suspension at 100 ℃ spent the night to remove whole traces of moisture.Obtain the dry weight of the cell of designated volume.Embodiment 2
2, the preparation of 6-difluorobenzamide
To be that 7 phosphoric acid buffer adds in the reactor according to 0.1mol, the pH of " biochemical research data " (the 3rd edition, Oxford Science Press, 1986,432 pages) of people such as Rex.M.C.Davison preparation.
Add 35 ℃ liquid D FBN and crystallization in medium again, crystallization adheres to reactor bottom.
Stirring is accelerated to 500rpm so that make its suspension and smash bigger crystal grain.
When t=0, add cell suspending liquid and stir speed (S.S.) is set in 500-600rpm.
Sealed reactor in process of the test.
Used container is a kind ofly to carry out well-beaten reactor with the stirring system, and described stirring system comprises paddle and balance blade.By the thermostatic bath attemperation.
Operational condition and result are listed as table (I):
| The total concn (mol/l) of the DFBN that adds | Temperature (℃) | Time (hour) | ????[DC] ????(g/l) | Generate the volumetric molar concentration (mmol/l) of acid amides | Activity specific (μ mol/hmg DC) |
| ????1.5 | ???15 | ????16 | ????4.75 | ????690 | ???????10 |
| ????1.7 | ???15 | ????8 | ????9.7 | ????1352 | ???????17.4 |
| ????1.66 | ???25 | ????6 | ????2.6 | ????728 | ???????44 |
| ????1.67 | ???25 | ????14 | ????2.8 | ????1005 | ???????25.5 |
| ????1.66 | ???25 | ????6 | ????5.5 | ????1600 | ???????48 |
| ????2 | ???25 | ????8 | ????5.5 | ????1536 | ???????35 |
2.5g/l or the stem cell concentration of 5g/l produces optimum activity in 6 little the reaction times.In order to obtain concentration in 6 hours, in the substratum of controlled pH is the acid amides of 1.5mol, needs the 5g/l stem cell.Embodiment 3
The effect of reaction product
At first, the powder acid amides of different concns is incorporated in the phosphate buffered saline buffer of 0.1mol/l pH 7, to the stem cell that wherein adds 5.3g/l tyrothricin sp.A4.
In 1 hour under 30 ℃, 0.5,1,2,3 or 4mol/DFBZ in the presence of measure the hydrolytic activity of DFBZ (815mmol during beginning), its result is shown in table (II):
Table (II)
| Initial DFBZ (mol/l) | Activity specific (μ mol/hmgDC) |
| ????0.5 | ????89 |
| ????1 | ????86 |
| ????2 | ????67 |
| ????3 | ????53 |
| ????4 | ????49 |
In the presence of high density reaction product (DFBZ), the activity of tyrothricin bacterial strain does not almost affect adversely.Embodiment 4:
The activity of separating enzyme
30 ℃ and stir under, make bacterial strain or enzyme contact 1 hour with DFBZ (500-900mmol/l).
Gained is active shown in table (III):
Embodiment 5
| Test conditions | Activity specific (μ mol.mg stem cell or protein) | |
| Bacterial strain (S) or enzyme (E) | ||
| Title | DC or proteinic concentration (g/l) | |
| Tyrothricin sp A4 (E) | ????0.2 | ????1108.3 |
| Tyrothricin sp A4 (S) | ????8.0 | ????102 |
| Tyrothricin R 312 (S) | ????4.2 | ????153 |
The preparation of 3-trifluoromethyl benzamide
To be that 7 phosphate buffered saline buffer adds in the pipe according to 0.1mol, the pH of " (biochemical research data " (the 3rd edition, Oxford Science Press, 1986,432 pages) preparation of people such as Rex.M.C.Davison.
Ratio with 300mmol/l adds the m-trifluoromethyl benzonitrile in phosphate buffered saline buffer.
When t=0, add cell suspending liquid (final reaction volume=1ml) and with stir speed (S.S.) be set in 500-600rpm.
Temperature of reaction is 30 ℃.
In 1 hour, whole nitriles can be hydrolyzed to acid amides with the 2g/l stem cell.
Claims (18)
1. replace the method that benzonitrile prepares substituted benzamide by enzymically hydrolyse, it is characterized in that replacing benzonitrile is α in structure
2β
2Tetramer enzyme have lower hydrolysis; Described enzyme has at least 50%, preferably is higher than 80% homology and has following amino acid sequence :-α chain MSVTIDHTTENAAPAQAPVSDRAWALFRALDGKGLVPDGYVEGWKKTFEEDFSPRR GAEL 60VARAWTDPEFRQLLLTDGTAAVAQYGYLGPQGEYIVAVEDTPTLKNVIVCSLCS CTAWP 119ILGLPPTWYKSFEYRARVVREPRKVLSEMGTEIASDIEIRVYDTTAETRYMVL PQRPAG 178TEGWSQEQLQEIVTKDCLIGVAIPQVPTV 207-β chain MDGVHDLAGVQGFGKVPHTVNADIGPTFHAEWEHLPYSLMFAGVAELGAFSVDEVR YV 58VERMEPRHYMMTPYYERYVIGVATLMVEKGILTQDELESLAGGPFP 104LSRPSESEGRPAPVETTTFEVGQRVRVRDEYVPGHIRMPAYCRGRVGTI 153SHRTTEKWPFPDAIGHGRNDAGEEPTYHVKFAAEELFGSDTDGGSVVVDLFEG YLEPAA 212
2. the method for claim 1 is characterized in that replacing benzonitrile as shown in the formula shown in (I):
In the formula (I):
R
1The expression hydrogen atom, halogen atom, preferred fluorine, chlorine or bromine atom, or haloalkyl, preferred perfluoroalkyl, or any other radicals R,
R
2With R
1Identical or different, the expression hydrogen atom, halogen atom, preferred fluorine, chlorine or bromine atom, or haloalkyl, preferred perfluoroalkyl, or any other radicals R,
R
1And R
2In at least one is not a hydrogen atom,
N equals 1-4.
3. the method for claim 1, it is characterized in that replacing benzonitrile is the halogenated benzyl nitrile shown in the following formula (Ia):
In the formula (Ia):
R
1The expression halogen atom, preferred fluorine, chlorine or bromine atom; Or haloalkyl, preferred perfluoroalkyl,
R
2With R
1Identical or different, the expression hydrogen atom; Halogen atom, preferred fluorine, chlorine or bromine atom; Or haloalkyl, preferred perfluoroalkyl, or any other radicals R,
N equals 1-4.
4. claim 2 or 3 method, it is characterized in that formula (I) or (Ia) shown in replace in the benzonitrile R
1And R
2In a group be positioned at ortho position, contraposition or a position of cyano group, but be preferably placed at the ortho position.
5. claim 2 or 3 method, it is characterized in that formula (I) or (Ia) shown in replace R in the benzonitrile
1And R
2Expression halogen atom and/or contain the haloalkyl of 1-12 carbon atom and 1-7 halogen atom.
7. claim 2 or 3 method, it is characterized in that formula (I) or (Ia) shown in replace R in the benzonitrile
1And R
2Expression contains 1-5 carbon atom and preferably contains the whole haloalkyl of 1-7 halogen atom.
8. claim 2 or 3 method, it is characterized in that formula (I) or (Ia) shown in replace R in the benzonitrile
1And R
2The expression haloalkyl, preferred fluoro-alkyl, for example fluoro methyl, difluoromethyl, trifluoromethyl, fluoro ethyl, 1,1,1-trifluoroethyl, pentafluoroethyl group, fluoro propyl group, fluoro butyl or trifluoro amyl group.
9. claim 2 or 3 method, it is characterized in that formula (I) or (Ia) shown in replace R in the benzonitrile
1And R
2The expression haloalkyl, preferred trifluoromethyl.
10. claim 2 or 3 method, it is characterized in that formula (I) or (Ia) shown in replace that R represents hydroxyl in the benzonitrile; Contain 1-6 carbon atom, the alkyl or the alkoxyl group of preferred 1-4 carbon atom; Amino or contained 1-6 carbon atom by one or two, the preferred amino that alkyl replaced of 1-4 carbon atom.
11. the method for claim 2 or 3, it is characterized in that formula (I) or (Ia) shown in replace R in the benzonitrile
1Expression fluorine or chlorine atom or trifluoromethyl, and R
2With R
1Identical or different, expression hydrogen atom, fluorine atom, chlorine atom or trifluoromethyl.
12. the method for claim 2 or 3, it is characterized in that replacing benzonitrile is 2,6-difluoro benzonitrile or m-trifluoromethyl benzonitrile.
13. each method among the claim 1-12 is characterized in that described enzyme is from the brevibacterium sp microorganism.
14. the method for claim 13 is characterized in that described enzyme is from bacterial strain tyrothricin R312 or tyrothricin sp A4.
15. each method among the claim 1-14, the hydrolytic process that it is characterized in that replacing benzonitrile is preferably carried out under about 7 pH in the pH of 6-8 scope.
16. each method among the claim 1-15, the hydrolytic process that it is characterized in that replacing benzonitrile is carried out in the preferably phosphate buffered substratum through the buffered substratum.
17. the method for claim 16 is characterized in that hydrolysising reacting temperature is 10 ℃-40 ℃, preferred 10 ℃-30 ℃.
18. the halobenzamides that each method makes among the claim 1-17.
19. according to each method among the claim 1-17 by 2, the hydrolysis of 6-difluoro benzonitrile obtain 2, the 6-difluorobenzamide.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR97/13368 | 1997-10-24 | ||
| FR9713368A FR2770214B1 (en) | 1997-10-24 | 1997-10-24 | PROCESS FOR THE PREPARATION OF A HALOGEN BENZAMIDE |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1277637A true CN1277637A (en) | 2000-12-20 |
Family
ID=9512621
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN98810505A Pending CN1277637A (en) | 1997-10-24 | 1998-10-23 | Method for preparing a substituted benzamide |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP1025255A1 (en) |
| JP (1) | JP2001520891A (en) |
| CN (1) | CN1277637A (en) |
| FR (1) | FR2770214B1 (en) |
| WO (1) | WO1999022012A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100336798C (en) * | 2006-05-08 | 2007-09-12 | 浙江大学 | Process of preparing 2,6-difluorobenzamide by 2.6-difluorobenz nitrile non catalyzing and hydrolyzing in near critical aqueous medium |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004067738A2 (en) * | 2003-01-27 | 2004-08-12 | Degussa Ag | Nitrile hydratases from rhodococcus erythropolis and their application |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2294999A1 (en) * | 1974-12-18 | 1976-07-16 | Anvar | PROCESS FOR THE PREPARATION OF AMIDES BY BIOLOGICAL HYDROLYSIS |
| FR2505676A1 (en) * | 1981-05-15 | 1982-11-19 | Rhone Poulenc Spec Chim | FLUORINE-CONTAINING SILICA CATALYSTS AND PROCESS FOR THEIR PREPARATION AND THEIR APPLICATION TO THE PREPARATION OF NITRILES |
| GB8616160D0 (en) * | 1986-07-02 | 1986-08-06 | Shell Int Research | Difluorobenzamide |
| FR2626289B1 (en) * | 1988-01-27 | 1990-06-08 | Rhone Poulenc Sante | PROCESS FOR THE PREPARATION OF OPTICALLY ACTIVE ALKANOIC ARYL-2 ACIDS |
| AU627648B2 (en) * | 1990-02-28 | 1992-08-27 | Teruhiko Beppu | Dna fragment encoding a polypeptide having nitrile hydratase activity, a transformant containing the gene and a process for the production of amides using the transformant |
-
1997
- 1997-10-24 FR FR9713368A patent/FR2770214B1/en not_active Expired - Fee Related
-
1998
- 1998-10-23 EP EP98951543A patent/EP1025255A1/en not_active Withdrawn
- 1998-10-23 JP JP2000518103A patent/JP2001520891A/en not_active Withdrawn
- 1998-10-23 CN CN98810505A patent/CN1277637A/en active Pending
- 1998-10-23 WO PCT/FR1998/002274 patent/WO1999022012A1/en not_active Application Discontinuation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100336798C (en) * | 2006-05-08 | 2007-09-12 | 浙江大学 | Process of preparing 2,6-difluorobenzamide by 2.6-difluorobenz nitrile non catalyzing and hydrolyzing in near critical aqueous medium |
Also Published As
| Publication number | Publication date |
|---|---|
| FR2770214B1 (en) | 1999-12-31 |
| WO1999022012A1 (en) | 1999-05-06 |
| JP2001520891A (en) | 2001-11-06 |
| FR2770214A1 (en) | 1999-04-30 |
| EP1025255A1 (en) | 2000-08-09 |
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