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Description  |
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This invention relates to processes for preparation of
N-aryl-S,S-dihydrocarbylsulfilimines by reaction of phenylisocyanate
compounds with dihydrocarbyl sulfoxides, and to processes using such
reaction in a route for converting nitrobenzene compounds to
ortho-thioalkylene anilines.
BACKGROUND OF THE INVENTION
Sulfilimine compounds are of interest as intermediates in procedures for
producing various o-alkylacetanilide compounds having herbicidal
properties. Sulfilimines have previously been produced by reacting an
aniline compound with dimethylsulfide in the presence of a source of
positive chlorine, e.g. N-chlorosuccinimide. The
N-phenyl-S,S-dimethylsulfilimine is then rearranged to an
o-methylthiomethyl aniline, and the latter compound or derivative thereof
is subjected to a reductive cleavage reaction to obtain an
o-methylaniline. An electrolytic reductive cleavage reaction and further
description of reactions leading to compounds with herbicidal properties
is set forth in a commonly assigned copending application of Richard D.
Goodin et al., Ser. No. 530,135, filed Sept. 7, 1983, and issued Jan. 15,
1985 as Patent No. 4,497,755 the disclosure of which is incorporated
herein by reference. In the described procedures for producing
sulfilimines it is necessary to have a source of positive chlorine, and it
would be desirable to have a process which did not use such an agent and
accompanying costs or need for recovery and regeneration procedures.
Certain activated isocyanate compounds have been reported to react with
dimethyl sulfoxide at room temperature. Thus Arbuzov et al, Izv. Akad.
Nauk. SSSR Ser, Khim, No. 5, pp. 1206-1207 (1975) states that
trifluoroacetylisocyanate, as a strong electrophile, reacts with dimethyl
sulfoxide to give N-trifluoroacetyl-S,S-dimethylsulfilimine, and C. King,
J. Org. Chem. Vol. 25, pp. 352-356 (1960), shows conversion of
p-toluenesulfonyl isocyanate to N-p-toluenesulfonyl dimethylsulfilimine.
Various aromatic isocyanates are reported to be produced by carbonylation
of aromatic nitro compounds, generally at elevated temperatures and
pressures with noble metal catalysts. The referred-to reports have not
utilized the preparations in conjunction with reactions of the product
with dimethyl sulfoxide to obtain sulfilimines, or with special compounds
of interest for obtaining particularly desired products in the present
invention, such as with o-nitro-trifluoromethylbenzene. U.S. Pat. Nos.
4,070,391 and No. 3,576,836 are among those describing carbonylation
procedures in which aromatic nitro compounds are contacted at elevated
temperatures and pressures with carbon monoxide in the presence of a noble
metal catalyst, such as a palladium halide or a rhodium oxide. Such
procedures, as well as those illustrated in the present specification, can
be used in preparing isocyanates for conversion to sulfilimines in accord
with the present invention. For example sub-atmospheric, atmospheric or
superatmospheric pressures can be used, but elevated pressures are
generally advisable to obtain good reaction rates with pressures generally
in the range of about 500 to 10,000 psi (3447.5 to 68,950 KPa) and more
commonly about 1500 to 5000 psi (10,342 to 34,475 KPa). Temperatures from
ambient to 400.degree. C. can be used, depending on the catalyst, with
some being conveniently used at about 100.degree. to 225.degree. C., while
others are employed about 150.degree. to 225.degree. C. or higher.
Aniline compounds can be converted to phenylisocyanate compounds by
reaction with phosgene, and this procedure can be utilized to obtain
isocyanate compounds for further reaction herein. This can serve as an
indirect route from nitrobenzenes to isocyanates herein, as nitrobenzenes
are readily reduced, as by hydrogenation, to aniline compounds. Particular
aniline compounds, e.g. ortho-trifluoromethylaniline, can be converted to
phenyl isocyanate compounds under conditions generally known in the art
for such conversion of other aniline compounds. For example, the aniline
compound in solution in an inert solvent can be contacted with phosgene,
possibly at low temperature to condense the phosgene, and then reacted
further by moderate heating, to 100.degree.-150.degree. C. or so, with
further addition of phosgene, or with use of pressure vessel to maintain
some phosgene content in the solution.
SUMMARY OF THE INVENTION
The invention involves the reaction of N-phenyl (including substituted
phenyl) isocyanates with sulfoxide compounds to produce phenyl
sulfilimines or rearrangement products thereof. The reaction is acid
promoted. The invention further concerns a process for preparing
ortho-alkyl anilines from nitrobenzenes, by carbonylating the
nitrobenzenes to phenylisocyanates, reacting the phenylisocyanates with
sulfoxides to produce N-phenylsulfilimines, rearranging the sulfilimines
to ortho-hydrocarbylthioalkyl anilines and desulfurizing to
orthoalkylanilines The invention particularly involves a process providing
intermediate compounds for the production of
N(ethoxymethyl)2'-methyl-6'-trifluoromethyl-2-chloroacetanilide, a
herbicidal compound particularly effective against such perennial weeds as
quackgrass and nutsedge in various crops. Thus o-nitrobenzotrifluoride is
carbonylated to o-trifluoromethylphenylisocyanate, the isocyanate is
reacted under acid catalyzed conditions with dimethylsulfoxide to produce
N-(2-trifluoromethyl)-phenyl-S-S-dimethylsulfilimine which is rearranged
to orthomethylthiomethyl, ortho-trifluoromethyl aniline, which can be
desulfurized to orthomethyl, orthotrifluoromethylaniline. The latter
compound can be reacted with chloroacetylchloride to obtain
2'-methyl-6'-trifluoromethyl-2-chloroacetanilide, which is then reacted
with chlorometyl ethyl ether to obtain the
N(ethoxymethyl)2'-methyl-6'-trifluoro-methyl-2-chloroacetanilide. The
sulfilimine product from the reaction of the isocyanate can generally be
purified readily as the by-product is carbon dioxide. The invention
further involves use of particularly suitable catalysts and solvents for
the reaction of the phenyl isocyanate, and reactions with
phenylisocyanates having various substituents leading to products having
desirable properties. As an alternate in the process from nitrobenzenes,
the nitrobenzenes can first be reduced to anilines and the latter can be
reacted with phosgene to obtain phenyl isocyanates, which can then be
further reacted as described. In the processes to produce sulfilimines, or
in their rearrangement, there may be some concomitant production of
aniline compounds, and the aniline compounds can be converted to
isocyanates by reaction with phosgene, and recycled to the reaction with
sulfoxide compounds.
DETAILED DESCRIPTION OF THE INVENTION
The reaction of the phenylisocyanate with a sulfoxide compound and
subsequent rearrangement can be illustrated:
##STR1##
in which: X and Y are each selected from hydrogen or non-interfering
substituents
R and R' are each selected from hydrocarbyl groups
R"CH is a hydrocarbyl group like R but with one less methylene group;
In the illustrated reaction, the isocyanate group is directly bonded to the
benzene ring. It has been found that such isocyanates are amenable to
reaction with sulfoxides in the presence of a suitable acid catalyst. The
fact that the reaction utilizes a phenylisocyanate as a reactant is
important in that the product can be rearranged to an orthoalkyl aniline,
and such anilines are of great interest as precursor compounds for various
herbicidal and similar compounds. The reaction occurs with phenyl
isocyanates containing no additional substituents on the phenyl ring, and
in general occurs without regard to the presence of such substituents.
Various substituents can be used and may have some effect on the rate of
the reaction and selectivity to, and stability of, the sulfilimine
product, while not determining operability of the process. Thus the
substituents used will generally be selected on the basis of known or
projected effect on product properties, or comparative availability or
ease of preparation of starting materials. Trifluoromethyl substituents
are of special interest, particularly when in ortho position to the
isocyanato group. Other groups which X and Y can represent include --CN,
--NO.sub.2, --Cl, --CH.sub.3, --OCH.sub.3, --CO.sub.2 alkyl, as well as
--H, and such groups can be in various positions, such as ortho, meta or
para to the isocyanato group, e.g. p--CN, p--NO.sub.2, p--Cl, m--CF.sub.3,
o--CH.sub.3, o--OCH.sub.3, p--CO.sub.2 ethyl, etc. X and Y can be the same
or different, and when both are hydrogen, the benzene ring is
unsubstituted except for the isocyanato group. Many compounds of interest
will have only one substituent in the benzene ring of the phenyl
isocyanate, with X or Y being hydrogen, and the other being one of the
above-described groups. However, two or more of the above or other groups
can be present as substituents in the phenylisocyanates which are
converted to corresponding sulfilimines in accord with the process
described herein, X and Y can be various alkyl or alkoxy groups in
addition to those illustrated, with lower alkyl or lower alkoxy generally
being of most interest, for example, those with 1 to 6 carbon atoms. Also
X and Y can be any of the halogens, although chlorine and to some extent
fluorine are more commonly used as substituents in herbicidal compounds. X
and Y can also be halo alkyl groups in general, especially halomethyl,
e.g. mono-, di- or trichloromethyl, and mono-, di- and trifluoromethyl.
The substituents can be used separately, or in various combinations, as
for example, ortho-trifluoromethylphenyl isocyanate,
ortho,para-di(trifluoromethyl)phenyl isocyanate, para-chloro,
ortho-trifluoromethylphenyl isocyanate, orthochloro, para-nitrophenyl
isocyanate, meta-trifluoromethylphenyl isocyanate, para-methylphenyl
isocyanate, ortho, para-dichlorophenyl isocyanate. Any of the illustrated
substitutents can be used as the single substituent, i.e. with the other
substituent being hydrogen, and it is also possible to utilize
phenylisocyanates with more than two substituents. However ordinarily
there would not be much purpose in reacting phenylisocyanates with two
ortho-substituents, as one of the usual objectives of the present process
is to provide some of the steps in a method of introducing an
ortho-substituent into a compound in producing aniline compounds with
ortho substituents.
The illustrated reaction involves a sulfoxide compound, which is
characterized by an SO group in which the sulfur is bonded to two
different carbon atoms. In the illustrated reaction above, the R and R'
groups are generally hydrocarbyl groups, such as alkyl groups of 1 to 10
carbon atoms, or a phenyl group. The sulfoxide compound reacts with the
aryl isocyanate, producing the sulfilimine with the R and R' groups still
bonded to sulfur. In the subsequent rearrangement, the R group becomes
bonded to the ortho-position of the benzene ring, with the bonding
occurring at the carbon to which the sulfur is attached. Upon
desulfurization of this thioether, an ortho-substituted aniline is
obtained. The reactions are of particular interest for obtaining
ortho-methylanilines, and hence dimethyl sulfoxide is preferred as the
sulfoxide reaction. Other sulfoxides in which one of R and R' is methyl
can also lead to o-thiomethylanilines and o-methylanilines. Other
sulfoxides lead to corresponding products, e.g. di-n-propyl sulfoxide will
produce N-phenyl-S,S-di-n-propylsulfilimine which can be rearranged to
2'[n-propylthio-(1-n-propyl)]aniline which will desulfurize to
ortho-n-propylaniline. In the rearrangements of sulfilimines to
thioalkylene aniline compounds, one of the methylene carbons attached to
sulfur becomes attached directly to the benzene, e.g. an
N-aryl-S,S-di-2-propyl sulfilimine would become a
2'[2-propylthio(2-propyl)]aniline. Since dimethyl sulfoxide is
conveniently available, it will generally be the reagent of choice,
particularly when the object is to produce an ortho-methyl aniline
compound. However, other dialkyl sulfoxides will be useful to provide
other alkyl groups in products, and there may be advantage in using
sulfoxides in which the two alkyl groups are the same, in order to avoid
the possibility of mixtures of products.
In the reaction to produce sulfilimines, one of the ortho positions in the
phenylisocyanate will generally be free of substituents, as the object of
the reactions is frequently to introduce an ortho-alkyl substituent and to
provide an ortho-alkyl aniline compound.
The process for preparing sulfilimines in accord with the present invention
involves contacting a phenyl isocyanate with a sulfoxide in the presence
of an effective strong acid catalyst. It is not necessary to have a
solvent present, but there will generally be some separation of phases in
the absence of solvent. Some of the isocyanate reactants are liquids,
which contributes to intermixing of reactants. Also excess of the
sulfoxide, particularly dimethyl sulfoxide, can serve as a solvent.
Solvents can be usefully employed to bring the components into a single
phase for reaction, and solvents which solubilize the reaction components
are suitable, provided they do not unduly interfere with the desired
reaction. Solvents which are relatively inert are preferred. Among
solvents which can be used are acetic acid or other alkanoic acids,
chloroform, acetonitrile, sulfuric acid, dimethyl sulfoxide,
tetramethylene sulfoxide and N-methylpyrrolidinone. Other chlorinated
hydrocarbon solvents can be employed, e.g. methylene chloride and
dichloroethane. Alkanes, including alicyclic and cycloalkanes can be used,
e.g. hexane and cyclohexane, but such solvents are generally less
efficient as solvents for the reactants and products than some of the
chlorinated solvents, acetonitrile, etc.
A strong acid is employed to cause the reaction to occur, as little or no
reaction occurs in the absence of such agent. The acid should be one which
causes the reaction to occur, but which does not unduly interfere by
causing other reactions of the components. Sulfur containing acids, such
as the various sulfonic acids and sulfuric acid are suitable, including
ion exchange resins with sulfonic acid groups. Examples of acids which can
be used are sulfuric acid, methanesulfonic acid, butanesulfonic acid,
other alkane sulfonic acids, p-toluenesulfonic acid, and Amerlyst XN-1010
ion exchange resin, an ion exchange resin characterized by acidic groups,
being a polystyrene with sulfonate groups (--SO.sub.3 H). Sulfurous acid,
and other sulfur acids can also be used. It will generally be desirable to
employ anhydrous, or virtually anhydrous, acids, as isocyanates react with
water, and any water present may interfere with the desired reaction or,
to some extent, use up the isocyanate reactant until all the water has
reacted. Acetic acid is also capable of reacting with isocyanates, but can
nevertheless be used as a solvent, particularly with provisions to have
adequate sulfoxide and strong acid present for the isocyanate to react in
the desired manner to produce sulfilimine. An acid is necessary to effect
the desired sulfilimine preparation. It can readily be determined if an
acid is effective for such purpose. In the absence of an acid, no
appreciable reaction occurs even on heating to in excess of 100.degree.
C., as evidenced by lack of observable reaction and determination of
unchanged reactant. In the presence of effective acid, there will be gas
evolution upon bringing the reactants together, and there will be reaction
between the isocyanate and sulfoxide and sulfilimine will be produced, as
determinable by analysis.
In the presence of strong acid, the reaction of phenyl isocyanates and
dihydrocarbyl sulfoxide occurs during contact without the application of
heat. Since the reaction is exothermic, provision may be made for heat
removal or controlling addition of reactants to avoid excessive exotherms.
In laboratory procedures, slow or dropwise addition of one reactant,
generally the isocyanate, to the reaction mixture is appropriate, but
other procedures for cooling or heat transfer may be better suited to
large-scale operation. With sulfuric acid as the strong acid agent, there
is heat evolution upon mixing with the sulfoxide and solvent, which can be
controlled by cooling or other suitable means. The strong acid agent does
not become part of the sulfilimine product, but even so appears to react
in stoichiometric fashion with the other reactants. possibly forming a
salt or complex at some stage of the reaction. In order to have complete
reaction, it is desirable to have the strong acid present in at least
about equimolar amount to the reactants, and the acid may be employed in
slight or considerable excess over equimolar amount. The phenyl isocyanate
and sulfoxide react in an equimolar reaction, so will generally be
employed in substantially equimolar quantities in order to have complete
reaction. In order to promote complete reaction of one of the reactants,
it may be desirable to employ the other reactant, e.g. the sulfoxide, in
slight excess. When the isocyanate and sulfoxide reactants are used in
unequal molar amounts, the amount of acid to use can be based on the
reactant present in lesser amount. While the isocyanate and sulfoxide
react in equimolar amounts, one or the other can be present in excess
during the reaction as, for example, when gradually adding the isocyanate
to a reaction mixture containing excess sulfoxide. There may be advantage
with particular isocyanates in the use of excess of one of the reactants,
in either batch or continuous reactions.
If a solvent is employed, the reactants can be used in widely varying
concentrations in the solvent, but will generally be used in ranges to
promote good reaction rates and solubility of reactants. Such
concentrations will often be a range such that each of the isocyanate and
sulfoxide reactants constitutes from about 5% to about 30% by weight of
the solvent, based on the total of the reactant added during a batch
reaction, and the amount of sulfoxide originally present may be, for
example, about 10% or so by weight. The reaction to obtain sulfilimines
will occur at ambient conditions, such as room temperature, or so, say
around 24.degree. to 30.degree. C. However, if desired the temperature can
be allowed to rise or the reaction mixture can be heated to temperatures
up to 80.degree. C. or higher, although in general the yields of
sulfilimine will be better at lower temperatures, such as not over
40.degree. C. or at room temperature or possibly even lower. As the
reaction temperature is increased, there is more tendency toward
decomposition reactions with production of aniline compounds corresponding
to the starting isocyanate, thereby causing a decline in the production of
the desired sulfilimine compound. In general there will not be much reason
to exceed 100.degree. C. or so, unless some particular reactants evidence
poor reaction under usual conditions. If desired, low temperatures, such
as temperatures well below ambient temperature can be used, with cooling
means to effect same.
Since isocyanates react readily with water, it is desirable to exclude
water from the solvents and other reaction system components. Many of the
solvents are hygroscopic and readily pick up moisture from the air. The
desired reaction can take place in the presence of moisture, but with some
loss of yield. In order to guard against contamination by moisture, it is
convenient to carry out the reaction under an inert atmosphere, as in an
atmosphere of nitrogen or argon, but other moisture-free gases can also be
used.
Following the reaction to produce the sulfilimine, the sulfilimine if
sufficiently stable can be isolated. The reaction mixture is generally
treated with base to neutralize the strong acid agent and convert any
sulfilimine acid salt to the free sulfilimine. Aqueous base can
conveniently be used for neutralization, as by slowly adding the reaction
mixture to a large portion of aqueous sodium hydroxide. The sulfilimine
can then be removed from the mixture by extraction with an organic
solvent, e.g., methylene chloride or other solvent with capability of
dissolving the sulfilimine. The organic solvent can then be removed by
distillation to leave the isolated sulfilimine. While solvent extraction
and distillation can be conveniently employed, other known methods of
isolating organic compounds can be adapted to and used with particular
sulfilimines.
Alternatively, the neutral sulfilimine obtained in the reaction can be
rearranged to a thioalkylene aniline compound without isolation. After
neutralization of the reaction mixture, for example with aqueous sodium
hydroxide, the sulfilimine can be extracted into an organic solvent. If
the original reaction solvent has sufficient solubilizing capability for
the sulfilimine and the contemplated rearrangement catalyst, it can be
employed to provide a solution for rearrangement. The rearrangement can
conveniently be effected in an inert organic solvent which should have
some solubilizing capability for both the sulfilimine and the
rearrangement catalyst. A wide variety of organic solvents are available
for selection, including, for example, methylene chloride, ethylene
dichloride, cyclohexane, heptane and toluene. Ethylene dichloride is one
of the preferred solvents. Succinimide is the preferred rearrangement
catalyst, although other imide and other catalysts as disclosed herein can
be used. Other preferred sulfilimine rearrangement catalysts include
imidazole, glutarimide, phthalimide, 2-pyrrolidone, 2-imidazolidone and
cyanuric acid. The arrangement catalyst can be used in varying amounts but
generally about 0.5% to 25% (by mol.) based upon the sulfilimine is used,
depending upon solubility of the particular catalyst in the organic
solvent, and with succinimide as the catalyst, as little as about 2 mol
percent is well suited for the desired catalysis. The rearrangement with
succinimide and the other improved catalyts can be conveniently carried
out over a wide range of temperatures. Typically, intermediate
temperatures of about 35.degree. to about 100.degree. C. are preferred,
particularly temperatures between about 60.degree. to about 90.degree. C.
Alternatively, a solution of the sulfilimine can be heated for short
periods under pressure at 120.degree. to 180.degree. C. to effect
rearrangement. If desired, temperatures of about 110.degree. to about
210.degree. C. can be used to decrease the rearrangement times to a matter
of minutes. The sulfilimine rearrangement can be conducted conveniently in
refluxing solvent as an easy way to control reaction conditions. While
succinimide and other preferred catalysts have certain advantages, it is
also possible to conduct the rearrangement in the presence of dry base
catalysts at elevated temperatures.
In the present invention the rearrangement of phenyl sulfilimines to
o-thioalkyleneanilines is preferably carried out with succinimide or
another member of a class of sulfilamine rearrangement catalysts selected
from the groups consisting of:
##STR2##
wherein R.sub.1 can be a hydrogen, a lower alkyl or an --NH-alkyl and
R.sub.2 can be a hydrogen, a lower alkyl, an aryl or a
##STR3##
provided that R.sub.1 and R.sub.2 are not both hydrogens, or
R.sub.1 and R.sub.2 can be joined to form a cyclic compound having up to a
7-member ring, and R.sub.3 and R.sub.4 can be a hydrogen, or a lower
alkyl; provided that R.sub.3 and R.sub.4 are not both hydrogens, or
R.sub.3 and R.sub.4 can be joined to form a cyclic compound having up to a
7-member ring.
The use of this class of rearrangement catalysts is described and claimed
in commonly assigned application Ser. No. 529,914, filed Sept. 7, 1983, of
Audrey Ku. While there are advantages to the described procedures and
class of catalysts, the sulfilimines in the present invention can be
rearranged in accord with any of the prior art procedures. Claus,
Tetrahedron Letters, p. 3607 (1968), describes the preparation of aromatic
sulfilimines from anilines and dimethylsulfoxide in the presence of
P.sub.2 O.sub.5 in a base such as triethylamine. Claus also discloses
thermal rearrangement of these sulfilimines to
ortho-(methylthiomethyl)anilines. See also, Gassman, Tetrahedron Letters,
p. 497 (1972) and Johnson, Tetrahedron Letters, P. 501 (1972). Gassman
discloses the use of N-t-butyl anilines to generate N-t-butyl-N-chloro
anilines and subsequently sulfilimine salts with dimethyl sulfide which,
upon treatment with a base under anhydrous conditions, were converted to
ortho-(methylthiomethyl)anilines.
Such prior procedures in general involve anhydrous conditions, high
temperatures, and the presence of alcohols and dry basic catalyst such as
amines, for example triethylamine. In the present sulfilimine
rearrangements, the rearrangement can be carried out with any sulfilimine
rearrangement catalyst and the procedure may consist of heating the
sulfilimine under basic conditions. Succinimide and other members of the
class of rearrangement catalysts set forth above are considered bases, as
they exhibit basic properties, but such compounds also exhibit acidic
properties and may be particularly efficacious because of exhibiting both
basic and acid properties.
The sulfilimines are often of interest as precursors to o-thioalkylene
aniline compounds, and one of the objectives of the present invention is
to prepare and utilize sulfilimines to prepare o-thioalkylene aniline
compounds. As stated above, some sulfilimine compounds are relatively
unstable, and in such instances it is convenient to rearrange such
compounds prior to isolation. With sulfilimines which are stable, it will
also often be convenient to rearrange such compounds prior to isolation.
Following base treatment of the sulfilimine containing reaction mixture,
the sulfilimine can be extracted into an organic solvent and rearranged.
Alternatively, an isolated sulfilimine can be dissolved in an organic
solvent and rearranged as described herein.
Aromatic sulfilimines with electron-withdrawing groups in ortho or para
positions to the nitrogen atom tend to be relatively stable and
susceptible to isolation. Thus trifluoromethyl, cyano, nitro and
carbalkoxy substituents tend to stabilize the sulfilimines, However,
sulfilimines with methyl, chloro, methoxy or no substituents tend to be
unstable; while these compounds can be identified in solution and
converted to methylthiomethyl aniline compounds, they are not readily
suceptible to isolation, except in salt or other derivative forms.
As stated, sulfilimines with strongly electron-withdrawing groups will tend
to be fairly stable, and this applies to those with groups having
.sigma..sub.p.sup.o values of at least 0.4, with the .sigma..sub.p.sup.o
value being that from the Hammett equation.
The Hammet equation is:
##EQU1##
and for XC.sub.6 H.sub.4 : k.sub.o is the rate constant for X=H
k is the constant for the group X
.rho. is the constant for a given reaction under given conditions
.sigma. is a constant characteristic of X
Hammet .sigma. values are available for various group substituted at the p
or m positions of phenyl rings. A positive value of .sigma. indicates an
electron withdrawing group, and such groups help reactions in which
.sigma. is positive. The .sigma..sub.p.sup.o value contemplates reactions
at site effectively insulated from .pi. electrons of the benzene rings.
The Hammet equation and sigma values are discussed in "Advanced Organic
Chemistry", Jerry March, 2nd Ed., McGraw-Hill, New York, N.Y., (1977), at
pages 251-259, and .sigma..sub.p.sup.o values are given in a table on page
256 which includes:
______________________________________
Group .sigma..sub.p.sup.o
______________________________________
CF.sub.3 0.54
CN 0.66
NO.sub.2 0.83
CH.sub.3 CO 0.47
CO.sub.2 R 0.46
______________________________________
Sulfilimines are useful for conversion to o-methylthiomethyl anilines
regardless of stability, buty yields in the rearrangement reaction are
generally better for the more stable sulfilimines. The unstable
sulfilimines are more apt to undergo loss of the sulfur moiety to produce
the aniline compound corresponding to the starting isocyanate, in some
cases the product may include up to 30% or more of such aniline along with
the desired o-methylthiomethylaniline compound. If desired, the
concomitant aniline product can be reacted with phosgene or by other means
to convert it to the corresponding isocyanate, and recycled to the
sulfilimine preparation reaction.
Herbicidal compounds with the trifluoromethyl group in ortho position to an
aromatic amino group are of particular interest, such as
N-(ethoxymethyl)-2'-methyl-6'-trifluoromethyl-2-chloroacetanilide, and
therefore the present process is of particular interest for converting
o-trifluoromethylphenyl isocyanates to sulfilimines en route to production
of 2-methyl-6-trifluoromethyl aniline, with the sulfilimine preparation
being illustrated:
##STR4##
The sulfilimine compound V is relatively stable, so it can be isolated as
such, or rearranged to 2-methylthiomethyl-6-trifluoromethylaniline before
isolation, and the latter compound can be reductively cleaved to
2-methyl-6-trifluoromethylaniline.
The present invention is illustrated by the following examples but is not
thereby limited. Some of the examples are included as comparison or
control procedures.
EXAMPLE 1
Preparation of .alpha., .alpha., .alpha.-Trifluoro-o-tolyl
Isocyanate by carbonylation of
(.alpha.,.alpha.,.alpha.-Trifluoromethylnitrobenzene
A solution of 0.67 (0.0037 moles) palladium dichloride, 0.60 g (0.0076
moles) pyridine, 7.23 g (0.0039 moles) of (.alpha.,
.alpha.,.alpha.-trifluoromethyl)nitrobenzene and 0.9826 of tridecane as an
internal standard in 75 ml of dry chlorobenzene was placed in a 300 ml
Hastelloy C autoclave. After flushing with argon and carbon monoxide, the
clave was charged with 2000 psi (13,790 KPa) of carbon monoxide and heated
to 200.degree. C. At 200.degree. C., the pressure was increased to 3000
psi (20,684 KPa) and maintained at that temperature and pressure for four
hours. A sample was withdrawn and analyzed by gas chromatography. This
analysis showed that the solution contained 0.940 g (87% conversion) of
(.alpha.,.alpha.,.alpha.-trifluoro-o-methyl)nitrobenzene and 5.85 g (95%
selectively) of .alpha.,.alpha.,.alpha.-trifluoro-o-tolyl isocyanate.
EXAMPLE 2
Preparation of p-Chlor-(.alpha.,.alpha.,.alpha.-Trifluoro-o-tolyl)
Isocyanate
A solution of 0.67 g (0.0039 moles) of palladium dichloride, 0.60 g (0.0076
moles) pyridine, 8.59 g (0.038 moles) of
p-chloro-.alpha.,.alpha.,.alpha.-trifluoromethyl-nitrobenzene and 1.0040 g
of tetradecane as an internal standard in 75 ml of dry chlorobenzene was
placed in a 300 ml Hastelloy C autoclave. After flushing with argon and
carbon monoxide, the clave was charged with 2000 psi (13,790 KPa) of
carbon monoxide and heated to 200.degree. C. At 200.degree. C., the
pressure was increased to 3000 psi (20,684 KPa) carbon monoxide and
maintained at this temperature and pressure for four hours. A sample was
withdrawn and analyzed by gas chromatography. This analysis showed that
the solution contained 0.42 g (95% conversion) of
p-chloro-.alpha.,.alpha.,.alpha.-trifluoromethylnitrobenzene and 7.46 (93%
selectivity) of p-chloro-.alpha.,.alpha.,.alpha.-trifluoro-o-tolyl
isocyanate.
EXAMPLE 3
Preparation of o-methoxyphenyl isocyanate
Into a 2 liter three-necked flask equipped with a dry ice condenser and an
overhead stirrer, was condensed 100 ml of phosgene. At .sup.- 5.degree.
C., was added a solution of 25 g (0.2032 moles) of o-anisidine in 350 ml
of chlorobenzene and a heavy white precipitate was observed. The mixture
was then heated at 125.degree. C. for three and a half hours while passing
phosgene slowly through the solution for the first hour and a half, and
then nitrogen for the last two hours. The solution was then distilled to
afford 27.0 g (89%) of o-methoxyphenyl isocyanate, bp
74.degree.-76.degree. C. at 3 mm Hg. 'H NMR (.delta.,CDCL.sub.3) 6.7-7.1
(multiplet, 4H) and 3.80 (s, 3H).
EXAMPLE 4
Control; Unreactivity of .alpha.,.alpha.,.alpha.-Trifluoro-o-tolyl
Isocyanate Towards Dimethyl Sulfoxide in the Absense of an Acid Catalyst
A solution of 2.0274 g (0.013 moles) of dry dimethyl sulfoxide, 2.2369 g
(0.012 moles of .alpha.,.alpha.,.alpha.-trifluoro-o-tolyl isocyanate and
0.7709 g of dodecane as in internal standard in 10 ml of dry chloroform
was refluxed for three hours under a nitrogen atmosphere. A sample was
withdrawn and analyzed by gas chromatography. In this manner the solution
was found to contain 2.23 g of .alpha.,.alpha.,.alpha.-trifluoro-o-tolyl
isocyanate indicating that no reaction had occurred.
EXAMPLE 5
Control; Unreactivity of .alpha.,.alpha.,.alpha.-trifluoro-o-tolyl
Isocyanate Towards Dimethyl Sulfoxide in the Absence of an Acid Catalyst
A solution of 1.1538 g (0.015 moles) dry dimethyl sulfoxide, 2.3155 g
(0.012 moles) .alpha.,.alpha.,.alpha.-trifluoro-o-tolyl isocyanate and
0.7812 g of dodecane as an internal standard in 10 ml of dry toluene was
refluxed under an argon atmosphere for four hours. A samples was withdrawn
and analyzed by gas chromatography. In this manner the solution was found
to contain 2.31 g of .alpha.,.alpha.,.alpha.-trifluoro-o-tolyl isocyanate
indicating that no reaction had occured.
EXAMPLE 6
Preparation of
N-.alpha.,.alpha.,.alpha.-trifluoro-o-tolyl)-s,s-dimethysulfilimine Using
Sulfuric Acid in Acetic Acid
To a solution of 1.13 g (0.014 moles) of dry dimethyl sulfoxide in 10 ml of
dry acetic acid at 0.degree. C. and under a nitrogen atmosphere, was
slowly added 0.60 ml (1.35 g, 0.014 moles) of 100% sulfuric acid. The
temperature rose to 15.degree. C. The ice bath was removed and 2.2366 g
(0.0120 moles) of .alpha.,.alpha.,.alpha.-trifluoro-o-tolyl isocyanate was
added dropwise. An immediate evolution of gas began which subsided after
approximately fifteen minutes. After stirring at room temperature for two
hours, the entire solution was poured into 150 ml of ice-cold 10% aqueous
sodium hydroxide solution. After extraction with methylene chloride, the
organic phase was dried over anhydrous sodium carbonate, filtered and the
solvent was removed under reduced pressure to afford 2.6249 g of a white
solid which was assayed by high pressure liquid chromatography (HPLC) to
be 92.2%, by weight, of the desired sulfilimine. This corresponded to a
yield of 2.4191 g (91.2%) of the sulfilimine. Other stable isolable
N-aryl-S,S-dimethylsulfilimines were prepared and analyzed in a similar
manner. The results can be found in Table I.
EXAMPLE 7
Preparation of
N-(.alpha.,.alpha.,.alpha.-trifluoro-o-tolyl)-S,S-dimethylsulfilimine
Using Sulfuric Acid in Acetonitrile
To a solution of 1.12 g (0.014 moles) of dry dimethyl sulfoxide in 10 ml of
dry acetonitrile at 0.degree. C. and under a nitrogen atmosphere, was
slowly added 0.60 ml (1.34 g, 0.014 moles) of 100% sulfuric acid. The
temperature rose to approximately 15.degree. C. The ice bath was removed
and 2.2435 g (0.012 moles) of .alpha.,.alpha.,.alpha.-trifluoro-o-tolyl
isocyanate was added dropwise. An immediate evolution of gas began which
subsided after approximately fifteen mintues. After stirring at room
temperature for two hours the standard workup (see Example 6) afforded
2.6150 g of a white solid which was assayed by HPLC to be 94.0%, by
weight, sulfilimine. This corresponds to a yield of 2.4591 g (92.7%) of
the desired sulfilimine. The results are included in Table I.
EXAMPLE 8
Preparation of
N-(p-chloro-.alpha.,.alpha.,.alpha.-trifluoro-o-tolyl)S,S-dimethylsulfilim
ine Using Butanesulfonic Acid in Chloroform
To a solution of 1.15 g (0.0147 moles) of dry dimethyl sulfoxide in 10 ml
of dry chloroform at 15.degree. C., was added 1.76 g (0.013 moles) of dry
n-butanesulfonic acid. After the addition, 2.3125 g (0.0104 moles) of
p-chloro-.alpha.,.alpha.,.alpha.-trifluoro-o-tolyl isocyanate was added
and the resulting mixture was stirred at room temperature for thirty
minutes and then refluxed for three hours. The standard workup (see
Example 6) afforded 2.6000 g of a white solid which was assayed by HPLC to
be 92.9% by weight, sulfilimine. This corresponds to a yield of 2.4154
(90.4%) of the desired sulfilimine. The results are included in Table I.
TABLE I
______________________________________
Preparation of N--Aryl-S,S--dimethylsulfilimines
Reaction
Substrate Temper- Yield of
X Y Acid Catalyst
Solvent
ature Sulfilimine
______________________________________
o-CF.sub.3
H H.sub.2 SO.sub.4
HOAc 50.degree. C.
83.7%
o-CF.sub.3
H H.sub.2 SO.sub.4
HOAc 24.degree. C.
91.2%
o-CF.sub.3
H H.sub.2 SO.sub.4
CH.sub.3 CN
24.degree. C.
92.7%
o-CF.sub.3
H H.sub.2 SO.sub.4
DMSO 24.degree. C.
90.7%
o-CF.sub.3
H n-BuSO.sub.3 H
CHCl.sub.3
24.degree. C.
85.3%
o-CF.sub.3
H n-BuSO.sub.3 H
CHCl.sub.3
64.degree. C.
93.3%
o-CF.sub.3
p-Cl H.sub.2 SO.sub.4
HoAc 50.degree. C.
87.1%
o-CF.sub.3
p-Cl n-BuSO.sub.3 H
CHCl.sub.3
64.degree. C.
90.4%
p-CN H H.sub.2 SO.sub.4
HOAc 50.degree. C.
63.6%
p-CN H n-BuSO.sub.3 H
CHCl.sub.3
64.degree. C.
83.5%
p-NO.sub.2
H H.sub.2 SO.sub.4
HOAc 50.degree. C.
72.4%
p-NO.sub.2
H n-BuSO.sub.3 H
CHCl.sub.3
64.degree. C.
84.2%
p-CO.sub.2 Et
H H.sub.2 SO.sub.4
HOAc 50.degree. C.
89.0%
p-CO.sub.2 Et
H n-BuSO.sub.3 H
CHCl.sub.3
64.degree. C.
93.8%
______________________________________
In Table I and elsewhere in this application nBu stands for nbutyl, HOAc
for acetic acid, and DMSO for dimethyl sulfoxide.
EXAMPLE 9
Preparation of 2-(methylthiomethyl)aniline Using Sulfuric Acid in Acetic
Acid
To a solution of 7.60 g (0.0974 moles) of dry dimethyl sulfoxide in 70 ml
of dry acetic acid at 0.degree. C. and under a nitrogen atmosphere, was
slowly added 9.76 g (0.0959 moles) of 100% sulfuric acid. The temperature
rose to 15.degree. C. The ice bath was removed and 9.9843 g (0.0838 moles)
of phenyl isocyanate was added dropwise. An immediate evolution of gas
began, which subsided after approximately fifteen minutes. After thirty
minutes at room temperature, the reaction mixture was warmed to 50.degree.
C. for an additional hour. The entire solution was then poured into 100 ml
of 10% aqueous sodium hydroxide solution and this was extracted with
methylene chloride. The organic layer was dried over anhydrous sodium
carbonate and filtered. Due to the instability of this sulfilimine, 0.33 g
of succnimide was added and the solution was then concentrated to 150 ml
and refluxed for sixteen hours. The solution was then washed with 10%
aqueous sodium hydroxide, dried over anhydrous magnesium sulfate and
filtered. To this was added dodecane as an internal standard and the
solution was analyzed by gas chromatography. In this manner, there was
obtained 1.751 g (22.4%) of aniline and 7.166 g (55.8%) of
2-methylthiomethylaniline. Other examples of the preparation and
rearrangement of unstable N-aryl-S,S-dimethylsulfilimines were performed
and these results can be found in Table II.
EXAMPLE 10
Preparation of 2-methoxy-6-(methylthiomethyl)aniline Using n-Butanesulfonic
Acid in Chloroform
To a solution of 1.429 g (0.018 moles) of dry dimethyl sulfoxide and 2.27 g
(0.015 moles) of dry n-butanesulfonic acid in 13 ml of dry chloroform, was
added 2.2110 g (0.0148 moles) of o-methoxyphenyl isocyanate. After thirty
minutes at room temperature, the reaction mixture was refluxed for three
and a half hours. After cooling to room temperature, the reaction mixture
was poured into 180 ml of ice-cold 10% aqueous sodium hydroxide solution.
After extracting with methylene chloride, the organic l | | |
