Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
The invention relates to a process for the preparation of
an ester of cycloprop3ne carboxylic acid esters.
~ccording to Ge~nall Auslegesc~ ift 2,231,312, addition Or
substituted cyclopropanecarbonyl halides and m-substituted
benzaldehydes, if uecessary dissolved in an aprotic solvent,
to an aqueous solution of sodium cyunide or potassium cyanide
and stirring of the rnixture obtained until no more conversion
takes place, affords alpha-cyano-m-substituted benzyl esters
of substituted cyclopropane carboxylic acids. The cyclopropane
carboxylic acids can be prepared and converted in a known
manner to the corresponding cyclopropanecarbonyl halides.
Such a process has the disadvantages that the cyclopropane-
carboxylic acids and their carbonyl halides must be prepared in
separate stages.
The present invention obviates this di,sadvantage.
The invention provides a process for the preparation of an
ester of the general formula:
R R
\C/
/ \ 0 H
RJ - C - C - C - 0 - C - R' (I)
R4 H CN
wherein R , R , R3, R and R5 each represents a substituted or
unsubstituted hydrocarbyl group or a hydrogen atom, which
comprises reacting:
(a) an aldehyde of the general formula:
R5 - C(O)H (II)
wherein R5 has the same meaning as in the general formula I,
with
(b) a salt of hydrocyanic acid, and
{)9
--3--
(c) a 2-halocyclobutanone o~ the general formula:
R - C - C = 0 (III)
R - C - C - ~lal
R4 H
wherein R1, R , R3 and R4 have the same meaning as in the
general formula I and Hal represents a halogen atom.
The present invention enables a three-step process comprisine
ring contraction of the 2-halocyclobutanone of the gen0ral ~ormula
III to a cyclopropanecarboxylic acid, conversion of this acid into
its carbonyl halide and reaction of this carbonyl halide with
an aldehyde and a cyanide, to be replaced by a one-step process.
~he one-step process according to the invention is pre~er-
ably carried out in the presence of an aprotic solvent which may
be water-miscible or water-immiscible, e.g., an alkane, cyclo-
alkane, aromatic hydrocarbon, ether halogenated hydrocarbon,
N,N-disubstituted carboxylic acid amide, nitrogen-oxygen or
sulphur heterocycle, acetonitrile or nitromethane. Substantially
water-immiscible aprotic solvents are preferably used in the
presence of water, because this promotes the formation o~ the
esters o~ the general formula I. ~he ~ormation o~ these esters
is most promoted in solvents comprising one or more alkanes.
Ex~mples of suitable alkanes are n-hexane, n-heptane, n-octane,
n-nonane, n-decane and their isomers, for example 2-methyl-
pentane, 3-methylpentane, 2-methylhexane, 3-methylhexane and
2,4,4-trimethylpentane. Gasolines rich in alkanes, such as
gasolines with a boiling range at atmospheric pressure between,
for example, 60 and 80 C are also very suitable. Very good
results have been obtained with n-heptane.
(3
-4
Exa~nples of other substantially water-immiscible solvents
are cycloalkanes, for example cyclohexane and methylcyclohexarle,
and aromatic hydrocarbons, such as benzene, toluene, o-, m- and
p-xylene and the trime-thyl benzenes, ethers, such as die-thyl
ether and di-isopropyl ether, alkanones, such as di-isobutyl
ketone and halogenated hydrocarbons, such as carbon tetrachloride.
The amount of water is not critical and may vary within
wide limits. On the one hand, it i5 preferably less than -the
amount required to obtain a 25%w and particularly 40%w a~ueous
solution with the starting amount of a water-soluble salt of
hydrocyanic acid so as to reduce the possibility of reaction
of the 2-halocyclobutanone of the general formula III, with
water with formation of cyclopropane carboxylic acid, and on
the other hand, it is preferably sufficiently large to dissolve
all of this cyanide at the temperature at which the process is
conducted so as to reduce the reaction time. However, the
presence of solid water-soluble salt of hydrocyanic acid is
not excluded.
The temperature at which the process is suitably conducted
is usually in the range of from 20 to 100C and is preferably in
the range of from 50 to ôO C. The esters of the general formula I
are usually obtained in the highest yield in the range of from
60 to 70C.
Water-miscible aprotic solvents are preferably used in the
absence of water. Examples of such solvents are N,N-dimethyl-
formamide, N,N-dimethylacetamide, dimethyl sulphoxide, N-methyl-
pyrrolidone, acetonitrile, tetrahydrothiophene, 1,1-dioxide,
nitromethane and tetrahydrofuran. Very good results have been
obtained with N,N-dimethylformamide.
Mixtures of solvents, for example of alkanes and aromatic
hydrocarbons, may be used, for instance n-heptane containing
up to 10%w of benzene and/or toluene.
09
--5--
The sal-t o~ hydrocyanic acid is soluble in wa-ter when a
substantially water-immiscible aprotic solvent is used in the
presence of water and soluble in ~he aprotic solvent when -the
aprotic solvent is substantially water-miscible~ Examples of
suitable salts of hydrocyanic acid are alkali metal cyanides,
alkaline earth metal cyanides and -tetrahydrocarbyl ammonium
cyanides. Alkali metal cyanides are preferred. Potassium
cyanide is particularly preferred, because it a~ords the
esters of the general formula I in a shorter reaction time
and in a higher yield than sodium cyanide.
The molar ratios of the aldehyde of the general formula II
to the 2-halocyclobutanone of the general formula III and of
the salt of hydrocyanic acid to the aldehyde of the general
formula II are not critical and may vary within wide limits.
The former molar ratio is preferably equal to one and the
latter is preferably in the range of from 1.0 to 1.5 and
particularly from 1.1 to 1.3.
The hydrocarbyl groups represented by R1, R2, R3 and R4
in the general formula III and by R5 in the general formula II
may be, for example, alkyl, cycloa~kyl, aryl, or ethylenically
unsaturated groupsO These groups may be substituted with, for
example, hydrocarbyloxy groups or halogen atoms. R5 preferably
represents a substituted or unsubstituted aryl group. These
aryl groups may be carbocyclic or heterocyclic. Examples of
carbocyclic groups are phenyl, 1-naphthyl, 2-naphthyl and
2-anthryl groups. Heterocyclic aromatic groups are deri~ed
from hetero-aromatic compounds which, according to Kirk-Othmer,
"Encyclopedia o~ C'hemical Technology", Second Edition, Volume 2
(1963), page 702, are defined ae being obtained by replacement
of one or more carbon atoms of a carbocyclic aromatic compound
by a hetero atom, for example, pyridine, pyrimidine, pyrazine,
quinoline and isoquinoline; the hetero-aromatic compounds include
O9
heterocyclic compounds having five-membered rings which show
aromatic characteristics and are mentioned on page 703 of said
volume, for example, -thiophene, pyrrole, furan, indole and
benzothiophene. As an aromatic group a substi-tuted or un-
substituted phenyl group is very suitable. Very good results
have been obtained with m-phenoxyb~nzaldehyde.
R , R , R3 and R in the general formula In preferably
represent alkyl groups, particularly alkyl groups with one to
six carbon atoms. The alkyl groups may be linear or branched.
Methyl groups are most preferred.
The Hal atom in the general formula I~ preferably re-
presents a chlorine or a bromine atom, in particular a chlorine
atom.
The process according to the invention may be carried out
lS by mixing the total amounts of the starting compounds with
vigorous stirring. If desired, the aldehyde of the general
formula II, the salt of hydrocyanic acid, the aprotic solvent
and water, if any, may be mixed, followed by gradual addition
of the cyclobutanone of the general formula III, but this
method generally offers no advantages over the other procedure.
Esters of the general formula I, for example, alpha-cyano-
3-phenoxy-benzyl-2,2,3,3-tetramethylcyclopropane carboxylate,
are valuable insecticides.
The Examples further illustrate the invention.
EXAMPLES I-VII
A 50-ml round-bottomed flask provided with a magnetic stirrer
was charged with 10 mmol. of 3-p~noxybenzaldehyde, 10 mmol. of
2-chloro-3,3,4,4-tetramethylcyclobutanone, 12 mmol. of a
cyanide, 20 ml of n-heptane and water. The reaction mixture
was stirred vigorously and analysed by gas-liquid chromatogr~phy
to determine the yield of the alpha-cyano-3-phenoxybenzyl-
2,2,3,3-tetramethylcyclopropane carboxylate formed. Se~en
V9
--7-
experiments were conducted ;n this manner, except where
indicated otherwise. The cyanide used, the amount o~ water
added, the reaction -temperature and the time of stirring are
stated in Table I. The starting ~mount of 12 mmol. of KCN in
Examples I, III and IV formed a 4ll%w aqueous solution, in
Examples II and V a 28~w aqueous solution. The starting amount
of 12 mmol. of NaCN in Examples VI and VII formed a 37%w
aqueous solution. Table I also presents the yield of the
desired ester, calculated on starting 3-phenoxybenzaldehyde.
ABLE I
.. __
Ex- Cyanide Water, Temper- Time, Yield of
ample - _ _ _ _ nl a~ re h ester, %
I KCN 1 65 6 ~1
II KCN 2 65 6 81 1)
III KCN 1 93 3 79 1)
IV KCN2) 1 25 20 46
V KCN 2 65 8 81
VI NaCN 1 65 20 55
VII NaCN 1 25 24 42
1) the 2-chloro-3,3,4,4-tetramethylcyclobutanone was fully
converted; the conversion of 3-phenoxybenzaldehyde was 85%,
2) the 2-chloro-3,3,4,4-tetramethylcyclo butanone was added to
the reaction mixture over a period of 1~ hours.
The reaction mixture of Example I was cooled to 25C, 10 ml
of water were added to dissolve precipitated potassium chloride,
the water layer was separated, the heptane layer was washed with
10 ml of water, dried over anhydrous calcium chloride and the
n-heptane was flashed off in a film evaporator to yield a pale
yellow oil which, according to quantitative gas-liquid
chromatography, contained the desired ester in an amount corre-
sponding to a yield of 88%.
0~3
- o -
EXAMPLE VIII
The experiment of Example I was repeated, but this time with
20 ml of cyclohexane instead Or 20 ml o~ n-hcptane and the re-
action mixture was kept at re~lux temperature (about 81 C).
After 6 hours' stirring the yield of the desired es-ter was 45%.
EXAMPL S IX and X
A 50 ml round-bottomed ~lask provided with a magne-tic
stirrer was charged with 10 mmol. o~-benzaldehyde, 10 mmol. of
2-chloro-3,3,4,4-tetramethylcyclobutanone, 12 mmol. of sodium
cyanide, 20 ml of a solvent and 1 ml of water. The reaction
mixture was stirred vigorously at a temperature of 23 C. Two
experiments were carried out in this manner. Table II states
the solvents used and presents the yields of the alpha-
cyanoben%yl-2,2,3,3-tetramethylcyclopropane carboxylate ~ormed.
TABLE II
. ~
Example Solvent Time, ¦ Yield of
~o. hI ester, %
. __ __
IX n-heptane 493 5 29
toluene 17 15
15E-XAMPLES XI and XII
A 50-ml round-bottomed ~lask provided with a magnetic stirrer
was charged with 10 mmol. of benzaldehyde9 10 mmol. of 2-chloro-
3,3,4,4-tetramethylcyclobutanone, 12 mmol. of a cyanide, 20 ml
of n-heptane and 1 ml of water. The reaction mixture was stirred
vigorously at a temperature of 70C. Two experiments were carried
out in this manner. Table III states the cyanides used and presents
the yields of the alpha-cyanobenzyl-2,2,3,3-tetramethylcyclopropane-
carboxylate formed.
_9_ ~ 9
TABLE II-[
Example Cyanide Time, Yield of
No. h ester, %
. _ . _ _ . __ . .. _ _
XI KCN 22-5 o12
XII NaCN ~ 61
EXAMPLE XIII
A mixture of 100 mmol. of benzaldehyde, 100 mmol. of sodium
cyanide and 50 ~1 of N7N-dimethylformamide was stirred at a temper-
ature of ôOC for 30 min. Then, an amount of 100 mmol. of
2-chloro-3,3,4,4-tetramethylcyclobutanone was added over a period
of 30 min. and stirring was continued for six hours. At the end
of this period the reactants ~ere fully converted and alpha-
cyanobenzyl-2,2,3,3-tetramethylcyclopropane carboxylate was
obtained in a yield of 65%.
EXAMPLE XIV
~ = .
A mixture of 100 mmol. of ~enzaldehyde, 100 mmol. o~ sodium
cyanide and 50 ml of di-isobutyl ketone was stirred at a
temperature of 60C for 30 minutes. Then, an amount of 100 mmol.
of 2-chloro-3,3,4,4-tetramethylcyclobutanone was added over a
period of 30 min. and stirring was continued for 100 hours.
The conversion of benzaldehyde was 75% and the yield of alpha-
cyanobenzyl-2,2,3,3-tetramethylcyclopropane carboxylate 52%,
calculated on starting benzaldehyde.
