USOO6911558B2

(12) United States Patent (10) Patent No.: US 6,911,558 B2

BOWman et al. (45) Date of Patent: Jun. 28, 2005

(54) METHOD FOR PURIFYING DE 38 26 584 2/1989 ........... CO7C/69/96

CHLOROMETHYL CHLOROFORMATE FR 2 621913 8/1989 ........... CO7C/69/96
JP 3OSO741 B2 6/2000 ........... E21 F/13/02
(75) Inventors: Mark P. Bowman, New Kensington,
PA (US); Charles B. Kreutzberger, OTHER PUBLICATIONS
Harrison City, PA (US) Blasser, Jane E., “Synthesis And Uses of Pure Chloromethyl
Chloroformate And An Economical Ne Route to Trichloro
(73) Assignee: PPG Industries Ohio, Inc., Cleveland, acryloyl Chloride”, 1993, UMI Dissertation Services.
OH (US) “March's Advanced Organic Chemistry, Reactions, Mecha
ss ti
(*) Notice: Subject to any disclaimer, the term of this nisms and Structures', 5' Edition, M.B. Smith and J.
patent is extended or adjusted under 35 March, Wiley-Interscience, 2001, pp. 105-109.
U.S.C. 154(b) by 169 days “2,2-Dichlorovinyl Choloroformate”, Mark P. Bowman and
R. A. Olofson; Journal of Organic Chemistry, 1990, vol. 55,
pp. 2240-2243.
(21) Appl. No.: 10/358,593 “An Efficient Synthesis of Some Substituted Vinylic Cholor
(22) Filed: Feb. 5, 2003 formates: Reaction Scope And Limitations”, Mark P. Bow
man, Jean-Pierre G. Senet, Thierry Malfroot and R. A.
(65) Prior Publication Data Olofson; Journal of Organic Chemistry, 1990, vol. 55, pp.
US 2004/0152911 A1 Aug. 5, 2004 5982-5986.
(51) Int. Cl................................................. C07C 51/58 Primary Examiner Johann Richter
(52) U.S. Cl. ... ... 562/840; 562/864; 562/856 ASSistant Examiner Karl Puttlitz
(58) Field of Search ................................. 562/226, 129; (74) Attorney, Agent, or Firm-Linda Pingitore
558/280, 283 (57) ABSTRACT
(56) References Cited Describes a method for obtaining Substantially pure chlo
U.S. PATENT DOCUMENTS romethyl chloroformate from a chloroformate mixture com
prising chloromethyl chloroformate and methyl chlorofor
4,592,872 A 6/1986 Cagnon et al. ............. 558/281 mate by heating the chloroformate mixture in a reaction
4,592.874 A 6/1986 Cagnon et al. ............. 558/283 Zone at temperatures ranging from at least 50 C. to the
E
4734,535 A
E. E. "...O.C. reaction
3/1988 Greif et al. ................. 570/261
reflux temperature of the chloroformate mixture in the
Zone while Simultaneously removing volatile gas
4,814,524. A 3/1989 Briody et al................ 570201 eous decomposition products from the reaction Zone.
5,712.407 A 1/1998 Kreutzberger et al. ...... 558/283 Dichloromethyl chloroformate may also be present in the
chloroformate mixture.
FOREIGN PATENT DOCUMENTS
DE 32 41568 5/1983 ........... CO7C/69/96 48 Claims, No Drawings
 US 6,911,558 B2
1 2
METHOD FOR PURIFYING chloride hydrochloride at 70° C. has been described. See,
CHLOROMETHYL CHLOROFORMATE Blasser, Jane E., “Synthesis and Uses of Pure Chloromethyl
Chloroformate and an Economical New Route to Trichlo
roacryloyl Chloride', a thesis submitted in partial fulfillment
DESCRIPTION OF THE INVENTION of the requirements for the degree of Doctor of Philosophy
The present invention relates to chloromethyl chlorofor in December 1993 to The Pennsylvania State University,
mate. In particular, the present invention relates to a method Department of Chemistry. Under the conditions described in
of recovering Substantially pure chloromethyl chloroformate the thesis, dichloromethyl chloroformate decomposes to
from a chloroformate mixture comprising chloromethyl phosgene, hydrogen chloride and carbon monoxide. Subse
chloroformate, and methyl chloroformate. The chlorofor quent distillation of the crude product from the catalyst
mate mixture may in addition contain dichloromethyl mixture is used to produce chloromethyl chloroformate in
chloroformate, and may also contain trichloromethyl chlo purities of from 86 to 97%. No destruction of methyl
roformate. chloroformate under the described conditions is described or
More particularly, the present invention comprises a noted by Blasser.
method of recovering Substantially pure chloromethyl chlo 15 It would be a significant economic benefit if substantially
roformate from said chloroformate mixture by the steps of pure chloromethyl chloroformate could be produced without
heating the mixture in a reaction Zone in the presence of a the need for a distillation Step to Separate it from methyl
nucleophilic catalyst while Simultaneously removing vola chloroformate. It has now been discovered that substantially
tile gaseous decomposition products resulting from the pure chloromethyl chloroformate can be recovered from a
heating Step, particularly hydrogen chloride, and Subse chloroformate mixture comprising methyl chloroformate
quently recovering from Said reaction Zone Substantially and chloromethyl chloroformate without a distillation step
pure chloromethyl chloroformate product. The chloromethyl by (1) heating the crude chloroformate mixture in a reaction
chloroformate product recovered is substantially free of Zone in the presence of a nucleophilic catalyst at tempera
methyl chloroformate. When dichloromethyl chloroformate tures of at least 50° C., more typically from 70° C. or 80°
25 C. to the reflux temperature of the mixture, and (2) simul
and/or trichloromethyl chloroformate are present in the
Starting chloroformate mixture, the chloromethyl chlorofor taneously removing from the reaction Zone volatile gaseous
mate product is also substantially free of dichloromethyl decomposition products resulting from the catalytic heating
chloroformate and trichloromethyl chloroformate. Step, e.g., carbon monoxide, hydrogen chloride and other
A number of Specialty chemicals are produced using low boiling gases. The Substantially pure chloromethyl
chloromethyl chloroformate as a building block. In chloroformate recovered from this proceSS is Substantially
particular, chloromethyl chloroformate is used to prepare free of methyl chloroformate and is also substantially free of
carbonate derivatives that are used in the pharmaceutical dichloromethyl chloroformate and trichloromethyl
industry, the agrochemical industry and the photoresist chloroformate, if Such polychlorinated chloroformates are
industry. Chloromethyl chloroformate can be prepared by present in the treated crude chloroformate mixture.
35
the catalytic photochlorination of methyl chloroformate or DETAILED DESCRIPTION OF THE
methyl formate (which first yields methyl chloroformate.) INVENTION
This process commonly produces a chloroformate mixture
comprising at least two, and possibly three, chlorinated AS used in this description and claims, all values express
products of methyl chloroformate, namely, chloromethyl 40 ing percentages, ratios, ranges, amounts, temperatures,
chloroformate (CMC), dichloromethyl chloroformate preSSures, etc., other than in the enumerated operating
(DCMC) and trichloromethyl chloroformate (TCMC) examples or where otherwise indicated, are to be understood
because the chlorination rates for these three chlorinated as modified in all instances by the term “about'.
materials are not very different. See Ullmann's Encyclope Chloromethyl chloroformate is commonly produced by
dia of Industrial Chemistry. Unreacted methyl chloroformate 45 the catalytic chlorination, e.g., photochlorination, of methyl
(MCF) in the chloroformate mixture can be separated easily chloroformate. As noted by Blasser (cited above-paragraph
from the chlorinated reaction products by distillation, but the bridging pages 3 and 4), this process yields a crude mixture
boiling points of the chlorinated reaction products, e.g., including the unreacted Starting material and the three
CMC and DCMC (ca 106° C. and 111° C.) are too close to possible chlorinated products because the chlorination rates
allow a clean Separation. 50 are not very different. Blasser Suggests that by Stopping the
German Offenlegenschrift 3.241,568 (May 19, 1983) reaction after adding less than one equivalent of chlorine, the
describes the reaction of formaldehyde and phosgene to generation of diphosgene (ClCOCOCl) can be avoided and
prepare CMC; however, the reaction is not clean because of the formation of dichloromethyl chloroformate
problems involving the thermal depolymerization of (ClCHOCOCl) minimized. However, as noted, the crude
paraformaldehyde and the facile reversal of that process. 55 reaction mixture also contains unreacted methyl chlorofor
See also Chem. Abstr. 1983, 99, 53164g. German Offen mate. Hence, the crude reaction mixture comprises unre
legenschrift 3,826,584 (Feb. 16, 1989) describes a process acted methyl chloroformate, the desired chloromethyl
for manufacturing CMC comprising 23 chlorination, distil chloroformate, dichloromethyl chloroformate and perhaps
lation and recycling steps. See also Chem. Abstr. 1989, 111, Some trichloromethyl chloroformate (diphosgene). Stated
117289c and French Demande 2,621,913 (Aug. 21, 1989). 60 differently, the desired chloromethyl chloroformate product
However, the product is reported by Blasser (cited below) to contains contaminating quantities of methyl chloroformate,
contain 3% of the dichlorinated product, i.e., DCMC. dichloromethyl chloroformate and possibly trichloromethyl
The purification of chloromethyl chloroformate (CMC) chloroformate.
from a mixture containing methyl chloroformate and dichlo In accordance with an embodiment of the present
romethyl chloroformate by decomposing the dichloromethyl 65 invention, Substantially pure chloromethyl chloroformate is
chloroformate (and any diphosgene) over benzyltributyl recovered from a chloroformate mixture comprising chlo
ammonium chloride (BTBAC) or hexabutyl guanidinium romethyl chloroformate and methyl chloroformate. In accor
 US 6,911,558 B2
3 4
dance with another embodiment of the present invention, recited temperatures and pressures, provided that the com
Substantially pure chloromethyl chloroformate is recovered bination of temperature and pressure Selected produces the
from a chloroformate mixture comprising chloromethyl desired decomposition of the contaminating amounts of
chloroformate, methyl chloroformate (MCF) and dichlo MCF and, if present, DCMC and TCMC-desirably in an
romethyl chloroformate (DCMC). Trichloromethyl chloro economic time frame. Generally, lower temperatures, par
formate (TCMC) may also be present in each of the men ticularly temperatures below 70° C. will require pressures
tioned chloroformate mixtures. By Substantially pure below atmospheric pressure.
chloromethyl chloroformate (CMC) is meant that the prod The period of time that the crude chloroformate mixture
uct recovered from the crude chloroformate mixture con is held at the Selected temperature and pressure within the
tains at least 95% CMC. Typically, the recovered product aforedescribed temperature and pressure ranges will vary
contains at least 98% CMC. Further, the product contains and will depend on (1) the temperature chosen since the
less than 5%, typically less than 1% MCF; and less than 2%, heating time is an inverse function of the temperature, i.e.,
typically less than 1% DCMC. More typically, the CMC the higher the temperature, the shorter the time required (and
product contains less than 0.2% of each of MCF, DCMC and Vice versa), (2) the catalyst chosen, since Some catalysts are
TCMC. All of the aforementioned percentages are area 15 more active than others, (3) the amount of contaminants,
percents, as determined by gas chromatography (GC) using e.g., MCF and DCMC, that it is desired be removed, and (4)
a thermal conductivity detector (TCD). whether means are employed to expedite the removal of the
The amount of MCF, DCMC and TCMC in the crude Volatile gaseous decomposition products from the reaction
chloroformate mixture will vary, and will depend on the Vessel, e.g., inert gas Sparging, Sub-atmospheric pressure
mole ratio of the reactants and the chlorination conditions (vacuum) conditions within the reaction vessel, etc. The
used to chlorinate the Starting methyl chloroformate. length of the heating time is not critical, i.e., it is not an
Generally, the crude chloroformate mixture will contain leSS important variable of the described process, although it
than 35 percent MCF, e.g., from 5 to 30% of MCF; less than would be important for economic considerations. Generally,
40 percent DCMC, e.g., from 2 to 35% of DCMC, and the heating time will extend for the period required to reach
usually not more than 1 percent of TCMC, e.g., from 0 to 1% 25 the minimum level of impurities desired, i.e., the level of
of TCMC. More typically, the crude chloroformate mixture impurities that can be tolerated for the use to which the CMC
will contain from 10 to 25 percent of MCF, from 15 to 30 product is to be put, or until the level of impurities, e.g.,
percent DCMC, and not more than 0.2 percent of TCMC. All MCF and DCMC, are not detectable by GC analysis. The
of the aforementioned percentages are area percents, as period of heating can range from as little as 15 minutes to as
determined by gas chromatography (GC) using a TCD. Such much as 17 hours. Typically, the period will range from 30
area percents correspond reasonably well with weight per minutes to 5 hours, more particularly from 45 minutes to 2
centages. or 3 hours. The heating period can range between any
In accordance with an embodiment of the present combination of the aforementioned times inclusive of the
invention, the crude chloroformate mixture is heated in a Specifically recited times.
suitable vessel attemperatures of at least 50° C. at pressures 35 In accordance with an embodiment of the process of the
of from 50 to 90 Torr (6.6 to 12 kPa). Typically, at atmo present invention, Vaporous decomposition products, most
Spheric preSSure, the temperature at which the crude chlo notably hydrogen chloride, and low boiling volatiles, Such as
roformate mixture is heated varies from 70° C. to the reflux carbon monoxide, carbon dioxide and phosgene, are
temperature of the crude chloroformate mixture in the removed from the vessel in which the crude chloroformate
reaction vessel, i.e., from 92 to 110° C. The reflux tempera 40 mixture is heated, i.e., from the reaction Zone within a
ture will vary depending on the pressure within the reaction Suitable reaction vessel, while the crude chloroformate mix
Zone, i.e., atmospheric or Sub-atmospheric pressures, the ture is undergoing heating in the presence of the nucleophilic
particular composition of the crude chloroformate mixture catalyst. As described by Blasser (cited above), dichlorom
charged to the reaction vessel, and also on the changing ethyl chloroformate decomposes to phosgene, hydrogen
composition of the chloroformate mixture remaining in the 45 chloride and carbon monoxide when heated over a catalyst
reaction vessel as various components of the mixture are such as benzyl tributyl ammonium chloride (BTBAC) or
destroyed and vaporous decomposition products are hexamethyl guanidinium chloride hydrochloride (HMGCl
removed from the reaction vessel. AS is well known to those HCl). Methyl chloroformate decomposes to methyl chloride
skilled in the art, the higher the temperature in the reaction and carbon dioxide under the described conditions. In one
Zone, the faster will be the decomposition rate at which 50 embodiment of the present invention, the aforementioned
contaminating products in the crude chloroformate mixture gaseous decomposition products at the conditions encoun
are destroyed. It is also well known to those skilled in the art tered in the reactor are removed from the reaction Zone, and
that a combination of lower temperatures and reduced more particularly from the reactor itself. In a particular
preSSures can be used to assist in the removal of low boiling embodiment of the present invention, at least hydrogen
volatiles from the chloroformate mixture in the reaction 55 chloride gas is removed from the reaction Zone Since it is
Zone. A pressure ranging from 50 Torr (6.6 kPa) to above believed that hydrogen chloride inhibits the decomposition
atmospheric preSSure can be employed. of methyl chloroformate.
In a further embodiment of the present invention, the The Volatile gaseous products present and/or generated
temperature to which the crude chloroformate mixture is within the reactor during the heating Step can be removed
heated can vary from 50° C. to the reflux temperature of the 60 from the reaction Zone, more typically from the reaction
chloroformate mixture in the reaction vessel, i.e., from 92 vessel itself, by methods or combination of methods known
C. to 110° C., e.g., 106° C., particularly from 86° C. to 100° to those skilled in the art. Conventionally, the reactor is
C. Pressure within the reaction vessel can range from 50 Torr equipped with a condenser, e.g., a water-cooled condenser,
(6.6 kPa) to greater than 1 bar (100 kPa). The temperatures Scrubber, and/or thermal oxidizer for condensing and treat
and pressures used in the process described can each be 65 ing (neutralizing) toxic gaseous products emanating from
Selected between any combination of the aforementioned the reactor during the described process. In Such an
temperatures and preSSures, inclusive of the Specifically arrangement, phosgene and HCl gas are allowed to pass
 US 6,911,558 B2
S 6
through the condenser to the scrubber and/or thermal in relatively Small amounts, i.e., catalytic amounts (but less
oxidizer, while liquid condensate is returned to the reactor. than equivalent amounts) compared to the chloroformates in
AS Some of the gas decomposition products are toxic, e.g., the Starting crude mixture, and catalyzes the decomposition
phosgene and hydrogen chloride, and condensing Systems of methyl chloroformate and, when present, higher chlori
are not perfect, a Scrubber is used to neutralize Such toxic nated chloroformates, Such as dichloromethyl chloroformate
gases, i.e., phosgene and HCl. In the Scrubber, the toxic and trichloromethyl chloroformate. In Some cases, the cata
gases are contacted with an aqueous alkaline Solution, Such lyst can be recovered from the chloromethyl chloroformate
as acqueous ammonium hydroxide, Sodium or potassium end product by methods known to those of ordinary skill in
hydroxide, an amine, etc. Gases, Such as carbon monoxide the art and reused. The catalyst can be a liquid or a Solid, and
or carbon dioxide, can be released to the environment after may be soluble in the crude chloroformate mixture. The
passing through a Scrubber or a thermal oxidizer. catalyst, if not Soluble in the crude chloroformate mixture, is
In one embodiment, the crude chloroformate mixture is dispersible in the mixture.
heated to reflux temperatures. At Such temperatures, volatile By the term “nucleophilic' is meant a material that is
gas decomposition products readily move from the crude capable of reacting with the chloroformate mixture in a
15 manner that results in the release of a labile chloride anion.
chloroformate mixture to the top of the reactor and thence The nucleophilic catalyst can be a Salt that has an anion
through the condenser, Scrubber, etc. In another capable of attacking the carbonyl group of a chloroformate.
embodiment, Sub-atmospheric pressures, i.e., a vacuum, are The cation of Such a Salt is one that allows the anion to be
imposed on the reactor, e.g., by use of a vacuum pump
downstream of the Scrubber, thereby lowering the pressure mobile So that it can carry out the nucleophilic attack. The
within the reactor and further increasing the volatility of the Salt can be an inorganic or organic Salt. Generally, the Salt is
low boiling components. When a vacuum is imposed on the a quaternary ammonium or phosphonium Salt, e.g., a chlo
ride Salt.
reactor, the pressure is less than atmospheric, i.e., 14.7
pounds per Square inch (at Standard conditions) (101 kPa). In one embodiment, the quaternary organic catalyst Salt
Such sub-atmospheric pressures can range from 6.6 kPa (50 can be represented by the expression:
25
Torr) to 95 kPa (720 Torr).
In another embodiment, a chemically inert gas is intro wherein M is nitrogen or phosphorus, Y is the organic
duced into the reactor to assist in the removal of the gaseous portion of the salt molecule bonded to M by covalent
products of decomposition from the reactor. The gas can be linkages, e.g., four independent monovalent aliphatic hydro
introduced into the reactor in the Space above the crude carbon groups, a is a number of from 1 to 4, and X is a
chloroformate mixture and/or below the liquid surface of the monovalent anion associated with the cation, (Y.H.L.M)".
crude chloroformate mixture, i.e., a gas Sparge can be used The organic quaternary Salts can be more graphically
to help carry the gaseous products of decomposition from illustrated by the following formulae:
the body of the liquid reaction mixture to and through the
condenser, Scrubber, etc. 35 II
The gas used in the foregoing embodiment should be
chemically inert, i.e., it should not be reactive with any of
the chloroformates in the crude chloroformate mixture or
with any of the vapors removed from the reaction Zone under
the conditions used in the process. Suitable inert gases that 40
III
can be used include, but are not limited to, nitrogen, carbon
dioxide, carbon monoxide argon, natural gas, etc. The
amount of inert gas used is not a variable of the process, but
should be sufficient to enhance the removal of the vapors
produced in the reactor. Too large a quantity of inert gas will 45
be an economic drawback because of the cost of the inert gas wherein R, R2, R and R (Y in formula I) are each
and the equipment needed to handle the inert gas exiting monovalent hydrocarbon groups containing from 1 to 25
from the reactor, particularly if the inert gas is to be treated carbon atoms, as for example, C-C alkyl groups, C-C,
and recycled to the reactor. The inert gas should be Substan cycloalkyl groups, aryl groupS Such as phenyl and p-tolyl; or
tially dry, i.e., be Substantially free of water, because water 50 alkylaryl groupS. Such as phenyl-Substituted alkyl groups
will react with chloroformates.
containing from 1 to 4 carbon atoms, e.g., benzyl, phenethyl,
In one embodiment of the present invention, only heat, phenpropyl and phenbutyl, and X is a monovalent anion,
e.g., reflux temperatures, is used to promote the removal of Such as a halide ion, i.e., chloride, bromide or iodide, the
gas decomposition products from the reactor. In another hydrogen sulfate anion (HSO), the hydroxyl anion (OH),
embodiment, heat and an inert gas Sparge are used in 55 the dihydrogen phosphate anion (H2PO), and the hydro
combination. In further embodiments, heat and Sub gen phosphate anion (HPOT). The organic quaternary Salts
atmospheric pressure (vacuum) or heat, Sub-atmospheric may also be depicted here in by the expressions
preSSure, and an inert gas Sparge are used in combination. (RRRRN)' X, and (RRRRP)" X.
Any combination of the aforementioned recited means (and The number of carbon atoms in each of the hydrocarbon
other means known to those skilled in the art) to promote 60 Substituents, R, R2, R and R can vary considerably. Each
and/or assist removal of the gaseous decomposition products can contain from 1 to 25 or more carbon atoms. Typically,
from the reaction Zone can be used. each hydrocarbon group will contain from 1 to 18 carbon
In accordance with the process of the present invention, a atoms. In the case of certain alkyl hydrocarbon groups
crude chloroformate mixture, as described above, is heated containing 8 or more carbon atoms, the number of carbon
in the presence of a nucleophilic catalyst. AS used herein, the 65 atoms in the group may be an average number, i.e., the
term “catalyst” is meant to include a material that does not hydrocarbon groups contains a distribution of alkyl groups
participate directly in the decomposition reaction(s), is used of varying carbon length.
 US 6,911,558 B2
7 8
The total carbon atom content of all of the groupS, R, R2, atoms, e.g., oxygen), dicyclohexano-18-crown-6, and
R and R, will in one embodiment be at least 12. The upper 15-crown-5. The crown ethers have the property of forming
limit of the number of carbon atoms will depend on eco complexes with positive ions, Such as ammonium or Sub
nomic and other practical factors. An upper total limit of 40 Stituted ammonium ions. Crown ethers, cryptates and calix
carbon atoms is a practical upper limit, although quaternary arenes are all commercially available.
compounds containing a total of 70 carbon atoms are Other compounds than can be used as the nucleophilic
contemplated. Generally, the total number of carbon atoms catalyst include, but are not limited to, those compounds that
in the quaternary Salt compound will be in the range of from
12 to 35 carbon atoms. react with chloroformates to form organic Salts. Non
Non-limiting examples of organic quaternary Salts limiting examples of compounds that can Serve as the
include: Tetramethyl ammonium bromide, tetramethyl nucleophilic catalyst include tertiary amines, Such as
ammonium chloride, tetraethyl ammonium bromide, tetra triethylamine, tributylamine, pyridine, N,N-dimethylaniline
ethyl ammonium chloride, tetraethyl ammonium iodide, and imidazole, amides, Such as dimethylformamide, Substi
benzyltriethyl ammonium chloride, tetrapropyl ammonium tuted ureas and thioureas, more particularly tetraalkyl(thio)
bromide, tetrapropyl ammonium chloride, tetrapropyl 15 ureas, Such as tetrabutylurea and tetrabutylthiourea; tertiary
ammonium iodide, triethylmethyl ammonium iodide, trieth phosphines, particularly aliphatic tertiary phosphines Such
ylpropyl ammonium iodide, tetrabutyl ammonium bromide, as trioctylphosphine; and Substituted phosphoramides, e.g.,
tetraabutyl ammonium chloride, tetrabutyl ammonium hexamethylphosphotriamide. Mixtures of nucleophilic cata
hydrogen Sulfate, tributylmethyl ammonium iodide, benzyl lysts can, of course, be used when the catalysts chosen are
tributyl ammonium chloride, tributylpropyl ammonium not chemically reactive with one another.
iodide, tetrahexyl ammonium bromide, tetrapentyl ammo In one embodiment, the tertiary amines can be more
nium bromide, tetraisopentyl ammonium iodide, tetrahexyl graphically illustrated by the following formula:
ammonium chloride, trioctyl methyl ammonium chloride,
trioctylmethyl ammonium chloride, trioctylpropyl ammo IV
nium bromide, tetradecyl trimethyl ammonium bromide, 25 R1
trioctylpropyl ammonium bromide, cetyldimethylethyl
ammonium bromide, cetyltrimethyl ammonium chloride,
dimethyldicetyl ammonium chloride, didodecyldimethyl RR3
ammonium bromide, tetraheptyl ammonium bromide, heXa
(C-C alkyl)guanidinium chloride Salts, tributylhexadecyl
phosphonium bromide, tetrabutyl phosphonium chloride wherein R', R, and R in formula IV are each monovalent
and tetraethyl phosphonium bromide. hydrocarbon groups containing from 1 to 25 carbon atoms,
Other analogous organic quaternary Salts may be similarly as for example, C-C alkyl groups, C-C cycloalkyl
named by Substituting another halide, i.e., chloride, bromide groups, aryl groupS. Such as phenyl and p-tolyl; or alkylaryl
or iodide, for the halide Specifically name in the aforesaid 35 groupS Such as phenyl-Substituted alkyl groups containing
examples, and/or by Substituting other alkyl, cycloalkyl, from 1 to 20 carbon atoms, e.g., benzyl, phenethyl, phen
alkylaryl, or aryl groups containing from 1 to 25 carbon propyl and phenbutyl. The tertiary amines of formula IV
atoms for the alkyl groupS Specifically name. In addition, may also be depicted herein by the expression (R'R'R''N).
phosphonium compounds corresponding to the quaternary Other tertiary amines that can be used as the catalyst include
ammonium Salts described above can also be used, i.e., 40
5 and 6 member monocyclic heteroatomic ring compounds
phosphorus can be Substituted for the nitrogen in the qua containing at least one, e.g., 1 or 2, tertiary nitrogen atoms,
ternary ammonium Salts named and Vice versa. Such other Such as pyridine and imidazole, i.e., wherein the hetero
quaternary ammonium or phosphonium Salts are contem atom(s) is nitrogen.
plated herein although they are not Specifically enumerated.
Mixtures of two or more of the above-described organic 45 The number of carbon atoms in each of the hydrocarbon
quaternary Salts can be used as the catalyst in the proceSS substituents, R', R, and R in formula IV can vary consid
described herein. erably. Each can contain from 1 to 25 or more carbon atoms.
Many organic quaternary ammonium Salts are available Typically, each hydrocarbon group will contain from 1 to 18
commercially. The quaternary ammonium or phosphonium carbon atoms. In the case of certain alkyl hydrocarbon
Salts can be prepared readily by alkylation of the corre 50 groups containing 8 or more carbon atoms, the number of
sponding primary, Secondary or tertiary amine or phosphine. carbon atoms in the group may be an average number, i.e.,
The alkylation reaction is usually conducted by heating (at the hydrocarbon groups contains a distribution of alkyl
50-100° C) stoichiometric amounts of the corresponding groups of varying carbon length.
amine (or phosphine) with the appropriate hydrocarbon The total carbon atom content of all of the groups, R', R,
halide, hydrogen Sulfate or dihydrogen phosphate in a polar 55
and R, in formula IV will in one embodiment be at least 4.
Solvent Such as methanol or acetonitrile for a few hours or
days. The upper limit of the number of carbon atoms will depend
Other nucleophilic catalysts that may be used include on economic and other practical factors. An upper total limit
crown ether, cryptand, Spherand or calixarene complexes of of 40 carbon atoms is a practical upper limit, although
organic or inorganic Salts. These are discussed in “March's 60 tertiary amine compounds containing a total of 70 carbon
Advanced Organic Chemistry, reactions, Mechanisms and atoms are contemplated. Generally, the total number of
Structures”, 5" Edition, M. B. Smith and J. March, Wiley carbon atoms in the tertiary amine compound will be in the
Interscience, 2001, pages 105-109, which discussion is range of from 4 to 35 carbon atoms.
incorporated herein by reference. Crown ethers are large Other nucleophilic compounds include tertiary phos
ring compounds containing Several oxygen atoms, usually in 65 phines and especially aliphatic tertiary phosphines, Such as
a regular pattern. Examples are 12-crown-4 (where 12 is the trioctylphosphine. The tertiary phosphines can be more
Size of the ring and 4 represents the number of coordinating graphically illustrated by the following formula:
 US 6,911,558 B2
10
particularly tetraalkyl(thio)ureas, Such as tetrabutylurea and
tetrabutylthiourea. The ureas and thioureas can be more
graphically illustrated by the following formula:
VII
R5 R8

wherein R', R, and R in formula V are each monovalent R--c-x--R

hydrocarbon groups containing from 1 to 25 carbon atoms,
as for example, C-C alkyl groups, C-C cycloalkyl
groups, aryl groupS. Such as phenyl and p-tolyl; or alkylaryl wherein X is oxygen or sulfur, and R,R,R,R, R and
groupS Such as phenyl-Substituted alkyl groups containing R' in formula VII are each selected from hydrogen and
from 1 to 20 carbon atoms, e.g., benzyl, phenethyl, phen monovalent hydrocarbon groups containing from 1 to 25
propyl and phenbutyl. The tertiary phosphines of formula V carbon atoms, as for example, C-C alkyl groups, C-C,
may also be depicted herein by the expression (R'RRP). 15 cycloalkyl groups, aryl groupS Such as phenyl and p-tolyl; or
The number of carbon atoms in each of the hydrocarbon alkylaryl groupS. Such as phenyl-Substituted alkyl groups
substituents, R', R, and R in formula V can vary consid containing from 1 to 20 carbon atoms, e.g., benzyl,
erably. Each can contain from 1 to 25 or more carbon atoms. phenethyl, phenpropyl and phenbutyl.
Typically, each hydrocarbon group will contain from 1 to 18 The number of carbon atoms in each of the hydrocarbon
carbon atoms. In the case of certain alkyl hydrocarbon substituents, R, R, R7, R, R and R' in formula VII can
groups containing 8 or more carbon atoms, the number of vary considerably. Each can contain from 1 to 25 or more
carbon atoms in the group may be an average number, i.e., carbon atoms. Typically, each hydrocarbon group will con
the hydrocarbon groups contains a distribution of alkyl tain from 1 to 18 carbon atoms. In the case of certain alkyl
groups of varying carbon length. hydrocarbon groups containing 8 or more carbon atoms, the
The total carbon atom content of all of the groups, R', R, 25
number of carbon atoms in the group may be an average
and R, in formula V will in one embodiment be at least 4. number, i.e., the hydrocarbon groups contains a distribution
The upper limit of the number of carbon atoms will depend of alkyl groups of varying carbon length. The upper limit of
on economic and other practical factors. An upper total limit the number of carbon atoms will depend on economic and
of 40 carbon atoms is a practical upper limit, although other practical factors. Generally, the total number of carbon
tertiary phosphine compounds containing a total of 60 atoms in the urea or thiourea compound will be in the range
carbon atoms are contemplated. Generally, the total number of from 3 to 35 carbon atoms.
of carbon atoms in the tertiary phosphine compound will be Other nucleophilic compounds that can Serve as the
in the range of from 4 to 35 carbon atoms. catalyst include Substituted phosphoramides and more par
Other nucleophilic compounds that can Serve as the ticularly hexaalkyl phosphoramides, Such as hexameth
catalyst include amides, Such as dimethylformamide. The ylphosphotriamide. The phosphoramides can be more
amides can be more graphically illustrated by the following 35 graphically illustrated by the following formula:
formula:

VI
R1
40
R--cos'
wherein R', R, R and R' in formula VI are each selected
from hydrogen and monovalent hydrocarbon groups con 45 wherein R. R. R. R. R. R. R', R', and R' in
taining from 1 to 25 carbon atoms, as for example, C-Co formula VIII are each selected from hydrogen and monova
alkyl groups, C-C cycloalkyl groups, aryl groupS Such as lent hydrocarbon groups containing from 1 to 25 carbon
phenyl and p-tolyl, or alkylaryl groupS Such as phenyl atoms, as for example, C-Co alkyl groups, Cs-Co
Substituted alkyl groups containing from 1 to 20 carbon cycloalkyl groups, aryl groupS Such as phenyl and p-tolyl; or
atoms, e.g., benzyl, phenethyl, phenpropyl and phenbutyl. 50 alkylaryl groupS. Such as phenyl-Substituted alkyl groups
The number of carbon atoms in each of the hydrocarbon containing from 1 to 20 carbon atoms, e.g., benzyl,
substituents, R, R, R and R' in formula VI can vary phenethyl, phenpropyl and phenbutyl.
considerably. Each can contain from 1 to 25 or more carbon The number of carbon atoms in each of the hydrocarbon
atoms. Typically, each hydrocarbon group will contain from substituents, R,R,R,R, R and R' in formula VIII can
1 to 18 carbon atoms. In the case of certain alkyl hydrocar 55 vary considerably. Each can contain from 1 to 25 or more
bon groups containing 8 or more carbon atoms, the number carbon atoms. Typically, each hydrocarbon group will con
of carbon atoms in the group may be an average number, i.e., tain from 1 to 18 carbon atoms. In the case of certain alkyl
the hydrocarbon groups contains a distribution of alkyl hydrocarbon groups containing 8 or more carbon atoms, the
groups of varying carbon length. number of carbon atoms in the group may be an average
The total carbon atom content of all of the groups, R', R, 60 number, i.e., the hydrocarbon groups contains a distribution
Rand R", in formula VI will in one embodiment be at least of alkyl groups of varying carbon length. The upper limit of
4. The upper limit of the number of carbon atoms will the number of carbon atoms will depend on economic and
depend on economic and other practical factors. Generally, other practical factors. Generally, the total number of carbon
the total number of carbon atoms in the amide compound atoms in the phosphoramide compound will be in the range
will be in the range of from 4 to 35 carbon atoms. 65 of from 6 to 35 carbon atoms.
Other nucleophilic compounds that can Serve as the Still other nucleophilic compounds include alkyl substi
catalyst include Substituted ureas and thioureas and more tuted guanidines and hexasubstituted guanidinium halides,
 US 6,911,558 B2
11 12
which may be graphically illustrated respectively by the Example 1 will vary. Further, when stored, the crude chlo
following formulae: rination reaction mixture will also change over time.
Analyses of the crude chloroformate mixtures and prod
(IX) ucts resulting from the described processes in the following
1 R18 examples were performed by gas chromatography (GC). A
Hewlett Packard 6890 Gas Chromatograph was used with a
R14 C
1-n R16 capillary column. A thermal conductivity detector (TCD)
R15
N NR17 was used unless otherwise Specified. When So Specified, a
flame ionization detector (FID) was used. All GC analyses
R (X)
are reported as area %.
19 1 R18
N EXAMPLE 1.
| X2
14 C Ya R 16
(Chlorination of Methyl Chloroformate)
R15
N R17
15
Methyl chloroformate (MCF, 1628.9 grams) and 2,2'-
azobisisobutyronitrile (AIBN, 10.32 grams) were added to a
2-liter flask purged with nitrogen gas and topped with a
wherein X is chloro or bromo, particularly chloro, and water-cooled condenser. The mixture was heated with a
R-R are the same or different, and each are hydrogen or heating mantel to 70° C. (Athermocouple was immersed in
a C-C alkyl group, particularly a C-C alkyl group, Such the reaction medium to measure its temperature.) Subnatent
as methyl, ethyl, propyl or butyl. addition of chlorine gas was started and after 2 hours of
Non-limiting examples of Such guanidine and guani chlorine addition at 70° C., 4.8 grams of additional AIBN
dinium halide compounds include: tetraSubstituted was added. After 2 hours of further chlorine addition, 5.9
guanidine, e.g., tetraalkyl guanidine Such as tetrabutyl grams of additional AIBN was added and chlorine addition
guanidine, pentaSubstituted guanidine, e.g., pentaalkyl 25
was continued for another hour. Then, 3.2 grams of AIBN
guanidine and their hydrogen halide, e.g., hydrochloride, was added and the chlorination reaction continued for an
Salts, guanidine and the hydrogen chloride Salt of pentabutyl additional 1.5 hours. Then 4.4 grams of AIBN was added
guanidine, he Xasubstituted guanidinium chloride or and the chlorination was continued for an additional 4 hours,
bromide, e.g., hexaalkyl guanidinium chloride or bromide at which time the chlorination reaction was discontinued.
Such as hexaethyl guanidinium chloride and hexabu The crude reaction mixture was analyzed by GC (FID
tylguanidinium chloride. detector). GC analyses found chloromethyl chloroformate
The foregoing guanidine and guanidinium halide com (CMC, 68.5 area 96), dichloromethyl chloroformate
pounds can be prepared by the methods described in U.S. (DCMC, 1.94 area %) and methyl chloroformate (MCF, 15.2
Pat. No. 5,712,407, column 6, line 45 to column 7, line 56. area 96).
The amount of catalyst required for the process of the 35
invention is that amount that will catalyze the decomposition EXAMPLE 2
of the chloroformate contaminants, namely, methyl
chloroformate, dichloromethyl chloroformate and trichlo A crude chloroformate mixture (268 grams) comprising
romethyl chloroformate (if present), i.e., a catalytic amount. CMC, (74.4 area %), MCF (14.1%), and DCMC (2.21 area
More particularly, the amount of catalyst utilized is at least 40 %) was mixed with benzyltributyl ammonium chloride (6.7
0.001 weight percent, based on the total weight of the crude grams) in a 250 milliliter (mL) flask equipped with a
chloroformate mixture, but leSS than an equivalent amount thermometer, water-cooled condenser and gas inlet. Agentle
(based on the amount of chloroformate). The amount of Subnatent nitrogen Sparge was maintained during the Sub
catalyst used can vary from 0.001 to 1 weight percent, e.g., sequent heating step. The flask was slowly heated to 96° C.
from 0.01 to 0.8 weight percent, or 0.1 to 0.5 weight percent. 45 with a heating mantel and maintained at from 96° C. to 100
The amount of catalyst used can range from any combina C. for 1 hour. The contents of the flask were analyzed by GC
and found to contain 0.2%. MCF and 0.02% DCMC. Vacuum
tion of the recited catalyst amounts, inclusive of the recited distillation of the contents of the flask using a short Vigreux
amounts. Generally, the lower the amount of catalyst used,
the longer the heating time required to remove the contami column (52–55° C. (a) 100 Torr) resulted in a distilled
nating chloroformates from the crude chloroformate 50 product (178.4 grams) that when analyzed by GC was found
mixture, and Vice versa. In an embodiment of the present to be 97.8% pure (CMC) and to contain 0.08 area % MCF
invention, a level of catalyst used is chosen So that the period and 0.0 area % DCMC. The remainder of the product was
of time utilized to remove the contaminating unidentified components, presumed to be unidentified lights
chloroformates, i.e., to non-detectable levels (as measured and heavies. Vacuum distillation was performed So that the
by GC), is from 30 minutes to from 2 to 3 hours. 55 yield for the decomposition proceSS could be measured
The process of the present invention is more particularly directly.
described in the following examples, which are intended as EXAMPLE 3
illustrative only Since numerous modifications and varia
tions therein will be apparent to those skilled in the art. A crude chloroformate mixture (1503.2 grams) compris
In the following examples, crude chloroformate mixtures 60 ing CMC (69.7 area %), MCF (4.2 area %) and DCMC (19.7
comprising chloromethyl chloroformate (CMC), methyl area %) was mixed with tricaprylylmethyl ammonium chlo
chloroformate (MCF) and dichloromethyl chloroformate ride ALIQUATOR 336 (17.67 grams) and heated in a
(DCMC) were used. The chloroformate mixtures were jacketed, stirred (100-200 rpm), baffled 2-liter glass flask
obtained by the catalytic chlorination of methyl chlorofor equipped with thermometer and water-cooled condenser.
mate. An example of Such a chlorination reaction is found in 65 The flask was heated at 73–79 C. for 4.3 hours and then the
Example 1. The chloroformate composition of crude chlo temperature was raised from 79 C. to 90° C. over a 2 hour
rination reaction mixtures that have been prepared as in period. The contents of the flask, which then weighed 1049
 US 6,911,558 B2
13 14
grams, was analyzed by GC and found to contain 0.51 area %) was mixed with tetraethyl ammonium iodide (0.254
%. MCF and 0.0 area 96 DCMC. grams) in a 10 mL flask equipped with a water-cooled
condenser. The flask was lowered into an 85 C. oil bath.
EXAMPLE 4
After 30 minutes at 85 C., the oil bath temperature was
A crude chloroformate mixture (13.61 grams) comprising 5 raised to 90° C. After 30 minutes at 90° C., the oil bath
CMC (69.8 area %), and MCF (21.1 area %) was mixed with temperature was raised to 95 C. After 15 minutes at 95 C.,
hexaethyl guanidinium chloride (0.0973 grams). The mix the contents of the flask were sampled and analyzed by G.C.
ture was heated in a 10 mL flask equipped with a water The analyses showed 7.92 area % MCF and 0.18 area %
cooled condenser. The flask was lowered into an 85 C. oil DCMC. The contents of the flask were held at 95 C. for an
bath. After 35 minutes at 85 C., the oil bath temperature additional 40 minutes and then Sampled and analyzed by
was raised to 90° C. After 45 minutes at 90° C., the oil bath GC. The levels of MCF and DCMC were found to be 7.60
temperature was raised to 100° C. After 30 minutes at 100 area % and 0.07 area % respectively. The oil bath tempera
C., the mixture in the flask was Sampled and analyzed by ture was then raised to 110° C. and held there for 40 minutes,
GC. The sample was found to contain 0.28 area % of MCF. whereupon the contents of the flask (8.60 grams) were again
The contents of the flask were held an additional 90 minutes 15 sampled and analyzed by GC. The levels of MCF and
at 100° C. and then re-analyzed by GC. The contents of the DCMC were found to be 0.0 area % and 0.01 area %
flask (8.83 grams) were found to contain 0.008 area 96 MCF. respectively.
EXAMPLE 5 EXAMPLE 9
A crude chloroformate mixture (13.13 grams) comprising A crude chloroformate mixture (11.40 grams) comprising
CMC (69.8 area %) and MCF (21.1 area %) was mixed with CMC (70.0 area %), MCF (19.4 area %) and DCMC (1.12
hexadecyl tributyl phosphonium bromide (0.2022 grams) in area 96) was mixed with 1-(N,N-dimethylcarbamoyl)-4-(2-
a 10 mL flask equipped with a water-cooled condenser. The sulfoethyl) pyridinium hydroxide, inner salt (0.200 grams)
flask was lowered into an 85 C. oil bath. After 35 minutes
in a 10 mL flask equipped with a water-cooled condenser.
at 85°C., the oil bath temperature was raised to 90° C. After 25 The flask was lowered into an 85 C. oil bath. After 30
25 minutes at 90° C., the contents of the flask was sampled minutes at 85°C., the oil bath temperature was raised to 90
and found to contain 3.3 area %. MCF by GC. After an C. After 30 minutes at 90° C., the contents of the flask were
additional 20 minutes at 90° C., the oil bath temperature was sampled and analyzed by GC. The amounts of MCF and
raised to 100° C. After 100 minutes at 100° C., the contents DCMC found were 9.65 area % and 0.05 area % respec
of the flask (8.83 grams) were re-analyzed by GC and found tively. The oil bath temperature was then raised to 95 C.
to contain 0.12 area %. MCF. After 45 minutes at 95 C., the contents of the flask were
EXAMPLE 6 sampled and analyzed by GC. The levels of MCF and
DCMC found were 1.77 area % and 0.01 area % respec
A crude chloroformate mixture (12.5 grams) comprising tively. The oil bath temperature was then raised to 110° C.
CMC (69.8 area %), MCF (21.1 area)% and DCMC (2.69 35
and the flask maintained at that temperature for 40 minutes,
area 96) was mixed with dibenzo-18-crown-6 (0.157 grams) whereupon the contents of the flask (7.79 grams) were
and potassium fluoride (0.162 grams) in a 10 mL flask sampled again and analyzed by GC. The levels of MCF and
equipped with a water-cooled condenser. The flask was DCMC found were 0.02 area % and 0.02 area % respec
lowered into a 90° C. oil bath. After 80 minutes at 90° C., tively.
the contents of the flask were sampled and analyzed by G.C. 40
The amount of MCF and DCMC were found to be 19.5 area EXAMPLE 10
% and 1.85 area % respectively. After an additional 50
minutes at 90° C., the oil bath temperature was raised to 95 A crude chloroformate mixture (13.78 grams) comprising
C. After 50 minutes at 95 C., the contents of the flask were CMC (70.2 area %), MCF (22.8 area %) and DCMC (2.76
again Sampled and analyzed by GC. This analysis found the 45 area %) was mixed with 0.0164 grams of benzyltributyl
MCF and DCMC to be 16.7 area % and 1.25 area % ammonium chloride (BTBAC) in a 10 mL flask equipped
respectively. After an additional 16 hours at 95 C., the with a water-cooled condenser. The flask was lowered in a
contents of the flask (8.65 grams) were sampled and ana 100° C. oil bath. After one hour at 100° C., the contents of
lyzed by GC. The levels of MCF and DCMC were found to the flask were sampled and analyzed by GC. The levels of
be 2.26 area % and 0.03 area % respectively. 50 MCF and DCMC found were 9.4 area % and 0.23 area %
respectively. After an additional 1 hour at 100 C., the
EXAMPLE 7 contents of the flask were Sampled again and analyzed by
A crude chloroformate mixture (9.938 grams) comprising GC. The levels of MCF and DCMC found were 0.65 area %
CMC (69.8 area %), MCF (21.1 area %) and DCMC (2.69 and 0.01 area % respectively. The oil bath temperature was
then raised to 105 C. and the contents of the flask held at
area %) was mixed with DOWEX(R) SBR resin ionic form 55
hydroxide, dry mesh (16-40 US Sieve mesh) (0.368 grams) this temperature for one hour. The contents of the flask (9.55
in a 10 mL flask equipped with a water-cooled condenser. grams) were again Sampled and analyzed by GC. The levels
The flask was lowered into a 90° C. oil bath. After 80 of MCF and DCMC found were 0.05 area % and 0.01 area
minutes at 90° C., the oil bath temperature was raised to 95 % respectively. The product was found to be 98.8 area
C. After 17 hours at 95°C., the contents of the flask (5.00 60 percent CMC (by GC).
grams) were sampled and analyzed by GC. The level of EXAMPLE 11
MCF and DCMC were found to be 1.10 area % and 0.09 area
% respectively. A crude chloroformate mixture (14.14 grams) comprising
EXAMPLE 8 CMC (70.1 area %), MCF (21.9 area %) and DCMC (2.16
65 area 96) was mixed with BTBAC (0.129 grams) in a 10 mL
A crude chloroformate mixture (11.75 grams) comprising flask equipped with a water-cooled condenser. The flask was
CMC (70 area %), MCF (19.4 area %) and DCMC (1.12 area lowered into an 80 C. oil bath and after 277 minutes at that
 US 6,911,558 B2
15 16
temperature, the flask was removed from the oil bath and its 6. The method of claim 5 wherein the sub-atmospheric
contents sampled and analyzed by GC. The levels of MCF pressure ranges from 50 Torr to 720 Torr.
and DCMC found were 0.03 area % and 0.01 area % 7. The method of claim 4 wherein the reaction Zone is
respectively. The flask contained 9.99 grams of crude prod maintained at Sub-atmospheric pressures during Steps (a)
uct (98.1 area % CMC by CC). and (b).
EXAMPLE 12 8. The method of claim 7 wherein the sub-atmospheric
pressure ranges from 50 Torr to 720 Torr.
A crude chloroformate mixture (14.47 grams) comprising 9. The method of claim 1 wherein the nucleophilic
CMC (68.8 area %), MCF (19.4%) and DCMC (0.54%) was catalyst is Selected from quaternary ammonium Salts, qua
mixed with N,N-dimethylformamide (0.315 grams) and the ternary phosphonium Salts, and crown ether, cryptand,
mixture heated in a 10 mL flask equipped with a water Spherand or calixarene complexes of organic or inorganic
cooled condenser. The flask was lowered into a 90° C. oil Salts.
bath. After 110 minutes at 90° C., the mixture in the flask 10. The method of claim 1 wherein the catalyst is a
was Sampled and analyzed by GC. The Sample was found to quaternary ammonium or phosphonium Salt.
contain MCF (0.00 area %), CMC (91.1 area %) and DCMC 11. The method of claim 10 wherein the catalyst is
(0.19 area %). 15 represented by the following general formulae:
EXAMPLE 13
A crude chloroformate mixture (13.40 grams) comprising
CMC (69.8 area %), MCF (21.1 area %) and DCMC (1.90
area %) was mixed with 0.8 weight percent of BTBAC in a
10 mL flask equipped with a water-cooled condenser and a
gas inlet tube that extended below the surface of the flask
contents. The flask was lowered into an 85 C. oil bath and wherein R, R2, R and R are each monovalent hydrocar
nitrogen was introduced into the gas inlet tube, thereby to bon groups containing from 1 to 25 carbon atoms, and X is
provide a gentle SubSurface nitrogen Sparge. After 60 min 25 a monovalent anion.
utes at 85 C., the contents of the flask were sampled and 12. The method of claim 11 wherein the total number of
analyzed by GC. The levels of MCF and DCMC found were carbon atoms in the monovalent hydrocarbon groups ranges
0.22 area % and 0.01 area % respectively. from 12 to 35, and the monovalent anion is selected from a
The preceding procedure was performed Simultaneously halide anion, hydrogen Sulfate anion, hydroxyl anion, dihy
in a similar 10 mL flask with a crude chloroformate mixture drogen phosphate anion, and hydrogen phosphate anion.
(13.96 grams) having MCF (21.3 area %) and DCMC (1.64 13. The method of claim 12 wherein the halide anion is a
area %), but with 0.9 weight percent BTBAC, no nitrogen chloride or bromide.
Sparge, and for an 80 minute residence time in the oil bath. 14. The method of claim 4 wherein inert gas introduced
The contents of the flask were sampled and analyzed by G.C. into the reaction Zone comprises nitrogen.
The levels of MCF and DCMC were found to be 5.1 area % 35 15. A method for recovering chloromethyl chloroformate
and 0.06 area % respectively. from a chloroformate mixture comprising chloromethyl
This example demonstrates the benefit of an inert gas chloroformate, methyl chloroformate and dichloromethyl
Sparge to assist in the removal of gaseous decomposition chloroformate, which method comprises heating Said chlo
products from the vicinity of the crude chloroformate mix roformate mixture in a reaction Zone in the presence of a
ture during the heating Step. 40 catalytic amount of nucleophilic catalyst, (b) simultaneously
While the invention has been described in detail with removing volatile gaseous products produced in Step (a)
respect to certain embodiments thereof, it is to be understood from Said reaction Zone, and (c) recovering chloromethyl
that the invention is not intended to be limited to Such details chloroformate product substantially free of methyl chloro
except as and insofar as they appear in the appended claims. formate and dichloromethyl chloroformate.
What is claimed is: 45 16. The method of claim 15 wherein the chloroformate
1. A method of removing methyl chloroformate from a mixture further comprises trichloromethyl chloroformate.
chloroformate mixture comprising chloromethyl chlorofor 17. The method of claim 15 wherein the chloroformate
mate and a contaminating amount of methyl chloroformate, mixture is heated attemperatures of from greater than 70° C.
which method comprises (a) heating said mixture in a to the reflux temperature of the mixture in the reaction Zone.
reaction Zone in the presence of a catalytic amount of 50 18. The method of claim 15 wherein the chloroformate
nucleophilic catalyst, (b) Simultaneously removing volatile mixture is heated at temperatures of from 86° C. to 100 C.
gaseous products resulting from Step (a) from Said reaction 19. The method of claim 17 wherein chemically inert gas
Zone, and (c) recovering chloromethyl chloroformate Sub is introduced into the reaction Zone to assist in the removal
stantially free of methyl chloroformate from said reaction of Volatile gaseous products from Said reaction Zone.
ZOC. 55 20. The method of claim 19 wherein the volatile gaseous
2. The method of claim 1 wherein the chloroformate products include hydrogen chloride and the inert gas com
mixture further comprises dichloromethyl chloroformate. prises nitrogen.
3. The method of claim 1 wherein the temperature at 21. The method of claim 15 wherein the chloromethyl
which the chloroformate mixture is heated ranges from at chloroformate product comprises at least 95% chloromethyl
least 50° C. to the reflux temperature of the mixture in the 60 chloroformate, less than 5% methyl chloroformate and less
reaction Zone. than 2% dichloromethyl chloroformate, as determined by
4. The method of claim 3 wherein chemically inert gas is gas chromatography analysis.
introduced into the reaction Zone to assist in the removal of 22. The method of claim 15 wherein the chloromethyl
the Volatile gaseous products from Said reaction Zone. chloroformate product comprises at least 98% chloromethyl
5. The method of claim 1 wherein the reaction Zone is 65 chloroformate, less than 1% methyl chloroformate and less
maintained at Sub-atmospheric pressures during steps (a) than 1% dichloromethyl chloroformate, as determined by
and (b). gas chromatography analysis.
 US 6,911,558 B2
17 18
23. The method of claim 17 wherein the reaction Zone is than 1% dichloromethyl chloroformate, as determined by
maintained at Sub-atmospheric pressures during steps (a) gas chromatography analysis.
and (b). 37. The method of claim 1 wherein the nucleophilic
24. The method of claim 17 wherein the catalyst is a catalyst is Selected from tertiary amines, amides, Substituted
quaternary ammonium or phosphonium Salt. ureas and thioureas, tertiary phosphines and Substituted
25. The method of claim 24 wherein the Salt is a chloride phosphoramides.
or bromide Salt.
26. A method comprising the steps of (a) heating a 38. The method of claim 37 wherein the nucleophilic
chloroformate mixture comprising chloromethyl chlorofor catalyst is Selected from triethylamine, tributyl amine,
mate and contaminating amounts of methyl chloroformate in pyridine, N,N-dimethyla niline, imidazole,
a reaction Zone attemperatures of from at least 50 C. to the dimethylformamide, tetrabutylurea, tetrabutylthiourea,
reflux temperature of the mixture in the reaction Zone in the trioctylphosphine, and hexamethylphosphotriamide.
presence of a catalytic amount of nucleophilic catalyst, (b) 39. The method of claim 15 wherein the nucleophilic
Simultaneously removing volatile gaseous products includ catalyst is Selected from tertiary amines, amides, Substituted
ing hydrogen chloride resulting from Step (a) from Said ureas and thioureas, tertiary phosphines and Substituted
reaction Zone, and (c) recovering chloromethyl chlorofor 15 phosphoramides.
mate product substantially free of methyl chloroformate 40. The method of claim 39 wherein the nucleophilic
from Said reaction Zone. catalyst is Selected from triethylamine, tributyl amine,
27. The method of claim 26 wherein the chloroformate pyridine, N,N-dimethyla niline, imidazole,
mixture further comprises contaminating amounts of dichlo dimethylformamide, tetrabutylurea, tetrabutylthiourea,
romethyl chloroformate, and the chloromethyl chlorofor trioctylphosphine, and hexamethylphosphotriamide.
mate product is substantially free of dichloromethyl chlo 41. The method of claim 26 wherein the nucleophilic
roformate. catalyst is Selected from tertiary amines, amides, Substituted
28. The method of claim 26 wherein the nucleophilic ureas and thioureas, tertiary phosphines and Substituted
catalyst is a quaternary ammonium or phosphonium Salt. 25
phosphoramides.
29. The method of claim 27 wherein the nucleophilic 42. The method of claim 41 wherein the nucleophilic
catalyst is represented by the following general formulae: catalyst is Selected from triethylamine, tributyl amine,
pyridine, N,N-dimethyla niline, imidazole,
dimethylformamide, tetrabutylurea, tetrabutylthiourea,
trioctylphosphine, and hexamethylphosphotriamide.
43. The method of claim 1 wherein the nucleophilic
catalyst is selected from alkyl Substituted guanidines and
heXasubstituted guanidinium halides.
wherein R, R, R and R are each monovalent hydrocar 44. The method of claim 43 wherein the nucleophilic
bon groups containing from 1 to 25 carbon atoms, and X is 35 catalyst is Selected from tetrabutyl guanidine, pentabutyl
a monovalent anion. guanidine, pentabutyl guanidine hydrogen chloride Salt,
30. The method of claim 29 wherein the total number of hexaethyl guanidinium chloride and hexabutylguanidinium
chloride.
carbon atoms in the monovalent hydrocarbon groups ranges 45. The method of claim 15 wherein the nucleophilic
from 12 to 35, and the monovalent anion is selected from a catalyst is Selected from alkyl Substituted guanidines and
halide anion, hydrogen Sulfate anion, hydroxyl anion, dihy 40
drogen phosphate anion, and hydrogen phosphate anion. heXasubstituted guanidinium halides.
31. The method of claim 30 wherein the halide anion is a 46. The method of claim 45 wherein the nucleophilic
chloride or bromide. catalyst is Selected from tetrabutyl guanidine, pentabutyl
32. The method of claim 29 wherein chemically inert gas guanidine, pentabutyl guanidine hydrogen chloride Salt,
is introduced into the reaction Zone to assist in the removal 45 hexaethyl guanidinium chloride and hexabutylguanidinium
of the Volatile gaseous products. chloride.
33. The method of claim 29 wherein the reaction Zone is 47. The method of claim 26 wherein the nucleophilic
maintained at Sub-atmospheric pressures during steps (a) catalyst is Selected from alkyl Substituted guanidines and
and (b). heXasubstituted guanidinium halides.
34. The method of claim 32 wherein the inert gas com 50 48. The method of claim 47 wherein the nucleophilic
prises nitrogen. catalyst is Selected from tetrabutyl guanidine, pentabutyl
35. The method of claim 34 wherein the inert gas is guanidine, pentabutyl guanidine hydrogen chloride Salt,
introduced directly into the chloroformate mixture. hexaethyl guanidinium chloride and hexabutylguanidinium
36. The method of claim 29 wherein the chloromethyl chloride.
chloroformate product comprises at least 98% chloromethyl 55
chloroformate, less than 1% methyl chloroformate and less