I N D U S T R I A L A N D E N G I N E E R I N G CHEMISTRY
186
TABLE XII. 60" C. PERSULFATE RUE;AT PLANT (X-645)
THE
INSTITUTE GR-S
TABLE XIII. 50" C . HYDROPEROXIDE-SUGtlR RECIPE
[Shortstops, sodium dimethyldithiocarbamate alone or plus sulfur ES sodium polysulfide; parts of shortstop, 0.15 part sodium dimethyldithiocarbamate or 0.1 part of the combination per 100 parts of monomer' aveiage reactqr RIooney, 51.4 RIL-4'; average recoyery discharge MooAey, 53.8 ML-4 ; average production Mooney. 54.8 RIL-4' (all at 212' F.)]
Physical Tests Compound hIooney (ML-4' a t 2 1 2 O F.) 50' X 292' F. tensile, lb./sq. in. 50' X 292' F. elongation, 7 ' 25' X 292' F 300% modulus lb./sq. in. 50' X 292' F: 300% modulus: lb./sq. in. 100' X 292' F. 300% modulus, Ib./sq. in. Strain test a t 400 25' X 292' F. e!ongation, % 50' X 292' F. elongation % 100' x 2920 F. elongation: Pounds of X-645 produced, 80,000.
620
330 710 1155 374 230 184
54.8 2710 650 355 780 1160 360 223 171
ACKNOWLEDGiMENT
The authors wish to thank the Synthetic Rubber Division, Reconstruction Finance Corp., for permission to publish these findings obtained in connection with the government synthetic rubber program and to acknowledge the cooperation of the B. F. Goodrich Chemical Co. Port Neches and Institute GR-S personnel during plant trials. LITERATURE CITED
Bovey and Kolthoff, J . Am. Chem. Soc., 69, 2143 (1947). Frank and Adams, Ibid., 68, 908 (1946). (3) Hohenstein and Mark, J . Polymer Sci., 1 , 548 (1946). (4) Houston, Anal. Chem., 20, 49 (1948). (5) Kluchesky and Wakefield, IXD. ENG. Cmnr., 41, 1768-71 (1) (2)
(1949).
Kolthoff and Bovey, J . Am. Chem. SOC.,70, 791-9 (1948). (7) Kolthoff and Harris, J. Polymer Sci., 2, 41 (1947). (6)
Parts 75 25 4.3 0.76 0.05 0.05 0.25 165
Butadiene Styrene Dresinate 731 DDN Cumene hydroperoxide Dextrose Trisodium phosphat,e phosphate Water
Tread Recipe X-64ba GR-9-18 54.0 2420
Vol. 45, No. 1
TABLEXIV.
50" C. HYDROPEROXIDE-SUGAR RCE; AT
THE
INSTITUTE GR-S PLAKT (X-655) (Shortstop, sodium dimethyldithiocarbamate plus sulfur a3 sodium polysulfide; parts of shortstop, 0.1 part shortstop solids per 100 parts of monomer; average reactor Mooney 50.2 ML-4' a t 212" F.; average production kIooney, 53.5 I L I L - ~a' t 2120 F:) Tread Recipe X-655a GR-8-18Physical Tests Compound RIooney (ML-4' a t 212' F.) 55.5 57.0 50' X 292' F. tensile, Ib./s 3085 2685 In. 50' x 2920 F elongation 620 645 25' X 292' F:300% modulus, lb./sq. in. 385 415 50' X 292' F. 300% modulus, lb./sq. in. 910 840 100' X 292' F. 300% modulus, lb./sq. in. 1286 1160 Strain test a t 400 Ib./sq. in. 25' X 292' F. elongation % ' 317 339 50' X 292' F. elongation' % 197 206 100' X 292' F. elongation: % 160 153 a Pounds of X-655 produced, 275,000.
8
(8) (9) (10)
(1 1) (12) (13)
Mark and Tobolsky, "Physical Chemistry of High Polymeiic Systems," pp. 401-24, Vol. 11, 2nd ed., Sew York, Interscience Publishers, Inc., 1950. Marvel and Higgins, J. Polymer Sci., 3, 448-54 (1948). Price and Durham, J . Am. Chem. Soc., 65, 757 (1943). Private communications to Synthetic Rubber Division, Raconstruction Finance Corp., Washington, D. C. Staudinger, Trans. Faradau Soc., 32, 323 (1936). Wakefield and Babb, IND.ENG.CHEM.,42, 838-41 (1950).
RECEIVED foi review M a y 20, 1952.
ACCEPrED
June 26, 1952.
Quaternary Ammonium Compounds with Bactericidal Properties H. STURM, E. ICONERMANN, R. AESCMBACHER,
AND
R. GR4DMANN
Friedrich Steinfels, P.O. Box 23, Zurich, Switerzland
T
HE interesting properties of the monoalkyl ethers of glycerol being well known, it was believed that the synthesis of the monoalkyl ethers of triethanolamine would furnish a series of new compounds of perhaps equal interest. Moreover, starting from these new ethers, which are tertiary amines, it is very easy to obtain a large number of quaternary ammonium salts-substances which would probably have applications as detergents, in the textile industry, and as germicides. Several quaternary ammonium compounds of different composition which contain, as radicals attached to the quaternary nitrogen atom, ethers, polyethers, or thioethers, are described by Leuchs, Taub, and Hahl in a number of U. S. patents (1, 3,4). Yone of these, however, contains, beside the ether radical, still other radicals whidi possess free hydroxyl groups. The two free hydroxy groups in quaternary ammonium salts derived from monoalkyltriethanolamine ethers were assumed to have a favorable influence on the solubility of these products in water; this was later confirmed.
PREPARATION OF TRIETHANOLA3lINE MONOALKYL ETHERS
The preparation of the triethanolamine monoalkyl ethers is rather simple. They are formed by the reaction between the monosodium compound of triethanolamine and alkyl halides. Starting from different fatty alcohols, as octyl, dodecyl, hexadecyl, and octadecenyl alcohols, the corresponding alkyl bromides were prepared by action of 48% hydrobromic acid solution on the alcohols after the method, described in Organic Synthesis ( 2 ) . Another method of preparing the alkyl bromides was also tried: With 1 mole of fatty alcohol only a slight excess of the calculated amount of hydrobromic acid mas used by means of a system of continuous bromination, but the yields obtained have not yet proved to be satisfactory. It appeared desirable to work with the bromides in preference t o the chlorides, because the action of the halides on the monosodium compound is rather slow. The monosodium compound was obtained by treating triethanolamine with technical sodium hydride in an inert solvent.
January 1953
INDUSTRIAL AND ENGINEERING CHEMISTRY
It may be added that, instead of sodium hydride, suspensions of metallic sodium in an inert solvent, as they are already in current use in the United States, should work as well. After refluxing the reaction mixture with vigorous stirring for about 3 hours, the evolution of hydrogen had ceased and the monosodium triethanolaminate had formed as a voluminous gray-white mass, suspended in the solvent. T o this mixture a solution of alkyl bromide was added and reacted with the sodium salt to form the triethanolamine monoalkyl ether and sodium bromide. It took 2 to 3 hours of refluxing with stirring to complete this reaction, the end of which was indicated by the deposition of sodium bromide as a crystalline precipitate a t the bottom of the flask. After filtering and removal of the solvent by distillation, the crude products thus obtained appeared as slightly colored oily liquids. The yields were about 80% of the theoretical amount. For purification the crude amines were dissolved in ethyl ether and washed several times with water. After drying over sodium sulfate and removal of the ethyl ether, further purification was obtained by distillation. All the triethanolamine monoalkyl ethers prepared could be distilled under reduced pressure. At a pressure of 0.02 to 0.05 mm. of mercury the boiling points range from 138" to 141" C. for the mono-octyl ether to 192" to 198' C. for the monohexadecyl ether. The mono-octadecenyl ether distilled at the same pressure at 196" to 198" c. The purity of these ethers was established by nitrogen determination, which was carried out either by the Kjeldahl method or by direct titration in water with hydrochloric acid. The pure triethanolamine ethers appear as colorless liquids with the exception of the cetyl ether, which is solid. They are insoluble in water but have a strong tendency to form emulsions with water. The liquid ethers in davlight appear as very strong blue-violet fluorescent oils.
187
ANTIBACTERIALPROPERTIES. Since it is generally recognized that a large number of known surface-active quaternary ammonium compounds possess bactericidal properties, there existed the probability that the salts prepared from the triethanolamine monoalkyl ethers would show a similar effect. Preliminary investigations, carried out with the benzyl bromide derivatives of the monocetyl and the monododecyl ether as well as the dimethyl sulfate derivative of the monododecyl ether, showed t h a t these compounds were bacteriostatic. The benzyl bromide salt of the triethanolamine monododecyl ether produced the best results in antibacterial activity. This substance was therefore selected for further tests. BACTERICIDAL PROPERTIES. The following dilutions of the benzyl bromide derivative of the triethanolamine monododecyl ether in sterile distilled water were used: 10-3, 10-5. To test tubes, each containing 5 ml. of the respective dilution, 0.05 ml. of a well-grown 12-hour culture of the respective organisms in glucose broth was added. After an exposure of 2, 5 , 10, 15, 30, and GO minutes, respectively, at room temperature 0.1 ml. from each tube was inoculated into 25 ml. of glucose broth, and the cultures which were kept at 37 O C. were examined daily during 6 days. The bactericidal test for M . tuberculosis was performed with 0.05 ml. of a well-grown 6-day culture in Dnbos medium, and growth was also tested in Dubos medium at 37" C. during 8 days (Table I). OF DILUTIONS EFFECTIVELY KILLING TABLE I. DETERMINATION VARIOUSBACTERIA AT DIFFERENT EXPOSURES
+-
= growth = no growth Growth in gluoose broth
2
Time of exlJosure, min.
5
10
15
60
30
IM.pyogenes var. aureus PREPARATION O F QUATERNARY AMMONIUM SALTS
I n order to arrive a t quaternary ammonium salts from the described triethanolamine ethers, the latter were treated with suitable substances. The most easy reaction was the addition of benzyl bromide. to each of them. The tertiary amines reacted readily at room temperature with the calculated amounts of the bromide with slight liberation of heat. No solvent was necessary for this reaction, and after a few hours, the quaternary ammonium compounds crystallized, the yields being quantitative. A11 other derivatives were prepared in a similar manner-Le., using equimolecular quantities, but with ethyl ether as a solvent. Thus with dimethyl sulfate, reaction products were obtained which deposited as heavy oils of high viscosity, and these could easily be separated from the ether. After removal of the last traces of ethyl ether, they formed colorless semisolid masses. Moreover, with triethanolamine monocetyl ether a solid acetate was obtained by action of glacial acetic acid on the amine. These are but a few examples, for i t is obvious that a large number of derivatives can as easily be prepared. PROPERTIES OF THE QUATERNARY AMMONIUM SALTS
The quaternary ammonium salts thus produced dissolve readily in water, forming clear solutions even in tap water. T h e watery solutions show excellent foaming qualities. Some of the salts, especially the benzyl bromide derivatives, possess a very good ability to. crystallize. They can be recrystallized from acetic acid ester and ethyl ether, forming small colorless plates, which are not hygroscopic. They have sharp melting points and do not decompose on melting. All these quaternary salts show a bright blue fluorescence under the ultraviolet lamp. It is possible that these quaternary ammonium compounds may have valuable properties in the field of detergency as well as in the textile industry. Their application as wetting agents or as "cationic" finishing agents and their possible ability to improve the fastness of dyed fabrics to water shall soon be investigated.
Dilution
_ _
1:lOO 1 : 1000 1 : Y0,ooO 1 : 100,000
_
++
++
-
++
_ _
++
-
++
_
+-
Pseudomonas aeruginosa
Dilution
_
1:lOO 1:1000 1 : 10,000 1 :100,000
_
++ +
+++
-
+++
-
-
++ +
++ +
..
+
-
++ +
Bacillua mesentericus Dilution 1:100
_
_
-
++
++
++
-
1:1000 1:10,000
1: 100.000
-
-
M . tuberculosis strain H 37rva Dilution
.. ..
1 :1000 1 :10,000
a
.. ..
-
+
..
-
-
+
Growth in Dubos medium.
BACTERIOSTASIS.The test was carried out in glucose broth with the following dilutions of the benzyl bromide derivative of the triethanolamine monododecyl ether: 10-8, 10-4, 10-6, 10-8, 10-7; each tube contained 10 ml. of the respective dilution. Each tube was inoculated with a loopful of a well-grown 12-hour culture of the respective or anisms and thep kept at 37" C . These were observed daily &ring 6 days. The test with M . tuberculosis was made in Dubos medium. Each tube was inoculated with a loopful from a &day well-grown culture in Dubos medium (Table 11). OF DILUTIONS INHIBITING GROWTH TABLE 11. DETERMINATION OF
VARIOUSBACTERIA
+ = growth - = rowth inhibition
Grow& in glucose broth Dilution
M . pyogenes var. aureus
1:lOOO
-
Pseudomonas aerugznosa Bacillus mesentericus IM. tuberculosis H 37 rva a Growth in Dubos medium.
-
1:10,000 1:100,000 1:106
-
+-
-
+
l:lO7
:- $ +
+
INDUSTRIAL AND ENGINEERING CHEMISTRY
188
INCO>X\IPATIBILITY WITH SOAP. I n order to determine the influence of soap on the bactericidal efficiency of the quaternary ammonium compound a 10% soap solution which contained 0.2% of the former substance was tested and compared with a 10% solution of pure soap.
ity in the behavior of the animals. andnorma'*
Vol. 45, No. 1 They also remained healthy
On the basis of the data given, the toxicity of the triethanolamine monododecy] ether may be considered vcq- low. I t is a stable substance and has good solubility in water as well as excellent foaming qualities; it might be used as a "detergent Samtizer. ''
T~ the tubes containing the under test 0.05 of a well-grown culture of the respective organisms in meat broth was added. After an exposure of 2, 5, 10, 15, 30, and 60 minutes CONSTITUTION AND CH4RACTERISTICS OF THE. one loopful from each tube of the soap solution was transferred to TRIETHANOLAMINE MONOALKY L ETHERS 5 ml. of glucose broth and incubated for 24 hours a t 37 C. Table I11 shows that both solutions produced the same resulta-Le., a bactericidal efficiency of the quaterHO--CHz--CH2\ R = CHa-(CHZ), CHzHO-CHz-CHz-N = CHI-( CH? i t - CHznary triethanolamine derivative cannot be observed in a 10% soap solution. R-O--CHz-CHz/ = CH~--(CHZ)~~-CHZCHj-( ('H~)~-CH=CH-(CHI)-CH~-O
TABLE111. BACTERICIDAL EFFICIENCY OF BENZYLBROMIDE DERIVATIVE OF TRIETHANOLAMINE MONODODECYL ETHERIN SOAPSOLCTION
+ - == growth no growth
P u r e aoap 10% solution Time of exposure, min. Pesudomonas aeruginosa
Escherichia coli M.-Puogenes var. aureus Streptococcus faecalis Bacillus mesentericus
2
-
++ ++
10
+++
+ ++
Solution: soap 9.8%, germicide 0.2% Time of expoeure, min. 2 5 Pasudomonas aeruginosa Escherichia c o l i M . pyogenesvar. aureus f Streptococcus faeca2i.s Bacillus mssentericus
+ ++
.~
+-
++
30
60
++
+ ++
+ ++
10
15
30
60
-
-
4-
++
-
-
+++
1.5
--
4-
-
+++
-
-
++
-
-
-
+
~
TOXICITY.
O
Triethanolamine monododecyl ether, G ~ H ~ O I N
5
-
Triethanolamine monooctyl ether, ClrH,,OJ Molecular weight: 261.40 Boiling point: 138-141 C./0.02mm. Hg Analysis: N calcd., 5.36%; found, 5.15% (titration) hlolecular weight: 317.50 Boiling point: 160-165" C./0.04 mm. Hg Analysis: N calcd., 4.41%; found, 4.30, 4.40% (Kjeldahl) Triethanolamine monohexadecyl ether, Cz2HnOsN Molecular weight: 373.61 Boiling point: 192-198" C./0.02 mm. Hg Analysis: N calcd., 3.75%; found, 3.69, 3.75% (Kjeldahl) Triethanolamine monooctadecenyl ether, Cz&OaN Molecular weight: 399.64 Boiling point: 196-198" C./0.025 mm. Hg Analysis: N calcd., 3.50'%; found, 3.47, 3.51% (Kjeldahl) ACKNOWLEDGMENT
Considering the application of the tested substance
as disinfecting agent, it was advisable to investigate its toxicity.
For this purpose the effect on white mice, which were given different doses of the quaternary salt by oral route, was studied. Six mice, which received daily doses of 50 mg. per kg. weight in two equal portions of a 0.1% solution, showed absolutely no symptoms of illness. The experiment was continired for 6 days, and the animals were afterwards observed for 10 additional days. They all continued to be healthy and normal. A similar experiment was carried out with a 1 yo solution, so that the dose was 500 mg. per kg. weight per day. After each administration of the substance the mice showed signs ot slight uneasiness and reduced activity. All, however, I ecovrred to normal within a few hours. Observatiorls during 8 days after completing the experiment failed to reveal any signs of abnormal-
The bactericidal tests as n-ell as the estimation of the toxicity of the described compounds were carried out by H. Mooser and H. Grumbach a t the Hygiene Institute of the Universityof Zurich. LITERATURE OITED
(1 j Leuchs, F., U. S. Patent 2,336,179 (1943). (2) O T ~Synthesis. . 1, 7 (1921); 15, 25 (1935); 21, 37 (1941). (3) Taub, L., Hahl, H., and Leuchs, F., G. 8 Patents 2,087,131 (1937)
and 2,152,047 (1939). (4) Taub. L., and Leuchs, F., Ibid., 2,086,585 (1937) (1937).
and 2,087,132
RECEIVFD for review November 19, 1951.
A c c E p r E D M a y 28, 1952. Presented before t h e International Congrebs of Pure and Applied Chemistrr, Kew York, 1951.
Chemically Machined Glass (LeJt to r i g h t ) perforation with hexagonal cell structure; photoengraved line cut with some lines inked in; concentric glass rings, 0.003 to 0.015 inch thick (see article page 115)
