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Description  |
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FIELD OF INVENTION
This invention relates to a process for haloethylating aromatic
hydrocarbons to form 1-halo-1-arylethanes.
BACKGROUND
As disclosed in March, Advanced Organic Chemistry, Second Edition,
McGraw-Hill, New York, 1977, pp. 501-502; Olah, Friedel-Crafts and Related
Reactions, Volume 2, Interscience Publishers, New York, 1963-1964, pp.
659-784; U. S. Pat. No. 2,516,971 (Galitzenstein et al.); and the
references cited therein, it is known that aromatic compounds can be
haloalkylated by reacting them with a hydrogen halide and an appropriate
aldehyde in the presence of a Lewis acid or a proton acid as a catalyst,
most commonly in the presence of zinc chloride.
The chloroalkylations utilizing formaldehyde as the aldehyde have been
successfully employed in providing fairly high yields of
1-chloro-1-arylalkanes; reasonably high yields of 1-chloro-1-arylalkanes
have also been obtained from chloroalkylations utilizing higher aldehydes
in some cases, e.g., when the aromatic compound has had an appropriate
functional substituent or a plurality of alkyl substituents; and
reasonably acceptable, although lower, yields of 1-halo-1-arylalkanes have
been obtained in comparable bromoalkylation reactions. However, when the
aromatic compound has been a less reactive compound, e.g., an
unsubstituted aromatic hydrocarbon or a monoalkylaromatic hydrocarbon, it
has not been found possible to provide commercially acceptable yields of
1-halo-1-arylalkane, even when the haloalkylation has been a
chloroalkylation rather than a bromoalkylation. There has been too much
co-formation of diarylalkane by-product, especially in the bromoalkylation
reactions.
Another disadvantage of the known haloalkylation processes utilizing the
higher aldehydes has been their providing too much o-isomer in processes
performed to provide 1-halo-1(4-alkylphenyl)alkanes, such as the compounds
which have been synthesized by other techniques to provide intermediates
for ibuprofen, related pharmaceuticals, detergents, etc. It would be
desirable to find a way of increasing the para/ortho ratio obtainable from
such processes to provide a more economical method of preparing the
1-halo-1-(4-alkylphenyl)alkanes which can be used in known processes, such
as those of U. S. Pat. No. 4,536,595 (Gardano et al.), Canadian Patent No.
1,197,254 (Francalanci et al.), British Patent No. 1,560,082 (Dynamit
Nobel), Czechoslovakian Certificate of Authorship 219,752 (Palecek et
al.), and Japanese Kokai 47-39050 (Miyatake et al.) and 52-111536
(Tokutake).
SUMMARY OF THE INVENTION
An object of this invention is to provide a novel process for
haloethylating an aromatic hydrocarbon with hydrogen chloride or bromide
and acetaldehyde to form a 1-halo-1-arylethane.
Another object is to provide such a process which minimizes co-formation of
a diarylalkane by-product.
Still another object is to provide such a process which maximizes the
para/ortho ratio in the product when the aromatic hydrocarbon is a
monoalkylbenzene.
A further object is to provide an improved method of preparing
1-halo-1-arylethanes useful as chemical intermediates.
These and other objects are attained by reacting a monoalkylaromatic
hydrocarbon with hydrogen chloride or bromide and acetaldehyde at a
temperature in the range of about +10.degree. C. to about -35.degree. C.
in the presence of at least about 1.4 mols of hydrogen sulfate per mol of
the aromatic hydrocarbon and in the absence of more than about 15% by
weight of water, based on the weight of the hydrogen sulfate; the
temperature being not higher than about -10.C when hydrogen chloride is
employed.
DETAILED DESCRIPTION
The aromatic hydrocarbon employed in the practice of the invention is a
monoalkylaromatic hydrocarbon, such as 1-methylnaphthalene,
2-methylnaphthalene, 9-methylanthracene, 9-butylanthracene,
9-dodecylanthracene, and the various monoalkylbenzenes, e.g., the methyl-,
ethyl-, propyl-, isobutyl-, sec-butyl-, t-butyl-, isopentyl-, t-pentyl-,
and hexylbenzenes. The most preferred aromatic hydrocarbons are the
monoalkylbenzenes wherein the alkyl group contains 1-5 carbons.
The hydrogen halide which is reacted with the aromatic hydrocarbon and
acetaldehyde is preferably anhydrous or at least substantially anhydrous.
However, some water in the hydrogen halide can be tolerated as long as it
is not an amount sufficient to raise the total amount of water in the
reaction mixture above about 15% by weight of the hydrogen sulfate,
although it is preferred to keep the total amount of water at a
concentration not higher than about 10% by weight of the hydrogen sulfate.
The hydrogen halide may be incorporated into the reaction mixture per se
or as a salt, such as sodium chloride or bromide, which reacts with
sulfuric acid to form hydrogen chloride or bromide under the reaction
conditions.
The acetaldehyde may be employed per se or may be introduced in the form of
a substance, such as paraldehyde, which decomposes to yield acetaldehyde
under the reaction conditions.
The aromatic hydrocarbon, hydrogen halide, and acetaldehyde are normally
employed in substantially equimolar amounts, but the proportions do not
appear to be critical. Thus, amounts of any of the reactants which are
smaller or larger than the equimolar amounts may be used if desired.
In order to avoid the presence of an excess of water in the reaction
mixture, the hydrogen sulfate is introduced in the form of 85-98% sulfuric
acid, preferably sulfuric acid having a concentration of 90-98%, most
preferably 93-98%. The amount employed is such as to provide at least
about 1.4 mols, preferably at least about 5 mols, per mol of aromatic
hydrocarbon. There does not appear to be any maximum to the amount of
hydrogen sulfate that may be used other than any maximum that might be
imposed by economic constraints.
When the hydrogen halide is hydrogen bromide, the reaction is conducted at
a temperature in the range of about +10.degree. C. to about -35.degree.
C., preferably about 0.degree. C. to about -35.degree. C., in order to
achieve the advantages of the invention. When the hydrogen halide is
hydrogen chloride, the reaction temperature is in the range of about
-10.degree. C. to about -35.degree. C., preferably about -25.degree. C. to
about -35.degree. C.
The process of the invention is exothermic, so the reactants should be
combined at a rate that permits control of the reaction temperature. In
conducting the process it is preferred to add a mixture of the aromatic
hydrocarbon and acetaldehyde to a sulfuric acid solution saturated with
the hydrogen halide and to add additional hydrogen halide during the
reaction. However, alternatively, the acetaldehyde and hydrogen halide can
be prereacted, or the aromatic hydrocarbon can be the first charge to the
reaction vessel.
The invention is particularly advantageous as a method of preparing
1-halo-1-arylethanes from aromatic hydrocarbons, such as monoalkylbenzenes
and other monoalkylaromatic hydrocarbons, that have not previously been
found to be capable of providing acceptable yields of such products by
haloalkylation processes utilizing acetaldehyde. The process is of
especial interest in the haloethylation of monoalkylbenzenes, where it has
the advantage of not only minimizing the co-formation of diarylalkane
by-product but of also increasing the para/ortho ratio in the product.
As is known, the products obtained by the process are useful as internal
standards, intermediates for the preparation of monomers, detergents,
pharmaceuticals, etc. When they are used as chemical intermediates, they
may be subjected to the same reactions as have previously been used to
convert them to desired products. For example, the 1-halo-1-arylethanes
can be dehydrohalogenated in any known manner to provide styrenes which
can then be polymerized by known techniques.
A particularly interesting application of the
1-halo-1-(4-alkylphenyl)ethanes which are prepared in a preferred
embodiment of the invention is as intermediates for the preparation of
ibuprofen and related pharmaceuticals. When they are used in such
applications, they may be converted to the desired products in any
suitable manner. For example, they may be reacted with carbon monoxide in
the presence of a carbonylation catalyst and then acidified to the
corresponding propionic acids as in Gardano et al., Francalanci et al., or
Dynamit Nobel; or they may be reacted with an alkali metal cyanide or a
tetraalkylammonium cyanide and then hydrolyzed to the corresponding
propionic acids as in Palecek et al. or Tokutake. Another useful synthesis
involves reacting the compounds with magnesium, carbonating the resultant
Grignard reagent with carbon dioxide, and hydrolyzing the carbonated
product to the propionic acid as in Miyatake et al.
The following examples are given to illustrate the invention and are not
intended as a limitation thereof.
EXAMPLE I
A suitable reaction vessel was charged with 60 mL of 93% sulfuric acid,
which was cooled to -3.degree. C. and saturated with anhydrous hydrogen
bromide. A solution of 7.8g of acetaldehyde and 21.3g of isobutylbenzene
was fed to the reaction vessel over a period of 50 minutes at -3.degree.
C. with hydrogen bromide bubbling into the reaction mass. The reaction
mass was stirred for one hour at -3.degree. C. and then poured into ice
water. Analysis showed a
1-bromo-1-(isobutylphenyl)ethane/1,1-di(isobutylphenyl)ethane mol ratio of
1.8.
EXAMPLE II
While maintaining a constant hydrogen bromide sparge, a solution of 1.2
molar proportions of acetaldehyde and one molar proportion of
isobutylbenzene was added over a period of five minutes to 4.8 molar
proportions of 93% sulfuric acid which had been precooled to a bath
temperature of -35.degree. C., and a reaction was conducted for 1.2 hours
before being terminated. Analysis of the product showed a
1-bromo-1-(isobutylphenyl)ethane/1,1-di(isobutylphenyl)ethane mol ratio of
11.
EXAMPLE III
A suitable reaction vessel was charged with 60 mL of 93% sulfuric acid,
which was cooled to -35 C and saturated with anhydrous hydrogen chloride.
A solution of 7.8g of acetaldehyde and 21.3g of isobutylbenzene was fed to
the reaction vessel over a period of 30 minutes at -35.C with hydrogen
chloride bubbling into the reaction mass. The reaction mass was stirred
for one hour at -35.C and then poured into ice water. Analysis showed a
1-chloro-1-(isobutylphenyl)ethane/1,1-di(isobutylphenyl)ethane mol ratio
of 7.3.
EXAMPLE IV
Crude 1-chloro-1-(isobutylphenyl)ethane containing 47g of
1-chloro-1-(isobutylphenyl)ethane was added to a mixture of 17g of sodium
cyanide in 126g of dimethyl sulfoxide (DMSO). The reaction mixture was
heated to 80.degree. C. with agitation for 10 hours, after which the DMSO
and inorganic salts were removed by water washing to yield
1-cyano-1-(isobutylphenyl)ethane. The crude nitrile was reacted with
excess 50% sodium hydroxide at 135.C for four hours to form the sodium
salt of 2-(isobutylphenyl)propionic acid, which was then acidified and
crystallized from hexane at -10.C. The para/ortho ratio of the resultant
2-(isobutylphenyl)propionic acid in hexane solution was approximately
200/1.
EXAMPLE V
While maintaining a constant hydrogen chloride sparge, a solution of 1.2
molar proportions of acetaldehyde and one molar proportion of
isobutylbenzene was added over a period of two minutes to 4.8 molar
proportions of 93% sulfuric acid which had been precooled to a bath
temperature of -19.C, and a reaction was conducted for 1.2 hours to
convert 61% of the isobutylbenzene. Analysis of the product showed a
1-chloro-1-(isobutylphenyl)ethane/1,1-di(isobutylphenyl)ethane mol ratio
of 6.
COMPARATIVE EXAMPLE A
Example V was essentially repeated except that the bath temperature was
0.degree. C., the addition time was one minute, and the reaction time was
0.2 hour. The conversion of isobutylbenzene at the end of the reaction was
64%, but the
1-chloro-1-(isobutylphenyl)ethane/1,1-di(isobutylphenyl)ethane mol ratio
was only 0.8.
EXAMPLE VI
While maintaining a constant hydrogen chloride sparge, a solution of 1.2
molar proportions of acetaldehyde and one molar proportion of
isobutylbenzene was gradually added to 2.5 molar proportions of 93.7%
sulfuric acid which had been precooled to a bath temperature of -20 C, and
a reaction was conducted for one hour. Analysis of the product showed a
1-chloro-1-(isobutylphenyl)ethane/1,1-di(isobutylphenyl)ethane mol ratio
of 8.
COMPARATIVE EXAMPLE B
Example VI was essentially repeated except that the amount of sulfuric acid
was decreased to 1.2 molar proportions. Analysis of the product showed a
1-chloro-1-(isobutylphenyl)ethane/1,1-di(isobutylphenyl)ethane mol ratio
of only 4.
It is obvious that many variations may be made in the products and
processes set forth above without departing from the spirit and scope of
this invention.
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