PREPARATION OF PHOSPHORUS-CONTAINING INTERMEDIATES FOR HERBICIDAL USE

PREPARATION D'INTERMEDIAIRE A TENEUR DE PHOSPHORE POUR EMPLOI A TITRE D'HERBICIDE

English Abstract

ABSTRACT
PREPARATION OF PHOSPHORUS-CONTAINING INTERMEDIATES FOR
HERBICIDAL USE
A process for the preparation of a compound of the
formula
<IMG>
(1)
wherein R1 represents an optionally substituted hydrocarbon
radical; R represents a hydrogen atom or a group within the
definition of R1; R2 and R3 are such that OR2 and OR3 are
hydrolysable groups; R8 represents a group of the formula
Ar(R5)(R6)C- in which Ar is an optionally substituted
aromatic group and R5 and R6 each represent hydrogen, alkyl,
or Ar, which comprises the reaction of a compound of the
formula:
<IMG> (II)
with a compound of the formula:
<IMG> (III)
wherein X represents a halogen.

Claims

The embodiments of the invention in which an
exclusive privilege or property is claimed, are defined
as follows:
1. A process for the preparation of a compound of
the formula:
<IMG> (I)
in which R1 represents a C1-18-alkyl, C6-18-aryl or
C3-18-cycloalkyl radical which is optionally
substituted by halogen, phenyl, cyano, C1-4-alkyl,
C1-4-alkoxy or C2-5-alkylcarboxylate; R represents the
hydrogen atom or a C1-18-alkyl, C6-18-aryl or
C3-18-cycloalkyl radical which is optionally
substituted by halogen, phenyl, cyano, C1-4-alkyl,
C1-4-alkoxy or C2-5-alkylcarboxylate; R2 and R3 each
represent a C1-12-alkyl, C3-12-cycloalkyl, C6-12-aryl
or C6-12-aryl-C1-12-alkyl group which is optionally
substituted by halogen, phenyl, cyano, C1-4-alkyl,
C1-4-alkoxy or C2-5-alkylcarboxylate or R2 and R3-
together represent an alkylene radical which contains
from 2 to 6 carbon atoms in the chain which is
optionally substituted by halogen, phenyl, cyano,
13

C1-4-alkyl, C1-4-alkoxy or C2-5-alkylcarboxylate;R8
represents a group which is an Ar(R5)(R6)C- radical, in
which Ar is C6-12-aryl group with optional
substituent(s) selected from C1-6-alkyl, C1-6-alkoxy,
nitro and halogen and R5 and R6 each represent a
hydrogen atom, a C1-6 alkyl group or an Ar group;
which process comprises the reaction of a compound of
the formula:
<IMG> (II)
wherein R2, R3 and R8 are as hereinbefore defined, with
a compound of the formula:
(III)
<IMG>
wherein X represents a halogen atom and R and R1 are as
hereinbefore defined.
2. A process according to claim 1 wherein the alkyl
radical represented by the symbol R1 contains from 1 to
7 carbon atoms or, when R1 represents a cycloalkyl
radical, from 3 to 7 carbon atoms.
14

3. A process according to claim 1 wherein R1
represents an optionally halogenated alkyl radical
containing from 1 to 4 carbon atoms.
4. A process according to claim 1 wherein R
represents an alkyl group containing from 1 to 4 carbon
atoms.
5. A process according to claim 1 wherein R2 and R3
each contain from 1 to 8 carbon atoms.
6. A process according to claim 1 wherein Ar
represents an optionally substituted phenyl group and
R5 and R6 each represent a hydrogen atom, a phenyl
group, or an alkyl group containing at most 6 carbon
atoms.
7. A process according to claim 1 wherein R and R1
each represent an alkyl group containing from 1 to 4
carbon atoms.
8. A process according to claim 1 wherein R2 and R3
each represent an alkyl, phenyl or benzyl group.
9. A process according to claim 1 wherein X
represents chlorine.
10. A process according to claim 1 in which the
reaction is carried out at from 30°C to 150°C.
11. A process according to claim 1 in which the
reaction is carried out at from 40°C to 120°C.
12. A process according to claim 1 wherein the
proportion of the compound of formula II relative to

the compound of formula III does not depart from
stoichiometry by more than 40%.
13. A process according to claim 1 in which the
reaction is carried out in the presence of an acid
acceptor.
14. A process according to claim 13 wherein the acid
acceptor is a tertiary amine, an alkali metal
hydroxide, carbonate or bicarbonate, or an alkaline
earth metal hydroxide or carbonate.
15. A process according to claim 1 wherein the
reaction is carried out in the presence of a solvent.
16. A process according to claim 15 wherein the
solvent is a nitrile, ketone, ester, optionally
halogenated hydrocarbon, or an aprotic polar solvent.
17. A process according to claim 1 followed by the
step of converting a compound of formula (I) thus
obtained by hydrogenolysis and/or hydrolysis and/or
salification into a compound of the formula:
<IMG> (IV)
wherein R and R1 are as defined in claim 1, or a salt
thereof.
16

Description

6~
-- 1 --
PREPARATION OF PHOSPHORUS~CONTAINING INTERM~DIATES FOR
HERBICIDAL USE
The present invention relates to a process for
preparing N sulphonyl-[N-(phosphonomethyl)glycyl]amine
derivatives which can be used either as herbicides or as
intermediates for manufacturing various phosphorus-oontaining
S products, in particular herbicides.
The present invention relates to a process for the
preparation of a compound of the formula:
R2 l8
l C~2 N - CH2 - CO - N - SO - R (I)
OR R
wherein
- Rl represents an optionally substituted hydrocarbon
radical, preferably an alkyl, aryl or cycloalkyl radical;
suitable substituents include halogen atoms and phenyl,
cyano, alkyl, alkoxy and alkylcarboxylate groups, in which
the alkyl groups or moieties preferably have from 1 to 4
carbon atoms; ~ost preferably Rl has from 1 to 18 carbon
atoms, preferably from 1 to 7 carbon atoms, and more
especially from 3 to 7 carbon atoms when it is a cycloalkyl
group; Rl is preferably an alkyl radical having from 1 to 4
carbon atoms, optionally halogenated, in particular

. - 2 -
chlorinated or fluorinated, e.g. CF3,
- R represents a hydrogen atom or a group within the
definition of Rlr and is preferably an alkyl group having 1
to 4 carbon atoms,
- R2 and R3 are such that oR2 and oR3 are hydrolysable
groups; R2 and R3 preferably represent an alkyl, aryl or
arylalkyl radical, which is optionally substituted; suitable
substituents are those given for Rl; or R2 and R3 together
represent a single divalent radical, preferably an optionally
substituted alkylene radical; they generally have from 1 to
12 carbon atoms, and preferably from 1 to 8 carbon atoms,
- R8 represents a group of the formula Ar(R5)(R6)C- in
which Ar is an aromatic group, preferably an optionally
substituted phenyl group, and R5 and R6 each represent a
hydrogen atom, an alkyl group preferably having at most 6
carbon atoms, or a group Ar as hereinbefore defined; and
- X represents a halogen atom such as chiorine, bromine or
iodine, preferably chlorine,
which process comprises ~he reaction of a compound of
the formula: 2
OR
O - P - CH - NH - R8 (II)
1 2
OR
wherein R2~ R3 and R8 are as hereinbefore defined, with a
compound of the formula:
X - C~2 - CO - N - S02 - Rl (III)
,

~29~
- 3 ~
wherein X represents a halogen atom and R and Rl are as
hereinbeore defined.
The symbols R and R1 preferably each represents an
alkyl group containing ~rom 1 to 4 carbon atoms. The symbols
R2 and R3 preferably each represent an alkyl, phenyl or~
group.
The process of the invention is performed in the
absence or~ preferably, in the presence of solvent. As
solvent, an organic solve~t which is inert when hot is
IQ; generally used~ The reaction is advantageously performed in
the presence of an acid acceptor.
The reaction temperature is generally between 30 and
150C, preferably between 40 and 120C.
The reagents of formula (II) and (II~) are generally
1~ employed in stoichiometric proportions, or do not depart from
the stoichiometry by more than 40% (~olar).
As solvents which can be used, there may be mentioned
nitriles (in particular acetonitrile), ketones, (in
particular acetone, cyclohexanone, methyl ethyl ketone,
Z~ methyl isobutyl ketone), optionally halogenated hydrocarbons
(in particular benzene, toluene, xylenes, chlorobenzene),
esters such as alkyl alkanoates (in particular ethyl acetate)
and aprotic polar solvents such as dimethylformamide and
N-methylpyrrolidoneO
2~ As acid acceptors, organic or inorganic basic agents
are preferred, in particular alkali metal hydroxides,
carbonates or bicarbonates, or alkaline-earth metal

hydroxide5 or c~rbonates, prefer~bly ~od~um carbon~te or
potas6ium carbonate or bicarbonate ~s well as terti~ry amines
~uch ~s tris~alkyl)amine~, in par~i~ulflr triethy1amine,
tripr~pylamine, tributylamine and N,N-dialkylanllines.
The reaction product can be isolated by any method
known per se.
Some compounds of formula ~II) are known (Tetrahedron
Letters No. 46, p. 4645, 1973). The compounds of formula
~II) are conveniently prepared by reaction of tris(aralkyl)
hexahydrotriazines with diorganophosphites.
According to a feature of the invention the compounds
of formula (I) prepared by the process of the invention are
converted by hydrogenolysis and/or hydrolysis and/or
~alification to compounds of the formula:
OH
0 ~ P - CH2 - NH - CH2 - CO - N - SO2 ~ Rl (IV)
H R
wherein R and Rl are as hereinbefore defined, and salts
thereof. The compounds of formula (IV) and salts thereof
have herbicidal properties.
The compounds of formula (III) are also known .
The single d~valent radical represented by R2 and R3
together preferably contains from 2 to 6 carbon atoms in
the chain, for example ethylee or propylene groups.
Suitable sub6tituents on the divalent radical are those eiven
for R .
?5 Suitable substituents on the group Ar hereinbefore
include C1 6 alkyl, alkoxy and nitro groups and haloen atoms,
The followin~ Examples illustrate the invention.

` ` ~Z~
5 i
xample 1:
A solution of diethyl N~benzylam;nomethylphos-
phonate (2 9; 7.78 millimoles) of for~ula:
~ 2 5
0 = P - CH2 - NH - CH2 C6 5
(V)
- C2H5
in acetonitrile (10 cc).i~ heated until i.~ boils under
reflux (80C). A.solution in aeetonitrile (10 cc) of N-
~ethyl-N-tmethylsuLphonyl)-chloroaC~tamide ~1.44 9 ; 7.76
millimoles)~of formula: ~
.. Cl - CH2 - C0 - N(CH3) - S02 CH3 tVI)
is add~d gradually in the course of 1/4 h at 50C.
The m;xture is h~ated for 2 h and KzC03 ~0.54 ~;
3.9 millimoles~ is then added, and th~ mixture is heated
for a further 8 h at the same te~peratur~. The mixture is
cooled and f;ltered.
It is found on chromatography that a product (1.9 g)
of formula:
~ - C2H5
0 = P - CH2 - N - CH - CO l ~ S2 ~ CH3 (VII)
~ ~2H5 CH2-C6~5 3
has been ob~ained~ e~uivalent to a 60X yield ~degree of

~Z~4~
.. 6 _
conversion of the product of formula (V): 85%~.
Ex~m
A solution of diethyl N-benzylaminom~thylphospho-
nate t1 9; 3.89 m;llimol~s) ;n methyL iso~utyL ketone
(MI8K) t10 cc) is heated to 80C. A solution of N-methyL-
N-(methylsulphonyl)chloroacetamid~ tO.721 9; 3.89 m;lli-
moles) in MI3K (10 cc) is added gradually to the above
solution, and the ~ixture is then heated for 2 hours at
115C: dry KzC03 tO.268 9; 1.94 millimoles) iç added;
tO heating is continued for 2 hours at this same tempera~ure
The mixture is cooled and filtered. It is found on chroma-
tography that ~ product o~ formula (VII) (0.934 9; 2.3
millimoles) has been obtained, equivalent to a 59~ yield.
CDegree of conversion of the product of for0ula 5V): 91X~.
Exa~ple 3:
A solution of diethyl N-benzylaminomethylphospho-
nate (1 g; 3.89 milli~oles) in chloro~enzene (10 cc) is
heated to 83C. A sol~tion of N-methyl-N-(~ethylsulphonyl)
chloroacetamide (0.721 9; 3.89 millimoles) in chlorob~nzene
(10 cc) is added gradually to the above solution~ and the
mixture is heated for 2 hours at 110C and dry K2C03 (0.268
9; 1.94 millimoles) is added; heating is continued for Z
hours at this sa~ te~perature. The m;xture is cooled and
then filtered.
It is found on chromatography that ~ product of
formula tVII) (0.772 9) has been obtained~ equivalent to a

~Z~ 6~
48.9X yield. CDegree of conversion of the product of for-
mula (V): 84.2X.
Exam
A solution of d;ethyl N-benzylaminomethylphospho-
nate t1 9; 3.89 millimoles) in aceton;tr;le (10 cc) is hea-
ted.to 60C. A solution of N-methyl~N-(methylsulphonyl)-
chloroacetamide (0.721 9) in acetonitril@ (10 CG) iS added
gradually to the above solution, and the mixture is then
heated for 2 hours at 80C; KHC03 (0.195 9; 1.945 ~;lli~
moles) is added; heating is con~inued for 5 hours at the
same temperature. The reaction mixture is cooled and ~
tered. It is found on chromatography that a product of
formula (VII) (0.804 g) has been obtained, equivalent to a
50.9X yield.
Example 5: .
;~ ~
Diethyl N-benzyla~inomethylphosphonate t1 9; 3.89
~illimoles), N-methyl-N-(methylsulphonyl)chloroaGetamide
(0~938 g; 5.05 millimoles) and ethyl acetate (10 cc) ar~
mixed. The mixture is heated under reflux (78C) for 3
hours and K2C03 (0.32 9; 2.32 millimol2s) is then added;
heating is continued for 6 h 33 ~in at this same tempera-
ture. The m;xture is cooled and then filtered. It is
found on chromatography that a product of formula (VII)
(1.139 9; 2.8 milli~oles~ has been obtained, equivalent to
ZS a 7Z% yield.

~4~
~ 8
Example b:
_._
A mix~ure of diisopropyl N-benzyla~inomethylphos-
phona~e (0.738 9; 2.59 millimoles) and N-methyl-N-(methyl-
sulphonyl)chloroacetamide (0.938 9; 5.05 m.ill;moles) is
heated for 5 h 30 min at 85C; K2C03 (O.t6 9) is then
added and the mixture is heated again for 3 hours. The
mixture is cooled and then filtered.
It is found on chromato~raphy that a product of
formuLa tVIlI) (00757 9; 1.745 ~illi~oles) has been ob~
tainedr e~uivalent to a 67.4X yield. The for~ula (VIII)
is as follo~s:
(CH3~2cH-o CH3
~ ~-C~2-~-cH2-cO-N-~o2-cH ~VIII)
( 3)2CH CH~_c6H
E~ampLe 7:
.
A mi~ture of diisopropyl N-benzylaminomethylphos-
phonate (5~13 g; 1~ millimoles), N-methyl-N-(m~thylsulpho-
nyl)chloroacetamide (3.33 9; 18 ~illimoles) and ethyl ace-
tate (45 cc) is hea~ed for 2 h at 50C; K2C03 t1.49 9;
10.8 ~illimoles) is ehen added. Heating i5 continued for
8 h at this same ee~perature. The mixture is cool2d and
then filtered.
It ig found on chrom~tography th~t a product of
formula (VIII) ~2~03 g, 4.68 miLlimoles) has been obtained,
equivalent to a 26X yield.

9 ~29L~4~
Exam
A mixture of diphenyl N-benzylaminomethylphospho-
na~e t1.269 9; 3nS9 millimolex)9 N-~thyl-N-tmethyls~lpho-
nyl)chloroac~tamide (0.9~8 9; 5.05 millimoLes) and toluene
(10 cc) is heated for 3 h 45 min at 80C; K~C03 ~0.26 9;
1.88 milli~oles) is then added. Heating is continued for
4 h, during Yhich a further quantity of K C03 (0.09 9; 0.65
millimoles) ;s added~ The mixture is cooled and then fil-
tered.
It is found on chromatography that a product of
~ormula (IX) ~0~946 g; 1~88 millimoles) has been obtained,
equivalent to a 52.4% yield (degree of conversion of the
phosphonate: 80%)~ The formula ~IX) is as follows:
~ C6H5
O = P - CH -- N - CH2 -- CO l S2 3
C6HS CH2-C6H5 C~3 ( I X )
Example 9:
A mixture of diphenyL N-benzyla~inomethylphospho-
nate (2.646 g; 7.495 millimoles), N-methyl-N-(methylsul-
phonyl)chloroaceta~ide (1.57 9; 8.46 millimoles) and N-
methyl-2-pyrrolidone (NMP) (6 cc) is heated for 6 h at
80C; triethyLamine (0.378 g; 3.74 millimoles) is then
added. The mixture is heated again at 80C for 5 hours,
. _ . , .. _ . . _ ., , .. . .. ___,. __ .. _, .. _ , ,_ . . . . .

~24~46~
_ 10 _
during ~hich a further quantity of triethylamine (0.37~ 9)
is added. The mixture is cooled, acetonitriLe (10 cc) is
added and the mixture is then filtered.
It is found on chromatography that a pruduct of
formula (IX) (2.25 9; 4.4B ~illimoles) has been obtained~
equivalent to a 6QX yield (degree of conversion of the
phosphonate: 62X)o
Example 10:
~ " ,, . _
Diphenyl N-~enzylam;nomethylphosphonate (0.932 9;
2.64 millimoles)~ N-~ethyl~N-(methylsulphonyl)ehloroace~-
am;de (VI) (0.49 9; 2.64 millimoles) and d;isopropylamine
- (0.272 9) are charged in dimethylformam;de (~MF) (2 cc).
After 7 hours' heat;ng at ROOC, ethyl aceta-te (10 cc) ;s
added and the di;sopropylam;ne hydrochlor;de formed is
recovered by f;ltration.
It ;s found on chromatography that a product o~
formula ~IX~ (0~670 9; 1.335 mill;moles) has been obta;ned,
equivalent to a 50.5% yield (degree of conversion of the
phosphonate: 69X).
Exa~Ple 11:
A mixture of dibenzyl N-benzylaminomethylphospho-
nate (3 9; 7.87 millimoles), N-methyl-N-(methylsulphonyl)-
chloroacetamide (1.45 9; 7.82 millimoles) and acetonitrile
(15 sc~ ;s h~ated for 6 h 45 ~in at 80C; at the same time,
triethylamine (0.792 9; 7.84 millimoles) dissolved in ace~
tonitrile (5 cc) ;s added gradually.

`- iL2~461
11
It ;s found on chromatography that a prodwct of
formula (X) (0.95 9) has been obtained, equivalent to a
22.9X yield. The formula (X) ;s as follows:
C6H5-CH2-0 CH'3
O - P-CH2-N-CE~2 CO-N-S02-CH3 (X)
~6H5 CH2 CH2-C6H5
Exa~ple 1Z:
Dimethyl N-benzyla~inom~thylphosphonate t5.5 9; 24
millimales), N-methyl-N-(methylsulphonyl)chloroacetamide
(4.45 9; 24 millimoles) and chlorobenzene (50 cc) are
charged. The mixture is heated at 125C for 2 h 30 min,
K2C03 (3 9; 21.7 millimoles) is added, the ~ixture is hea-
ted again for ~ h 30 min, and is cooled and filtered; the
product of formula (XI) has been obtained
in a 30X yield.
f -CH3
n - P - CH2 -N - CH2 - CO ~ i SO2 CH3
0-CH3 CH2-C6H5 C~3 (XI)

~-z~
~ 12 -
Example 13:
A solution of d;ethyl N-benzylaminomethylphospho-
nate (2 g; 7.78 millimoles) in acetonitrile (10 cc) is
heat~d to 80C; a solu~ion in acetonitrile (10 cc~ of N-
~ethyl-N-tmethylsulphonyl)chloroacetamide (1.88 9; 10.13
oles) is added. The mixture is heated ~or 1 h and
K2C03 tO.64 9; 4.63 milli~oles) is then added, and heating
is continued for 8 h 30 min at the same temperature. the
~;xture is cooled and filtered.
t~ It is found on chromatography that a product of
for~ula (VII) tZ.56 9; 6.31 milli~oles) has been ob~ained,
~quivalent to an 81X yield ~degree of conversion of the
produc~ of for~ula (V): 81XJ.