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IFI
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Record
| Title: |
PROCESS FOR THE
PREPARATION OF DERIVATIVES OF BIS(AMINO-METHYL) PHOSPHINIC ACID -
ESTERIFYING AMINO-PROTECTED BIS/AMINOMETHYL/PHOSPHINIC ACID, REMOVING
PROTECTIVE GROUPS, REACTING WITH IMINE OR KETONE, REACTING WITH BASE
AND ALKYLATING AGENT, TREATING WITH ACID |
| Inventor(s): |
Budt Karl-Heinz, DE
Li Jian-Qi, CN
Peyman Anuschirwan, DE
Spanig Jorg, DE
Stowasser Bernd, DE |
| Patent
Assignee(s): |
Hoechst AG DE |
| Patent Number: |
US 5510504 |
| Patent Date: |
19960423 |
| Application
Number: |
US 313044 |
| Application
Date: |
19950104 |
| Exemplary
Claim(s) |
1. A process for
the preparation of Alpha - or Alpha , Alpha
'-substituted derivatives of the bis(aminomethyl)phosphinic acid of the
formula I and their acid or basic salts
NH2-CH(-R2)-P(=O)(-O-R1)-CH(-R3)-NH2 I
in which R1 is R6 C1-C18 alkyl, C2-C18 alkenyl, C2-C18 alkynyl,
C6-C12 aryl or C7-C20 arylalkyl and aryl or arylalkyl may be mono- or
polysubstituted by fluorine, chlorine, bromine, NO2, CN, OH, COOH,
C1-C6 alkyl, C1-C6 alkoxy, C(O)-O-(C1-C6) alkyl, C(O)(C1-C6) alkyl or
O-C(O)-(C1-C6) alkyl and R1 is also hydrogen or basic or acid salt
radicals of Alpha -or Alpha , Alpha '-substituted derivatives of the
bis(aminomethyl)phosphinic acid, R2 and R3 are identical or different
and are, independently of each other, hydrogen, C1C18 alkyl, C2-C18
alkenyl, C2-C18 alkynyl, C6-C12 aryl or C7C22 arylalkyl, where alkyl,
alkenyl or alkynyl may each be mono- or polysubstituted by fluorine,
chlorine, bromine, NO2, NH2, CN, OH, COOH, C(O)-O-(C1-C6) alkyl,
C(O)-(C1-C6) alkyl, OC(O)-(C1-C6) alkyl or C1-C6 alkoxy and aryl or
arylalkyl may be mono- or polysubstituted by fluorine, chlorine,
bromine, NO2, CN, OH, COOH, C1-C6 alkyl, C1-C6 alkoxy, C(O)-O-(C1-C6)
alkyl, C(O)-(C1-C2) alkyl or O-C(O)-(C1-C6) alkyl, with the proviso
that if R2 hydrogen and R3 has the abovementioned meaning, R3 must not
also be hydrogen, and vice versa, which comprises a) esterifying
bis(aminomethyl)phosphinic acid, after introducing amino protective
groups, with a compound of the formula R6-OH in which R6 has the
meaning mentioned under R1, or b) initially esterifying
bis(chloromethyl)phosphinyl chloride with a compound of the formula
R6-OH , reacting the compound thus obtained with benzylamine to give
the bis(Nbenzylaminomethyl) phosphinate, then, after removing the amino
protective groups from the compounds obtained by a) or b), reacting the
bis(aminomethyl)phosphinate of the formula IV
NH2-CH2-P(=O)(-O-R6)-CH2-NH2 IV
in which R6 is as defined above, with a compound of the formula
VI R7-C(-R8)=NH VI
or a compound of the formula VII
R7-CO-R8 VII
in which R7 and R8 are identical or different and are hydrogen,
C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl or C6C12 aryl or R7 and R8
together form a ring system, under conditions in which water is
removed, to give a compound of the formula V
R7-C(-R8)=N-CH2-P(=O)(-O-R6)-CH2-N=C(-R7)-R8 V
in which R6, R7 and R8 have the abovementioned meaning, e1)
converting the compound of the formula V to a compound of the formula
VIII R7-C(-R8)=N-CH(-R2)-P(=O)(-O-R6)-CH(-R3)-N=C(-R7)-R8
VIII
in which R2=R3 and R3, R6, R7 and R8 have the abovementioned
meaning, except for R3 hydrogen, after reaction with 2-3 equivalents of
base, with 2-5 equivalents of a compound of the formula R3-X, in which
R3 has the abovementioned meaning, except for hydrogen, and X is a
leaving group, or e2) proceeding in an analogous manner to e1), but
using 1 to 1.2 equivalents of base and 1 to 1.2 equivalents of R3-X,
obtaining a compound of the formula VIII in which R2 is hydrogen and
R3, R6, R7 and R8 have the abovementioned meaning, except for R3
hydrogen, optionally e3) reacting the compound of the formula VIII
obtained in e2), after reaction with a further 1 to 1.2 equivalents of
a base, with 1 to 1.2 equivalents of a compound of the formula R2-X in
which R2 and X have the abovementioned meaning, except for R2 hydrogen,
to give a compound of the formula VIII in which R2, R3, R6, R7 and R8
have the abovementioned meaning, except for R2 and R3 hydrogen, or f1)
reacting the compound of the formula V with a catalyst of the formula
R9R10R11R12NZ 2 to 3 equivalents of a compound of the formula R3-X and
2-25 equivalents of an alkali metal hydroxide or alkaline earth metal
hydroxide, where N is nitrogen or phosphorus, Z is an anion of an
inorganic salt, , R9, R10, R11 and R12 are identical or different and,
independently of each other, are C6-C10 alkyl, C2-C20 alkenyl, C2-C20
alkynyl, C6-C12 aryl or C7-C20 arylalkyl and R3 and X are as defined in
e1), in the presence of a water-immiscible solvent with water, to give
a compound of the formula VIII in which R2 R3 and R3, R6, R7 and R8
have the abovementioned meaning, except for R3 hydrogen, or f2)
proceeding in an analogous manner to f1), but using 2-10 equivalents of
an alkali metal or alkaline earth metal hydroxide and 1 to 1.2
equivalents of R3-X obtaining a compound of the formula VIII in which
R2 is hydrogen and R3, R6, R7 and R8 have the abovementioned meaning,
except for R3 hydrogen, optionally f3) reacting the compound of the
formula VIII obtained by f2), under the conditions mentioned in f1),
with R2-X instead of R3-X to give a compound of the formula VIII in
which R2, R3, R6, R7 and R8 have the abovementioned meaning, except for
R2 and R3 hydrogen, using, however, 2 to 10 equivalents of the alkali
metal or alkaline earth metal hydroxide and 1 to 1.2 equivalents of
R2-X, or g) proceeding in an analogous manner to f1)-f3), but using no
solvent, and with methyltrioctylammonium chloride instead of
R9R10R11R12NZ obtaining a compound of the formula VIII with the
meanings mentioned in f1)-f3), h) reacting the compound of the formula
VIII obtained by e), f) or g) with 5-15% strength aqueous HCl or HBr to
give a compound of the formula I, in which R1 is R6 and R2 and R3 have
the meaning mentioned in e), f) or g), or i) reacting the compound of
the formula VIII obtained by e), f) or g) or optionally the compound of
the formula I obtained by h) with 30% strength HBr or HCl in glacial
acetic acid to give a compound of the formula I in which R2 and R3 have
the meaning mentioned in e), f) or g) and R1 is defined as above, R1,
however, not being R6. |
| Main US
Classification |
558145000 |
| Secondary US
Classification |
558166000
562016000 |
| Main
International Classification |
C07F-009/32 |
| Secondary
International Classification |
C07F-009/30 |
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12.08.2026