US2602791A - N, n-dialkyl morpholinium alkyl-sulfates - Google Patents

Description

Patented July 8, 1952 OFFICE.

mar-Dmitri. MoRPHoLiNnm/i ALKYL- SULFATES Joseph B. Niederl and Martin E. McGreal, Brooklyn, N. Y., assignors to J. B. Niederl and Associates, Inc., New York, N. Y., a corporation of New York No Drawing. Application November 21, 1947, Serial No. 787,468

1 Claim. I,

This invention is an amplification of the invention disclosed in Patent No. 2,417,992 issued March 25, 1947, and relates to N,N-dialkyl morpholinium alkyl sulfates. Whereas, the patent, cited above, relates to N-alkyl-N-methyl inorpholinium methyl sulfates and N-alkyl-N-ethyl morpholinium ethyl sulfates, the present invention relates also to the above type of compounds in which, however, the methyl or the ethyl group has been replaced by longer chain aliphatic radicals such as: n-propyl-; n-b-utyl-'; iso-butyl-; n-amyl-; iso-amyl-; n-hexyl-; iso-hexyl-; nheptyl-; n-octyl-; n-nonyl-; n-decyl-; n-dodecyl-g n-tetradecyl-; n-hexadecyl-; n-octadecyl-.

The replacement of the short chain methyl and ethyl radicals by longer chain aliphatic radicals oi the general formula CnH2n1 brings about a fuller realization of intramolecular synchronization of desirable physical, chemical and physiological properties, not so fully realizable with the short chain radicals. This synchronization manifests itself in several outstanding ways and characteristics of the final products. Most important of this particular feature is the evolvement of molecules having capillary active groups in both the cationic as well as the anionic part of the molecule. This outstanding property is realized in cases where the aforementioned short chain radicals are replaced by radicals possessing twelve, fourteen, sixteen or even eighteen carbon atoms in their skeleton, with the lower chain radicals butyl to decyl showing intermediate staggered solubility and surface active behaviour,

while retaining an unexpected chemical stability I towards acids or alkalies.

Of importance, also, is the physiological behaviour of these new substances. Thus entirely unexpected bactericidal properties are exhibited by several of these new series of substances. It

is a well known fact, that high bactericidal "invert soaps, a group of substances, to which the lower members of the series claimed in the (Cl. Mill-247.1)

2 I typhosa. In contrast to this, some of the compounds described inthis invention show a lesser specificity and selectivity, but a greater uniformity in bactericidal or bacteriostatic action. Thus, for instance, the NIIPtGtI'adBCYI-N-II- hexyl sulfate and the N-n-hexadecyl-N-n-hexyl morpholinium n-hexylsulfate exhibit a phenol coefficient of 200 towards E. typhoso, while still retaining a phenol coefiicient towards S. aureus of more than 300. p

Also, in regards to detergent-qualities, an unusual behaviour is exhibited as the part of anionic part in the molecule of these substances is enlarged. Thus, a gradual and staggered transition in surface activity is noted as the detergent groups appear in both the cation and the anion. This again brings about profound Di-n-propyl sulfate, (n-C3I-Iv)2SO4, B. P. /20 Di ii butyl sulfate, tIl-CQHQZSOL B. P. 914/3 Dit i -butyl sulfate, '(i-clnmsol, B. Pisa/19 Di n amyl sulfate, (n-o5H11 ,-2so-4, B. P. iii 2.5 Di ii hexyl suuate, (n-oeinmsoi, B. P. 125.3 2 Di i i octyl sulfate, (h-CiHrflzSr, B. P. 166/2 mm.

.Di-n-nonyl'sulfate, (n-CsHuflzSCM, M; P. 41.9-

42.1 Di-n-decyl sulfate, (n-C1oI-Iz1)zS04, M. P. 37.6.8 Di-n-dodecyl sulfate, '(n-Cizl-lzs) 2804, M.v

48.4.5 Di-n-tetradecyl sulfate (n-CmHzs) 2804,," M.

57.8-8.0 Di-n-hexaclecyl sulfate (H-C1GH33)2SO4, M.

66.2 Di-n-octadecyl sulfate. (nCisH3i)2SO MI.

3 The tertiary N-alkyl morpholines utilized in this invention include the following:

N-methyl morpholine, (C2H02NCH3, B. P. 115

N-ethyl morpholine, 0(C2H4) 2NC2H5, B. P. 135

N-n-propyl morpholine, O(C2I-I4)2Nn-CsH1, B.

N-iso-propyl morpholine, O(C2H4)2Ni-C3H7, B.

N-n-butyl morpholine, O(C2H4)2NI1-C4H9, B.

N-n-amyl morpholine, 0(CzH4)2Nn-C5H11, B.

N-n-hexyl morpholine, 0(C2H4) 2Nn-C6H13, B.

N-n-octyl morpholine, O(C2H4)2NI1'CBH17, B.

N-n-decyl morpholine, O(C2H4)2NI1-C1OH21, B.

N-n-dodecyl morpholine, O(C2H4)zNn-C12H25,

B. P. 155/4 mm., M. P. 14.5

N-n-tetradecyl morpholine, 0(C2Hi) 2NI1-C14H29,

B. P. 170/4 mm., M. P. 17.0

N-n-hexadecyl morpholine, O(C2H4)2N11-C16H33,

B. P. 184/4 mm., M. P. 25.0

N-n-octadecyl morpholine, 0(C2H4) 2NI1-Cl8H37,

B. P. 200/4 mm., M. P. 40.0 Although, while N-alkylated morpholines are the preferred starting materials for the quaternary ammonium ester-salts claimed in this invention. the reaction isby no means limited to the above examples. In-fact any tertiary amine, either aliphatic, aromatic or heterocyclic can be utilized in these chemical transformations. Thus trimethylamine, tri-ethylamine, triethanolamine etc. or di-methyl aniline, di-ethyl aniline, benzyldi-methyl-amine etc. may be utilized successfully, as well as simple N-heterocyelic compounds, such as pyridine, quinoline, nicotine, etc., all of them leading to the formation of quaternary ammonium ester-salts of comparable physical and chemical properties.

The reaction is usually carried out by heating equimolar portions of the symmetrical di-alkyl sulfate with the tertiary morpholine. The reaction may be carried out in a closed system or under reflux. An inert solvent, such as an aromatic hydrocarbon (benzene, toluene, xylene, etc.) or an aliphatic hydrocarbon (gasoline, kerosene) mixture may be used. The following examples disclose illustrative embodiments of the invention, but are not to be considered a limitation upon it.

wr r r r r Example 1 An N-alkyl morpholine is introduced into an appropriate reaction vessel. Thereafter, an equimolar proportion of the di-alkyl sulfate is gradually introduced under constant stirring. In case either or both reactants are solids, they are first melted and then mixed in the above manner while still warm and in liquid condition. The reaction mixture is then heated on a steam bath until no longer soluble in hydrocarbons or ethers. The heating usually takes between six and twelve hours depending on the reactivity of the di-alkyl sulfate. Upon completion of the reaction the mixture is allowed to cool and is then crystallized from hot ethyl acetate or any other suitable solvent.

Example 2 One-hundredth mole of di-n-butyl sulfate and one-hundredth mole of N-n-tetradecyl morpholine are put into a soft glass test tube. The tube is sealed and heated in a water bath for 60 hours. The tube is cooled and the mass is crystallized from ethyl acetate. The product melted -90 C.

In a similar manner of procedure and using other N-alkyl morpholines, such as N-n-dodecyl morpholine, N-n-hexadecyl morpholine, N-noctadecyl morpholine, with di-n-butyl sulfate, the following crystalline products are prepared: N-n-dodecyl-N-n-butyl morpholinium n-butyl sulfate, M. P. 41 C.; N-n-hexadecyl-N-n-butyl morpholinium n-butyl sulfate, M. P. -2 C.; N-n-octadecyl-N-n-butyl morpholinium n-butyl sulfate, M. P. -4 C.

Example 3 One-fiftieth mole of di-n-hexyl sulfate and one-fiftieth mole of N-n-dodecyl morpholine are mixed together and placed in a soft glass test tube. The tube is sealed by the flame of the Bunsen burner and the cooled tube is placed in a water bath. The water is kept at its boiling point for ten hours. After cooling, the tube is broken; the solid is removed. Upon crystallizing from ethyl acetate a crystalline product is obtained melting at C.

With the same procedure, using other N-alkyl morpholines, such as N-n-tetradecyl morpholine, N-n-hexadecyl morpholine, N-n-octadecyl morpholine, with di-n-hexyl sulfate, the following crystalline products are obtained: N-n-tetradecyl-N-n-hexyl morpholinium n-hexyl sulfate, M. P. 167 C.; N-n-hexadecyl-N-n-hexyl morpholinium n-hexyl sulfate, M. P. 1'73 C.; N-n-octadecyl-N-n-hexyl morpholinium n-hexyl sulfate, M. P. C.

Example 4 A mixture of one-tenth mole of di-n-octyl sulfate, one-tenth moleof N-n-hexadecyl morpholine and 200 ml. of toluene are refluxed for twelve hours. After cooling the toluene is distilled and the solid material remaining is dissolved in hot ethyl acetate. Upon cooling the crystalline N-nhexadecyl-N-n-octyl morpholinium n-octyl sulfate comes out. Its melting point is 208 C.

With the same method of procedure, using other N-alkyl morpholines, such as N-n-dodecyl morpholine, N-n-tetradecyl morpholine, N-noctadecyl morpholine, with di-n-octyl sulfate, the following crystalline products are prepared: N-ndodecyl-N-n-octyl morpholinium n-octyl sulfate M. P. C.; N-n-tetradecyl-N-n-octyl morpholinium n-octyl sulfate M. P. 198 C.; N-n-octadecyl-N-n-octyl morpholinium n-octyl sulfate M. P. 217 0.

Example 5 Equimolar quantities of di-dodecyl sulfate (13.0 and N-methyl morpholine (3.0 g.) are added to 100 ml. of toluene. The mixture is refluxed for eight hours. The toluene is distilled off and the remaining residue is crystallized from ethyl acetate. The crystalline N-methyl-N-n-dodecyl morpholinium n-dodecyl sulfate melts at 209 C.

The following crystalline products are prepared, usin the same method of procedure and using other N-alkyl morpholines with di-n-dodecyl sulfate: N-ethyl-N-n-dodecyl morpholinium n-dodecyl sulfate, M. P. 203 C.; N-n-butyl-N-n-dodecyl morpholinium n-dodecyl sulfate, M. P. 193 C.; N-n-hexyl-N-n-dodecyl morpholinium n-dodecyl sulfate, M. P. 184 C.; N-n-octyl-N-n-dodecyl morpholinum n-dodecyl sulfate, M. P. 173 C.; N-n-decyl-N-n-dodecyl morpholinium n-dodecyl sulfate, M. P. 162 C.; N-n-dodecyl-N-n-dodecyl morpholinium n-dodecyl sulfate, M. P. 150 C.; N-n-tetradecyl-N-n-dodecyl morpholinium n-dodecyl sulfate. M.'P. 1410.; N-n-hexadecyl-N-ndodecyl morpholinium n-dodecyl sulfate, M. P. 121 C.; N-n-octadecyl-N-n-dodecyl morpholinium n-dodecyl sulfate, M. P. 101 C.

Example 6 One-fiftieth mole of di-tetradecyl sulfate, onefiftieth mole of N-methyl morpholine and 150 ml. of toluene are mixed in a round bottom flask. After refluxing for twelve hours, the reaction mixture is allowed to stand overnight. The toluene is distilled off and the residue is crystallized from hot ethyl acetate. The product, N- methyl-N-n-tetradecyl morpholinium n-tetradecyl sulfate, melts at 190 C.

Following the same method of procedure and using other N-alkyl morpholines with di-ntetradecyl sulfate, the resulting compounds are obtained: N-ethyl-N-n-tetradecyl morpholinium n-tetradecyl sulfate, M. P. 181 C.; N-butyl-N-ntetradecyl morpholinium n-tetradecyl sulfate, M. P. 172 C.; N-n-hexyl-N-n-tetradecyl morpholinium n-tetradecyl sulfate, M. P. 164 C.; N-noctyl-N-n-tetradecyl morpholinium n-tetradeoyl sulfate, M. P. 155 C.; N-n-decyl-N-n-tetradecyl morpholinium n-tetradecyl sulfate, M. P. 147C.

N-n-dodecyl-N-n-tetradecyl morpholinium ntetradecyl sulfate, M. P. 140 C.; N-n-tetradecyl- N-n-tetradecyl morpholinium n-tetradecyl sulfate, M. P. 130 C.; N-n-hexadecyl-N-n-tetradecyl morpholinium n-tetradecyl sulfate, M. P.

110 C.; N-n-octadecyl-N-n-tetradecyl morpholinium n-tetradecyl sulfate, M. P. 90 C.

Example 7 'hexadecyl morpholinium n-hexadecyl sulfate,

M. P. 156 C.; N-n-hexyl-N-n-hexadecyl morpholinium n-hexadecyl sulfate, M. P. 150 C.; N-noctyl-N-n-hexadecyl morpholinium n-hexadecyl 6 sulfate, M. P. 146 C.; N-n-decyl-N-n-hexadecyl morpholinium n-hexadecyl sulfate, M. P. 140 C.; N-n-dodecyl-N-n-hexadecyl morpholinium nhexadecyl sulfate, M. P. 134 C.; N-n-tetradecyl- N-n-hexadecyl morpholinium n-hexadecyl sulfate, M. P. C.; N-n-hexadecyl-N-n-hexadecyl morpholinium n-hexadecyl sulfate, M. P. 94 C.;

N-n-octadecyl-N-n-hexadecy1 morpholinium n-- hexadecyl sulfate, M. P. 76 C.

' Example 8 One-fiftieth mole of di-octyl sulfate, onefiftieth mole of N-methyl morpholine and 150 ml. of toluene are mixed and refluxed for twenty hours. The toluene is distilled off and the residue is crystallized from ethylacetate. The crystalline product melts at 158 C.

Following the same procedure, using other N- alkyl morpholines with di-octadecyl sulfate, the resulting compounds are obtained: N-ethyl-N-noctadecyl morpholinium n-octadecyl. sulfate, M. P. 150 C.; N-n-butyl-N-n-octadecyl morpholinium n-octadecyl sulfate, M. P. 146 C.; N-nhexyl-N-n-octadecyl morpholinium n-octadecyl sulfate, M. P. 142 C.; N-n-octyl-N-n-octadecyl morpholinium n-octadecyl sulfate, M. P. 138 C.; N-n-decyl-N-n-octadecyl morpholinium n-octadecyl sulfate, M. P. C.; N-n-dodecyl-N-noctadecyl morpholinium n-octadecyl sulfate, M. P. 131 C.; N-n-tetradecyl-N-n-octadecyl morpholinium n-octadecyl sulfate, M. P. 110 C.; N-n-hexadecyl-N-n-octadecy1 morpholinium noctadecyl sulfate, M. P. 80 C.; N-n-octadecyl- N-n-octadecyl morpholinium n-octadecyl sulfate, M. P. 60 C.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date 2,271,707 Munz Feb. 3, 1942 2,380,325 Niederl et a1. July 10, 1945 2,417,992 Niederl et a1. Mar. 25, 1947