US2566132A - Quaternary ammonium compounds - Google Patents
Quaternary ammonium compounds Download PDFInfo
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- US2566132A US2566132A US721153A US72115347A US2566132A US 2566132 A US2566132 A US 2566132A US 721153 A US721153 A US 721153A US 72115347 A US72115347 A US 72115347A US 2566132 A US2566132 A US 2566132A
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- quaternary ammonium
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- 150000003856 quaternary ammonium compounds Chemical class 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 32
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 13
- 230000002421 anti-septic effect Effects 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 150000001450 anions Chemical class 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 150000001721 carbon Chemical class 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
- 125000000217 alkyl group Chemical group 0.000 description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- -1 sulfamyl radical Chemical class 0.000 description 16
- 238000000034 method Methods 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 238000002844 melting Methods 0.000 description 9
- 230000008018 melting Effects 0.000 description 9
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 230000002070 germicidal effect Effects 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 231100000419 toxicity Toxicity 0.000 description 5
- 230000001988 toxicity Effects 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 229910021607 Silver chloride Inorganic materials 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 150000004820 halides Chemical class 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 4
- 125000001453 quaternary ammonium group Chemical group 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 3
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229940027983 antiseptic and disinfectant quaternary ammonium compound Drugs 0.000 description 3
- 230000003385 bacteriostatic effect Effects 0.000 description 3
- 125000001246 bromo group Chemical group Br* 0.000 description 3
- 239000013058 crude material Substances 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 150000003526 tetrahydroisoquinolines Chemical class 0.000 description 3
- 150000003530 tetrahydroquinolines Chemical class 0.000 description 3
- KOFZTCSTGIWCQG-UHFFFAOYSA-N 1-bromotetradecane Chemical compound CCCCCCCCCCCCCCBr KOFZTCSTGIWCQG-UHFFFAOYSA-N 0.000 description 2
- YFVBASFBIJFBAI-UHFFFAOYSA-M 1-tetradecylpyridin-1-ium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCC[N+]1=CC=CC=C1 YFVBASFBIJFBAI-UHFFFAOYSA-M 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical group C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 2
- RRQWVJIFKFIUJU-UHFFFAOYSA-N 1-bromooctadec-9-ene Chemical compound CCCCCCCCC=CCCCCCCCCBr RRQWVJIFKFIUJU-UHFFFAOYSA-N 0.000 description 1
- RNHWYOLIEJIAMV-UHFFFAOYSA-N 1-chlorotetradecane Chemical compound CCCCCCCCCCCCCCCl RNHWYOLIEJIAMV-UHFFFAOYSA-N 0.000 description 1
- JKFYKCYQEWQPTM-UHFFFAOYSA-N 2-azaniumyl-2-(4-fluorophenyl)acetate Chemical compound OC(=O)C(N)C1=CC=C(F)C=C1 JKFYKCYQEWQPTM-UHFFFAOYSA-N 0.000 description 1
- NYPYPOZNGOXYSU-UHFFFAOYSA-N 3-bromopyridine Chemical compound BrC1=CC=CN=C1 NYPYPOZNGOXYSU-UHFFFAOYSA-N 0.000 description 1
- HIFMOXUWNNCDNR-UHFFFAOYSA-M 3-chloro-1-tetradecylpyridin-1-ium;bromide Chemical compound [Br-].CCCCCCCCCCCCCC[N+]1=CC=CC(Cl)=C1 HIFMOXUWNNCDNR-UHFFFAOYSA-M 0.000 description 1
- PWRBCZZQRRPXAB-UHFFFAOYSA-N 3-chloropyridine Chemical compound ClC1=CC=CN=C1 PWRBCZZQRRPXAB-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- IFTHAEOKDMQJFY-UHFFFAOYSA-N I.C1=CC=C2CCCNC2=C1 Chemical compound I.C1=CC=C2CCCNC2=C1 IFTHAEOKDMQJFY-UHFFFAOYSA-N 0.000 description 1
- 241001125831 Istiophoridae Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical group O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- 229910021612 Silver iodide Inorganic materials 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001347 alkyl bromides Chemical class 0.000 description 1
- 150000001348 alkyl chlorides Chemical class 0.000 description 1
- 150000001351 alkyl iodides Chemical class 0.000 description 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- 150000003868 ammonium compounds Chemical class 0.000 description 1
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 1
- 229940064004 antiseptic throat preparations Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000010410 dusting Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229940070891 pyridium Drugs 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- ADZWSOLPGZMUMY-UHFFFAOYSA-M silver bromide Chemical compound [Ag]Br ADZWSOLPGZMUMY-UHFFFAOYSA-M 0.000 description 1
- 229940045105 silver iodide Drugs 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940098465 tincture Drugs 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/61—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/04—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
- C07D215/06—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms having only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/04—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
- C07D215/10—Quaternary compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/10—Quaternary compounds
Definitions
- This invention concerns three new classes of quaternary ammonium compounds having antiseptic properties such that germicidal action is obtainable in very dilute solutions, while at the same time additional dilution can be practiced while still retaining bacteriostatic action.
- These compounds are derivatives of heterocyclic nitrogen parent compounds, with an alkyl group bonded to the quaternary nitrogen, which alkyl is of the higher alkyl, or long, type, in the sense that it contains not less than ten carbon atoms.
- the parent compounds are: (l) negatively substituted 3-pyridines, (2) tetrahydroquinolines and (3) tetrahydroisoquinolines.
- antiseptic refers to a substance which prevents or arrests the growth of microorganisms either by in- 2 and sulfamyl (SONH2) did not enhance the properties of this type of antiseptic.
- the carboxyl group in the 3-position of the pyridinium molecule almost completely destroys the germicidal activity and the sulfamyl radical greatly decreases the activity.
- negative groups is here used to refer to those groups of atoms which when attached to an organic compound make that compound more negative, 1. e. more acidic. Included inthis classification are the above mentioned groups and others such as sulfonic, nitro, nitrosyl, etc.
- germicide refers to an agent which destroys microorganisms.
- GROUP 1 The first group of compounds is the quaternary ammonium derivatives of negatively substituted S-pyridines which have the general structure:
- toxicity refers to the amount that will kill of the animals tested. This toxicity is commonly expressed as L. D. 50.
- the compounds of this group may be prepared b allowing the desired 3-substituted pyridine to react with the appropriate alkyl halide.
- a solvent is not needed but one such as alcohol, benzene, toluene, carbitol and the like may be used in some instances. It is advantageous to have a slight excess of alkyl halide.
- the temperature required to effect reaction depends largely on the halogen employed in the X position and to a lesser extent on the nature of the group in the 3-position (as Y). In general, it may be stated that for alkyl chlorides temperatures are required somewhat over 150 C. to effect condensation; alkyl bromides react well at about 130 C. (or lower if longer reaction times are employed); while alkyl iodides condense readily at about 100 C.
- EXAMPLE 3 3-chloro-N-tetradecylpyridinium bromide.-A mixture of 22.7 grams of 3-chloropyridine and about 65 grams of tetradecyl bromide is heated for 1820 hours at about 115-120 C. At the end of this time, the reaction mixture solidifies on cooling. It is stirred thoroughly with petroleum ether and the solid separated by filtration and washed well with petroleum ether. The crude material thus obtained may be purified by recrystallization from ethyl acetate, yielding glistening plates melting at 7l-'72.
- GROUP 2 The second group of compounds is the quaternary ammonium derivtives of tetrahydroquinolines. These new compounds have a partiall reduced quinoline nucleus.
- reaction mixture is allowed to cool and is then poured into petroleum ether.
- the gray crystalline solid is separated from the mixture by filtration, and washed well with petroleum ether.
- the crude product thus obtained may be purified by recrystallization from ethyl acetate, yielding fine, colorless needles melting at about 90--91 C.
- EXAMPLE 2 3 bromo N 9 octadecenylpyridinium bromide-Reaction is elfected between 16 grams of 3-bromopyridine and about l0 grams of 9-octadecenyl bromide by heating this mixture for about 20 hours at somewhat over 100 C. The reaction mixture is then cooled and stirred thoroughly with pcntane. The somewhat mushy, soapy solid is separated from the liquid phase by centrifugation and washed several times with pentane by the same process. Finally, after separating the crude material and drying in a vacuum desiccator, it is recrystallized from ethyl acetate containing a few percent of methyl alcohol.
- Process A Bacteriostatic Germicidal Toxicity Com ound Concentrw Concentration mgi/kgl" p tion,5min., Oral; amen? S. aurcus S. fccalis Mme CH; 01 CuHzv l
- Process B is the preferred since it gives excellent yields and is more satisfactory in general.
- N-alkyl-N-methi l-1,z,8,4-tztrahydroguinolinium halides The conversion of the quaternary ammonium iodides to the corresponding bromides or chlorides is described in the specific examples belows:
- N-tetradecyltetrahydroquinoline instead of preparing N-tetradecyltetrahydroquinoline by the method referred to above, one may prepare it by heating 66.0 grams of tetrahydroquinoline and about 140 grams of tetradecyl bromide in 200 cc. of dry benzene at refluxing temperature for 18 hours. After removing the solvent at the end of this time by distillation in vacuo, the residue is made alkaline with. excess 10% sodium hydroxide solution and the oily product extracted with benzene. The benzene layer is separated, dried and concentrated in the absenceof air under vacuum. Then the residue is distilled under diminished pressure and the N-tetradecyl-l, 2, 3, 4-tetrahydroquinoline is collected at about 205 at 4 mm.
- N-methyZ-N-tetradecyl-l, 2, 3, 4-tetrahydroquinolinium chloride About 10 grams of N- methyl N tetradecyltetrahydroquinolinium iodide is treated with an excess of freshly precip itated silver chloride by refluxing in 200 cc. of of alcohol ford-8 hours. At the end of this time the precipitated silver iodide plus excess silver chloride is separated by filtration and the filtrate evaporated to dryness under vacuum on the water bath. The oily residue is then taken up in the smallest amount of water to afford complete solution, frozen and lyophilized from the solid state. The material is a clear, sticky mass at room temperature and fails to crystallize on standing.
- the iodide may be converted to N-methyl- N-tetradecyltetrahydroquinolinium bromide by the same procedure.
- This iodide salt maybe converted to the corresponding chloride by the silver chloride procedure given in theabove Example 5.
- N-hexachloride is a colorless solid melting at about 134-135 C.
- the third group of quaternary ammonium compounds to be considered in this invention are the quaternary ammonium derivatives of the tetrahydroisoquinolines. These compounds are derivatives of a partially reduced isoquinoline nucleus having a higher alkyl group attached to the quaternary ammonium nitrogen atom. These fsilver chloride in water. as a solvent in place of water, in which case the 7 compounds may be represented by the following general formula:
- R is a monovalent higher alkyl group containing at least ten carbon atoms;
- R is a. low molecular weight alkyl group;
- Y is a monovalent group such as hydrogen, alkyl, hydroxyl, etc.;
- X is an anion
- Conversion of the iodide to N methyl N tetradecyl 1,2,3,4 tetrahydroisoquinolinium chloride can be accomplished by shaking overnight 5.0 grams of the former with an excess of Alcohol may be used mixture is refluxed instead of being shaken.
- EXAMPLE 8 processes as given for the tetrahydroqulnolmium 1o compounds above. These compounds are very N m thyl methyl N dodecyl 1,2,3,4 effective germicides and Show fairly 1 toxicity tetmhydrozsoqumolzmum wdzde.A solution. of to warm-blooded animals.
- a suitable tincture'using S bromo N tetra decylpyridinium chloride may be made up as fol- IOWSI EXAMPLE A composition in the following concentrations: For 100 cc. volume- 0.1 gm. 3-brom0 N-tetradecylpyridinium chloride 54.0 cc. ethyl alcohol denatured 5.0 cc. acetone Q. S. distilled water EXAMPLE 1 l
- the antiseptic compounds herein disclosed may be made up for use in powder form in conventional ways such as embodying about 1% of the active ingredient in a therapeutically inert vehicle.
- One suitable vehicle is carboxymethylcellulose and a convenient way for incorporating these materials in such a vehicle is to make up an acetone and water solution to be mixed with the vehicle, after which the combined mass is dried in conventional ways.
- alkyl groups mentioned in the foregoing description are straight chain, or normal, alkyl groups.
- An antiseptic composition of matter consisting of a solution containing as the active ingredient a compound consisting of a 1,2,3,4-tetrahydroquinoline nucleus; the nitrogen in said nucleus carrying as substituents a lower alkyl group, a higher alkyl group of more than 9 and less than 19 carbon atoms, and an anion.
- An antiseptic composition of matter consisting of a solution containing as the active ingredient a compound consisting of a 1,2,33,4- tetrahydroisoquinoline nucleus; the nitrogen in said nucleus carrying substituents including an alkyl group of more than nine and less than nineteen carbon atoms, and an anion; said nitrogen having no hydrogen bonded to it.
- R' is an alkyl group containing more than nine and less than nineteen carbon atoms; R is a low molecular weight alkyl group; Y is a monovalent group selected from a class consist- 10 ing of hydrogen, hydroxyl, methoxyl and halogen: X is an anion.
- R is an alkyl group containing more than nine and less than nineteen carbon atoms;
- R. is a low molecular weight alkyl group;
- Y is a monovalent group selected from a class consistr ing of hydrogen, hydroxyl, methyl, and halogen;
- N-methyl-N-tetradecyl-1,2,3,4 tetrahydroquinolinium chloride represented by the following formula:
- N-methyl-N hexadecyl-1,2,3,4-tetrahydro quinolinium iodide represented by the following formula:
- a 1, 2, 3, 4-tetrahydroquinolinium halide characterized by the presence of a Iii-methyl group and as an additional substituent a N- higher alkyl group having ten to eighteen carbon atoms inclusive.
- a 1,2,3,4-tetrahydroisoquinolinium halide characterized by the presence of a NT-methyl er alkyl group having ten to eighteeh ca'i'kien" atoms -inciusive'; h V V MARLIN T. LEFFLER; WAVERLY' D. KRUEGER.
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Description
Patented Aug. 28,- 1951 UNITED STATES FA-TENT OFFICE ouArsaNAav AMMONIUM COMPOUNDS;
of Illinois No Drawing. Application January 9, 1947, Serial No. 721,153
12 Claims.
This invention concerns three new classes of quaternary ammonium compounds having antiseptic properties such that germicidal action is obtainable in very dilute solutions, while at the same time additional dilution can be practiced while still retaining bacteriostatic action. These compounds are derivatives of heterocyclic nitrogen parent compounds, with an alkyl group bonded to the quaternary nitrogen, which alkyl is of the higher alkyl, or long, type, in the sense that it contains not less than ten carbon atoms. The parent compounds are: (l) negatively substituted 3-pyridines, (2) tetrahydroquinolines and (3) tetrahydroisoquinolines.
The term antiseptic as used in this specification refers to a substance which prevents or arrests the growth of microorganisms either by in- 2 and sulfamyl (SONH2) did not enhance the properties of this type of antiseptic. In fact, and it is rather surprising, the carboxyl group in the 3-position of the pyridinium molecule almost completely destroys the germicidal activity and the sulfamyl radical greatly decreases the activity.
The designation, negative groups, is here used to refer to those groups of atoms which when attached to an organic compound make that compound more negative, 1. e. more acidic. Included inthis classification are the above mentioned groups and others such as sulfonic, nitro, nitrosyl, etc.
The lowering of the toxicit brought about by the introduction of a halogen atom into the 3- position of the pyridinium nucleus is illustrated by the following comparison:
Compound Toxicity: Mice: MgJKg.
Name Structure 331E535 i t g gsl Oral Br CmHas 60 400 3-Bromo-N-cety1pyridinium halide N 0151333 8 8 N-Cetylpyridinium halide N:
hibiting their activity or destroying them. The word germicide refers to an agent which destroys microorganisms.
GROUP 1 The first group of compounds is the quaternary ammonium derivatives of negatively substituted S-pyridines which have the general structure:
The definition of toxicity as used here refers to the amount that will kill of the animals tested. This toxicity is commonly expressed as L. D. 50.
To illustrate the effectiveness of these negatively substituted pyridinium antiseptics, data on 3- bromo-N-tetradecy1pyridinium chloride are given below: 0
Concentration Compound Bactcriostatic Germicidal, 45 51nin..
S. aurcus S. aureus S. fecalzs -Br 50, 000 1, 000, 000 500, 000 .0 l
55 The figures given are the highest dilution for other negative groups as the carboxyl (--COOH) killing the germs in five minutes, and the highest dilution for inhibiting germ growth according to the Food and Drug Administration method.
The compounds of this group may be prepared b allowing the desired 3-substituted pyridine to react with the appropriate alkyl halide. Generally, a solvent is not needed but one such as alcohol, benzene, toluene, carbitol and the like may be used in some instances. It is advantageous to have a slight excess of alkyl halide. The temperature required to effect reaction depends largely on the halogen employed in the X position and to a lesser extent on the nature of the group in the 3-position (as Y). In general, it may be stated that for alkyl chlorides temperatures are required somewhat over 150 C. to effect condensation; alkyl bromides react well at about 130 C. (or lower if longer reaction times are employed); while alkyl iodides condense readily at about 100 C.
Given below are some of the compounds prepared from the 3-substituted pyridines.
it Y
EXAMPLE 3 3-chloro-N-tetradecylpyridinium bromide.-A mixture of 22.7 grams of 3-chloropyridine and about 65 grams of tetradecyl bromide is heated for 1820 hours at about 115-120 C. At the end of this time, the reaction mixture solidifies on cooling. It is stirred thoroughly with petroleum ether and the solid separated by filtration and washed well with petroleum ether. The crude material thus obtained may be purified by recrystallization from ethyl acetate, yielding glistening plates melting at 7l-'72.
GROUP 2 The second group of compounds is the quaternary ammonium derivtives of tetrahydroquinolines. These new compounds have a partiall reduced quinoline nucleus. Compounds coming 3-(Y) Substituted Pyridium Alkyl Halides Substituents M. P., C.
Y R (normal) X O H2 Decyl 75 76. C11H2a, Undecyl. O11.
C15H3:l, can. 98-100; 85; 81-82.
C sH37, Octadecyl l05.5l06.5. -C1sl135, 9-Octadeccnyl 82-83. (CH2)2"'O(CHZ)ZOC6H4CH3*P, p-Toloxyethoxyethyl. 73-74.
C1 C14H2g, Tetradecyl 71-72.
. Examples are given below of the preparation of three of the above compounds:
3-halogen0-N-alkylpyridinium halides EXAMPLE 1 3-bromo-N-tetmdecylpyridinium chZ0rz'de..A mixture of 16 grams of 3-brornopyridine and about grams of tetradecyl chloride is heated for about 20 hours at approximately l-160 C.
At the end of this time, the reaction mixture is allowed to cool and is then poured into petroleum ether. The gray crystalline solid is separated from the mixture by filtration, and washed well with petroleum ether. The crude product thus obtained may be purified by recrystallization from ethyl acetate, yielding fine, colorless needles melting at about 90--91 C.
EXAMPLE 2 3 bromo N 9 octadecenylpyridinium bromide-Reaction is elfected between 16 grams of 3-bromopyridine and about l0 grams of 9-octadecenyl bromide by heating this mixture for about 20 hours at somewhat over 100 C. The reaction mixture is then cooled and stirred thoroughly with pcntane. The somewhat mushy, soapy solid is separated from the liquid phase by centrifugation and washed several times with pentane by the same process. Finally, after separating the crude material and drying in a vacuum desiccator, it is recrystallized from ethyl acetate containing a few percent of methyl alcohol.
-3-bromo-N-octadecenylpyridinium bromide crystallizes in colorless clusters melting at 82-83" C.
within the scope of this invention may be represented by the following general formula:
decyl-l, 2, 3, atetrahydroquinolinium chloride gives the following results:
- Bacteriostatic Germicidal Toxicity Com ound Concentrw Concentration mgi/kgl" p tion,5min., Oral; amen? S. aurcus S. fccalis Mme CH; 01 CuHzv l Two syntheses are available for the preparation of these compounds: Process A and Process B. Of the two, Process B is the preferred since it gives excellent yields and is more satisfactory in general.
Process A CHQX RX (NaOH) i i i H OH; R X CH:
Tetrahydroqulnoline N-methyltetrahydrcquinolinc PTOCCSS B 2H1 CHSX (Ni) (NaOH) l R X B. R X OH: Long chain alkyl N-R-tetrahydroquinolinium halide quinohne Given below are some of the compounds which have been prepared by Process B:
N-alkyl-N-methi l-1,z,8,4-tztrahydroguinolinium halides The conversion of the quaternary ammonium iodides to the corresponding bromides or chlorides is described in the specific examples belows:
EXAMPLE 4 N-methyl-N-tetradecyl-l, 2, 3, 4-tetrahydroquinolinium iodide.-A solution of 32.9 grams of N-tetradecyltetrahydroquinoline (for the preparation of this compound see co-pending application, Serial Number 721,154, filed January 9, 1947, now Patent 2,524,392) and about 16 grams (slight excess) of methyl iodide in '75 cc. of dry benzene is refluxed on the steam bath for approximately 20 hours. Atthe end of this time, the benzene is removed by warming the reaction mixture under vacuum and the residue remaining is treated with an excess of petroleum ether. The crude solid is separated by filtration and purified by recrystallization from ethyl acetate, forming fine light yellow crystals melting at 7576 C.
- decyl-G -hydroxy-N-methylquinolinium Instead of preparing N-tetradecyltetrahydroquinoline by the method referred to above, one may prepare it by heating 66.0 grams of tetrahydroquinoline and about 140 grams of tetradecyl bromide in 200 cc. of dry benzene at refluxing temperature for 18 hours. After removing the solvent at the end of this time by distillation in vacuo, the residue is made alkaline with. excess 10% sodium hydroxide solution and the oily product extracted with benzene. The benzene layer is separated, dried and concentrated in the absenceof air under vacuum. Then the residue is distilled under diminished pressure and the N-tetradecyl-l, 2, 3, 4-tetrahydroquinoline is collected at about 205 at 4 mm.
The latter procedure is less satisfactory than the former, particularly with respect to yield.
EXAMPLE 5 N-methyZ-N-tetradecyl-l, 2, 3, 4-tetrahydroquinolinium chloride.About 10 grams of N- methyl N tetradecyltetrahydroquinolinium iodide is treated with an excess of freshly precip itated silver chloride by refluxing in 200 cc. of of alcohol ford-8 hours. At the end of this time the precipitated silver iodide plus excess silver chloride is separated by filtration and the filtrate evaporated to dryness under vacuum on the water bath. The oily residue is then taken up in the smallest amount of water to afford complete solution, frozen and lyophilized from the solid state. The material is a clear, sticky mass at room temperature and fails to crystallize on standing.
By using silver bromide instead of silver chloride, the iodide may be converted to N-methyl- N-tetradecyltetrahydroquinolinium bromide by the same procedure.
EXAMPLE 6 N hemadecyl-fi-hydroxy- N methyZ-1,2,3,4-tetrahydroquinolinium; iodide.--A dry benzene cc.) solution of 3.5 grams of N-hexadecyl-S-hydroxy-quinoline (for the preparation of this compound see co-pending application, Serial Number 721,154, filed January 9, 1947, now Patent 2,524,392) and about 2.0 grams of methyl iodide is refluxed on the steam bath for 20 hours. At the end of the first 10 hours of this refluxing period, a further 1 gram quantity of methyl iodide is added to replace any that may have been lost through volatilization. The solvent is then removed by heating under vacuum and the residue washed well with petroleum ether by decantation. The crude product remaining is dissolved in hot ethyl acetate plus a trace of methanol and cooled. On standing, colorless crystals of the iodide separate, melting about 117 C. Repeated crystallization of this material from this solvent does not raise the melting point above 1l'7-118 C.
This iodide salt maybe converted to the corresponding chloride by the silver chloride procedure given in theabove Example 5. N-hexachloride is a colorless solid melting at about 134-135 C.
GROUP 3 The third group of quaternary ammonium compounds to be considered in this invention are the quaternary ammonium derivatives of the tetrahydroisoquinolines. These compounds are derivatives of a partially reduced isoquinoline nucleus having a higher alkyl group attached to the quaternary ammonium nitrogen atom. These fsilver chloride in water. as a solvent in place of water, in which case the 7 compounds may be represented by the following general formula:
t R H I wherein R is a monovalent higher alkyl group containing at least ten carbon atoms; R is a. low molecular weight alkyl group; Y is a monovalent group such as hydrogen, alkyl, hydroxyl, etc.;
X is an anion.
These compounds may be prepared by the same After removal of the silver halide by filtration,
Below are several specific examples of th preparation of these compounds:
EXAMPLE 7 N methyl N tetradecyZ-I ,2,3,4-tetrahydroisoquinolz'nium iodide.--Asolution of 16.4 grams of N-tetradecyl-12,3,4-tetrahydroisoquinoline (for the'preparation of this compound see co-pending application, Serial Number 721,154, filed January 9, 1947, n0w Patent 2,524,392) and about 8 grams of :methyl iodide in 100 cc. of dry benzene is refluxed on the'steam bath for approximately imay lee-purified by recrystallization from ethyl acetate giving pale yellow crystals melting at 92-93 C.
Conversion of the iodide to N methyl N tetradecyl 1,2,3,4 tetrahydroisoquinolinium chloride, can be accomplished by shaking overnight 5.0 grams of the former with an excess of Alcohol may be used mixture is refluxed instead of being shaken.
. EXAMPLE 8 processes as given for the tetrahydroqulnolmium 1o compounds above. These compounds are very N m thyl methyl N dodecyl 1,2,3,4 effective germicides and Show fairly 1 toxicity tetmhydrozsoqumolzmum wdzde.A solution. of to warm-blooded animals. Given below are some 22 grams y y rlBfiA-t w of the compounds which have been prepared from hydrolsoqllmolme (for the preparatlon, ee 00- these methods and a few of their antiseptic 2O p d g pp Serial Number ,-fi d pro'pertiesz January 9, 1947, now Patent 2,524,392) and about 10 grams of methyl iodide in 100 cc. of ethyl i 1: I 1 h ld N,N dmlkyl1,2,5,t etra LII/(ZZZSOQMMLOZMHIHH at es a cohol is refluxed for 14 hours" At the end-of this time, thesolvent is removed by vacuum dis- R tillation and the residue allowed to s'tand'for 24 hours at room temperature. It is then dissolved in 100 cc. of ethyl acetate and cooled for several hours. The solid product 'Substituents Concentration P" Germk Bacteriostatic' C cidal, R (Normal) R X 5 min 1 S. mucus S. aurcus S. jecalis IC10Hn CH3...
"C13H25 CH3...
P0141129 CH3...
" C16H33 CH3. B
4118113, oh3 .l C l]129 C2115" (CH2)r-O(CH2)2O-CsH5CHa-p CH3.-- 1 2H2: Y=3CH3 CH3...
which separates is removed by filtration and dried in a vacuum drying oven at C. This crude material may be purified by recrystallization from light yellow crystals melting at -101 C.
EXAMPLE 9 N ethyl N tetmdecyl 1,2,3,4 tetrahydroisoquinolz'm'um iodide-A solution of 16.4 grams N tetradecyl 1,2,3/i tetrahydroisoquinoline PREPARATIONS Compounds according to the invention may be made up into a variety of pharmaceutical vehicles for the application of thes antiseptic compounds. Among the types of compositions of matter which have been prepared and used successfully are aqueous solutions, tinctures, dusting powders, etc. r
Due to the highly germicidal propertiesv and low toxicities of the quaternary ammonium-compounds described, these preparations have many and-varied applications in preventing and curingprepared inany desirable amount bydissolving 1 unit by weight of the quaternary ammonium compound in 1009 units of distilled water.
A suitable tincture'using S bromo N tetra decylpyridinium chloride may be made up as fol- IOWSI EXAMPLE A composition in the following concentrations: For 100 cc. volume- 0.1 gm. 3-brom0 N-tetradecylpyridinium chloride 54.0 cc. ethyl alcohol denatured 5.0 cc. acetone Q. S. distilled water EXAMPLE 1 l The antiseptic compounds herein disclosed may be made up for use in powder form in conventional ways such as embodying about 1% of the active ingredient in a therapeutically inert vehicle. One suitable vehicle is carboxymethylcellulose and a convenient way for incorporating these materials in such a vehicle is to make up an acetone and water solution to be mixed with the vehicle, after which the combined mass is dried in conventional ways.
All of the alkyl groups mentioned in the foregoing description are straight chain, or normal, alkyl groups.
Others may readily adapt th invention for use under various conditions of service, by employing one or more of the novel features disclosed, or equivalents thereof. As at present advised with respect to the apparent scope of our inventions, we desire to claim the following subject matter.
We claim:
1. An antiseptic composition of matter consisting of a solution containing as the active ingredient a compound consisting of a 1,2,3,4-tetrahydroquinoline nucleus; the nitrogen in said nucleus carrying as substituents a lower alkyl group, a higher alkyl group of more than 9 and less than 19 carbon atoms, and an anion.
2. An antiseptic composition of matter consisting of a solution containing as the active ingredient a compound consisting of a 1,2,33,4- tetrahydroisoquinoline nucleus; the nitrogen in said nucleus carrying substituents including an alkyl group of more than nine and less than nineteen carbon atoms, and an anion; said nitrogen having no hydrogen bonded to it.
3. Tetrahydroquinoline derivatives of the following type:
wherein R' is an alkyl group containing more than nine and less than nineteen carbon atoms; R is a low molecular weight alkyl group; Y is a monovalent group selected from a class consist- 10 ing of hydrogen, hydroxyl, methoxyl and halogen: X is an anion.
4. Tetrahydroisoquinoline derivatives of the following type;
bi -R ti X wherein R is an alkyl group containing more than nine and less than nineteen carbon atoms; R. is a low molecular weight alkyl group; Y is a monovalent group selected from a class consistr ing of hydrogen, hydroxyl, methyl, and halogen;
Xis an anion.
5. N-methyl-N-tetradecyl-1,2,3,4 tetrahydroquinolinium chloride represented by the following formula:
N C1 CuH29 6. N-methyl-N hexadecyl-1,2,3,4-tetrahydro quinolinium iodide represented by the following formula:
N i CH3 I CmHss '7. G-hydroxy-N methyl-N-hexadecyl 1,23,4-
tetrahydroquinolinium iodide represented by the following formula:
N of, I o,.n2g
8. N-methyl-N-tetradecyl 1,2,3,4-tetrahydroisoquinolinium chloride represented by the following formula:
10. A compound selected from the group consisting of l,2,3,4-tetrahydroquinoline and 1,2,31,4- tetrahydroisoquinoline, the nitrogen in the quinoline heterocyclic nucleus carrying as a substituent an anion and as additional substituents a N -lower alkyl group and a N -higher alkyl group, said higher alkyl group containing 10-18 carbon atoms.
11. A 1, 2, 3, 4-tetrahydroquinolinium halide, characterized by the presence of a Iii-methyl group and as an additional substituent a N- higher alkyl group having ten to eighteen carbon atoms inclusive.
12. A 1,2,3,4-tetrahydroisoquinolinium halide, characterized by the presence of a NT-methyl er alkyl group having ten to eighteeh ca'i'kien" atoms -inciusive'; h V V MARLIN T. LEFFLER; WAVERLY' D. KRUEGER.
mm'eer Name- Date 2,104,723 Ber'ts'ch'et a1 Jeri. 11, 1938 2,194,399 Lange Maf.19,'194'0' 2,264,150 Hlitei et 'al NOV. 25, 1941 2,295,504 Shelton Sept 8,1942 2,295,505 sheltbn Se t; 8, 1942 2,386,936 DeGi'Odt efi'aJ 0017.16; 1945' OTHER REFERENCES 10 Sidgwick: Organic Chemistry- 0f (OxiordUniv. Press, 1937), pages 563 12111} 564:
' 757-759 (Ma 194 v Hoogerbeide: J. of Bacteriology, March 1915;
Claims (1)
1. AN ANTISEPTIC COMPOSITION OF MATTER CONSISTING OF A SOLUTION CONTAINING AS THE ACTIVE INGREDIENT A COMPOUND CONSISTING OF A 1,23,4-TETRAHYDROQUINOLINE NUCLEUS; THE NITROGEN IN SAID NUCLEUS CARRYING AS SUBSTITUTENTS A LOWER ALKYL GROUP, A HIGHER ALKYL GROUP OF MORE THAN 9 AND LESS THAN 19 CARBON ATOM, AND AN ANION.
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US2846435A (en) * | 1953-07-27 | 1958-08-05 | Monsanto Chemicals | 6-ether substituted 1, 2, 3, 4-tetrahydroalkylquinolines |
US3093479A (en) * | 1958-12-12 | 1963-06-11 | Eastman Kodak Co | Use of quaternary ammonium compounds for stabilizing processed photographic elements |
US3970454A (en) * | 1974-01-10 | 1976-07-20 | Eastman Kodak Company | Photographic developing agents |
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US3093479A (en) * | 1958-12-12 | 1963-06-11 | Eastman Kodak Co | Use of quaternary ammonium compounds for stabilizing processed photographic elements |
US3970454A (en) * | 1974-01-10 | 1976-07-20 | Eastman Kodak Company | Photographic developing agents |
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