Method of manufacturing anhydrous 2-hydroxy-3-chloropropane trimethylammonium chloride

Process for manufacturing anhydrous 2-hydroxy-3-chlorophropane trialkylammonium chloride by conversion of trialkylammonium chloride with epichlorohydrin by forming an aqueous solution of trialkylammonium chloride in an organic solvent inert to epichlorohydrin, the solvent forming an azeotrope with ater which boils at temperatures up to the normal boiling point of the solvent, distilling off the azeotrope to form a suspension of trialkylammonium chloride in the solvent reaction product and reacting the reaction product in the solvent with epuichlorohydrin at a temperature of 20.degree. to 120.degree. C.

The invention relates to a method of manufacturing 
2-hydroxy-3-chloropropane trimethylammonium chloride by converting 
trialkylammonium chloride with epichlorohydrin. 
Converting trimethylammonium chloride with epichlorohydrin to form 
2-hydroxy-3-chloropropane trimethylammonium chloride is known, from U.S. 
Pat. No. 2,876,217 for example. In the known process the trimethylammonium 
chloride is employed in an aqueous solution and the reaction product is an 
aqueous solution of 2-hydroxy-3-chloropropane trimethylammonium chloride. 
This aqueous solution must usually be purified before it can be used to 
manufacture cation-active starch products. 
A disadvantage of the method described in U.S. Pat. No. 2,876,217 is the 
necessity of working with an aqueous medium, which leads to a series of 
side reactions like the formation of 
1,3-bis-trimethylammonium-2-hydroxypropane dichloride. This byproduct 
precipitates with and usually can not be separated from the desired 
product, of which it is an undesirable component because it does not react 
with starch. 
1,3-Dichloropropanol-2 will also occur with the method disclosed in U.S. 
Pat. No. 2,876,217 because of the reaction of the epichlorohydrin with 
hydrochloric acid. Since this propanol reacts with starch during 
cross-linkage, its participation in the final product must be limited to 
less than 50 ppm. 
Obtaining an anhydrous 2-hydroxy-3-chloropropane trimethylammonium chloride 
as the precipitate from an anhydrous organic solvent and filtering out the 
crystals has been proposed (Cf. NR-OS 78 04 880). This method starts with 
gaseous trimethylamine, which reacts with the solvent. Since, however, the 
solvent is dangerous to health, it is difficult to carry out this process 
on an industrial scale without detrimentally affecting the atmosphere in 
the work place. 
The problem remains, then, of how to manufacture an anhydrous form of 
2-hydroxy-3-chloropropane trialkylammonium chloride from an aqueous 
initial solution of trialkylammonium chloride, obtaining a high yield of a 
product that is as pure as possible and that contains as little of such 
byproducts as 1,3-bis-trimethylammonium-2-hydroxypropane chloride or 
1,3-dichloropropanol-2. 
As a solution to this problem a method has been discovered for 
manufacturing anhydrous 2-hydroxy-3-chloropropane trialkylammonium 
dichloride by converting trialkylammonium chloride with epichlorohydrin, 
characterized by making an aqueous solution of trialkylammonium chloride 
in an organic solvent that combines with water to form an azeotrope 
boiling at temperatures below its normal boiling point, by heating the 
solution to temperatures as high as the boiling point of the solvent, by 
distilling the azeotrope off as it forms, and finally by converting in the 
solvent with epichlorohydrin at temperatures ranging from 20.degree. to 
120.degree. C. 
This method leads directly to yields of over 80% of the desired product in 
solid form. The product is up to 99.8% pure as determined by its 
chlorohydrin content and by nuclear magnetic resonance. It is thus 
practically free of 1,3-bis-trialkylammonium-2-hydroxypropane chloride 
when manufactured in accordance with the preferred embodiment of the 
method. 
It is important to select the right solvent when employing this method. The 
solvent must form an azeotrope with water, and the boiling point of the 
azeotrope must be below that of the solvent alone. The azeotrope should 
also be easy to separate into layers. The solvent or mixture of solvents 
must also not react with epichlorohydrin under the prevailing reaction 
conditions. This prerequisite is generally satisfied by organic solvents 
that do not readily form a solution with water. Among such solvents are 
aliphatic alcohols with 4 to 6 carbon atoms, aliphatic saturated 
hydrocarbons with 5 to 8 carbon atoms, aromatic hydrocarbons like toluene 
and benzene, trichloroethylene, tetrachloroethylene, and methyl ethyl 
ketone. Mixtures of these substances may also be employed. Since the 
mixtures often work better than the individual solvents, one preferred 
embodiment of the method employs mixtures. 
Among preferred mixtures are combinations of aliphatic alcohols with 
toluene or benzene in proportions that will result in an azeotropic 
mixture. Mixtures of other applicable solvents must also be azeotropic. 
In the first stage of the method of the invention a hydrous solution of 
trialkylammonium chloride is dissolved in or dispersed through the solvent 
or mixture of solvents. A 60 to 75% aqueous solution is usually employed, 
although higher or lower concentrations can also be used. It is practical 
to use a solution of trialkylammonium chloride that will not have to be 
further diluted, to avoid having to distill too much water out later. 
The amount of trialkylammonium chloride solution to be employed depends on 
how readily the solvent selected will dissolve the salt. About 5 to 8 mol 
of trialkylamine hydrochloride per 2000 g of solvent or solvents is 
usually employed. Lower concentrations of trialkylamine hydrochloride may 
also be used, of course, although there would be no advantage to doing so. 
The trialkylamine hydrochloride solution is then heated in the organic 
solvent or solvents to the boiling point of the solvent or solvents and 
the resulting azeotropic mixture reflux-distilled out. Water is separated 
from the azeotrope distillate by a known method (by decanting for 
instance) and the recovered solvent returned if possible to the reaction 
mixture. The materials can also be fractionated, with only the azeotropic 
mixture distilling over. Heating continues until an amount of water equal 
to that of the original aqueous solution of trialkylamine hydrochloride is 
left in the distillate. How long this takes can easily be determined with 
preliminary tests and is a function of several known factors. 
As the water is being distilled off, some or all, depending on the selected 
reaction medium, of the trialkylammonium chloride should precipitate in 
solid form. This precipitation will not affect the further course of the 
reaction, although care must be taken that the resulting dispersion 
remains easy to stir. More anhydrous solvent or solvents may be added if 
necessary. After the azeotropic distillation of the water, any solvent, 
like a lower, water-miscible alcohol, can be added. 
Epichlorohydrin, preferably in equimolar amounts, is added to the solution 
or suspension after the water has been distilled off. The reaction with 
trialkylammonium chloride will begin at only slightly elevated 
temperatures. Temperatures will range preferably from 40.degree. to 
60.degree. C. Since conversion is exothermic, the mixture may have to be 
cooled. The reaction may be followed by determining the epichlorohydrin 
content of the solution by gas-chromatography. The desired end-product 
will precipitate into the solvent or solvents in the form of a white, 
crystalline powder. When the reaction stops, the product can be filtered 
out directly and processed further by known methods to obtain the grade of 
purity mentioned above.

The preferred trialkylammonium chloride is trimethylammonium chloride. 
Other possible alkyl groups are those with 2 to 4 carbon atoms. The alkyl 
groups may also be different. 
EXAMPLE 1 
A 3-l round-bottom flask equipped with a stirrer, a thermometer, a drop 
funnel, and a still with water separator and reflux condenser was charged 
with 2100 ml of toluene, to which 680 g of a 70% aqueous solution of 
trimethylammonium chloride was added. The theoretical trimethylammonium 
chloride content was 5 mol. 
The mixture was heated to the boiling point and the water distilled off 
azeotropically and separated for 6 hours. A total of 201 ml of water was 
collected. A total of 462.5 g of epichlorohydrin was added to the 
remaining mass of crystals and toluene for 11/2 hours at an initial 
temperature of 70.degree. to 75.degree. C., while the internal temperature 
increased to between 98.degree. and 100.degree. C. When all the 
epichlorohydrin had been added, the reaction mixture was stirred 6 hours 
longer while it gradually cooled. 
The resulting solid was filtered out, rewashed, first with toluene and then 
with acetone, and dried in a vacuum. The yield was 812 g of a white powder, 
83.7% in terms of trimethylamine hydrochloride. 
EXAMPLE 2 
The apparatus described in Example 1 was charged with 2000 ml of 
trichloroethylene, to which 543 g of a 70% aqueous solution of 
trimethylammonium chloride was added. The mixture was heated to the 
boiling point and an azeotropic mixture of trichloroethylene and water 
distilled off for 11 hours. A total of 159.5 ml of water was collected. 
The resulting mixture was cooled to 75.degree. C., at which temperature the 
addition of epichlorohydrin was commenced. A total of 370.1 g (4 mol) of 
epichlorohydrin was allowed to drip into the mixture for 3 hours, while 
the internal temperature of the mixture increased to 90.degree. C. The 
reaction mixture was stirred 2 hours longer until gas chromatography 
indicated no more epichlorohydrin. 
The resulting solid was filtered out, washed with trichloroethane, and 
dried. A total of 672 g, with an active content of 93.4% was obtained, a 
yield of 83.5% in terms of trimethylammonium chloride. 
EXAMPLE 3 
The apparatus described in Example 1 was charged with 2000 ml of methyl 
isobutyl ketone, to which 545.7 g of a 70% aqueous solution of 
trimethylammonium chloride was added. The water was distilled off as an 
azeotropic mixture. A total of 160.4 ml of water was collected in 7 hours. 
The mixture was cooled to 80.degree. C., and 370.7 g of epichlorohydrin 
added for 5 hours, while the temperature increased to between 90.degree. 
and 95.degree. C. The resulting product was immediately filtered out 
without further stirring, washed with methyl isobutyl ketone, and dried in 
a vacuum. 
A total of 577 g of 2-hydroxy-3-chloropropane trimethylammonium chloride, 
97 to 98% pure, was obtained. This yield was 75.1%. 
EXAMPLE 4 
The three-necked flask described in Example 1 was charged with 2000 ml of 
n-butyl alcohol, which was heated to an internal temperature of 
117.degree. C. while being reflux distilled. Into this was dripped 1090 g 
of a 70% aqueous solution of trimethylamine hydrochloride for 4 hours, 
while the internal temperature decreased to between 95.degree. and 
98.degree. C. The mixture was kept at this temperature and 
reflux-distilled for 8 hours, with a total of 306 g of water and butanol 
collected. This mixture contained about 285 ml of water. 
The reaction mixture was cooled to between 60.degree. and 70.degree. C. and 
740 g of epichlorohydrin added for 3 hours. The temperature rose so rapidly 
that the mixture had to be cooled. When all the epichlorohydrin had been 
added, the mixture was stirred for 5 hours. The resulting solid was 
filtered out, washed with butanol, and immediately dried. The yield was 
1373 g of 88 to 93% pure 2-hydroxy-3-chloropropane trimethylammonium 
chloride. 
EXAMPLE 5 
A 3-l three-necked flask was charged with a mixture of 540 g of n-butyl 
alcohol and 1460 g of toluene. This mixture boils at 105.6.degree. C. It 
was reflux heated to this boiling point. Into it was dripped 1090 g of a 
70% aqueous solution of trimethylamine hydrochloride, with the interior 
temperature decreasing to 100.degree. C. Reflux was continued for 7 hours 
and the aqueous azeotropic mixture was collected, resulting in 335 g of a 
distillate that was 97.8% water. 
The crystalline residue of trimethylammonium chloride was cooled in the 
toluene-alcohol mixture to 50.degree. C. To it was added 740 g of 
epichlorohydrin for 31/2 hours. The temperature was kept at or below 
70.degree. C. by cooling. After all the epichlorohydrin had been added, 
the mixture was stirred for another 4 hours until gas chromatography 
indicated no more epichlorohydrin. 
The reaction mixture was cooled and the solid matter filtered out, rewashed 
with toluene, and dried. The yield was 1299 g of a white crystalline powder 
with an active content of from 99.6 to 99.7% of 2-hydroxy-3-chloropropane 
methylammonium chloride. Only 24 ppm of dichloropropanol were 
demonstrable. 
It will be understood that the specification and examples are illustrative 
but not limitative of the present invention and that other embodiments 
within the spirit and scope of the invention will suggest themselves to 
those skilled in the art.