Process for preparing N-chloroimides

N-chlorophthalimide, N-chlorosuccinimide, and N-chloroglutarimide are prepared by contacting the corresponding imide with molecular chlorine under substantially non-aqueous conditions in an inert organic solvent in the presence of a poly(4-vinylpyridine)-divinylbenzene copolymer.

This invention relates to a process for the manufacture of 
N-chlorophthalimide, N-chlorosuccinimide, or N-chloroglutarimide. 
The principal prior art processes for preparing N-chloroimides customarily 
have employed an aqueous reaction medium. In general, such processes can 
be classified as follows: 
(1) Chlorination of the corresponding imide using an inorganic hypochlorite 
in a mixture of acetic acid and water; 
(2) Chlorination by passing chlorine into an aqueous solution comprising 
equivalent amounts of the corresponding imide and a strong base, e.g., 
sodium hydroxide or potassium hydroxide; 
(3) Chlorination of the corresponding imide using t-butyl hypochlorite in a 
mixture of t-butyl alcohol and water. 
Of the above general methods, only method (2) involves the use of molecular 
chlorine. However, because of the presence of the aqueous system, this 
method has been found to have serious drawbacks. First, chlorine is only 
very slightly soluble in water. Secondly, and more importantly, it is 
known that an imide, when present in an alkaline aqueous medium such as 
would result from potassium or sodium hydroxide and water, undergoes rapid 
hydrolysis. When, for example, phthalimide is subjected to alkaline 
aqueous conditions, the following decomposition sequence occurs: 
##STR1## 
Even more importantly, it has been established [Arthur R. Hurwitz, 
"Degradation of N-Chlorosuccinimide in Aqueous Solution", Diss. Abst., B, 
28 (3), 971 (1967)] that an N-chloroimide product, when present in an 
aqueous alkaline medium, such as would be the case under the conditions of 
chlorination provided by method (2) above, degrades with possible 
formation of the highly explosive and toxic gas, nitrogen trichloride. The 
following sequences are postulated for the decomposition of 
N-chlorosuccinimide: 
##STR2## 
Non-aqueous processes for preparing N-chloro compounds have been few. U.S. 
Pat. No. 2,686,203 describes a process for preparing N-halo-t-alkyl 
cyanamides by treating a t-alkyl cyanamide with molecular chlorine in an 
inert solvent in the presence of a molar equivalent of a halogen acid 
acceptor, typically pyridine. U.S Pat. No. 4,082,766 discloses a method 
for preparing N-chlorophthalimide under substantially non-aqueous reaction 
conditions by contacting an alkali metal salt of phthalimide with chlorine 
in the presence of a halogenated aliphatic hydrocarbon at a temperature of 
from about -10.degree. C. to about +40.degree. C. 
An even more advantageous method employs a substantially non-aqueous medium 
and permits use of the imide itself as starting material instead of the 
previously required alkali metal salt. The N-chloroimide is prepared by 
contacting the corresponding imide with molecular chlorine at a 
temperature of from about -10.degree. C. to about +50.degree. C. under 
substantially non-aqueous conditions in the presence of (1) an epoxy 
compound in an amount representing at least about one epoxy moiety per 
each imide moiety and (2) at least a catalytic amount of a tertiary amine. 
This method is the subject of co-pending application of T. S. Chou Ser. 
No. 861,582, filed Dec. 19, 1977. 
The invention sought to be patented constitutes a process for preparing 
N-chlorophthalimide, N-chlorosuccinimide or N-chloroglutarimide which 
comprises contacting phthalimide, succinimide, or glutarimide with 
molecular chlorine at a temperature of from about -10.degree. C. to about 
50.degree. C. under substantially non-aqueous conditions in the presence 
of poly(4-vinylpyridine)-divinylbenzene copolymer in a ratio by weight of 
said copolymer to phthalimide, succinimide, or glutarimide of between 1:1 
and about 1:5, said copolymer containing between about 1% to about 10% 
cross linking. 
The poly(4-vinylpyridine)-divinyl benzene copolymer is weakly basic and is 
insoluble in organic solvents. the copolymer effects the rapid removal of 
hydrogen chloride from the reaction medium and shifts the reaction 
equilibrium to favor N-chloroimide formation. Further, the 
4-vinylpyridine-divinylbenzene copolymer is readily removed from the 
reaction medium by filtration or other suitable means. 
Whereas the use of an epoxy compound for removing hydrogen chloride during 
the reaction of an imide with chlorine require the presence of a tertiary 
amine catalyst (e.g. quinoline), as described in the aforesaid co-pending 
application Ser. No. 861,582, the use of the 
4-vinylpyridine-divinylbenzene copolymer does not require the use of a 
tertiary amine catalyst. Comparable yields are obtained in the process 
with or without a tertiary amine catalyst. 
In practicing the process of the invention, the chlorine can be introduced 
into the reaction medium containing the desired imide either by passing 
the gas directly into the reaction medium or by first absorbing chlorine 
onto the polymer and then adding the polymer-chlorine complex to the 
reaction medium. It will be understood that both techniques are within the 
scope of the invention. 
In the reaction of chlorine with the imide moiety one mole of chlorine is 
consumed for each mole of available imide moiety. Therefore, it is highly 
preferred that at least one mole of chlorine is present per each mole of 
imide moiety. Even more preferably, about a 10% molar excess of chlorine 
is brought into contact with the imide. The temperature at which the 
reaction is carried out generally ranges from about -10.degree. C. to 
about +50.degree. C. and, preferably, from about -5.degree. C. to about 
+25.degree. C. The reaction generally is completed after a period of from 
about 1 hour to about 24 hours, and, preferably, is carried out over a 
period of from about 3 to 15 hours. 
The reaction between the imide and chlorine is carried out in an inert 
organic solvent under substantially non-aqueous conditions. The term 
"substantially non-aqueous conditions" does not mean the total absence of 
water from the reaction system; instead, this term prescribes the exercise 
of reasonable precautions to ensure its preclusion, including the 
avoidance of any deliberate addition of water to the reaction medium prior 
to or during the time in which the reaction is being effected. Amounts of 
water which are customarily present in such commercial solvents and 
reactants as may be employed in the process of this invention need not 
first be removed in order to comply with the "substantially non-aqueous" 
requirement. By the term "solvent" is meant a medium which partially or 
completely solubilizes the imide starting material. The term "inert" 
defines a solvent which generally does not react with the reactants, 
principally, with the chlorine, under the conditions of the process. 
Typical such solvents are halogenated aromatic and aliphatic hydrocarbons. 
Examples of halogenated aromatic hydrocarbons are chlorobenzene, 
1,2-dichlorobenzene, 1,4-dichlorobenzene, bromobenzene, and the like. 
Examples of halogenated aliphatic hydrocarbons are methylene chloride, 
chloroform, 1,1,2-trichloroethane, 1,2-dichloroethane, 1,1-dichloroethane, 
1,1,1-trichloroethane, and the like. Of the above, the halogenated 
aliphatic hydrocarbons are preferred, and, of these, the preferred solvent 
is methylene chloride. 
The copolymeric resin of 4-vinylpyridine and divinylbenzene employed in the 
process of this invention is a weakly basic resin which is insoluble in 
the inert organic solvents and in particular, the reaction medium employed 
in the present process. The polymer contains cross-linking of from about 
1% to about 10% based on the weight of polymer. The cross-linked 
poly(4-vinylpyridine) polymer is prepared with divinylbenzene as described 
by Hallensleben and Wurm, Angew. Chem. Int. Ed. Engl. 15, 163 (1976). 
Alternatively the cross-linked polymer can be prepared in water via 
emulsion polymerization with surfactants such as polyvinyl alcohol or 
polyethylene oxide. Macroreticular beads of the cross-linked polymer can 
be prepared by procedures known in the art, for example, as described by 
U.S. Pat. No. 3,816,355. 
The preferred extent of cross-linking in the polymer is between about 2% 
and about 5%. The desired range of cross-linking is obtained by using the 
appropriate amount of divinylbenzene in the polymerization of the 
4-vinylpyridine. The poly(4-vinylpyridine) having the desired 
cross-linking rapidly absorbs the hydrogen chloride formed during the 
reaction of the phthalimide, succinimide or glutarimide with chlorine. 
Further, since the polymer is insoluble in the reaction medium, the acid 
is rapidly and completely removed from the reaction system. This rapid 
removal of the acid side product shifts the equilibrium of the reaction to 
favor chlorination. 
The cross-linked poly(4-vinylpyridine) can be used in a variety of forms. 
For example, it can be in the form of a fine powder or in the form of 
small beads, or in the form of macroporous beads. Preferably the form of 
the copolymer has a high surface area which is a measure of the 
availability of the basic sites of the polymer to the acid. Accordingly, 
the lower the average particle size of the polymer the higher will be the 
surface area and the greater availability of basic groups. Likewise, the 
copolymer in the form of macroporous beads has a high surface area 
including internal surface area with concomitant high exposure of the 
basic groups in the copolymer. For copolymer in the form of relatively 
uniform shape such as bead shaped, for example macroreticular beads, the 
preferred size is between about 20 microns and about 120 microns in 
diameter. For copolymer of irregular particle shape, such as may be 
obtained by crushing the copolymer resin in a hammer mill, the preferred 
particle size is obtained by collecting the particles passing through a 
sieve of about 120 mesh. 
Copolymer having the cross-linking content of between about 1% and about 
10% displays characteristic swelling in the organic solvents employed in 
the process. Copolymer having a higher cross-linking content swells to a 
lesser degree and, the extent of swelling decreases as the extent of 
cross-linking increases. The increased volume of the copolymer due to 
swelling allows for greatly enhanced access to the basic sites in the 
polymer by hydrogen chloride. Copolymers which are cross-linked to greater 
than 10% swell much less than those which are cross-linked to less than 
10%, or within the preferred range, and although insoluble in the organic 
solvents are not efficient HCl binders. 
The ratio of the amount of polymer employed per amount of imide starting 
material is between about 1:1 and about 1:5 by weight. Preferably, the 
ratio is about 1:2 to about 1:3. 
N-chlorophthalimide, N-chlorosuccinimide and N-chloroglutarimide produced 
by the process of this invention are highly useful reagents for carrying 
out chlorination reactions which require a source of positive chlorine. 
Examples of such reactions are, for example, oxidation of sulfides, 
alcohols, amines, and imines; chlorination of amines, reactive aromatic 
systems, carbonyl compounds having .alpha.-hydrogens, and the like.

The following examples further illustrate the process of this invention. 
EXAMPLE 1 
Preparation of poly(4-vinylpyridine)-divinylbenzene copolymer 
To a 2-liter, 3-necked round bottom flask were added 1100 ml. of water and 
4.8 g. of poly(vinyl alcohol) and the solution was heated under nitrogen 
to 80.degree. C. A solution of 50 g. of 4-vinylpyridine and 3.0 g. of 
divinylbenzene in 100 ml. of toluene was rapidly added with stirring to 
the hot solution, followed by the addition of 2 g. of 
azobisisobutyronitrile. The copolymer began to form at once and the 
suspension was stirred vigorously at 80.degree. C. for about 16 hours. 
The copolymer was collected by filtering the reaction mixture through cloth 
and was washed extensively with water, acetone, diethyl ether, methylene 
chloride and lastly with methyl alcohol. Swelling was encountered during 
the diethyl ether washing and with the methylene chloride and methyl 
alcohol washings. The copolymeric resin was then dried in vacuo to yield 
45.05 g. of the dried resin. 
The resin was finished by grinding and collecting the material which passed 
through 60 mesh sieve. 
The nitrogen content of the resin was 12.35% as determined by combustion. 
EXAMPLE 2 
N-Chlorophthalimide (Method A) 
To 2.45 g. of 4-vinylpyridine-divinylbenzene copolymer (7.38 mcg./g., 10% 
excess) in 200 ml. of methylene chloride was introduced chlorine until the 
solvent turned slightly greenish yellow. Phthalimide (7.35 g, 50 mM) was 
added in one portion. Quinoline (three drops) was added, and the reaction 
mixture was stirred at room temperature for five hours. 
The reaction mixture was filtered to remove reacted and unreacted polymer. 
The polymer was washed twice with methylene chloride (15 ml.). The 
original filtrate and the washing were combined and evaporated slowly to 
about one-third volume. White crystals formed at this step, but the 
mixture was kept in a refrigerator overnight to complete the 
crystallization. The crystals were collected by filtration. After drying 
under vacuum, there was obtained 8.70 g. (95.9% yield) of the title 
product, m.p. 179.5.degree.-180.degree. C., identified by infrared 
spectral analysis. Percent chlorine: Found 17.6; calculated 19.5%. 
Repeating the above procedure but omitting the quinoline catalyst there was 
obtained 8.05 g. of the title product, m.p. 180.degree.-183.degree. C. 
(Yield 88.7%). Percent chlorine: Found, 10.7; calculated 19.5%. The 
infrared spectra of the product is identical to that obtained above. 
EXAMPLE 3 
N-Chlorophthalimide (Method B) 
To 7.45 g. of 4-vinylpyridine-divinylbenzene copolymer (55 mM/eg), in 100 
ml. of methylene chloride, was added chlorine until there was produced a 
persistent yellow color in the solvent. The polymer was collected by 
filtration under slight vacuum. The wet polymer-chlorine complex was then 
placed in 100 ml. of phthalimide (7.35 g.). The mixture was stirred at 
room temperature for three hours. By thin layer chromatography, it was 
shown that at least 50% of the phthalimide is converted to the 
N-chlorinated product.