GB2146644A - Process for preparing phosphinic acid intermediates - Google Patents
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- GB2146644A GB2146644A GB08423458A GB8423458A GB2146644A GB 2146644 A GB2146644 A GB 2146644A GB 08423458 A GB08423458 A GB 08423458A GB 8423458 A GB8423458 A GB 8423458A GB 2146644 A GB2146644 A GB 2146644A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/62—Isoquinoline or hydrogenated isoquinoline ring systems
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/301—Acyclic saturated acids which can have further substituents on alkyl
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/303—Cycloaliphatic acids
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- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/304—Aromatic acids (P-C aromatic linkage)
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/306—Arylalkanephosphinic acids, e.g. Ar-(CH2)n-P(=X)(R)(XH), (X = O,S, Se; n>=1)
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/32—Esters thereof
- C07F9/3205—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/3211—Esters of acyclic saturated acids which can have further substituents on alkyl
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- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/32—Esters thereof
- C07F9/3205—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/3223—Esters of cycloaliphatic acids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/32—Esters thereof
- C07F9/3205—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/3241—Esters of arylalkanephosphinic acids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/572—Five-membered rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/572—Five-membered rings
- C07F9/5728—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems
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Abstract
A process is provided for preparing phosphinic acid prodrug intermediates which are useful in preparing phosphinic acid angiotensin-converting enzyme inhibitors which method includes the step of coupling a phosphonous acid or its ester of the structure <IMAGE> wherein R is H or lower alkyl and R<1> is lower alkyl, aryl, arylalkyl, cycloalkyl or cycloalkylalkyl,with a conjugated compound of the structure <IMAGE> wherein R<2>, R<3> and R<4> may be the same or different and each is independently H, lower alkyl or aryl, and Z is lower alkyl, -CO2R<5> (wherein R<5> is H or lower alkyl), <IMAGE> (wherein R<6> is H, lower alkyl aryl or arylalkyl), -CN, <IMAGE> (wherein R<7> and R<8> are the same or different and are selected from the group consisting of H, lower alkyl, aryl, aryl-lower alkyl, cycloalkyl or cycloalkylalkyl and at least one of R<7> and R<8> is other than H, or R<7> and R<8> can be taken together with N to form a 5-, 6- or 7-membered heterocyclic ring <IMAGE> which may or may not include a COOR<5> substituent, which 5-or 6-membered N-containing ring may or may not be fused to an aryl ring), in the presence of a silylating agent, to form the phosphinic acid intermediate of the structure <IMAGE> wherein R, R<1>, R<2>, R<3> and R<4> and Z are as defined above.
Description
SPECIFICATION
Process for preparing phosphinic acid intermediates
The present invention relates to a process for preparing phosphinic acid intermediates having the structure
wherein R is H or lower alkyl;
R1 is lower alkyl, aryl, arylalkyl, cycloalkyl, or cycloalkylalkyl; R2, R3 and R4 may be the same or different and each is independently H, lower alkyl or aryl; and Z is lower alkyl, CN, -C02R5 (wherein R5 is H or lower alkyl),
(wherein R6 is H or lower alkyl, aryl or arylalkyl), -CN, or
(wherein R7 and R8 are the same or different and can be H, lower alkyl, aryl, aryl-lower alkyl, cycloalkyl or cycloalkylalkyl and at least one of R7 and R8 is other than H, or R7 and R3 can be taken with N to form a 5-, 6-or 7-membered heterocvclic ring
which ring may or may not include a carboxyl substituent -C02R5, and which nitrogen containing ring containing 5 or 6 members may or may not include a fused aryl ring, such as a phenyl ring, so that the nitrogen containing ring
together with its fused aryl ring may form indole or tetrahydroisoquinoline systems such as
,wherein the above formulae n' isO to 1), which intermediates are useful in the preparation of phosphinic acid angiotensin-converting enzyme inhibitors such as described in U.S. Patents Nos. 4,168,267 and 4,337,201.
The process of the present invention for making phosphinic acid intermediates of formula I includes the step of reacting a phosphonous acid or ester of the structure
wherein R is H or lower alkyl and R1 is lower alkyl, aryl, arylalkyl, cycloalkyl or cycloalkylalkyl, with a conjugated compound of the structure
R2, R3 and R4 may be the same or different and each is H, lower alkyl or aryl, and Z is lower alkyl, CO2R5 (wherein R5 is H or lower alkyl),
(wherein R6 is H, lower alkyl aryl or arylalkyl), CN, or
(wherein R7 and R8 are the same or different and can be H, lower alkyl, aryl, aryl-lower alkyl, cycloalkyl or cycloalkylalkyl and at least one of R7 and R8 is other than H, or R7 and R8 can be taken with N to form a 5-, 6- or 7-membered heterocyclic ring
which ring may or may not include a carboxyl substituent -C02R5, and which 5- or 6-membered
N-containing ring may or may not include a fused aryl ring, such as a phenyl ring, which fused systems are exemplified above), in the presence of a silylating agent and an inert organic solvent to form the phosphinic acid intermediate I which may be separated from the reaction mixture and used in the preparation of phosphinic acid angiotensin-converting enzyme inhibitors such as described in U.S. Patents Nos. 4,168,267 and 4,337,201.
The term "aryl", as used throughout the specification either by itself or as part of a larger group, refers to phenyl or phenyl substituted with halogen, alkyl, alkoxy, alkylthio, hydroxy, alkanoyl, nitro, amino, dialkylamino, ortrifluoromethyl groups. Phenyl and monosubstituted phenyl are preferred and phenyl is the most preferred.
The term "alkyl" or "lower alkyl" as used throughout the specification either by itself or as part of a larger group, refers to groups having 1 to 10 carbon atoms. Alkyl groups having 1 to 4 carbon atoms are preferred.
The term "cycloalkyl", as used throughout the specification either by itself or as part of a larger group, refers to groups having 3 to 7 carbon atoms.
The term "alkoxy" or "alkylthio", as used throughout the specification either by itself or as part of a larger group, refers to groups having 1 to 8 carbon atoms. Alkoxy or alkylthio groups having 1 to 3 carbon atoms are preferred.
The term "arylalkyl" or "cycloalkylalkyl", as used throughout the specification either by itself or as part of a larger group, refers to an "alkyl" group as defined above containing an "aryl" or "cycloalkyl" substituent.
The term "alkanoyl" as used throughout the specification either by itself or as part of a larger group, refers to an "alkyl" group as defined above linked to a carbonyl
group.
In carrying out the process of the invention to prepare compounds of formula lithe phosphonous acid or ester starting material II will be reacted with the conjugated compound in the presence of the silylating agent employing a temperature of within the range of from about O"C to about reflux temperature (about 1 20 C), and preferably from about 1 0 C to about 50"C. The reaction will be carried out for a period ranging from about 2 to about 10 hours and preferably from about 5 to about 8 hours in the presence of an inert organic solvent such as chloroform, acetonitrile, dichloromethane, ethyl ether, tetrahydrofuran or dioxane, and optionally, in the presence of an organic base, such as triethylamine, pyridine or N,N-dimethylamine.
Examples of phosphonous acids or esters II useful as starting materials in carrying out the present invention include, but are not limited to,
or esters thereof being preferred.
Examples of conjugated compounds ll useful in carrying out the present invention include, but are not limited to,
H
H2C=CCN, H(C6H5)C=CHCOOH, CH2 = CHCO2H, CH2 = CHCOOCH3, H(CôH5-CH2)C=CHCOC6H5,
,with H2C=CHCN being preferred.
Examples of silylating agents suitable for use in carrying out the method of the present invention include, but are not limited to, trimethylsilyl chloride and triethylamine, monosilylacetamide, bissilylacetamide, monosilyltrifluoroacetamide and bissilyltrifluoroacetamide.
In carrying out the method of the invention as descibed above the amount of phosphonous acid or ester II employed vis-a-vis the conjugated compound Ill and the silylating agent will depend upon the R substituent in the starting phosphonous acid or ester II and the Z substituent in the conjugated compound Ill. Thus, where R is lower alkyl and Z is CO2alkyl, lower alkyl,
CN or
then the phosphonous acid or ester II will be employed in a molar ratio to the conjugated compound Ill of within the range of from about 0.5:1 to about 10:1 and the phosphonous acid of ester II will be employed in a molar ratio to the silylating agent of within the range of from about 0.5:1 to about 1:10.
Where in the phosphonous acid or ester II, R is H and in the conjugated compound Ill, Z is lower alkyl,
C02R5 (wherein R5 is lower alkyl),
the phosphonous acid or ester Il will be employed in a molar ratio to the conjugated compound Ill of within the range of from about 0.5:1 to about 10:1 and the phosphonous acid or ester il will be employed in a molar ratio to the silylating agent of within the range of from about 0.2:1 to about 1:10.
Where a phosphonous acid starting material is used, that is in formula II, R is H, and in the conjugated compound Ill, Z is CO2H, or
then the phosphonous acid II will be employed in a molar ratio to the conjugated compound Ill of within the range of from about 0.5:1 to about 10:1 and the phosphonous acid II will be employed in a molar ratio to the silylating agent of within the range of from about 0.1:1 to about 1:15.
Where a phosphonous acid ester of formula II (that is, R is alkyl) is employed and the conjugated compound used is an acid, that is in formula III, Z is CO2H, or
,the phosphonous acid ester II will be employed in a molar ratio to the conjugated compound of within the range of from about 0.5:1 to about 10:1 and the phosphonous acid ester II will be employed in a molar ratio to the silylating agent of within the range of from about 0.2:1 to about 1:10.
Where the phosphinic acid intermediate I is obtained in the form of an ester, such ester may be converted to the free acid by conventional means such as by reacting the ester with sodium hydroxide.
The esters of formula I where B is lower alkyl can be obtained from the carboxylic acid compounds, that is wherein R is H, by conventional esterification means, for example, by esterification with diazomethane or by reaction with methyl iodide (or other alkyl halide) and a base such as triethylamine, potassium carbonate and the like.
The following Examples represent preferred embodiments of the present invention. Unless otherwise indicated, all temperatures are expressed in degrees Centigrade.
EXAMPLE 1 3-[Hydroxy- (4-phen ylbutyl)phosphinyl]propiononitrile To a solution of 4-phenylbutyl phosphonous acid (0.44 g, 0.0022 mole) in chloroform (15 ml) was added triethylamine (0.68 ml), trimethyl silylchloride (0.61 ml) and acrylonitrile (0.17 ml) and the reaction mixture was stirred at room temperature for 18 hours; the mixture was poured into crushed ice (15 gm) containing 10 ml 10% HCI acid. It was shaken in a separatoryfunnel; a chloroform layer was evaporated, and the aqueous layer extracted once with 20 ml chloroform. The combined organic phase was washed with water, dried over anhydrous sodium sulphate and the organic solvent removed on a rotavap to produce the title compound as a highly crystalline solid (99% yield).
EXAMPLE 2 3-[Hydroxy-F4-phenylbutyl)phosphinyljpropionic acid
Following the procedure of Example 1, except substituting acrylic acid for acrylonitrile, the title compound is obtained.
EXAMPLE 3 3-[Hydroxy(phenyl)phosphin yl]-3-phenylpropionic acid, methyl ester
Following the procedure of Example 1, except substituting phenyiphosphonous acid for 4-phenylbutyl phosphonous acid and substituting methylcinnamate for acrylonitrile, the title compound is obtained.
EXAMPLE 4 3- (Eth ox yphosphin yip rop yl)-3-phenyl-2-meth yl-propionic acid
Following the procedure of Example 1, except substituting propylphosphonous acid ethyl ester for 4-phenylbutylphosphonous acid and substituting 2-methyl-3-phenylacrylic acid for acrylonitrile, the title compound is obtained.
EXAMPLE 5 3-[EthoxyfCyclohexylphosphinyl)]-3-methyl-2-phenylpropionic acid, methyl ester
Following the procedure as set out in Example 1, except substituting cyclohexylphosphonous acid for 4-phenylbutylphosphonous acid and substituting 2-phenyl-3-methyl-acrylic acid, methyl ester for acrylonitrile, the title compound is obtained.
EXAMPLE 6 3-[Hydroxyrcyclopentylphosphinyl)]-3,3-diethylpropionic acid, methyl ester
Following the procedure as set out in Example 1, except substituting cyclopentylphosphonous acid for 4-phenylbutylphosphonous acid and substituting 3,3-diethyl-acrylic acid methyl ester for acrylonitrile, the title compound is obtained.
EXAMPLE 7 3-[HydroxyZphenylphosphinyl)j-3-methyl-propionicacid, methyl ester
Following the procedure as set out in Example 1, except substituting phenylphosphonous acid for 4-phenylbutylphosphonous acid and substituting 3-methyl-acrylic acid, methyl ester for acrylonitrile, the title compound is obtained.
EXAMPLE 8 3-[Hydroxyrbenzyl phosphinyl)J-propionic acid, benzyl ester
Following the procedure as set out in Example 1, except substituting benzylphosphonous acid for 4-phenylbutylphosphonous acid and substituting benzyl acrylate for acrylonitrile, the title compound is obtained.
EXAMPLE 9 3-fKydroxy(prop ylphosphin yl)J-3, 3-dim eth ylpropion onitrlle Following the procedure as set out in Example 1, except substituting propylphosphonous acid for 4-phenylbutylphosphonous acid and substituting 3,3-dimethyl acrylonitrile for acrylonitrile, the title compound is obtained.
EXAMPLE 10 3-[Methoxy(hutylphosphinyl)-3-eth yl-propionic acid, benzyl ester
Following the procedure as set out in Example 1, except substituting butylphosphonous acid methyl ester for 4-phenylbutylphosphonous acid and substituting 3-ethyl-acrylic acid, benzyl ester for acrylonitrile, the title compound is obtained.
EXAMPLE 11 3-[Hydroxy-f4-phenylbutyl)phosphinyllpropionic acid, N,N-dimethylamide
Following the procedure of Example 1 except substituting N,N-dimethylacrylamide for acrylonitrile, the title compound is obtained.
EXAMPLE 12 3-[Hydroxy- (4-phenylb utyl)ph osphin yljpropion yI-L-prolin e, methyl ester
Following the procedure of Example 1 except substituting N-acryloyl-L-proline, methyl ester for acrylonitrile, the title compound is obtained.
EXAMPLE 13
1-[3-Hydroxy-(4-phenylbutyl)phosphinyl]propionyl]-indoline-3-carboxylic acid
Following the procedure of Example 1 except substituting 1-acryloyil indoline-3-carboxylic acid for acrylonitrile, the title compound is obtained.
EXAMPLE 14 2-f3-JHydroxy-(4-phenylbutyl)phosphinyljpropionylj- 1,23,4-tetrahydroisoquinoline- l-carhoxyllc acid
Following the procedure of Example 1 except substituting 2-acryloyil-1 ,2,3,4-tetrahydroisoquinoline-1 - carboxylic acid for acrylonitrile, the title compound is obtained.
EXAMPLE 15 2-[3-Hydroxy-(4-phenylbutyl)phosphinyl]propionyl]-1,2,3,4-tetrahydroisoquinoline
Following the procedure of Example 1 except substituting 2-acryloyil-1 ,2,3,4-tetrahydroisoquinoline for acrylonitrile, the title compound is obtained.
EXAMPLE 16 1-[3-[Hydroxy-(4-phenylnutyl)phosphinyl]propionyl]-indoline
Following the procedure of Example 1 except substituting 1 -acryloyil indoline for acrylonitrile, the title compound is obtained.
EXAMPLE 17 2-3-Hydroxy-/4-phenylbufyllphosphin yl/-3-methylpropionyl/- 1,2,3,4tetrahydroisoquinoline- 1-carboxylic acid
Following the procedure of Example 1 except substituting 2-crotonoyil-,1 ,2,3,4-tetrahydroisoquinoline-1 - carboxylic acid for acrylonitrile, the title compound is obtained.
Claims (16)
1. A process for preparing a phosphinic acid intermediate of the structure
wherein R is H or lower alkyl; Bi is lower alkyl, aryl, arylalkyl, cycloalkyl, or cycloalkylalkyl;
R2, R3,,d R4 are the same or different and each is independently H, lower alkyl or aryl;;
Z is lower alkyl, -Co2R5 (wherein R5 is H or lower alkyl),
(wherein B5 is H, lower alkyl, aryl or arylalkyl), -CN, or
wherein R7 and R8 are the same or different and are selected from the group consisting of H, lower alkyl, aryl, aryl-lower alkyl, cycloalkyl or cycloalkylalkyl and at least one of R7 and R8 is other than H, or R7 and R8 can be taken together with N to form a 5-, 6-or 7-membered heterocyclic ring
,which may or may not include a COOR5 substituent, which 5- or 6-membered N-containing ring may or may not be fused to an aryl ring, and n is O orl, which comprises reacting a phosphonous acid or ester thereof of the structure
wherein R and R1 are as defined above with an conjugated compound of the structure
wherein R2, R3, R4 and Z are as defined above, in the presence of a silylating agent and an inert organic solvent to form the phosphinic acid intermediate.
2. The process as defined in Claim 1 wherein the reaction is carried out in the presence of a base.
3. The process as defined in Claim 2 wherein the base is triethylamine, pyridine or N,N-dimethylamine.
4. The process as defined in Claim 1 wherein the inert organic solvent is chloroform, acetonitrile, dichioromethane, ethyl ether, tetrahydrofuran or dioxane.
5. The process as defined in Claim 1 wherein the silylating agent is trimethyl silylchloride and triethylamine, monosilylacetamide, bissilylacetamide, monosilyltrifluoroacetamide or bissilyltrifluoroacetamide.
6. The process as defined in Claim 1 wherein the silylating agent is trimethyl silylchloride and triethylamine.
7. The process as defined in Claim 1 wherein in the phosphonous acid or ester, R is lower alkyl, and in the conjugated compound Z is an ester, lower alkyl,
8. The process as defined in Claim 7 wherein the phosphonous acid ester is employed in a molar ratio to the conjugated compound of within the range of from about 0.5:1 to about 10:1, and the phosphonous acid ester is employed in a molar ratio to the silylating agent of within the range of from about 0.5:1 to about 1:10.
9. The process as defined in Claim 1 wherein in the phosphonous acid or ester, R is H and in the conjugated compound Z is an ester, lower alkyl,
10. The process as defined in Claim 9 wherein the phosphonous acid is employed in a molar ratio to the conjugated compound of within the range of from about 0.5:1 to about 10:1, and the phosphonous acid is employed in a molar ratio to the silylating agent of within the range of from about 0.2:1 to about 1:10.
11. The process as defined in Claim 1 wherein in the phosphonous acid or ester, R is lower alkyl, and in the conjugated compound Z is COOH or
12. The process as defined in Claim 11 wherein the phosphonous acid ester is employed in a molar ratio to the conjugated compound of within the range of from about 0.5:1 to about 10:1, and the phosphonous acid ester is employed in a molar ratio to the silylating agent of within the range of from about 0.2:1 to about 1:10.
13. The process as defined in Claim 1 wherein in the phosphonous acid or ester, R is H, and in the conjugated compound Z is COOH or
14. The process as defined in Claim 13 wherein the phosphonous acid is employed in a molar ratio to the conjugated compound of within the range of from about 0.5:1 to about 10:1, and the phosphonous acid is employed in a molar ratio to the silylating agent of within the range of from about 0.1:1 to about 1:15.
15. The process as defined in Claim 1 wherein the reaction between the phosphonous acid or ester and the conjugated compound is carried out at a temperature of within the range of from 0 C to 1200C.
16. The process as defined in Claim 1 wherein the phosphonous acid is
the conjugated compound is H2C=CHCN, and the silylating agent is (CH3)3SiCI and (C2H5)3N.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US53348683A | 1983-09-19 | 1983-09-19 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| GB8423458D0 GB8423458D0 (en) | 1984-10-24 |
| GB2146644A true GB2146644A (en) | 1985-04-24 |
| GB2146644B GB2146644B (en) | 1987-05-13 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB08423458A Expired GB2146644B (en) | 1983-09-19 | 1984-09-17 | Process for preparing phosphinic acid intermediates |
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| Country | Link |
|---|---|
| JP (1) | JPS6087293A (en) |
| CA (1) | CA1258458A (en) |
| DE (1) | DE3434124A1 (en) |
| FR (1) | FR2552090B1 (en) |
| GB (1) | GB2146644B (en) |
| IT (1) | IT1176710B (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE102006010352A1 (en) * | 2006-03-07 | 2007-09-13 | Clariant International Limited | Mixtures of mono-carboxyl-functionalized dialkylphosphinic salts and other components, a process for their preparation and use |
| DE102008055914A1 (en) * | 2008-11-05 | 2010-05-06 | Clariant International Limited | A process for the preparation of mono-hydroxy-functionalized dialkylphosphinic acids, esters and salts by means of acroleins and their use |
| EP2346885B1 (en) * | 2008-11-05 | 2013-08-28 | Clariant International Ltd. | Method for producing mono-carboxy-functionalized dialkylphosphinic acids and esters and salts thereof by means of allyl alcohols/acroleins and use thereof |
| DE102008056341A1 (en) * | 2008-11-07 | 2010-05-12 | Clariant International Limited | Process for the preparation of mono-amino-functionalized dialkylphosphinic acids, esters and salts by means of acrylonitriles and their use |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4168267A (en) * | 1978-10-23 | 1979-09-18 | E. R. Squibb & Sons, Inc. | Phosphinylalkanoyl prolines |
-
1984
- 1984-09-17 GB GB08423458A patent/GB2146644B/en not_active Expired
- 1984-09-17 JP JP59195642A patent/JPS6087293A/en active Granted
- 1984-09-17 DE DE19843434124 patent/DE3434124A1/en active Granted
- 1984-09-18 IT IT22707/84A patent/IT1176710B/en active
- 1984-09-18 CA CA000463513A patent/CA1258458A/en not_active Expired
- 1984-09-19 FR FR8414378A patent/FR2552090B1/en not_active Expired
Non-Patent Citations (1)
| Title |
|---|
| NONE * |
Also Published As
| Publication number | Publication date |
|---|---|
| FR2552090B1 (en) | 1987-01-09 |
| GB2146644B (en) | 1987-05-13 |
| FR2552090A1 (en) | 1985-03-22 |
| GB8423458D0 (en) | 1984-10-24 |
| IT8422707A1 (en) | 1986-03-18 |
| CA1258458A (en) | 1989-08-15 |
| IT8422707A0 (en) | 1984-09-18 |
| JPS6087293A (en) | 1985-05-16 |
| JPH0473437B2 (en) | 1992-11-20 |
| DE3434124A1 (en) | 1985-04-04 |
| IT1176710B (en) | 1987-08-18 |
| DE3434124C2 (en) | 1993-07-01 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PE20 | Patent expired after termination of 20 years |
Effective date: 20040916 |