Ammonolysis-alkylation reactions using ammonia and an alcohol to prepare N-alkyl maleimides and N-alkyl succinimides

Ammonolysis-alkylation using a C.sub.1 to C.sub.8 alkanol and ammonia is used to prepare cyclic N-alkylated compounds in a one-step process. In the presence of hydrogen added as a reducing agent, a reduced N-alkylated compound can be formed.

BACKGROUND OF THE INVENTION 
This invention relates to the preparation of N-alkylated compounds by 
reaction of an organic diacid, diester, anhydride or a lactone with 
ammonia and an alcohol. More particularly, the invention relates to the 
one-step preparation of a cyclic N-alkylated compound, such as a 
N-alkylsuccinimide, from an organic diacid, diester, anhydride or lactone 
by reaction with ammonia and a C.sub.1 to C.sub.8 alkanol either added or 
formed in situ. The ammonolysis-alkylation may be thermal or catalyzed. In 
another aspect of the invention a cyclic N-alkylated compound is formed in 
the presence of a reducing agent such that reduction of the process feed 
is accomplished together with the ammonolysis-alkylation reaction. 
Previous syntheses making the N-alkylated derivatives from such compounds 
as a dialkyl succinate, succinic acid, succinic anhydride or 
4-butyrolactone were carried out stepwise by first making a metal salt of 
the corresponding imide and reacting the latter with an alkyl halide or 
directly employing the reaction of a primary amine with the 
oxygen-containing starting material. These techniques are either multistep 
and expensive or simply expensive because of the price of primary amines. 
In a search for a low-cost, simple technique for carrying out these and 
similar reactions, it has been found that ammonolysis-alkylation can be 
accomplished in a single step in a thermal or catalyzed reaction employing 
ammonia and an alkanol, the alkanol either added or generated by the 
reaction in situ. The new reaction is capable of high conversions and high 
selectivities to the desired N-alkylated products, a finding of major 
commercial significance. 
In the past, N-alkylated compounds have been prepared from 
dialkylsuccinates by thermal reaction with a primary amine. See U.S. Pat. 
No. 2,643,257. Of interest also is a two-step process for their 
preparation. A compound containing an imide nitrogen is first reacted to 
form an alkali metal salt, for example, potassium phthalimide, which is 
then reacted with an alkyl halide. See, for example, Gibson, M. and 
Bradshaw, R., Angew. Chem. Int. Ed. 7,919 (1963). Related to the present 
invention is (1) imide and amide alkylation with alcohols, see O. 
Mitsunobu et al. JACS 94,679 (1972), E. White et al., JACS 87,5261 (1965) 
and V. Evgrasin, et al., Kinet. Katal, 14,440 (1973) and (2) the reaction 
of maleic anhydride with a primary amine. See, for example, U.S. Pat. No. 
2,262,262 and British Pat. No. 1,123,515. 
SUMMARY OF THE INVENTION 
The invention described herein is a process comprising forming a first 
compound containing the 
##STR1## 
from a scond compound containing the 
##STR2## 
wherein R is H or a C.sub.1 to C.sub.8 alkyl radical, by contacting under 
reaction conditions said second compound with ammonia and the 
corresponding C.sub.1 to C.sub.8 alkanol. 
In another aspect, the invention described herein is a process comprising 
forming a first compound containing the 
##STR3## 
from a second compound containing the 
##STR4## 
wherein R is a C.sub.1 to C.sub.8 alkyl radical, by contacting under 
reaction conditions said second compound with ammonia and the 
corresponding C.sub.1 to C.sub.8 alkanol. 
In a third aspect, the invention described herein is a process comprising 
forming a first compound containing the 
##STR5## 
from a second compound containing the 
##STR6## 
wherein R is a C.sub.1 to C.sub.8 alkyl radical, by contacting under 
reaction conditions said second compound with ammonia and the 
corresponding C.sub.1 to C.sub.8 alkanol. 
In still another variant, the invention described herein relates to 
carrying out the above-described one step processes in the presence of 
hydrogen such that ammonolysis-alkylation and a reduction of the organic 
substrate are accomplished together. 
DETAILED DESCRIPTION OF THE INVENTION 
The feed for process of the instant invention can be a diacid such as 
maleic acid, succinic acid, phthalic acid and the like or substituted 
derivatives thereof. The diacid must be of the appropriate carbon number 
and capable of cyclizing in the reaction to form the N-alkylated compound. 
The alkyl diesters of such diacids are also useful. By alkyl is meant a 
C.sub.1 to C.sub.8 alkyl radical, such as the methyl, ethyl, isopropyl, 
butyl, isobutyl, pentyl, hexyl, heptyl and octyl radicals, more 
preferably, the methyl, ethyl and propyl radicals, and most preferably, 
the methyl radical. Anhydrides of such acids are also useful. Acids such 
as succinic and phthalic are preferred as are their anhydrides and their 
diesters, particularly their dimethyl or diethyl esters. 
Lactones useful in the process of the instant invention include both 
saturated and unsaturated compounds, which compounds may or may not be 
alkyl or aryl substituted. In particular, butyrolactone is useful which 
may be produced either by Reppe chemistry or by hydrogenation of a maleic 
derivative. Formation of a N-alkylpyrrolidone starting with a maleic 
derivative and using ammonolysis-alkylation can form the basis of a 
particularly desirable process. 
Additionally, ammonia and a C.sub.1 to C.sub.8 alkanol are also used in the 
process, the latter not being necessary in the event a diester is used 
which can form the corresponding alkanol in situ during the reaction. The 
alkanols which are preferred are methanol, ethanol and propanol, and 
methanol and ethanol are the most preferred alkanols. 
The reaction of the substrate, ammonia and the C.sub.1 to C.sub.8 alkanol 
is carried out under a pressure of about near ambient pressure to about 
200 atms., and more preferably, about 2 atms. to about 100 atms. The 
reaction temperature is suitably between about 80.degree. C. and about 
400.degree. C., and more preferably, between about 100.degree. C. and 
about 350.degree. C.. Reaction times depend to some extent upon the 
pressure and the temperature employed but generally are in the range of 
about 0.25 hrs. to about 8 hrs., more preferably about 1 hr. to about 4 
hrs. It has been found that longer reaction times are required for N-butyl 
compounds than are required for N-ethyl compounds. N-methyl derivatives 
appear to form most rapidly under equivalent reaction conditions. The 
reactions are conveniently carried out batchwise with agitation although a 
continuous process in a plug flow, tubular or other type of reactor is 
possible. The substrate can conveniently be added to the reactor as a 
mixture in the alkanol. The reactions can be carried out thermally or, if 
necessary with the addition of a catalyst. 
In the slower reactions where the N-alkyl group is large, for example, 
where a C.sub.2 to C.sub.8 alkanol is used, use of a catalyst can be 
beneficial. For example, a trace of iodine, bromine, an alkali metal 
bromide or iodide, or an alkyl bromide or iodide can usefully increase the 
speed of the reaction. Transition metal catalysts can also be used for 
this purpose. 
In general, the reaction of the substrate, ammonia and alkanol can be 
effected with good conversion and selectivity. For example, 
N-methylsuccinimide can be formed from the corresponding anhydride with at 
least 90 percent selectivity and 100 percent conversion. 
In general, the reactants, i.e., substrate and ammonia, are used in about 
stoichiometric proportions. Too little ammonia results in incomplete 
conversion and too much ammonia is wasteful and can produce undesirable 
byproducts. The alkanol can be used in about stoichiometric proportions 
also, however, it is sometimes convenient to use excess alkanol to aid in 
introduction and removal of feed and product. 
The N-alkyl products are generally easily separated from the reaction 
mixture because of the high conversions and selectivities. Where product 
separations are required they may be usefully carried out by distillation 
or crystallization. 
Reduction of the organic substrate together with the ammonolysis-alkylation 
reaction can be accomplished catalytically by adding hydrogen and a 
reduction catalyst to the reaction mix. By reduction is meant either 
reduction of a carbon-carbon double bond or a carbonyl group, or both. 
Catalysts useful for the heterogeneous reduction reaction are, generally, 
nickel supported on a metal oxide, copper chromite, cobalt supported on a 
metal oxide, and other similar catalysts. In general, temperature and 
pressure ranges are those expected for a reaction of this kind and are 
consistent with those required for ammonolysis-alkylation. A reduction 
temperature between about 100.degree. C. and about 500.degree. C., more 
preferably between about 150.degree. C. and about 300.degree. C., and a 
reduction pressure of between about 10 atms. and about 600 atms., more 
preferably between about 20 atms. and about 400 atms. can be used, as can 
be understood by one skilled in the art. Advantageously, the reaction 
mixture is agitated by stirring, or otherwise mixed, in order to improve 
contact between the reactants. Reaction times of course vary with the 
reaction temperature and pressure used, as may be expected by one skilled 
in the art, but in general lie between about 1 hr. and about 12 hrs.

The following Examples will serve to illustrate certain specific 
embodiments of the herein disclosed invention. These Examples should not, 
however, be construed as limiting the scope of the novel invention as 
there are many variations which may be made thereon without departing from 
the spirit of the disclosed invention, as those of skill in the art will 
recognize. 
EXAMPLES 
General 
All reactions were run in a 300cc 316SS stirred Autoclave Engineer 
autoclave at the reaction times, temperatures and pressures noted in the 
Examples below. In addition, a one-gallon autoclave was used for Example 
2. Products were analyzed using both liquid chromatography and gas 
chromatography and all conversion and selectivity percentages given are in 
mole percent. 
In general the substrate, for example, succinic anhydride, and the alcohol 
were first added to the reactor followed by an argon purge. Ammonia gas 
was then added, and, optionally hydrogen gas; the autoclave was then 
sealed and agitation begun. The reactor was heated to reaction 
temperature, and the reaction time taken to be the time the reactor was 
held at reaction temperature. 
EXAMPLE 1 
A 67 g amount of succinic anhydride (SAN), 62 g of methanol, and 12.53 g of 
ammonia were heated 5 hrs. at 300.degree. C. while stirring at 900 RPM. 
The SAN was 100% converted and selectivity to N-methylsuccinimide was 90%. 
EXAMPLE 2 
A 67 g amount of SAN, 89 g of ethanol and 12.53 g of ammonia were heated 5 
hrs. at 292.degree. C. while stirring at 900 RPM. The SAN was 100% 
converted with a 40% selectivity to N-ethylsuccinimide and a 40% 
selectivity to succinimide. 
EXAMPLE 3 
A 50 g amount of SAN, 106 g of butanol and 9.4 g of ammonia were heated 22 
hours at 300.degree. C. while stirring. The SAN was 100% converted with a 
40% selectivity to N-butylsuccinimide and a 40% selectivity to 
succinimide. 
EXAMPLE 4 
A 99 g amount of phthalic anhydride (PAN), 65 g of ethanol and 12.5 g of 
ammonia were heated 22 hrs. at 300.degree. C. while stirring. The PAN was 
100% converted with a 91% selectivity to N-ethylphthalimide. 
EXAMPLE 5 
A 120 cc amount of dimethylsuccinate (DMS) and 32 cc of anhydrous ammonia 
were heated 2 hours at 300.degree. C. while stirring. The DMS was 100% 
converted with a 90% selectivity to N-methylsuccinimide. 
COMISON EXAMPLE 6 
A 12 g amount of succinimide and 120 cc of methanol were heated 4 hrs. at 
230.degree. C. while stirring. The succinimide was 90% converted with a 
40% selectivity to N-methylsuccinimide and a 50% selectivity to DMS. 
EXAMPLE 7 
A 57.7 g amount of butyrolactone (BL), 50 g of methanol and 12.53 g of 
ammonia were heated 15 hours at 290.degree. C. while stirring. The BL was 
95% converted with a 35% selectivity to N-methylpyrrolidone and a 55% 
selectivity to pyrrolidone. 
EXAMPLE 8 
a 79 g amount of succinic acid (SA), 40 g of methanol and 12.53 g of 
ammonia were heated 3 hrs. at 290.degree. C. while stirring. The SA was 
100% converted with a 90% selectivity to N-methylsuccinimide. 
EXAMPLE 9 
A 60 g amount of SAN, 40 g of methanol, 12.53 g of ammonia, and 4 g of NaI 
were heated 15 hours at 200.degree. C. while stirring. The SAN was 100% 
converted with an 80% selectivity to N-methylsuccinimide and a 15% 
selectivity to succinimide. The same reaction conditions except for 
elimination of the NaI produced 100% SAN conversion with a 50% selectivity 
to N-methylsuccinimide and a 40% selectivity to succinimide. 
EXAMPLE 10 
A 73 g amount of dimethylsuccinate (DMS), 36.6 g of ammonium hydroxide, and 
900 psig of hydrogen were heated 16 hrs. at 260.degree. C. over 12 g of a 
5% palladium on carbon catalyst while stirring. The DMS was 100% converted 
with a 70% selectivity to N-methylsuccinimide and a 20% selectivity to 
N-methylpyrrolidone. 
EXAMPLE 11 
A 65 g amount of SAN, 41 g of methanol, 12.15 g of ammonia, 12 g of 5% 
palladium on carbon catalyst, and 700 psig of hydrogen were heated 21 
hours at 290.degree. C. while stirring. The SAN was 100% converted with a 
60% selectivity to N-methylsuccinimide and a 30% selectivity to 
N-methylpyrrolidone.