PROCESS FOR THE PREPARATION OF N-ACYL-N-ALKYL-2,6- DIALKYL-3-CHLORO-ANILINES

PROCEDE POUR LA PREPARATION DE N-ACYL-N-ALKYL-2,6-DIALKYL- 3-CHLOROANILINES

English Abstract

Process for the preparation of N-acyl-N-alkyl-2,6-dialkyl-3-chloro-
anilines
Abstract of the Disclosure
N-acyl-N-alkyl-2,6-dialkyl-3-chloroanilines of the formula
<IMG>
wherein R1 is methyl or ethyl, R2 is alkoxymethyl, chloromethyl or
2-tetrahydrofuryl, R3 is alkoxymethyl, carboxy or alkoxycarbonyl and
R4 is hydrogen or methyl and, if R3 is carboxy or alkoxycarbonyl, R4
is also 2-alkoxyethyl and 2-alkoxypropyl, and R3 and R4, together
with the carbon atom to which both radicals are attached, may also
form a 2-oxotetrahydro-3-furyl radical or a 2-oxo-5-methyltetra-
hydro-3-furyl radical, are prepared by reacting a 2,6-dialkylaniline
of the formula
<IMG>
with a halide of the formula
<IMG>
wherein X is chlorine or bromine, to give an N-alkyl-2,6-dialkyl-
aniline of the formula

<IMG>
then converting said compound by further reaction with an acylating
agent of the formula
X1-CO-R2
wherein X1 is chlorine, bromine or -O-CO-R2, into an N-acyl-N-alkyl-
2,6-dialkylaniline of the formula
<IMG>
and subsequently converting said compound by reaction with chlorine
into an N-acyl-N-alkyl-2,6-dialkyl-3-chloroaniline of the above
formula.

Claims

- 11 -
What is claimed is:
1. A process for the preparation of an N-acyl-N-alkyl-2,6-dialkyl-
3-chloroaniline of formula I
<IMG> (I)
wherein R1 is methyl or ethyl, R2 is alkoxymethyl, chloromethyl or
2-tetrahydrofuryl, R3 is alkoxymethyl, carboxy or alkoxycarbonyl and
R4 is hydrogen or methyl and, if R3 is carboxy or alkoxycarbonyl, R4
is also 2-alkoxyethyl and 2-alkoxypropyl, and R3 and R4, together
with the carbon atom to which both radicals are attached, may also
form a 2-oxotetrahydro-3-furyl radical or a 2-oxo-5-methyltetra-
hydro-3-furyl radical, which process comprises reacting a 2,6-di-
alkylaniline of formula II
<IMG> (II)
wherein R1 is as defined for formula I, with a halide of formula III
<IMG> (III)
wherein R3 and R4 are as defined for formula I and X is chlorine or
bromine, to give an N-alkyl-2,6-dialkylaniline of formula IV
<IMG> (IV)
wherein R1, R3 and R4 are as defined for formula I, then reacting
the N-alkyl-2,6-dialkylaniline of formula IV with an acylating agent
of formula V
X1-CO-R2 (V)

- 12 -
wherein R2 is as defined for formula I and X1 is chlorine, bromine
or -O-CO-R2, and subsequently converting the resultant N-acyl-N-
alkyl-2,6-dialkylaniline of formula VI
<IMG> (VI)
wherein R1, R2, R3 and R4 are as defined for formula I, by reaction
with chlorine into an N-acyl-N-alkyl-2,6-dialkyl-3-chloroanilire of
formula I.
2. A process according to claim 1, wherein the 2,6-dialkylaniline
of formula II is 2,6-dimethylaniline or 2,6-diethylaniline.
3. A process according to claim 2, wherein the 2,6-dialkylaniline of
formula II is 2,6-dimethylaniline.
4. A process according to claim 1, wherein the halide of for-
mula III is 2-methoxyethyl chloride, 2-ethoxyethyl chloride,
2-methoxy-1-methylethyl chloride, methyl 2-chloroacetate, ethyl
2-chloroacetate, methyl 2-bromopropionate, ethyl 2-bromopropionate
or .alpha.-bromo-.gamma.-butyrolactone.
5. A process according to claim 4, wherein the halide of formula III
is .alpha.-bromo-.gamma.-butyrolactone.
6. A process according to claim 1, wherein the acylating agent of
formula V is methoxyacotyl chloride, chloroacetyl chloride or
tetrahydrofuran-2-carboxylic acid chloride.
7. A process according to claim 6, whewrein the acylating agent of
formula V is methoxyacetyl chloride.

-13-
8. A process according to claim 1, wherein the reaction of a
2,6-dialkylaniline of formula II with a halide of formula III is
carried out in an inert solvent and in the presence of an acid
acceptor.
9. A process according to claim 8, wherein the inert solvent is
benzene, toluene, xylene, chlorobenzene, o-dichlorobenzene, N,N-di-
methylformamide or N,N-dimethylacetamide.
10. A process according to claim 8, wherein the inert solvent is
toluene or xylene.
11. A process according to claim 8, wherein the acid acceptor is an
alkali metal hydroxide, carbonate or bicarbonate, an alkaline earth
metal hydroxide, carbonate or bicarbonate, triethylamine or
pyridine.
12. A process according to claim 8, wherein the acid acceptor is
sodium carbonate.
13. A process according to claim 1, wherein the reaction of a
2,6-dialkylaniline of formula II with a halide of formula III is
carried out at a temperature in the range from 80°C to the reflux
temperature of the reaction medium.
14. A process according to claim 13, wherein the reaction of a
2,6-dialkylaniline of formula II with a halide of formula III is
carried out at the reflux temperature of the reaction medium.
15. A process according to claim 1, wherein the reaction of a
2,6-dialkylaniline of formula II with a halide of formula III is
carried out in toluene or xylene as solvent, in the presence of
sodium carbonate as acid acceptor and at the reflux temperature of
the reaction medium.

-14-
16. A process according to claim 1, wherein the reaction of an
N-alkyl-2,6-dialkylaniline of formula IV with an acylating agent of
formula V is carried out in an inert solvent.
17. A process according to claim 16, wherein the reaction of an
N-alkyl-2,6-dialkylaniline of formula IV with an acylating agent of
formula V is carried out in hexane, benzene, toluene, xylene,
chlorobenzene, methylene chloride, chloroform, carbon tetrachloride
or ethylene chloride as solvent.
18. A process according to claim 16, wherein the reaction of an
N-alkyl-2,6-dialkylaniline of formula IV with an acylating agent of
formula V is carried out in toluene or xylene as solvent.
19. A process according to claim 1, wherein the reaction of an
N-alkyl-2,6-dialkylaniline of formula IV with an acylating agent of
formula V is carried out in the absence of a base, in toluene or
xylene as solvent and under reduced pressure.
20. A process according to claim 1, wherein the chlorination of an
N-acyl-N-alkyl-2,6-dialkylaniline of formula VI is carried out in an
inert solvent.
21. A process according to claim 20, wherein the inert solvent is
formic acid, acetic acid, chlorobenzene, methylene chloride,
chloroform, carbon tetrachloride or ethylene chloride.
22. A process according to claim 20, wherein the inert solvent is
formic acid or acetic acid with a water content of up to 40 % by
weight.
23. A process according to claim 1, wherein the chlorination of an
N-acyl-N-alkyl-2,6-dialkylaniline of formula VI is carried out in
the temperature range from 20° to 40°C.

- 15 -
24. A process according to claim 1, wherein the chlorination of an
N-acyl-N-alkyl-2,6-dialkylaniline of formula VI is carried out in
the presence of 1 to 5 % by weight of a Lewis acid.
25. A process according to claim 24, wherein the Lewis acid is
aluminium chloride, iron(III) chloride, boron trifluoride or
titanium tetrachloride.
26. A process according to claim 24, wherein the Lewis acid is
iron(III) chloride.
27. A process according to claim 1, wherein the chlorination of an
N-acyl-N-alkyl-2,6-dialkylaniline of formula VI is carried out in
the temperature range from 20° to 40°C, in formic acid with a water
content of up to 40 % by weight and in the presence of 1.5 to 2.5 %
by weight of iron(III) chloride, based on the N-acyl-N-alkyl-2,6-di-
alkylaniline of formula VI employed.
FO 7.5/GOT/we*/cw*/wv

Description

12866~
5-16062/~
Process for the preparation of N-acyl-N-alkyl-2,6-dialkyl-3-chloro-
anilines
The present invention relates to a process for the preparation of
N-acyl-N-alkyl-2,6-dialkyl-3-chloroanilines of formula I
Cl\ /R~ ~4
H-R3 (I)
.=.\ C0-R2
R1
wherein R1 is methyl or ethyl, R2 is alkoxymethyl, chloromethyl or
2-tetrahydrofuryl, R3 is alkoxymethyl, carboxy or alkoxycarbonyl and
R4 is hydrogen or methyl and, if R3 i9 carboxy or alkoxycarbonyl, R4
is also 2-alkoxyethyl and 2-alkoxypropyl, and R3 and R4, together
with the carbon atom to which both radicals are attached, may also
form a 2-oxotetrahydro-3-furyl radical or a 2-oxo-5-methyltetra-
hydro-3-furyl radical.
Some of the compounds of formula I have fungicidal activity and some
of them have herbicidal activity~ Compounds of this type are
described for example in US patent specifications 4 564 629 and
3 933 860, British patent specification 1 455 471, published
European patent application 0 028 011 and published British patent
application 2 006 783.
It is known from published British patent application 2 098 210 to
prepare N-acylated N-alkoxycarbonylmethyl-2,6-dialkyl-3-haloanilines
and N-(l-alkoxycarbonylethyl)-2,6-dialkyl-3-haloanilines by reacting

12866~4
-- 2 --
halogen with corresponding N-alkoxycarbonylmethyl-2,6-dialkyl-
anilines and N-(1-alkoxycarbonylethyl)-2,6-dialkylanilines in the
presence of at least 2 moles of Lewis acid per mole of N-alkoxy-
carbonylalkyl-2,6-dialkylaniline, and subsequently acylating the
resultant N-alkoxycarbonylmethyl-2,6-dialkyl-3-haloanilines and
N-(l-alkoxycarbonylethyl)-2,6-dialkyl-3-haloanilines. Suitable Lewis
acids are aluminium chloride, aluminium bromide, boron trifluoride,
tin tetrachloride and titanium tetrachloride. This process i9
disadvantageous in that very large amounts of Lewis acid have to be
employed in order to obtain the desired effect. For example, 2 parts
by weight of aluminium chloride are necessary per part of N-alkoxy-
carbonylalkyl-2,6-dialkylaniline. Since this large amount of
aluminium chloride must first be decomposed with water before the
reaction mixture is worked up, not only i8 the process costly with
respect to the starting materials and auxiliaries required, but it
is also complicated to perform.
It is also known to prepare 3-chloro-2,6-dimethylacetanilide in a
yield of 80 % of theory by chlorinating 2,6-dimethylacetanilide
(q.v. Synthsesis, 1971, p. 467). In accordance with this method, the
N-acyl-N-alkyl-2,6-dialkyl-3-chloroanilines of formula I are
obtainable by acetylating a corresponding 2,6-dialkylaniline,
chlorinating the 2,6-dialkylacetanilide, hydrolysing the resultant
3-chloro-2,6-dialkylacetanilido to give the 3-chloro-2,6-dialkyl-
aniline, alkylating said compound and subsequently effecting
acylation according to the following scheme:
-NHz --~~ ~ -NH-COCH3 --~~ ~ NH-COCH3
\Rl \Rl R
\--NH-C~H-R3 ~~~
R

lZt 36~8~
-- 3 --
In accordance with this method, the N-acyl-N-alkyl-2,6-dlalkyl-3-
chloroanllines of formula I can be prepared in a yield of about 40 ~o
of theory, based on the starting 2t6-dialkyldianiline. This method
is complicated on account of the large number of reaction steps
required and is unsatisfactory with respect to the yields which can
be obtained.
It is therefore the object of the present invention to provide a
process which makes it possible to prepare the N-acyl-N-alkyl-2,6-
dialkyl-3-chloroanilines of formula I in simple manner and in good
yield.
It has been found that this object can be advantageously accom-
plished by converting a corresponding 2,6-dialkylaniline by alkyl-
ation and subsequent acylation into a corresponding N-acyl-N-alkyl-
2,6-dialkylaniline, and then converting said compound by reaction
with chlorine into an N-acyl-N-alkyl-2,6-dialkyl-3-chloroaniline of
formula I.
In accordance with the present invention~ it is therefore proposed
to prepare the N-acyl-N-alkyl-2,6-dialkyl-3-chloroanilines of
formula I by reacting a 2,6-dialkylaniline of formula II
._./
~ ~--NHz (II)
\Rl
wherein R1 is as defined for formula I, with a halide of formula III
X- ~ -R3 (III)
wherein R3 and R4 are as defined for formula I and X is chlorine or
bromine, to give an N-alkyl-2,6-dialkylaniline of formula IV
/RI
~ ~--NH-~H-R3 (IV)
Rl

12~3~68~
-- 4 --
wherein Rl, R3 and R4 are as defined for formula I, then reacting
the N-alkyl-2,6-dialkylaniline of formu]a IV wlth an acylating agent
of formula V
xl-cO-R2 (V)
wherein R2 is as defined for formula I and Xl is chlorine, bromine
or -O-CO-Rz, and subsequently converting the resultant N-acyl-N-
alkyl-2,6-dialkylaniline of formula VI
RI IR4
H-R3 (VI)
.=. CO-R2
I
wherein Rl, R2, R3 and R4 are as defined for formula I, by reaction
with chlorine into an N-acyl-N-alkyl-2,6-dialkyl-3-chloroaniline of
formula I.
Suitable 2,6-dialkylanilines of formula II are 2,6-dimethylaniline
and 2,6-diethylaniline. 2,6-Dimethylaniline is particularly
suitable.
Suitable halides of formula III are 2-alkoxyethyl chloride,
2-alkoxyethyl bromide, 2-alkoxypropyl chloride, 2-alkoxypropyl
bromide, 2-chloroacetic acid, 2-bromoacetic acid, 2-chloroproplonlc
acid, 2-bromopropionic acid, 2-chloroacetic acid alkyl esters,
2-bromoacetic acld alkyl esters, 2-chloropropionic acid alkyl
esters, 2-bromopropionic acld alkyl esters, 2-chloro-4-alkoxybutyric
acid, 2-bromo-4-alkoxybutyric acid, 2-chloro-4-alkoxyvaleric acid,
2-bromo-4-alkoxyvaleric acid, 2-bromo-4-alkoxybutyric acid alkyl
esters, 2-bromo-4-alkoxybutyric acid alkyl esters, 2-chloro-4-
alkoxyvaleric acid alkyl esters, 2-bromo-4-alkoxyvaleric acid alkyl
esters, ~-chloro-~-butyrolactone, ~-bromo-r-butyrolactone, ~-chloro-
r-valerolactone and ~-bromo-~-valerolactone. ~he alkoxy and alkyl
ester groups present in said halides of formula III contain alkyl
radicals each of 1 to 4 carbon atoms. Specifically, said alkyl
radicals may be methyl, ethyl, propyl, isopropyl, butyl, sec-butyl,
tert-butyl and isobutyl.

lZ~661Y4
-- 5 --
When uslng halides of formula III wherein X i8 chlorine, the
reactlon of a 2,6-dlalkylanlllne of formula II with the halide of
formula III is advantageously carried out ln the presence of an
alkall metal lodide, in partlcular potassium lodide, as catalyst.
Preferred halides of formula III are 2-methoxyethyl chlorlde,
2-ethoxyethyl chlorlde, 2-methoxy-1-methylethyl chloride, methyl
2-chloroacetate, ethyl 2-chloroacetate, methyl 2-bromopropionate,
ethyl 2-bromoproplonate and u-chloro-y-butyrolactone. A partlcularly
preferred hallde of formula III is ~-bromo-y-butyrolactone.
Suitable acylating agents of formula V are chlorides and bromldes of
chloroacetic acld, alkoxyacetic acid and tetrahydrofuran-2-car-
boxylic acid as well as the anhydrides of these acids. Alkoxyacetic
acids shall be understood as meaning in particular those containing
a C~-C"alkoxy radical such as methoxy, ethoxy, propoxy, isopropoxy,
butoxy, sec-butoxy, tert-butoxy and isobutoxy. Preferred acylating
agents are methoxyacetyl chloride, chloroacetyl chloride and
tetrahydrofuran-2-carboxyllc acld chloride, with methoxyacetyl
chloride being particularly preferred.
The reaction of a 2,6-dialkylaniline of formula II with a halide of
formula III is advantageously carried out ln an inert solvent in the
presence of an acid acceptor. Suitable lnert solvents are aromatic
hydrocarbons and hydrogenated hydrocarbons such as benzene, toluene,
xylene, chlorobenzene and o-dichlorobenzene, as well as N,N-disub-
stituted carboxamides such as N,N-dimethylformamide and N,N-dimethy-
acetamide, and also excess 2,6-dialkylaniline of formula II. Pre-
ferred solvents are toluene and xylene. Suitable acid acceptors are
inorganic and organic bases such as alkali metal hydroxides,
carbonates and bicarbonates, alkaline earth metal hydroxides,
carbonates and bicarbonates, triethylamine, pyridine or excess
2,6-dialkylaniline of formula II. A preferred base is sodium
carbonate. The reaction temperatures are as a rule in the range from
80C to the reflux temperature of the reaction medium. It is

12~ 4
-- 6 --
advantageous to carry out the alkylation at the reflux temperature
of the reaction medium. The reaction of a 2,6-dialkylaniline of
formula II with a halide of formula III is therefore preferably
carried out in toluene or xylene as solvent, in the presence of
sodium carbonate as acid acceptor and at the reflux temperature of
the reaction medium.
The reaction of an N-alkyl-2,6-dialkylaniline of formula IV with an
acylating agent of formula V is advantageously carried out in an
inert solvent in the absence or presence of an acid acceptor.
Suitable inert solvents are in particular water-immiscible solvents
such as aliphatic and aromatic hydrocarbons and halogenated hydro-
carbons. Examples of suitable solvents are hexane, benzene, toluene,
xylene, chlorobenzene, methylene chloride, chloroform, carbon
tetrachloride and ethylene chloride. Preferred solvents are toluene
and xylene.
Suitable acid acceptors in the presence of which the reaction of an
N-alkyl-2,6-dialkylaniline of formula IV with an acylating agent of
formula V can be carried out are inorganic and organic bases such as
alkali metal hydroxides, carbonates and bicarbonates, alkaline earth
metal hydroxides, carbonates and bicarbonates, triethylamine and
pyridine. The reaction of an N-alkyl-2,6-dialkylaniline of fo-
rmula IV with an acylating agent of formula V is preferably carried
out in the absence of a base, in toluene or xylene and under reduced
pressure. Suitable pressures under which the reaction of an N-alkyl-
2,6-dialkylaniline of formula IV with an acylating agent of
formula V can be carried out are in the range from 50 to 150 mbar,
preferably from 60 to 100 mbar.
The chlorination of an N-acyl-N-alkyl-2,6-dikalkylaniline of
formula VI is also advantageously carried out in an inert solvent.
Suitable solvents are in particular lower aliphatic carboxylic acids
such as formic acid and acetic acid. Further suitable solvents are
chlorinated aromatic and aliphatic hydrocarbons such as chloro-
benzene, methylene chloride, chloroform, carbon tetrachloride and

~2~6684
-- 7 --
ethylene chloride. The carboxylic acids employed as solvents may
contain up to 60 % by weight of water. A preferred solvent in whlch
the chlorination of an N-acyl-N-alkyl-2,6-dialkylanillne of for-
mula VI can be carried out is formic acid ~ith a water content of up
to 40 % by weight.
The chlorination is advantageously carried out in the temperature
range from 20 to 40C. The chlorination can also be carried out
either at more elevated or at lower temperatures. However, it must
be borne in mind that at temperatures above 40C increasingly
dichlorinated products are formed, whereas at temperatures below
20C there is a danger that the reaction will no longer begin
immediately on commencement of the introduction of chlorine, but
will only start when a relatively high concentration of chlorine has
built up. This delayed-start reaction is often very vigorous and it
ls difficult to control the temperature of the reaction mixture. In
this case the formation of dichlorinated products must also be
expected.
It i8 also advantageous to carry out the chlorination in the
presence of Lewis acids such as aluminlum chloride, iron(III)
chloride, boron trifluoride and titanium tetrachloride. Iron(III)
chloride is a preferred Lewis acid. The Lewis acids are employed in
an amount of l to 5 % by weight, preferably l.5 to 2.5 % by weight,
based on the N-acyl-N-alkyl-2,6-dialkylaniline of formula VI to be
chlorinated. The Lewls acids do not as such have a substantial
influence on the chlorination, however they greatly increase the
solubility in aqeuDus formic acid or aqueous acetic acid of the
N-acyl-N-alkyl-2,6-dialkylanilines of formula VI to bè chlorinated.
Therefore, in order to obtain a higher volume yield, it is advisable
to add Lewis acids in particular when emplyoying formic acid or
acetic acid as solvent. The chlorination of an N-acyl-N-alkyl-2,6-
dialkylaniline of formula VI is thus preferably carried out in the
temperature range from 20 to 40C, in formic acid with a water

121Y6684
-- 8 --
content of up to 40 % by weight and in the presence of 1.5 to 2.5 %
by weight of iron(III) chloride, based on the N-acyl-N-alkyl-2,6-
dialkylaniline of formula VI employed.
The chlorination is usually carried out under normal pressure. When
using formic acid or acetic acid as solvent, the reaction may be
carried out under slightly excess pressure since no gas escapes from
the reaction mixture when these solvents are in use.
The process of the present invention makes it possible to prepare
the N-acyl-N-alkyl-2,6-dialkyl-3-chloroanilines of formula I from
2,6-dialkylanilines of formula II in simple manner and in a sub-
stantially better yield than by the known processes. Compared with
the process described in published British patent applica-
tion 2 089 210, which process is 'oased on the chlorination of
N-alkyl-2,6-dialkylanilines in the presence of at least 2 moles of a
Lewis acid, the use of large amounts of Lewis acid and the con-
comitant difficulties in working up can be avoided. Compared with
the process mentioned at the outset which is based on the chlorina-
tion of N-acetyl-2,6-dialkylanilines, two reaction steps can be
dispensed with, i.e. the introduction of the acetyl group before
chlorination and the removal thereof after chlorination. The
N-alkylation of 2,6-dialkylanilines affords better yields than the
corresponding N-alkylation of 2,6-dialkyl-3-chloroanilines. More-
over, surprisingly, the chlorination of N-acyl-N-alkyl-2,6-di-
alkylanilines of formula VI affords better yields than the known
chlorination of 2,6-dialkylacetanilides. The concept of the present
invention makes it possible for the first time to utilise these
sdvantages. It i9 an essential feature of this concept that the
introduction of the chlorine atom into the 3-positon of the phenyl
radical i8 carried out in the final step.
The process of the present invention is illustrated in more detail
by the following Example.

lZ8661~34
g
Example 1: Preparatlon of N-methoxyacetyl-N-(2-oxotetrahydro-3-
furyl)-3-chloro-2,6-dlmethylaniline
a~ 64 g (O 6 mole) of anhydrous sodium carbonate solution are
suspended in a solution of 121 g (1.0 mole) of 2,6-dimethylaniline
in 500 ml of xylene. Over 2 hours, 206 g (1.25 moles) of ~-bromo-y-
butyrolactone (3-bromo-2-oxotetrahydrofuran) are added to this
suspension at reflux temperature (about 140C). When the addition of
the ~-bromo-~-butyrolactone is complete, the reaction mixture is
stirred for 4 hours at room temperature. The water of reaction is
removed during the addition of the ~-bromo-~-butyrolactone and
during the subsequent stirring. The reaction mixture is then cooled
to 50C, washed first wlth 200 ml of water and then with 200 ml of
5 % hydrochloric acid and subsequently dried by distilling off
50-60 ml of solvent. According to gas chromatographic analysis, the
reaction mixture contains 174 g (~5 % of theory) of N-(2-oxotetra-
hydro-3-furyl)-2,6-dimethylaniline, part of which precipitates when
the reaction mixture cools. The resultant suspension can be further
processed direct in the next step. However, the product may also be
recovered by distilling off the solvent and crystallising the
residue from isopropanol. The melting point is 82-84C.
b) Over 2 hours, 113 g (1.04 moles) of methoxyacetyl chloride are
added at 60-70C and under a pressure of 70-80 mbar to a suspension
of 205 g (1.0 mole) of N-(2-oxotetrahydro-3-furyl)-2,6-dimethyl-
aniline in 500 ml of xylene. Towards the end of the addition of
methoxyacetyl chloride the reaction mixture begins to boil, with
hydrogen chloride gas evolving. When the addition of methoxyacetyl
chloride is complete, the reaction mixture is stirred for 3 hours
under weak reflux at 60-65C and under a pressure of 70-80 mbar, and
the hydrogen chloride evolving during the reaction is removed.
Subsequently, half of the xylene is distilled off, the reaction
mixture is cooled to 20C, the precipitated product is filtered off,
washed with xylene and dried, affording 263 g (95 % of theory) of
N-methoxyacetyl-N-(2-oxotetrahydro-3-furyl)-2,6-dimethylaniline with
a melting point of 118-120C.

~2~36684
-- 10 --
c~ Over 2 hours, 74.6 g (1.05 moles) of chlorine are introduced at
25-30C into a solution of 277 g (1.0 mole) of N-methoxyacetyl-N-
(2-oxotetrahy~ro-3-furyl)-2,6-dimethylaniline and 5 g of iron(III)
chloride in 300 ml of 85 % formic acid. The reaction is exothermic
and virtually no gas evolves. ~hen the addition of chlorine is
complete, the reaction mixture is stirred for 30 minutes at 25~C,
the formic acid is then distilled off in vacuo, the residue is taken
up in 500 ml of toluene and the toluenic solution is washed with
100 ml of water. The oily residue obtained after the toluene has
been distilled off is crystallised from a mixture of isopropanol and
hexane, affording 287 g (92 % of theory) of N-methoxyacetyl-N-(2-
oxotetrahydro-3-furyl)-3-chloro-2,6-dimethylaniline with a melting
point of 80-82C.

Representative Drawing