Novel substituted propane phosphinic acid compounds

Claim 2

A process for the manufacture of compounds of the formula I wherein R denotes an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic or araliphatic radical having 2 or more carbon atoms, and wherein one of the groups R¹, R² and R³ represents hydrogen or an aliphatic, cyclo­aliphatic, araliphatic or aromatic radical, another one of R¹, R² and R³ is hydrogen or, in the case of R¹ and R² is hydroxy, and the remaining one of R¹, R² and R³ is hydrogen, provided that R is different from 1,1-di(C₁-C₄-alkoxy)-C₁-C₅-alkyl if one of R¹, R² and R³ represents hydrogen or an aliphatic, cycloaliphatic, araliphatic or aromatic radical and the other two of R¹, R² and R³ is hydrogen, and to their salts, provided that salts of compounds of the formula I, wherein R denotes an unsubstituted aliphatic, cycloaliphatic or araliphatic hydrocarbon radical, R¹ and R₃ denote hydrogen and R² is hydrogen or alkyl, with bases are different from alkali metal and ammonium salts; and of their salts, characterized in that a) in a compound of formula II in which R, R¹, R² and R³ have their previous significances, Z represents -NH₂ and R⁴ denotes a hydroxy-protective group R⁵ or, when R¹ and R³ denote hydrogen and R² denotes hydrogen or alkyl, denotes an alkali metal or ammonium ion R⁶, or Z represents a protected or latent amino group Z o and R⁴ denotes hydrogen or a hydroxy-protective group R⁵, any group R⁵ or R⁶ is replaced by hydrogen and/or any group Z o is converted into -NH₂; or b) in a compound of the formula III in which R, R¹ and R² have their previous significances and X is a group capable of being converted into a group of formula -CH(R³)NH₂, the group X is converted into a group of formula wherein R³ has its previous significance; or c) a compound of formula I′, said compound of formula I′ being otherwise identical to a compound of formula I but having one or more carbon-­carbon-double bond(s) is reduced to produce a compound of formula I, and, if desired, a resulting salt obtained in this process may be converted into the free compound or into another salt and/or, if desired, a resulting free compound is converted into a salt to suit the above definition and/or, if desired, a resulting mixture of isomers is separat­ted into the individual isomers.

Claim 3

Process as claimed in claim 1 for the manufacture of compounds of the formula I, wherein R has 2 or more carbon atoms and denotes alkyl, alkenyl, alkynyl, alkyl or alkenyl substituted by halogen and/or hydroxy, alkyl being interrupted by one or two mutually spaced atoms selected from oxygen and sulfur, alkyl being interrupted by one or two mutually spaced atoms selected from oxygen and sulfur and substituted by halogen and/or hydroxy, cycloalkyl, cycloalkyl substituted by hydroxy, cycloalkyl being interrupted by one or two mutually spaced atoms selected from oxygen and sulfur, cycloalkyl-lower alkyl, cycloalkyl-lower alkyl substituted in the cycloalkyl moiety by hydroxy or lower alkylthio and/or in the alkylene moiety by hydroxy, cycloalkyl-lower alkyl being interrupted by one or two mutually spaced atoms selected from oxygen and sulfur in the cycloalkyl moiety, phenyl-lower alkyl, phenyl-lower alkyl substituted in the phenyl moiety by halogen, lower alkyl, lower alkoxy and/or trifluoromethyl and/or in the alkylene moiety by hydroxy or naphthyl-lower alkyl and wherein one of the groups R¹, R² and R³ represents hydrogen, lower alkyl, cycloalkyl, phenyl or naphthyl, phenyl or naphthyl substituted by halogen, lower alkyl, lower alkoxy and/or trifluoromethyl, phenyl-lower alkyl or phenyl lower alkyl substituted in the phenyl moiety by halogen, lower alkyl, lower alkoxy and/or trifluoromethyl, another one of R¹, R² and R³ is hydrogen or, in the case of R¹ and R², is hydroxy and the remaining one of R¹, R² and R³ is hydrogen, and of their salts.

Claim 4

Process as claimed in claim 1 for the manufacture of compounds of the formula I, wherein R has 2 or more carbon atoms and is lower alkyl, lower alkenyl, lower alkynyl, alkyl being interrupted by one or two mutually spaced atoms selected from oxygen, sulfur and cycloalkyl, cycloalkyl being interrupted by one or two mutually spaced atoms selected from oxygen and sulfur, cycloalkyl or cycloalkyl-lower alkyl being interrupted by one or two mutually spaced atoms selected from oxygen and sulfur in the cycloalkyl moiety; and wherein one of the groups R¹, R² and R³ represents hydrogen, lower alkyl, cycloalkyl, phenyl, phenyl substituted by halogen, lower alkyl, lower alkoxy and/or trifluoromethyl, phenyl lower alkyl or phenyl lower alkyl substituted inthe phenyl moiety by halogen, lower alkyl, lower alkoxy and/or trifluoromethyl, or one of R¹ and R² is hydroxy; and the remaining two of R¹, R² and R³ are hydrogen, and of their salts.

Claim 5

Process as claimed in claim 1 for the manufacture of compounds of the formula I, wherein R has 2 or more carbon atoms and is lower alkyl, lower alkenyl, lower alkynyl, a cycloalkyl, hydroxycycloalkyl, cycloalkyl-lower alkyl, cycloalkyl-(hydroxy)lower alkyl or lower alkyl-­thiocycloalkyl-(hydroxy)lower alkyl group having 3 to 6 ring carbon atoms, mono-or dihydroxy-lower alkyl, hydroxy-lower alkenyl, mono, di-or polyhalogeno-lower alkyl, mono-, di-or polyhalogeno-lower alkenyl, mono-, di- or polyhalogeno-(hydroxy)lower alkyl, mono-, di- or polyhalogeno-­(hydroxy)lower alkenyl, lower alkoxy-lower alkyl, lower alkylthio-lower alkyl, lower alkanesulfinyl-lower alkyl, lower alkanesulfonyl-lower alkyl, di-lower alkoxy-lower alkyl, di-lower alkylthio-lower alkyl, lower alkoxy-(hydroxy)lower alkyl, lower alkoxy-(halogeno)lower alkyl, phenyl-­lower alkyl, phenyl-lower hydroxyalkyl, phenyl-lower alkyl or phenyl-­ lower hydroxyalkyl mono- or disubstituted, in the phenyl moiety, by halogen, lower alkyl, lower alkoxy and/or trifluoromethyl, naphthyl-lower alkyl, oxa- or thiacycloalkyl having 2 to 6 ring carbon atoms, or dioxa-, oxathia- or dithiacycloalkyl having 3 to 5 ring carbon atoms, and wherein one of R¹, R², R³ represents hydrogen, lower alkyl, cyclo-­alkyl having 3 to 6 ring carbon atoms, phenyl, phenyl mono- or disubsti­tued by halogen, lower alkyl, lower alkoxy and/or trifluoromethyl, phenyl-lower alkyl or phenyl-lower alkyl mono- or disubstitued by halogen, lower alkyl, lower alkoxy and/or trifluoromethyl, another one of R¹, R² and R³ is hydrogen or, in the case of R¹ and R², is hydroxy; and the remaining one of R¹, R² and R³ is hydrogen, and of their salts.

Claim 6

Process as claimed in claim 1 for the manufacture of compounds of formula I, wherein R has 2 or more carbon atoms and is lower alkyl, lower alkenyl, lower alkynyl, a cycloalkyl, hydroxycycloalkyl, cycloalkyl-­lower alkyl, cycloalkyl-(hydroxy)lower alkyl or lower alkylthiocyclo­alkyl-(hydroxy)lower alkyl group having 3 to 6 ring carbon atoms, mono-­or dihydroxy-lower alkyl, hydroxy-lower alkenyl, mono-, di- or poly­halogeno-lower alkyl, mono-, di-or polyhalogeno-lower alkenyl, mono-, di-or polyhalogeno-(hydroxy)lower alkyl, mono-, di- or polyhalogeno-­(hydroxy)lower alkenyl, phenyl-lower alkyl, phenyl-lower hydroxyalkyl, phenyl-lower alkyl mono- or disubstituted, in the phenyl moiety, by halogen, lower alkyl, lower alkoxy and/or trifluoromethyl or naphthyl-­lower alkyl, and wherein one of the groups R¹, R² and R³ represents hydrogen, lower alkyl, cycloalkyl, phenyl, phenyl substituted by halogen, lower alkyl, lower alkoxy and/or trifluoromethyl, phenyl lower alkyl or phenyl lower alkyl substituted inthe phenyl moiety by halogen, lower alkyl, lower alkoxy and/or trifluoromethyl, another one of R¹, R² and R³ is hydrogen or, in the case of R¹ and R², is hydroxy; and the remaining one of R¹, R² and R³ is hydrogen, and of their salts.

Claim 7

Process according to claim 1 for the manufacture of compounds of the formula I, wherein R has 2 or more carbon atoms and is lower alkyl, lower alkenyl or lower alkynyl, and wherein one of the groups R¹, R² and R³ represents hydrogen, lower alkyl, cycloalkyl, phenyl, phenyl substituted by halogen, lower alkyl, lower alkoxy and/or trifluoromethyl, phenyl lower alkyl or phenyl lower alkyl substituted in the phenyl moiety by halogen, lower alkyl, lower alkoxy and/or trifluoromethyl, or one of R¹ and R² is hydroxy; and the remaining two of R¹, R² and R³ are hydrogen, and of their salts.

Claim 8

Process as claimed in claim 1 for the manufacture of compounds of the formula I, wherein R is represented by lower alkoxy-lower alkyl, lower alkylthio-lower alkyl, lower alkanesulfinyl-lower alkyl, lower alkanesul­fonyl-lower alkyl, di-lower alkoxy-lower alkyl, di-lower alkylthio-lower alkyl, lower alkoxy-(hydroxy)lower alkyl, lower alkoxy-(halogeno)lower, oxa- or thiacycloalkyl having 2 to 6 ring carbon atoms, or dioxa- or dithiacycloalkyl having 3 to 5 ring carbon atoms, and wherein one of the groups R¹, R² and R³ represents hydrogen, lower alkyl, cycloalkyl, phenyl, phenyl substituted by halogen, lower alkyl, lower alkoxy and/or trifluoromethyl, phenyl lower alkyl or phenyl lower alkyl substituted in the phenyl moiety by halogen, lower alkyl, lower alkoxy and/or trifluoro­methyl, another one of R¹, R² and R³ is hydrogen or, in the case of R¹ and R², is hydroxy; and the remaining one of R¹, R² and R³ is hydrogen, provided that, if one of R¹ and R² is hydrogen, lower alkyl, cycloalkyl, phenyl, phenyl substituted by halogen, lower alkyl, lower alkoxy and/or trifluoromethyl, phenyl lower alkyl or phenyl lower alkyl substituted in the phenyl moiety by halogen, lower alkyl, lower alkoxy and/or tri­fluoromethyl, and the other two of R¹, R² and R³ are hydrogen, R is different from hydroxy, R is different from 1,1-di(C₁-C₄-alkoxy)-C₁-C₅-­alkyl group, and of their salts.

Claim 9

Process as claimed in claim 1 for the manufacture of compounds of the formula I, wherein R is C₂-C₁₂-alkyl, C₂-C₇-alkenyl, C₂-C₇-alkynyl, mono-­or dihydroxy-C₂-C₇-alkyl, mono-, di- or trihalogeno-α-hydroxy-C₃-C₇-­alkyl, α-saturated mono-, di- or trihalogeno-α-hydroxy-C₃-C₇-alkenyl, C₁-C₄-alkoxy-C₁-C₄-alkyl, di-C₁-C₄-alkoxy-C₁-C₄-alkyl, α-hydroxy-C₃-C₆-­cycloalkyl, C₃-C₆-cycloalkyl-C₁-C₄-alkyl, C₃-C₆-cycloalkyl-α-hydroxy-­C₁-C₃-alkyl or 1-C₁-C₄-alkylthiocycloalkyl-α-hydroxy-C₁-C₄-alkyl, R² represents hydrogen, hydroxy, C₁-C₄-alkyl, phenyl or phenyl substituted by halogen or C₁-C₄-alkyl and R¹ and R³ are hydrogen or one of R¹ and R² denotes hydroxy and the other one as well as R³ represents hydrogen, and of their salts.

Claim 10

Process as claimed in claim 1 for the manufacture of compounds of the formula I, wherein R denotes C₂-C₇-alkyl, α-saturated C₃-C₇-alkenyl, α-saturated C₃-C₇-alkynyl, α-, β-, γ- or δ-hydroxy-C₂-C₇-alkyl, α,β-di-­hydroxy-C₂-C₇-alkyl mono-, di- or trifluoro-α-hydroxy-C₃-C₇-alkyl, α-saturated mono-, di- or trifluoro-α-hydroxy-C₃-C₇-alkenyl, C₁-C₄-­alkoxy-C₁-C₄-alkyl, C₃-C₆-cycloalkyl-C₁-C₄-alkyl, α-hydroxy-C₃-C₆-cyclo­alkyl or C₃-C₆-cycloalkyl-α-hydroxy-C₁-C₄-alkyl and R¹, R² and R³ represent hydrogen, and of their salts.

Claim 11

Process according to claim 1 for the manufacture of compounds of formula I, wherein R is either C₂-C₇-alkyl, C₂-C₇-alkenyl, C₂-C₇-alkynyl or C₁-C₄-alkoxy-C₁-C₄-alkyl and R¹, R² and R³ are hydrogen, and of their salts.

Claim 12

Process according to claim 1 for the manufacture of compounds of formula I, wherein R is C₃-C₇-alkyl and R¹, R² and R³ are hydrogen, and of their salts.

Claim 13

Process for the manufacture of compounds of the formula I wherein R is diethoxymethyl, one of R¹ and R² is p-chlorophenyl or methyl and R³ and the other one of R¹ and R² are hydrogen; or wherein R is a group of the formula -CH(OR′)₂ in which R′ represents C₁-C₄-alkyl and R¹, R² and R³ denote hydrogen, and their salts, characterized in that a) in a compound of formula II in which R, R¹, R² and R³ have their previous significances, Z represents -NH₂ and R⁴ denotes a hydroxy-protective group R⁵ or, when R¹ and R³ denote hydrogen and R² denotes hydrogen or alkyl, denotes an alkali metal or ammonium ion R⁶, or Z represents a protected or latent amino group Z o and R⁴ denotes hydrogen or a hydroxy-protective group R⁵, any group R⁵ or R⁶ is replaced by hydrogen and/or any group Z o is converted into -NH₂; or b) in a compound of the formula III in which R, R¹ and R² have their previous significances and X is a group capable of being converted into a group of formula -CH(R³)NH₂, the group X is converted into a group of formula wherein R³ has its previous significance; or c) a compound of formula I′, said compound of formula I′ being otherwise identical to a compound of formula I but having one or more carbon-­carbon-double bond(s) is reduced to produce a compound of formula I, and, if desired, a resulting salt obtained in this process may be converted into the free compound or into another salt and/or, if desired, a resulting free compound is converted into a salt to suit the above definition and/or, if desired, a resulting mixture of isomers is separa­ted into the individual isomers.

Claim 14

Process for the manufacture of compounds of the formula I wherein R is diethoxymethyl, one of R¹ and R² is p-chlorophenyl or methyl and R³ and the other one of R¹ and R² are hydrogen; or wherein R is a group of the formula -CH(OR′)₂ in which R′ represents C₁-C₄-alkyl and R¹, R² and R³ denote hydrogen, and their salts, characterized in that a) in a compound of formula II in which R, R¹, R² and R³ have their previous significances, Z represents -NH₂ and R⁴ denotes a hydroxy-protective group R⁵ or, when R¹ and R³ denote hydrogen and R² denotes hydrogen or alkyl, denotes an alkali metal or ammonium ion R⁶, or Z represents a protected or latent amino group Z o and R⁴ denotes hydrogen or a hydroxy-protective group R⁵, any group R⁵ or R⁶ is replaced by hydrogen and/or any group Z o is converted into -NH₂; or b) in a compound of the formula III in which R, R¹ and R² have their previous significances and X is a group capable of being converted into a group of formula -CH(R³)NH₂, the group X is converted into a group of formula wherein R³ has its previous significance; or c) a compound of formula I′, said compound of formula I′ being otherwise identical to a compound of formula I but having one or more carbon-­carbon-double bond(s) is reduced to produce a compound of formula I, and, if desired, a resulting salt obtained in this process may be converted into the free compound or into another salt and/or, if desired, a resulting free compound is converted into a salt to suit the above definition and/or, if desired, a resulting mixture of isomers is separa­ted into the individual isomers.

Claim 15

A novel process for the manufacture of compounds of the formula I wherein R denotes an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic or araliphatic radical having 2 or more carbon atoms, and wherein one of the groups R¹, R² and R³ represents hydrogen or an aliphatic, cyclo­aliphatic, araliphatic or aromatic radical, another one of R¹, R² and R³ is hydrogen or, in the case of R¹ and R² is hydroxy, and the remaining one of R¹, R² and R³ is hydrogen, and of their salts, characterised in that a compound of the formula wherein R¹, R², and R⁵ have the meanings given hereinbefore, X denotes cyano, carbamoyl or a group of the formulae -CH(R³)-Z o (XVa) or -C(R³)=Y (XVb) in which Z o denotes a protected or latent amino group as specified hereinbefore, Y denotes an optionally acetalised, thio­acetalised, ketalised or thioketalised oxo group and Q′ denotes a group of the formula -C(R⁸)-(OR⁹)(OR¹⁰) (XIVa) in which R⁸ denotes hydrogen or lower alkyl and R⁹ and R¹⁰, independently of one another, represent lower alkyl or together represent lower alkylene, is treated with an anhydrous protic medium, the resulting compound of the formula wherein R¹, R², R⁵ and X have their previous significances is reacted with a compound of the formula R-Hal (XIIc), wherein R has its previous significance and Hal is halogen, or, for the manufacture of compounds of formula I, in which R is an aliphatic, cycloaliphatic-aliphatic or araliphatic radical having at least 2 carbon atoms in each of the aliphatic moieties, in which radical R the carbon atom via which R is bonded to the P-atom is unsubsti­tuted and the adjacent carbon atom is not substituted by hydroxy or, in the case of aliphatic radicals R, by halogen or, in the case of cycloaliphatic-aliphatic radicals R, by lower alkylthio, is reacted with a terminally unsaturated aliphatic, cycloaliphatic-aliphatic or araliphatic compound R‴-H (XII 6), wherein R‴ is a group otherwise identical to the radical R in the desired end product I but has one additional terminal double bond between the carbon atom via which R is bonded to the P-atom and the adjacent carbon atom, or, for the manufacture of compounds of formula I, in which the carbon atom via which R is bonded to the P-atom is substituted by one hydroxy group, is reacted with an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic or araliphatic aldehyde or ketone, which aldehyde or ketone corresponds, if the aldehyde or ketone functional group is replaced by one free valence and one hydroxy group, to the group R in the desired end product I, in the resulting compound of formula VI wherein R¹, R², R⁵, R and X have their previous significances; the group X is converted into a group of formula -CH(R³)-NH₂ (IIa′) and the resulting compound of formula IIa wherein R, R¹, R², R³ and R⁵ have their previous significances is converted into the corresponding compound of formula I and, if desired, a resulting salt obtained in this process may be converted into the free compound or into another salt and/or, if desired, a resulting free compound is converted into a salt to suit the above definition and/or, if desired, a resulting mixture of isomers is separated into the individual isomers.

Claim 16

A novel process for the manufacture of compounds of the formula I wherein R denotes an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic or araliphatic radical having 2 or more carbon atoms, and wherein one of the groups R¹, R² and R³ represents hydrogen or an aliphatic, cyclo­aliphatic, araliphatic or aromatic radical, another one of R¹, R² and R³ is hydrogen or, in the case of R¹ and R² is hydroxy, and the remaining one of R¹, R² and R³ is hydrogen, and of their salts, characterised in that a compound of the formula wherein R¹, R², and R⁵ have the meanings given hereinbefore, X denotes cyano, carbamoyl or a group of the formulae -CH(R³)-Z o (XVa) or -C(R³)=Y (XVb) in which Z o denotes a protected or latent amino group as specified hereinbefore, Y denotes an optionally acetalised, thio­acetalised, ketalised or thioketalised oxo group and Q′ denotes a group of the formula -C(R⁸)-(OR⁹)(OR¹⁰) (XIVa) in which R⁸ denotes hydrogen or lower alkyl and R⁹ and R¹⁰, independently of one another, represent lower alkyl or together represent lower alkylene, is treated with an anhydrous protic medium, the resulting compound of the formula wherein R¹, R², R⁵ and X have their previous significances is reacted with a compound of the formula R-Hal (XIIc), wherein R has its previous significance and Hal is halogen, or, for the manufacture of compounds of formula I, in which R is an aliphatic, cycloaliphatic-aliphatic or araliphatic radical having at least 2 carbon atoms in each of the aliphatic moieties, in which radical R the carbon atom via which R is bonded to the P-atom is unsubsti­tuted and the adjacent carbon atom is not substituted by hydroxy or, in the case of aliphatic radicals R, by halogen or, in the case of cycloaliphatic-aliphatic radicals R, by lower alkylthio, is reacted with a terminally unsaturated aliphatic, cycloaliphatic-aliphatic or araliphatic compound R‴-H (XII 6), wherein R‴ is a group otherwise identical to the radical R in the desired end product I but has one additional terminal double bond between the carbon atom via which R is bonded to the P-atom and the adjacent carbon atom, or, for the manufacture of compounds of formula I, in which the carbon atom via which R is bonded to the P-atom is substituted by one hydroxy group, is reacted with an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic or araliphatic aldehyde or ketone, which aldehyde or ketone corresponds, if the aldehyde or ketone functional group is replaced by one free valence and one hydroxy group, to the group R in the desired end product I, in the resulting compound of formula VI wherein R¹, R², R⁵, R and X have their previous significances; the group X is converted into a group of formula -CH(R³)-NH₂ (IIa′) and the resulting compound of formula IIa wherein R, R¹, R², R³ and R⁵ have their previous significances is converted into the corresponding compound of formula I and, if desired, a resulting salt obtained in this process may be converted into the free compound or into another salt and/or, if desired, a resulting free compound is converted into a salt to suit the above definition and/or, if desired, a resulting mixture of isomers is separated into the individual isomers.

Claim 17

Process according to claim 13 for the manufacture of compounds of the formula I, wherein R has 2 or more carbon atoms and denotes alkyl, alkenyl, alkynyl, alkyl or alkenyl substituted by halogen and/or hydroxy, alkyl being interrupted by one or two mutually spaced atoms selected from oxygen and sulfur, alkyl being interrupted by one or two mutually spaced atoms selected from oxygen and sulfur and substituted by halogen and/or hydroxy, cycloalkyl, cycloalkyl substituted by hydroxy, cycloalkyl being interrupted by one or two mutually spaced atoms selected from oxygen and sulfur, cycloalkyl-lower alkyl, cycloalkyl-lower alkyl substituted in the cycloalkyl moiety by hydroxy or lower alkylthio and/or in the alkylene moiety by hydroxy, cycloalkyl-lower alkyl being interrupted by one or two mutually spaced atoms selected from oxygen and sulfur in the cycloalkyl moiety, phenyl-lower alkyl or phenyl-lower alkyl substituted in the phenyl moiety by halogen, lower alkyl, lower alkoxy and/or trifluoro­methyl and/or in the alkylene moiety by hydroxy or naphthyl-lower alkyl, and wherein one of the groups R¹, R² and R³ represents hydrogen, lower alkyl, cycloalkyl, phenyl or naphthyl, phenyl or naphthyl substituted by halogen, lower alkyl, lower alkoxy and/or trifluoromethyl, phenyl-lower alkyl or phenyl lower alkyl substituted in the phenyl moiety by halogen, lower alkyl, lower alkoxy and/or trifluoromethyl, another one of R¹, R² and R³ is hydrogen or, in the case of R¹ and R² is hydroxy and the remaining one of R¹, R² and R³ is hydrogen, and of their salts.

Claim 18

Process according to claim 13 for the manufacture of compounds of the formula I, wherein R has 2 or more carbon atoms and is lower alkyl, lower alkenyl, lower alkynyl, a cycloalkyl, hydroxycycloalkyl, cycloalkyl-­lower alkyl, cycloalkyl-(hydroxy)lower alkyl or lower alkylthiocyclo­alkyl-(hydroxy)lower alkyl group having 3 to 6 ring carbon atoms, mono-­ or dihydroxy-lower alkyl, hydroxy-lower alkenyl, mono-, di-or poly­halogeno-lower alkyl, mono-, di-or polyhalogeno-lower alkenyl, mono-, di-or polyhalogeno-(hydroxy)lower alkyl, mono-, di- or polyhalogeno­(hydroxy)lower alkenyl, lower alkoxy-lower alkyl, lower alkylthio-lower alkyl, lower alkanesulfinyl-lower alkyl, lower alkanesulfonyl-lower alkyl, di-lower alkoxy-lower alkyl, di-lower alkylthio-lower alkyl, lower alkoxy-(hydroxy)lower alkyl, lower alkoxy-(halogeno)lower alkyl, phenyl­lower alkyl, phenyl-lower hydroxyalkyl, phenyl-lower alkyl or phenyl­lower hydroxyalkyl mono- or disubstituted, in the phenyl moiety, by halogen, lower alkyl, lower alkoxy and/or trifluoromethyl, naphthyl-lower alkyl, oxa- or thiacycloalkyl having 2 to 6 ring carbon atoms, or dioxa-, oxathia- or dithiacycloalkyl having 3 to 5 ring carbon atoms, and wherein one of R¹, R², R³ represents hydrogen, lower alkyl, cycloalkyl having 3 to 6 ring carbon atoms, phenyl, phenyl mono- or disubstitued by halogen, lower alkyl, lower alkoxy and/or trifluoromethyl, phenyl-lower alkyl or phenyl-lower alkyl mono- or disubstitued by halogen, lower alkyl, lower alkoxy and/or trifluoromethyl, another one of R¹, R² and R³ is hydrogen or, in the case of R¹ and R², is hydroxy; and the remaining one of R¹, R² and R³ is hydrogen, and of their salts.

Claim 19

Process according to claim 13 for the manufacture of compounds of formula I, wherein R denotes 1,1-di(C₁-C₄-alkoxy)-C₁-C₄-alkyl, one of the groups R¹, R² and R³ represents hydrogen, or an aliphatic, cycloali­phatic, araliphatic or aromatic radical and the remaining two of R¹, R² and R³ are hydrogen, and of their salts.

Claim 20

Process according to claim 13 for the manufacture of compounds of formula I, wherein R denotes 1,1-di(C₁-C₄-alkoxy)-C₁-C₄-alkyl and wherein one of the groups R¹, R² and R³ represents hydrogen, lower alkyl, phenyl or phenyl substituted by halogen or lower alkyl, and the remaining two of R¹, R² and R³ are hydrogen, and of their salts.

Claim 21

Process according to claim 13 for the manufacture of compounds of the formula I, wherein R is C₂-C₁₂-alkyl, C₂-C₇-alkenyl, C₂-C₇-alkynyl, mono-­or dihydroxy-C₂-C₇-alkyl, mono-, di- or trihalogeno-α-hydroxy-C₃-C₇-­alkyl, α-saturated mono, di- or trihalogeno-α-hydroxy-C₃-C₇-alkenyl, C₁-C₄-alkoxy-C₁-C₄-alkyl, di-C₁-C₄-alkoxy-C₁-C₄-alkyl, α-hydroxy-C₃-C₆-­cycloalkyl, C₃-C₆-cycloalkyl-C₁-C₄-alkyl, C₃-C₆-cycloalkyl-α-hydroxy-­C₁-C₃-alkyl or 1-C₁-C₄-alkylthiocycloalkyl-α-hydroxy-C₁-C₄-alkyl, R² represents hydrogen, hydroxy, C₁-C₄-alkyl, phenyl or phenyl substituted by halogen, such as chloro, or C₁-C₄-alkyl and R¹ and R³ are hydrogen or one of R¹ and R² denotes hydroxy and the other one as well as R³ re­presents hydrogen, and of their salts.

Claim 22

Process according to claim 12 or 13 for the manufacture of compounds of the formula I, wherein R denotes di-C₁-C₄-alkoxy-C₁-C₄-alkyl, and R¹, R² and R³ represent hydrogen, and of their salts.

Claim 23

Process according to claim 1 or 13, wherein 3-aminopropyl(n-butyl)-­phosphinic acid or a salt thereof is manufactured.

Claim 24

Process according to claim 1 or 13, wherein 3-aminopropyl(2-hydroxy-­butyl)phosphinic acid or a salt thereof is manufactured.

Claim 25

Process according to claim 1 or 13, wherein 3-aminopropyl(but-3-­enyl)phosphinic acid or a salt thereof is manufactured.

Claim 26

Process according to claim 1 or 13, wherein 3-aminopropyl(isopentyl)-­phosphinic acid or a salt thereof is manufactured.

Claim 27

Process according to claim 1 or 13, wherein 3-aminopropyl(2-ethoxy-­ethyl)phosphinic acid or a salt thereof is manufactured.

Claim 28

Process according to claim 1 or 13, wherein 3-aminopropyl(2-methyl-­allyl)phosphinic acid or a salt thereof is manufactured.

Claim 29

Process according to claim 12 or 13, wherein 3-aminopropyl(dieth­oxymethyl)phosphinic acid or a salt thereof is manufactured.

Claim 30

Process according to claim 1 or 13, wherein 3-aminopropyl(n-propyl)phosphinic acid, 3-aminopropyl(isobutyl)phosphinic acid, 3-aminopropyl(n-pentyl)phosphinic acid, 3-aminopropyl(cyclopropylmethyl)phosphinic, 1-methyl-3-amino-propyl(n-butyl)phosphinic acid, 3-aminopropyl(pent-3-ynyl)phosphinic acid, 3-aminopropyl(but-3-inyl)phosphinic acid, 3-aminopropyl(2-methylbutyl)-phosphinic acid, 3-aminopropyl-(3-ethoxypropyl)-phosphinic acid, 3-aminopropyl(3-methoxypropyl)phosphinic acid, 3-aminopropyl(but-2-inyl)phosphinic acid, 3-aminopropyl[2-(2-ethoxyethoxy)ethyl]phosphinic acid, 3-aminopropyl(4,4,4-triflurorbutyl)phosphinic acid, 3-amino-2-hydroxy-propyl(diethoxymethyl)phosphinic acid 3-aminobutyl(diethoxymethyl)phosphinic acid, 3-aminopropyl(2-phenylethyl)phosphinic acid, 3-aminopropyl(dodecyl)phosphinic acid, 3-aminopropyl(benzyl)phosphinic acid, 3-aminopropyl(propargyl)-phosphinic acid, 3-aminopropyl(1-hydroxybutyl)phosphinic acid, 3-aminopropyl(1-hydroxyisobutyl)phosphinic acid, 3-aminopropyl(1-hydroxyethyl)phosphinic acid, 3-aminopropyl(1-hydroxybenzyl)phosphinic acid, 3-aminopropyl(1-hydroxy-4,4,4-trifluoro-butyl)phosphinic acid, 3-aminopropyl[1-hydroxy-(Z)-2-fluoro-but-2-enyl]phosphinic acid, 3-aminopropyl(1-hydroxy-1-cyclopropylmethyl)phosphinic acid, 3-aminopropyl[1-hydroxy-1-(2-methylthiocyclopropyl)-methyl]phosphinic acid, 3-aminopropyl(cyclohexylmethyl)phosphinic acid, 3-aminopropyl(1-hydroxy-1-cyclobutyl-methyl)phosphinic acid, 3-aminopropyl[2-(R)hydroxy-3-methylbutyl]phosphinic acid, 3-aminopropyl(1,2-dihydroxyprop-2-yl)phosphinic acid, 3-amino-2-hydroxy-propyl(propyl)phosphinic acid, 3-amino-1-hydroxy-propyl(propyl)phosphinic acid, 3-aminopropyl(4-hydroxybutyl)phosphinic acid, 3-aminopropyl(3-hydroxybutyl)phosphinic acid or 3-aminopropyl(2-(S)-methylbutyl)phosphinic acid or a salt thereof is manufactured.

Claim 31

Process according to claim 12 or 13, wherein 3-amino-2-(p-chlorophenyl)-propyl(diethoxymethyl)phosphinic acid, 3-amino-1-(p-chlorophenyl)-propyl(diethoxymethyl)phosphinic acid, 3-aminopropyl(di-n-propyloxymethyl)phosphinic acid, 3-aminopropyl(diisopropyloxymethyl)phosphinic acid or 3-aminopropyl(di-n-butyloxymethyl)phosphinic acid or a salt thereof is manufactured.

Claim 32

Process for the manufacture of pharmaceutical compositions, wherein a compound obtainable according to any one of claims 1 to 28 is admixed to a conventional pharmaceutical carrier system.

Claim 33

Process for the manufacture of nootropic, antidepressive and/or anti­epileptic medicaments, characterised in that a compound according to anyone of claims 1-28 is admixed to conventional pharmaceutical carriers.

Claim 34

Process for the manufacture of nootropic, antidepressive and/or anti­epileptic medicaments, characterised in that a) in a compound of formula II in which R, R¹, R² and R³ have their previous significances, Z represents -NH₂ and R⁴ denotes a hydroxy-protective group R⁵ or, when R¹ and R³ denote hydrogen and R² denotes hydrogen or alkyl, denotes an alkali metal or ammonium ion R⁶, or Z represents a protected or latent amino group Z o and R⁴ denotes hydrogen or a hydroxy-protective group R⁵, any group R⁵ or R⁶ is replaced by hydrogen and/or any group Z o is converted into -NH₂; or b) in a compound of the formula III in which R, R¹ and R² have their previous significances and X is a group capable of being converted into a group of formula -CH(R³)NH₂, the group X is converted into a group of formula wherein R³ has its previous significance; or c) a compound of formula I′, said compound of formula I′ being otherwise identical to a compound of formula I but having one or more carbon-­carbon-double bond(s) is reduced to produce a compound of formula I, and, if desired, a resulting salt obtained in this process may be converted into the free compound or into another salt and/or, if desired, a resulting free compound is converted into a salt to suit the above definition and/or, if desired, a resulting mixture of isomers is separa­ted into the individual isomers and the resulting compound of the formula I wherein R denotes an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic or araliphatic radical having 2 or more carbon atoms, and wherein one of the groups R¹, R² and R³ represents hydrogen or an aliphatic, cyclo­aliphatic, araliphatic or aromatic radical, another one of R¹, R² and R³ is hydrogen or, in the case of R¹ and R² is hydroxy, and the remaining one of R¹, R² and R³ is hydrogen or a pharmaceutically acceptable salt thereof is admixed to conventional pharmaceutical carriers.

Claim 35

Process for the manufacture of nootropic, antidepressive and/or anti­epileptic medicaments, characterised in that a) in a compound of formula II in which R, R¹, R² and R³ have their previous significances, Z represents -NH₂ and R⁴ denotes a hydroxy-protective group R⁵ or, when R¹ and R³ denote hydrogen and R² denotes hydrogen or alkyl, denotes an alkali metal or ammonium ion R⁶, or Z represents a protected or latent amino group Z o and R⁴ denotes hydrogen or a hydroxy-protective group R⁵, any group R⁵ or R⁶ is replaced by hydrogen and/or any group Z o is converted into -NH₂; or b) in a compound of the formula III in which R, R¹ and R² have their previous significances and X is a group capable of being converted into a group of formula -CH(R³)NH₂, the group X is converted into a group of formula wherein R³ has its previous significance; or c) a compound of formula I′, said compound of formula I′ being otherwise identical to a compound of formula I but having one or more carbon-­carbon-double bond(s) is reduced to produce a compound of formula I, and, if desired, a resulting salt obtained in this process may be converted into the free compound or into another salt and/or, if desired, a resulting free compound is converted into a salt to suit the above definition and/or, if desired, a resulting mixture of isomers is separa­ted into the individual isomers and the resulting compound of the formula I wherein R denotes an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic or araliphatic radical having 2 or more carbon atoms, and wherein one of the groups R¹, R² and R³ represents hydrogen or an aliphatic, cyclo­aliphatic, araliphatic or aromatic radical, another one of R¹, R² and R³ is hydrogen or, in the case of R¹ and R² is hydroxy, and the remaining one of R¹, R² and R³ is hydrogen or a pharmaceutically acceptable salt thereof is admixed to conventional pharmaceutical carriers.

Claim 36

A novel process for the manufacture of compounds of the formula wherein X denotes cyano, carbamoyl or a group of the formulae -CH(R³)-Z o (XVa) or -C(R³)=Y (XVb) in which Z o denotes a protected or latent amino group as specified hereinbefore, Y denotes an optionally acetalised, thioacetalised, ketalised or thioketalised oxo group, one of R¹, R² and R³ is hydrogen, hydroxy, C₁-C₈-alkyl, C₃-C₆-­cycloalkyl, phenyl optionally substituted by halogen, C₁-C₄-alkyl, C₁-C₄-alkoxy and/or trifluoromethyl or is C₇-C₁₀-phenylalkyl optionally substituted in the phenyl moiety by halogen, C₁-C₄-alkyl, C₁-C₄-alkoxy and/or trifluoromethyl and the others of R¹, R² and R³ are hydrogen, and R⁵ denotes an aliphatic radical, characterised in that a compound of the formula wherein R¹, R², R⁵ and X have the meanings given hereinbefore and Q′ denotes a group of the formula -C(R⁸)-C(OR⁹)(OR¹⁰) (XIVa) in which R⁸ denotes hydrogen or lower alkyl and R⁹ and R¹⁰, independently of one another, represent lower alkyl or together represent lower alkylene, is treated with an anhydrous protic medium.

Claim 37

A novel process for the manufacture of compounds of the formula wherein X denotes cyano, carbamoyl or a group of the formulae -CH(R³)-Z o (XVa) or -C(R³)=Y (XVb) in which Z o denotes a protected or latent amino group as specified hereinbefore, Y denotes an optionally acetalised, thioacetalised, ketalised or thioketalised oxo group, one of R¹, R² and R³ is hydrogen, hydroxy, C₁-C₈-alkyl, C₃-C₆-­cycloalkyl, phenyl optionally substituted by halogen, C₁-C₄-alkyl, C₁-C₄-alkoxy and/or trifluoromethyl or is C₇-C₁₀-phenylalkyl optionally substituted in the phenyl moiety by halogen, C₁-C₄-alkyl, C₁-C₄-alkoxy and/or trifluoromethyl and the others of R¹, R² and R³ are hydrogen, and R⁵ denotes an aliphatic radical, characterised in that a compound of the formula wherein R¹, R², R⁵ and X have the meanings given hereinbefore and Q′ denotes a group of the formula -C(R⁸)-C(OR⁹)(OR¹⁰) (XIVa) in which R⁸ denotes hydrogen or lower alkyl and R⁹ and R¹⁰, independently of one another, represent lower alkyl or together represent lower alkylene, is treated with an anhydrous protic medium.

Claim 38

Process according to claim 32, characterized in that ethyl 2-cyano-­ethyl(1-hydroxybutyl) phosphinate is manufactured.