U.S. patent application number 09/811487 was filed with the patent office on 2001-08-16 for process for preparing diketone compounds and precursors thereto.
Invention is credited to Cramp, Susan Mary, Ellwood, Charles Walter, Gadras, Alain, Pevere, Virginie.
Application Number | 20010014761 09/811487 |
Document ID | / |
Family ID | 8224816 |
Filed Date | 2001-08-16 |
United States Patent
Application |
20010014761 |
Kind Code |
A1 |
Pevere, Virginie ; et
al. |
August 16, 2001 |
Process for preparing diketone compounds and precursors thereto
Abstract
A process for preparing compounds of the formula: 1 wherein
R.sub.2 is lower alkyl; or phenyl optionally substituted by from
one to five groups, the same or different, which are lower alkyl,
lower haloalkyl, halogen or --SR.sub.4; R.sub.3 is halogen, lower
alkyl, lower haloalkyl, lower alkoxy, lower haloalkoxy, --S-alkyl,
cycloalkyl having from 3 to 7 carbon atoms in the ring, alkenyl or
alkynyl having from 3 to 7 carbon atoms, or
--(CR.sub.5R.sub.6)--SR.sub.2 wherein q is one or two; R.sub.4 is
lower alkyl; R.sub.5 and R.sub.6 independently represent hydrogen,
lower alkyl or lower haloalkyl; and n is zero or an integer from
one to three; intermediate compounds of the formula: 2 and
processes for preparing them.
Inventors: |
Pevere, Virginie; (Lyon,
FR) ; Gadras, Alain; (Lyon, FR) ; Cramp, Susan
Mary; (Ongar, GB) ; Ellwood, Charles Walter;
(Ongar, GB) |
Correspondence
Address: |
Mary Katherine Baumeister
BURNS, DOANE, SWECKER & MATHIS, L.L.P.
P.O. Box 1404
Alexandria
VA
22313-1404
US
|
Family ID: |
8224816 |
Appl. No.: |
09/811487 |
Filed: |
March 20, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09811487 |
Mar 20, 2001 |
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09117372 |
Oct 28, 1998 |
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6235942 |
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09117372 |
Oct 28, 1998 |
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PCT/EP97/00370 |
Jan 28, 1997 |
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Current U.S.
Class: |
568/42 |
Current CPC
Class: |
C07C 205/11 20130101;
C07C 205/45 20130101; C07C 2601/02 20170501; C07C 319/20 20130101;
C07C 319/20 20130101; C07C 323/22 20130101 |
Class at
Publication: |
568/42 |
International
Class: |
C07C 319/02 |
Foreign Application Data
Date |
Code |
Application Number |
Feb 1, 1996 |
EP |
96 300718.2 |
Claims
What is claimed is:
1. A process for preparing a compound of formula (II) which
comprises reacting a compound of formula (V) with a mercaptan
HSR.sub.2 of formula (IV) according to reaction scheme Sc2
indicated below: 6wherein: R.sub.2 is lower alkyl; or phenyl which
is unsubstituted or is substituted by from one to five groups which
are the same or different selected from the group consisting of
lower alkyl, lower haloalkyl, halogen and --SR.sub.4; R.sub.3 is
halogen, lower alkyl, lower haloalkyl, lower alkoxy, lower
haloalkoxy, --S-alkyl, cycloalkyl having from 3 to 7 carbon atoms
in the ring, alkenyl or alkynyl having from 3 to 7 carbon atoms, or
--(CR.sub.5R.sub.6)q--SR.sub.2 wherein q is one or two; R.sub.4 is
lower alkyl; R.sub.5 and R.sub.6 independently represent hydrogen,
lower alkyl or lower haloalkyl; and n is zero or an integer from
one to three.
2. A process according to claim 1, wherein the reactant of formula
(IV) is employed as solvent.
3. A process according to claim 2, wherein the compound of formula
(IV) is in the form of a mercaptan, and the reaction is performed
in the presence of a base.
4. A process according to claim 3, wherein the base is a hydroxide
of an alkali metal or alkali earth metal, or a carbonate or
hydride.
5. The process according to claim 1, carried out in the presence of
a catalyst.
6. The process according to claim 5, wherein the catalyst is a
phase transfer catalyst.
7. The process according to claim 6, wherein the phase transfer
catalyst is a quaternary ammonium salt.
8. The process according to claim 2, carried out in the presence of
a catalyst.
9. The process according to claim 8, wherein the catalyst is a
phase transfer catalyst.
10. The process according to claim 9, wherein the phase transfer
catalyst is a quaternary ammonium salt.
11. The process according to claim 3, carried out in the presence
of a catalyst.
12. The process according to claim 11, wherein the catalyst is a
phase transfer catalyst.
13. The process according to claim 12, wherein the phase transfer
catalyst is a quaternary ammonium salt.
14. The process according to claim 4, carried out in the presence
of a catalyst.
15. The process according to claim 14, wherein the catalyst is a
phase transfer catalyst.
16. The process according to claim 15, wherein the phase transfer
catalyst is a quaternary ammonium salt.
17. A process for the preparation of a compound of formula (VI):
7wherein: R.sub.3 is halogen, lower alkyl, lower haloalkyl, lower
alkoxy, lower haloalkoxy, --S-alkyl, cycloalkyl having from 3 to 7
carbon atoms in the ring, alkenyl or alkynyl having from 3 to 7
carbon atoms, or --(CR.sub.5R.sub.6)q--SR.sub.2 wherein q is one or
two; R.sub.5 and R.sub.6 independently represent hydrogen, lower
alkyl or lower haloalkyl; and n is zero or an integer from one to
three; which comprises reacting a compound of formula (VII): 8in
which R.sub.3 and n are as defined above and X is halogen, with
nitroethane, wherein the reaction is performed in the presence of a
base selected from the group consisting of a hydroxide, a
carbonate, a hydride, an alkoxide of an alkali or alkaline earth
metal, and guanidine; in the presence of a solvent selected from
the group consisting of nitroethane and an inert solvent.
18. A process according to claim 17, wherein the reaction
temperature is from 0.degree. C. to 50.degree. C.
19. A process according to claim 18, wherein the reaction is
performed in the presence of a phase transfer catalyst.
20. A process according to claim 19, wherein the phase transfer
catalyst is a quaternary ammonium salt.
21. A process according to claim 17, wherein the reaction is
performed in the presence of a phase transfer catalyst.
22. A process according to claim 21, wherein the phase transfer
catalyst is a quaternary ammonium salt.
23. A compound of the formula (II): 9wherein: R.sub.2 is lower
alkyl; or phenyl which is unsubstituted or is substituted by from
one to five groups which are the same or different selected from
the group consisting of lower alkyl, lower haloalkyl, halogen and
--SR.sub.4; R.sub.3 is halogen, lower alkyl, lower haloalkyl, lower
alkoxy, lower haloalkoxy, --S-alkyl, cycloalkyl having from 3 to 7
carbon atoms in the ring, alkenyl or alkynyl having from 3 to 7
carbon atoms, or --(CR.sub.5R.sub.6)q--SR.sub.2 wherein q is one or
two; R.sub.4 is lower alkyl; R.sub.5 and R.sub.6 independently
represent hydrogen, lower alkyl or lower haloalkyl; and n is zero
or an integer from one to three.
24. The compound according to claim 23, which is
2-methylthio-4-trifluorom- ethylacetophenone or
3,4-dichloro-2-(methylthio)acetophenone.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a divisional of U.S. patent application
Ser. No. 09/117,372, filed Oct. 28, 1998, now allowed, incorporated
by reference herein in its entirety and relied upon, which is the
U.S. national stage of International Patent Application No.
PCT/EP97/00370, filed Jan. 28, 1997 and designating the United
States, and published by the International Bureau in English on
Aug. 7, 1997 as WO 97/28122.
BACKGROUND OF THE INVENTION
[0002] This invention relates to a process for preparing ketone
compounds and the products obtained by this process. More
particularly, the invention relates to the preparation of
intermediate compounds in the manufacture of pesticides.
[0003] Pesticidal 4-benzoylisoxazoles, particularly
5-cyclopropylisoxazole herbicides and intermediate compounds in
their synthesis, are described in the literature, for example in
European Patent Publication Nos. 0418175, 0487357, 0527036,
0560482, 0609798 and 0682659.
[0004] Various methods for preparing these compounds are known. It
is an object of the present invention to provide improved methods
for the preparation of these compounds and the intermediate
compounds thereto.
SUMMARY OF THE INVENTION
[0005] According to a first aspect of the invention, there is
provided a process for the preparation of a compound of formula (I)
by the reaction of a compound of formula (II) with a compound of
formula (III), according to the reaction scheme Sc1 indicated
below: 3
[0006] wherein:
[0007] R.sub.1 is lower alkyl;
[0008] R.sub.2 is lower alkyl; or phenyl optionally substituted by
from one to five groups which may be the same or different selected
from lower alkyl, lower haloalkyl, halogen and --SR.sub.4;
[0009] R.sub.3 is halogen, lower alkyl, lower haloalkyl, lower
alkoxy, lower haloalkoxy, --S-alkyl, cycloalkyl having from 3 to 7
ring carbon atoms, alkenyl or alkynyl having from 3 to 7 carbon
atoms, or --(CR.sub.5R.sub.6)q--SR.sub.2 wherein q is one or
two;
[0010] n is zero or an integer from one to three;
[0011] R.sub.4 is lower alkyl;
[0012] and R.sub.5 and R.sub.6 independently represent hydrogen,
lower alkyl or lower haloalkyl.
[0013] According to a second aspect of the present invention, there
is provided a process for the preparation of a compound of formula
(II) by the reaction of a compound of formula (V) with a mercaptan
of formula (IV), optionally present in the form of the thiolate,
according to reaction scheme Sc2 indicated below: 4
[0014] wherein R.sub.2, R.sub.3 and n in formulae (II) and (V) have
the same meanings as given before in reaction scheme Sc1. The group
--NO.sub.2 is generally present in the 2- or 4-position, preferably
the 2-position of the phenyl ring.
[0015] According to a third aspect of the invention there is
provided a process for the preparation of a compound of formula (V)
by the reaction of a compound of formula (VII) or (VI), as well as
a process for the preparation of a compound of formula (VI) from a
compound of formula (VII), according to the reaction scheme Sc3
indicated below: 5
[0016] wherein R.sub.3 and n have the same meanings as in reaction
schemes Sc2 and Sc1, and X represents halogen, preferably chlorine
or fluorine. Preferably, the group --NO.sub.2 in formula (VII) is
in the 2- or 4-position, most preferably in the 2-position of the
phenyl ring.
[0017] Certain intermediate compounds of formula (II) are novel and
as such constitute a further feature of the present invention, in
particular 2-methylthio-4-trifluoromethylacetophenone and
3,4-dichloro-2-(methylthio- )acetophenone.
DETAILED DESCRIPTION OF THE INVENTION
[0018] The compounds of formula (I) and a number of processes for
their preparation have been described in the European Patent
Applications cited above.
[0019] By the term "lower" is meant radicals comprising at least
one hydrocarbon chain, it being understood that such radicals
contain from one to six carbon atoms linked together in a straight-
or branched-carbon chain.
[0020] Preferably, R.sub.1 and R.sub.2 are lower alkyl (most
preferably, methyl).
[0021] Preferably, the group --SR.sub.2 occupies the 2-, 3- or
4-position of the phenyl ring (most preferably, the
2-position).
[0022] Preferably, n is one or two.
[0023] The reaction generally proceeds in better yield when a group
R.sub.3 is not halogen in the 2-position of the phenyl ring.
[0024] Preferably, R.sub.3 is halogen or trifluoromethyl. More
preferably, (R.sub.3)n is 4-CF.sub.3 or 3,4-dichloro.
[0025] The compounds of formula (III) above used in Scheme Sc1 are
known in the literature and their preparation has been expressly
described in the prior art known to the skilled worker. Some
references particularly pertinent to the preparation of this
reagent may be found by the skilled worker in various sources of
chemical literature, including Chemical Abstracts and information
databases available to the public.
[0026] The preparation of compounds of formula (I) using compounds
of formula (II) and (III) according to scheme Sc1 above may be
preferably effected in a polar or apolar aprotic solvent. Examples
of polar aproptic solvents include dimethylsulfoxide,
dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, a
compound of formula (III); an ether compound, particularly dioxane
and tetrahydrofuran; or an aromatic or aliphatic halogenated
hydrocarbon, particularly chlorobenzenes. Examples of apolar
aprotic solvents include aromatic or aliphatic hydrocarbons,
particularly toluene and xylenes.
[0027] Generally, the reaction temperature used in Sc1 above is
from 0.degree. C. to the boiling point of the solvent, preferably,
between 0.degree. C. and 100.degree. C. Generally the Sc1 reaction
takes place in the presence of a strong base, which is most
preferably selected from an alkoxide of an alkali or alkaline earth
metal, notably sodium ethoxide, sodium methoxide, sodium or
potassium t-butoxide; and a metal hydride (notably sodium
hydride).
[0028] According to a preferred variant of the process of Sc1 of
the present invention, the reaction is performed with continuous
distillation of the alcohol R.sub.1--OH formed in the course of the
reaction, at atmospheric pressure or under reduced pressure
(preferably from 1 to 20% below atmospheric pressure). Optionally,
the alcohol R.sub.1--OH formed may be removed by the use of a
suitable molecular sieve, for example a 4 Angstrom molecular
sieve.
[0029] Compounds of formula HSR.sub.2 used in reaction scheme Sc2
are known in the literature and their preparations are expressly
described in the prior art known to the skilled worker. The
references particularly pertinent to the preparation of this
reagent may be found by the skilled worker in various sources of
classical chemistry including Chemical Abstracts and information
databases available to the public. The salts or thiolates derived
from the compound of formula (IV) may be prepared by means known to
the skilled worker. These thiolates are preferably alkaline salts,
particularly sodium or potassium thiolate.
[0030] The preparation of compounds of formula (II) according to
scheme Sc2 from the acetophenone of formula (V) and a compound of
formula (IV) is preferably performed in a solvent of the compound
of formula (IV) which may be inert to the reaction conditions.
Examples of other suitable solvents include sulfoxides such as
dimethylsulfoxide; amides such as dimethylformamide,
N,N-dimethylacetamide and N-methylpyrrolidone; ketones such as
acetone and methyl isobutyl ketone; ether solvents, particularly
dioxane and tetrahydrofuran; aromatic, aliphatic and cycloaliphatic
hydrocarbons and halogenated or non-halogenated hydrocarbons,
particularly chlorobenzene, dichloromethane and toluene. The
presence of a small quantity of water is also acceptable in
allowing the solubilization of the thiolate.
[0031] When the reaction according to scheme Sc2 takes place using
a compound of formula (IV) in the form of the mercaptan and not in
the form of a thiolate salt, the reaction is preferably effected in
the presence of a base such as a hydroxide of an alkali metal or
alkali earth metal (preferably, sodium or potassium), or a
carbonate or hydride (such as sodium hydride). The reaction may
also be performed using various forms of catalyst, particularly
phase transfer catalysts such as a quaternary ammonium salt, for
example, tetrabutylammonium bromide.
[0032] The two reactions which comprise together the reaction
scheme Sc3 above are generally distinct but preferably they may
occur in succession. That is, the compounds of formula (V) may be
prepared from the compounds of formula (VII) via an intermediate of
formula (VI) which may be isolated or used in situ in the course of
the reaction.
[0033] The reaction conditions for the preparation of the compound
of formula (V) from the compound of formula (VI) are known in the
art and described in the literature, notably by J. G. Reid and J.
M. Reny Runge in Tetrahedron Letters, Vol. 31 (1990), pp.
1093-1096; G. A. Olah et al. Synthesis (1980), pp. 662-663; N.
Kornblum et al, J. Org. Chem., Vol. 47 (1982), pp. 4534-38; S.
Chandrasekaran et al, Synthetic Communications, Vol. 17 (1987), pp.
195-201.
[0034] The invention is thus also concerned with the preparation of
compounds of formula (VI) from compounds of formula (VII) by the
reaction of nitroethane in the presence of a base in a solvent
which is selected from a compound of formula (VII), nitroethane, a
solvent inert to the reaction conditions, and the base being
selected from an hydroxide, a carbonate, a hydride, an alkoxide of
an alkaline metal or an alkaline earth metal, and guanidine. An
advantage of this aspect of the present invention is that
relatively simple bases may be used in the reaction scheme Sc3.
[0035] Solvents suitable for use in preparing compounds (VI) from
compounds (VII) include nitroethane itself (used in excess compared
to the quantity normally used as a reactant); aromatic or aliphatic
halogenated or non-halogenated hydrocarbons, particularly
chlorobenzene; aromatic or aliphatic hydrocarbons, particularly
toluene and xylenes; polar aproptic solvents such as
dimethylsulfoxide, dimethylformamide, N,N-dimethylacetamide,
N-methylpyrrolidone; acetonitrile; ether solvents, particularly
dioxane and tetrahydrofuran. The presence of a small quantity of
water is also acceptable in allowing the solubilization of the
reaction mixture, while not reacting with the reactants
themselves.
[0036] The reaction temperature for converting (VII) to (VI) is
generally from 0.degree. C. to 50.degree. C. The reaction may also
be carried out in an aqueous or non-aqueous medium. Among the bases
suitable for the use in this process, one may cite hydroxides or
carbonates of alkali metals or alkaline earth metals, preferably
sodium or potassium, sodium carbonate, potassium carbonate or
cesium carbonate; or tetramethylguanidine. These bases may be used
alone or in mixture with others. The reaction may also be
conveniently performed using various types of catalyst,
particularly phase transfer catalysts such as a quaternary ammonium
salt, for example, tetrabutylammonium bromide.
[0037] The following non-limiting examples illustrate the
invention.
EXAMPLE 1
[0038] Preparation of
1-cyclopropyl-3-(2-methylthio-4-trifluoromethylpheny-
l)propane-1,3-dione (reaction scheme Sc1).
[0039] In a reaction vessel under an inert atmosphere, one adds
1.15 g of sodium methoxide and 22 ml of toluene. This is heated to
80.degree. C. at a pressure of 400 mbars. A mixture of 3.3 ml of
methyl cyclopropylcarboxylate and 3.8 g of
2-methylthio-4-trifluoromethylacetoph- enone in 6 ml of anhydrous
toluene is added over 3 hours with constant distillation of
methanol formed. The reaction is stirred for one hour at 80.degree.
C. The reaction is then cooled and the diketone precipitated in a
mixture of 80 ml of ice water containing 0.75 ml of concentrated
sulfuric acid. The organic phase is retained, washed with water and
the toluene removed under reduced pressure to give 3.67 g of
1-cyclopropyl-3-(2-methylthio-4-trifluoromethylphenyl)propane-1,3-dione
in the form of an orange powder, m.p. 64.degree. C. Yield=75%.
[0040] By proceeding in a similar manner, but heating at a
temperature of 70.degree. C. and a pressure of 230 mbars,
3-(4-chloro-2-methylthiophenyl- )-1-cyclopropylpropan-1,3-dione was
prepared in 98% yield (purity greater than 80%). This compound was
also similarly prepared wherein the reaction took place at a
temperature of 70.degree. for 6.5 hours and in the presence of 4
Angstrom molecular sieves in place of constant distillation of the
methanol formed.
EXAMPLE 2
[0041] Preparation of
1-cyclopropyl-3-[3,4-dichloro-2-(methylthio)phenyl]p-
ropane-1,3-dione (reaction scheme Sc1).
[0042] Sodium hydride (0.178 g, 60% oil dispersion, 0.0045 M) is
suspended in tetrahydrofuran (1.8 ml), stirred and heated at reflux
while a solution of a mixture of methyl cyclopropanecarboxylate
(0.42 g, 0.0042M) and 3,4-dichloro-2-(methylthio)acetophenone (0.5
g, 0.0021M) in tetrahydrofuran (3 ml) is added. The mixture is
stirred and heated at reflux for 3.5 hours, then cooled and poured
onto saturated aqueous sodium bicarbonate. The mixture is then
extracted with ether, washed with brine, dried over magnesium
sulfate, filtered and evaporated to give a gum (which is purified
by dry column flash chromatography eluted with ethyl acetate in
cyclohexane to give 3-cyclopropyl-1-[3,4-dichloro-2-(met-
hylthio)phenyl]propane-1,3-dione (0.35 g, 55%) as a yellow oil.
EXAMPLE 3
[0043] Preparation of 2-methylthio-4-trifluoromethylacetophenone
(reaction scheme Sc2).
[0044] To 0.15 g of 2-nitro-4-trifluoromethylacetophenone diluted
in 0.5 ml of acetone is added 0.256 g of an aqueous solution of 21%
wt/wt sodium thiomethoxide and the mixture is stirred for five
hours at 20.degree. C. The aqueous phase is separated, then
removed, then 2 ml of water are added and the acetone removed under
reduced pressure. The mixture is then treated with dichloromethane
and the aqueous phase removed. The organic phase is washed with
fresh water, then the solvent is evaporated under reduced pressure
to obtain 0.085 g of 2-methylthio-4-trifluoromethylaceto- phenone
with a melting point of 71.degree. C.
[0045] By proceeding in a similar manner,
3,4-dichloro-2-(methylthio)aceto- phenone may be prepared, .sup.1H
NMR (CDCl.sub.3)2.4 (s,3H), 2.6 (s,3H), 7.15 (d,1H), 7.5
(d,1H).
EXAMPLE 4
[0046] Preparation of
1-(2-nitro-4-trifluoromethylphenyl)-1-nitroethane (Reaction Scheme
Sc3).
[0047] 0.87 g of sodium carbonate in 5 ml of anhydrous toluene are
placed in a 30 ml reaction vessel, and 0.11 g of
benzyltriethylammonium chloride and 1.13 g of
4-chloro-3-nitrobenzotrifluoride and 0.38 g of nitroethane are
added at the same time. The mixture is stirred for 16 hours at
20.degree. C., 10 ml of water are added and the aqueous phase is
separated, then acidified by a 4N solution of sulfuric acid. It is
then extracted with 5 ml of methyl t-butyl ether. After removing
the organic solvent, 0.18 g of a mixture is obtained which is
separated by column chromatography using reverse phase silica
eluting with a mixture of water and acetonitrile to obtain 0.12 g
of the title compound, m.p. 48.degree. C.
* * * * *