[0001] The present invention relates to compositions and processes for halogenating carboxylic
acids, acid halides and acid anhydrides at the og-carbon atom in the presence of a
cyanoquinone compound.
[0002] The halogenation of organic compounds at a specific carbon atom (i.e., regiospecifically)
is difficult, especially on an industrial scale. In general, halogenation reactions
tend to occur to some extend at all available carbon-hydrogen linkages in the molecule
undergoing halogenation.
[0003] Some regioselectivity in halogenation reactions has been achieved heretofore. For
example, the treatment of aliphatic carboxylic acids having at least one α-hydrogen
atom with halogens such as bromine or chlorine in the presence of a phosphorus halide
catalyst comprises the well-known Hell-Volhard-Zelinsky preparation of a-halo acids.
However, chlorination reactions carried out according to the HVZ procedure are not
regiospecific and mixtures of chlorinated products are typically secured. For the
most part, the HVZ halogenation is used to brominate carboxylic acids and is, therefore,
expensive as compared with the corresponding chlorination reaction.
[0004] By the present invention, it has been discovered that cyanoquinone compounds can
be used in the α-halogenation of carboxylic acids, carboxylic acid anhydrides and
carboxylic acid halides. The resulting a-halogenated products are useful as lubricant
additives and as intermediates for the production of lubricants, and as surfactants
and surfactant intermediates.
RELATED REFERENCES
[0005] The general topic of the directive effect of the carboxyl group on the chlorination
of aliphatic systems is treated by Little, Sexton, et al., Journal of the American
Chemical Society 91 7098, (1969). See also, U.S. Patent 3,584,036 to Sexton, et al.,
which relates to a-chlorination reactions.
[0006] Other publications relating to regiospecific halogenation reactions include: Y. Ogata,
et al., J. Org. Chem., 40, 2960 (1975); Y. Ogata, et al., Tetrahedron, 26, 5929 (1970);
Y. Ogata, et al., Nippon Kagaku Kaislii, 1517 (1975) [Chem. Abstr. 83, 178239 (1975)];
Y. Ogata, et al., Japanese Patent 75-135024; Y. Ogata, et al., Japanese Patent 74-24913;
A. F. Young, U.S. Patent 3,634,504; D. N. Harpp, et al., J. Orq. Chem., 40, 3420 (1975);'and
H. Haschke, German Patent 2,440,213.
[0007] While the foregoing references relate to various means for achieving the regiospecific
halogenation of organic compounds, especially carboxylic acids, the present invention
employs an entirely new catalyst for this purpose. This invention also provides higher
yields of the desired mono-chlorinated product, and in shorter times, than do the
art-disclosed processes. Moreover, the process herein is especially suitable for a-halogenating
both short chain and the longer-chain fatty acids, i.e., those in the chain length
range above about C
10 which are especially useful as detersive surfactants. In this regard, the present
invention provides a marked improvement over the process disclosed in U.S. 3,584,036,
cited above.
[0008] In addition to the foregoing, U.S. Patent 3,988,369 to Pearson, October 26, 1976,
teaches a process for halogenating organic compounds in the presence of a trialkyl
phosphate.
SUMMARY OF THE INVENTION
[0009] The present invention encompasses a process for halogenating carboxylic acids, acid
anhydrides and acid halides (all hereinafter "carboxylate compounds") having at least
one reactive alpha hydrogen substituent, comprising contacting said carboxylate compound
with a halogen (especially chlorine) or halogen source in the presence of an effective
amount of a cyanoquinone compound and acidic auxiliary agent, as described more fully
hereinafter.
[0010] The present invention also encompasses, as a composition of matter, a mixture comprising
the cyanoquinone material and the acidic auxiliary agent. The invention also encompasses,
as a composition of matter, a halogenation reagent comprising a halogen (especially
chlorine) or halogen source and the aforesaid mixture of cyanoquinone material and
auxiliary agent. The foregoing compositions-of-matter are especially adapted for the
halogenation, especially chlorination, of carboxylate compounds
[0011] A representation of the reaction of the present process with organic acids is as
follows:

where R and R' are hydrocarbyl or hydrogen substituents, as described more fully hereinafter.
DETAILED DESCRIPTION OF THE INVENTION
[0012] The present invention encompasses a process for halogenating carboxylate compounds.
The carboxylate compounds used herein are characterized by at least one reactive a-hydrogen
substituent, which is displaced by a halogen atom duri..g the process. In the practice
of the invention, the carboxylic acids. acid chlorides, or carboxylic acid anhydrides
are contacted with a halogen or halogen source in the presence of an effective amount
of a cyanoquinone material and an acidic auxiliary agent.
[0013] By "halogenating" herein is meant displacing an a-hydrogen substituent with halogens
other than fluorine. As is well known, fluorination reactions are carried out under
special conditions and are therefore not contemplated in the practice of this invention.
The present process is particularly useful for chlorinating or brominating carboxylate
compounds and, on an industrial scale, is especially useful for chlorination reactions.
[0014] By "carboxylate compound" herein is meant carboxylic acids (and salts), carboxylic
acid halides and carboxylic acid anhydrides.
[0015] By "effective amount" herein is meant an amount of the cyanoquinone material and
auxiliary agent sufficient to direct the halogenation reaction regiospecifically such
that it occurs almost exclusively at the a-hydrogen substituent of the carboxylate
compound.
[0016] The cyanoquinone materials and acidic auxiliary agents are described in more detail
hereinafter.
[0017] By "comprising" herein is meant that various other compatible materials may be present
in the reaction mixtures during the halogenation reaction in such proportions as will
not adversely affect the a-halogenation of the carboxylate compounds. For example,
various solvents and the like can optionally be present. The term "comprising" thus
encompasses and includes the more restrictive terms "consisting of" and "consisting
essentially of" within its scope, so long as the processes and compositions of this
invention include the specified ingredients, which are critical to the practice of
the invention.
[0018] All percentages herein are on a mole basis, unless otherwise specified.
[0019] The carboxylate compounds which are a-halogenated in the manner of this invention
comprise carboxylic acids and carboxylic acid-derived materials. These carboxylate
compounds include the free acids and salts, the acid anhydrides and the acid halides.
[0020] The present process can be used to a-halogenate carboxylate compounds, especially
carboxylic acids, comprising from about 2 to about 30 carbon atoms. (Of course, for
the corresponding symmetrical carboxylic acid anhydride, equivalent compounds will
comprise from about 4 to about 60 total carbon atoms.) The process herein is especially
useful for a-halogenating the C
3 to C
18 carboxylic acids. However, for halogenating the shorter members in this class, other
art-disclosed processes are adequate, albeit sub-optimal. The special economic advantages
of the present process are particularly noteworthy when a-halogenating, especially
a-chlorinating, the C
6-C
18 carboxylate materials for which the art-disclosed processes yield mixed results.
Accordingly, the present process is especially useful for a-halcgenating, especially
a-chlorinating, carboxylate materials based on lauric acid, myristic acid, palmitic
acid, stearic acid, and mixtures thereof.
[0021] The process of this invention is not limited with regard to the halogenation agent.
Elemental halogens, liquid or gaseous, can be used. Chlorine gas is especially convenient,
economical and preferred for use herein. Bromine can also bo used, but is more expensive,
as is iodine. Halogen sources other than elemental halogens can also be used. Such
alternate halogen sources include, for example, well-known organic halogenating agents
such as N-chlorosuccinimide (NCS) and N-bromosuccinimide (NBS).
Cyanoguinones
[0022] The cyanoquinone materials used herein are all members of the well-known class of
compounds which have recently been the subject of intensive study as electrically-
conductive organic solids. Reviews of these materials, methods of preparation and
a list of references to additional compounds and preparative methods appear in the
articles by Wheland and
Gillson,Journal of the American Chemical Society, 98, 3916 (1976) and Wheland and Martin,
J. Org. Chem., 40, 3101 (1975), incorporated herein by reference.
[0023] In general, the cyanoquinones useful herein are characterized by the moiety:

where R can be H or one or more substituent groups, e.g., halogen, alkoxyl, alkyl,
thioalkyl, CN, etc. See Wheland and Martin, above.
[0024] The tetracyanoquinodimethane (TCNQ) compounds preferred for use herein are of the
formula (R as above):

[0025] Other, specific examples of cyanoquinones useful herein include hexacyanobutadiene
(HCBD) and tetracyano- naphthoquinodimethane (TNAP), represented by the following
formulas

TCNQ,TNAP and HCBD are prepared by techniques known in the literature. (While HCBD
is not, in the most formal sense, a quinone structure, its extended conjugated system
of electrons is "quinone-like". Accordingly, HCBD is considered a cyanoquinone in
the present invention.)
Auxiliary Agents
[0026] The auxiliary agents used in the practice of this invention include many of the common
acidic materials known in the art for use in halogenation reactions. Such acidic materials
include both Lewis acids and inorganic protonic acids which are of considerably greater
acid strength than hydrocarbyl carboxylic acids. Typical examples of such acidic auxiliary
agents include acetyl chloride, PBr
3. PC1
3, thionyl chloride, sulfuryl chloride, oxalyl chloride, sulfonyl chloride, PCl
5, phosgene, fluorosulfonic acid, chlorosulfonic acid, and trifluoromethanesulfonic
acid. The most highly preferred auxiliary agent herein is chlorosulfonic acid.
[0027] It is to be understood that carboxylic acid halides (especially acid chlorides) are
operative in the practice of this invention as auxiliary agents when a-halogenating
carboxylic acids or anhydrides thereof. However, carboxylic acid halides can themselves
be halogenated if they contain an a-hydrogen substituent. The a-halogenation of carboxylic
acid halides is carried out in the presence of a more acidic auxiliary agent such
as ClSO
3H, PC1
3, etc., and the cyanoquinone material. This is not a preferred halogenation method,
inasmuch as it requires the separate preparation of a stoichiometric amount of acid
chloride, which is thereafter a-halogenated.
[0028] The most preferred catalyst system herein comprises a mixture of TCNQ and chlorosulfonic
acid. Various ratios of these materials can be employed, but a ca. 1:5-1:50 mole ratio
of TCNQ:ClS0
3H is convenient.
[0029] The most preferred halogenation reagent herein comprises gaseous chlorine and the
aforesaid mixture of TCNQ and chlorosulfonic acid. Of course, the chlorine in this
reagent is replenished as it is exhausted during the reaction. Replenishment of the
chlorine is most conveniently carried out by bubbling gaseous chlorine into the reaction
mixture.
[0030] The halogenation reaction of this invention is carried out by contacting the carboxylate
compound with the halogen or halogen source in the presence of a cyanoquinone material
and acidic auxiliary agent at a temperature of about 70°C, or greater. Chlorination
reactions using elemental chlorine as the halogen are carried out at temperatures
above about 130°C, preferably at temperatures within the range from about 150°C to
about 250°C. When halogen sources such as the N-halo- succinimides are used, temperatures
of about 70°C-250°C are operative and convenient. Bromination and iodination reactions
are carried out under similar temperature conditions.
[0031] The process herein can be carried out in the presence or absence-of inert solvents.
Preferably, the reaction is carried out without the use of solvents, and this is both
convenient and economical on a commercial scale. Indeed, the use of solvents can lead
to undesirable side-reactions involving halogenation of many of the common hydrocarbon
solvents. Under the reaction temperatures specified hereinabove, the carboxylate compounds
are liquids and are quite convenient to use in that state without additional solvents.
[0032] Typical use concentrations of the cyanoquinones relative to the carboxylate compounds
are 0.01-10.0 mole percent, preferably 0.05-5.0 mole percent, most preferably 0.05-0.5
mole percent.
[0033] Typical use concentrations of the acidic auxiliary agents relative to the carboxylate
compounds are 0.1-10 mole percent, preferably 1-5 mole percent.
[0034] The following examples illustrate the practice of this invention but are not intended
to be limiting thereof. Percentage yields are in parentheses.
EXAMPLE I
Prenaration of 2-Chlorostenric Acid
[0035] A 1-liter five-neck round bottom flask is placed in an efficient fume hood and is
fitted with a mechanical stirrer, thermometer, Dry Ice condenser, and two fritted
gas dispersion tubes (opposite necks). The two dispersion tubes are connected via
PVC tubing to a T-connector, the third arm of which is connected to a chlorine gas
source containing an in-line flowmeter capable of reading 200-1000 ml/min.
[0036] The dispersion tubes are removed temporarily, and the flask is charged with 569.0
g (2.0 moles) of powdered stearic acid. The stearic acid is melted by warming the
flask with a heating mantle while stirring at low speed. When the acid has melted
(temperature approximately 80°C), 1.65 g (0.008 mole) of TCNQ (Aldrich Chemical Co.)
is added. The chlorine gas flow to the dispersion tubes is started and set at a rate
of 250 ml/min. Chlorosulfonic acid, 4.0 ml (0.063 mole) is pipetted rapidly into the
flask (temp. <90°C) and the dispersion tubes are immediately fitted to the flask so
that the chlorine is evolved well beneath the surface of the liquid. The stirrer is
adjusted to a high speed setting, and the solution is heated as rapidly as possible
to 150°C. (Immediately prior to the addition of chlorosulfonic acid, full line voltage
is applied to the heating mantle. When the solution temperature reaches 130°C, the
voltage is cut to 0, allowing the temperature to coast to 150°C.) During the heating
period, the Dry Ice condenser is filled with a Dry Ice-alcohol slurry. When the temperature
reaches 148°C, the chlorine flow rate is increased to 1000 ml/min. This point is considered
time 0 for purposes of timing.the reaction.
[0037] Throughout the reaction, the solution temperature is maintained at 150°±3°C by careful
adjustment of the current to the heating mantle. Since the reaction is mildly exothermic,
this temperature is usually maintained during the first half hour with no current
applied to the mantle. During the second half hour, the cooling effect of condensing
chlorine necessitates constant monitoring of the solution temperature and mantle setting.
At 65 minutes reaction time, the chlorine flow rate is reduced to 250 ml/min. At 75
min., the heating mantle is removed and is replaced by an ice bath, and the dispersion
tubes and condenser are removed. When the solution temperature reaches 80-90°C, the
entire reaction mixture is poured into 1500 ml of acetonitrile. The resulting mixture
is warmed on a steam bath until a clear, yellow, homogeneous solution is obtained.
The solution is placed in an ice bath and stirred or swirled vigorously to effect
crystallization of the product. After standing at 0°C overnight, the product is collected
by suction filtration, washed thoroughly with cold acetonitrile, and vacuum dried
to afford 535.5 g (84%) of 2-chlorostearic acid, M.P. 63.5-64°C.
[0038] As an optional modification of the foregoing procedure, an additional 0.8 g portion
of TCNQ can be added at 50 min. reaction time. This serves to prevent the formation
of minor by-products that result if the reaction is allowed to run beyond the time
when starting material is consumed. With this modification, the yield of recrystallized
2-chlorostearic acid is increased to 89%.
[0039] The process of Example I is carried out with lauric acid, myristic acid, palmitic
acid, and commercial tallow fatty acids, i.e., mixtures of lauric, myristic, palmitic
and stearic acids, respectively. High yields (ca. 90%) of the a-chlorinated acids
are secured in each instance.
[0040] The process of Example I is carried out using the following acidic auxiliary agents
in place of the chlorosulfonic acid: PBr
3; PCl
3: PCl
5; acetyl chloride; thionyl chloride; sulfuryl chloride; oxalyl chloride; sulfonyl
chloride; phosgene; fluorosulfonic acid; chlorosulfonic acid; stearoyl chloride; and
trifluoromethane sulfonic acid. In each instance, excellent yields of pure 2-chlorostearic
acid are secured.
[0041] The process of Example I is carried out using HCBD and TNAP, respectively, as the
cyanoquinone agent (0.008 moles). In each instance, good yields of the desirr. 2-chlorostearic
acid are secured.
[0042] The process of Example I is repeated using acetic, propionic, butyric, pelargonic,
pentadecanoic, margaric, arachidic, behenic, tricosanoic, and cerotic acids, respectively,
and their respective anhydrides, and the a-chlorinated products are secured.
EXAMPLE II
α-Halogenation of Acid Halides and Anhydrides
[0043] Following the procedure of Example I, stearoyl chloride is reacted with chlorine
in the presence of CIS03H and
TCNQ. The product is distilled to provide substantially pure 2-chlorostearoyl chloride.
[0044] The foregoing reaction is repeated using stearic anhydride and the a-chlorinated
anhydride is secured.
[0045] In a modification of the process of Example II, the chlorine gas is replaced by liquid
bromine and the corresponding a-brominated compound is secured.
EXAMPLE III
[0046] Mixtures especially adapted for use in the a-halogenation of carboxylate compounds
are as follows:

[0047] The foregoing mixtures are typically used at concentrations of 0.01%-10% of the carboxylate
compound being halogenated and the reaction proceeds substantially exclusively at
the α-CH group.
EXYAMPLE IV
[0048] The process of the present invention can be carried out using free halogens in the
manner described hereinbefore. Organic halogenating agents such as N-chlorosuccinimide
can also be employed, as follows.
[0049] Into a 50 ml 3-neck round bottom flask fitted with a condenser, thermometer, and
magnetic stirrer were placed 11.4 g (0.04 mole) stearic acid, 8.0 g (0.06 mole) N-chlorosuccinimide,
0.1 ml (0.0015 mole) chlorosulfonic acid, and 0.04 g (0.0002 mole) TCNQ. The flask
was placed in a heating bath set at 150°C. The mixture was stirred during heating,
and a homogeneous liquid phase was formed. The solution temperature continued to rise
above that of the heating bath, and a sudden exothermic reaction occurred in which
the reaction temperature increased to ca. 220°C. The reaction mixture was cooled and
dissolved in chloroform, and the resulting solution was washed thoroughly with dilute
aqueous sodium chloride solution. After drying and removal of the chloroform, the
residue was recrystallized from acetonitrile to afford 8.9 g (70%) of 2-chlorostearic
acid which was equivalent in purity to the product of Example I.
EXAMPLE V
[0050] Following the procedures of Examples I and II herein, carboxylate compounds are a-chlorinated,
a-brominated and a-iodinated in the presence of the following mixtures of substituted
TCNQ and acidic auxiliary agents:

[0051] The foregoing mixtures are typically used at concentrations of 0.01%-10.0% of the
carboxylate compound being halogenated and the reaction proceeds substantially exclusively
at the α-CH group to provide the a-halogenated carboxylate compound.
[0052] As can be seen from the foregoing, the present process provides an improved means
for carrying out a-halogenations, especially a-chlorinations, of carboxylate compounds,
especially carboxylic acids. By the present invention, the use of cyanoquinone materials
substantially improves yields of a-chlorinated products and greatly decreases side-reactions
which have heretofore led to undesirable by-product formation. TCNQ, HCBD, TNAP and
derivatives thereof are available by art-disclosed processes for use in the present
invention.
1. A process for oC-halogenating carboxylate compounds having at least one reactive
α-hydrogen substituent, comprising contacting said carboxylate compounds with a halogen
or halogen source in the presence of an effective amount of a mixture of a cyanoquinone
material and an acidic auxiliary agent.
2. A process according to Claim 1 wherein the cyanoquinone material is selected from
the group consisting of TCNQ, HCBD, and TNAP, and derivatives thereof, and the auxiliary
agent is a Lewis acid or an inorganic protonic acid.
3. A process according to Claim 1 wherein the cyanoquinone material is a member selected
from the group consisting of TCNQ, HCBD and TNAP, and derivatives thereof, and the
auxiliary agent is a member selected from the group consisting of PCl3, PCl5, PBr3, thionyl chloride, sulfuryl chloride, oxalyl chloride, sulfonyl chloride, acetyl
chloride, phosgene, fluorosulfonic acid, chlorosulfonic acid, and trifluoromethanesulfonic
acid.
4. A process according to Claim 1 which is carried out at a temperature of about 70°C,
or greater and wherein the halogen or halogen source is a chlorinating or brominating
agent.
5. A process according to Claim 4 wherein the halogen source is a member selected
from the group consisting of N-chlorosuccinimide and N-bromosuccinimide, and wherein
the process is carried out at a temperature within the range from about 70°C to about
250°C.
6. A process according to Claim 1 wherein the carboxylate compound is a carboxylic
acid which comprises from about 2 to about 30 carbon atoms.
7. A process according to Claim 6 wherein the carboxylic acid is selected from the
group consisting of lauric acid, myristic acid, palmitic acid, stearic acid, and mixtures
thereof.
8. A process according to Claims 1 and 6 for chlorinating carboxylic acids on the
α-carbon, comprising contacting said carboxylic acid with chlorine at a temperature
at or above about 150°C in the presence of an effective amount of a catalyst system
comprising TCNQ, or derivatives thereof, and chlorosulfonic acid, wherein the mole
ratio of the TCNQ or the TCNQ-derivative: ClSO3H is in the range of about 1:5 to 1:50.
9. A catalyst system comprising a cyanoquinone material and an acidic auxiliary agent.
10. A catalyst system according to Claim 9 wherein the cyanoquinone material is selected
from the group consisting of TCNQ, HCBD, and TRAP, and derivatives thereof, and the
auxiliary agent is a Lewis acid or an inorganic protonic acid.
11. A catalyst system according to Claim 9 wherein the cyanoquinone material is selected
from TCNQ and derivatives thereof, and the auxiliary agent is selected from PC13, PCl5, PBr3, thionyl chloride, sulfuryl chloride, oxylyl chloride, sulfonyl chloride, acetyl
chloride, phosgene, fluorosulfonic acid, chlorosulfonic acid, and trifluoromethanesulfonic
acid, and wherein the mole ratio of the TCNQ or the TCNQ derivative to the auxiliary
agent is in the range of 1:5 to 1:50.
12. A halogenating medium comprising a halogne selected from chlorine and bromine
and a catalyst system comprising a cyanoquinone material and an acidic auxiliary agent.