NO128892B - - Google Patents
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- NO128892B NO128892B NO437172A NO437172A NO128892B NO 128892 B NO128892 B NO 128892B NO 437172 A NO437172 A NO 437172A NO 437172 A NO437172 A NO 437172A NO 128892 B NO128892 B NO 128892B
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- urea
- butyl
- water
- melting point
- solution
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- 229940100389 Sulfonylurea Drugs 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 3
- 125000004442 acylamino group Chemical group 0.000 claims description 2
- 230000000844 anti-bacterial effect Effects 0.000 claims description 2
- 230000003178 anti-diabetic effect Effects 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- 150000001875 compounds Chemical class 0.000 description 14
- 239000004202 carbamide Substances 0.000 description 12
- 238000002844 melting Methods 0.000 description 12
- 230000008018 melting Effects 0.000 description 12
- -1 p-toluenesulfonyl Chemical group 0.000 description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000008280 blood Substances 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 238000000354 decomposition reaction Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000000706 filtrate Substances 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
- 239000012948 isocyanate Substances 0.000 description 4
- 150000002513 isocyanates Chemical class 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- VDTNNGKXZGSZIP-UHFFFAOYSA-N carbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(N)C=C1 VDTNNGKXZGSZIP-UHFFFAOYSA-N 0.000 description 3
- 229960003362 carbutamide Drugs 0.000 description 3
- 239000000155 melt Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 235000011121 sodium hydroxide Nutrition 0.000 description 3
- TXTQURPQLVHJRE-UHFFFAOYSA-N 3-nitrobenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC([N+]([O-])=O)=C1 TXTQURPQLVHJRE-UHFFFAOYSA-N 0.000 description 2
- YDIFNVIRTXGGCM-UHFFFAOYSA-N CCCCNC(=O)NS(=O)(=O)C1=CC=CC([N+]([O-])=O)=C1 Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=CC([N+]([O-])=O)=C1 YDIFNVIRTXGGCM-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 150000003941 n-butylamines Chemical class 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- KJFMBFZCATUALV-UHFFFAOYSA-N phenolphthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2C(=O)O1 KJFMBFZCATUALV-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- ARSTYWCBFCDLSO-UHFFFAOYSA-N 1-(3-aminophenyl)sulfonyl-3-butylurea Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=CC(N)=C1 ARSTYWCBFCDLSO-UHFFFAOYSA-N 0.000 description 1
- DRLPMNZMHZQGRN-UHFFFAOYSA-N 2-(3-nitrophenyl)sulfonylguanidine Chemical class NC(N)=NS(=O)(=O)C1=CC=CC([N+]([O-])=O)=C1 DRLPMNZMHZQGRN-UHFFFAOYSA-N 0.000 description 1
- JOUQRBQVLURJGK-UHFFFAOYSA-N 3-nitro-n-(oxomethylidene)benzenesulfonamide Chemical compound [O-][N+](=O)C1=CC=CC(S(=O)(=O)N=C=O)=C1 JOUQRBQVLURJGK-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical compound NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 description 1
- 206010013700 Drug hypersensitivity Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241001397173 Kali <angiosperm> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
- LIMQQADUEULBSO-UHFFFAOYSA-N butyl isothiocyanate Chemical compound CCCCN=C=S LIMQQADUEULBSO-UHFFFAOYSA-N 0.000 description 1
- CNWSQCLBDWYLAN-UHFFFAOYSA-N butylurea Chemical compound CCCCNC(N)=O CNWSQCLBDWYLAN-UHFFFAOYSA-N 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- AOCYHPQXGJBAQQ-UHFFFAOYSA-N ethyl n-sulfonylcarbamate Chemical compound CCOC(=O)N=S(=O)=O AOCYHPQXGJBAQQ-UHFFFAOYSA-N 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- HNHVTXYLRVGMHD-UHFFFAOYSA-N n-butyl isocyanate Chemical compound CCCCN=C=O HNHVTXYLRVGMHD-UHFFFAOYSA-N 0.000 description 1
- HKTBRYQNVRPBCF-UHFFFAOYSA-N nitrobenzene;sulfurochloridic acid Chemical compound OS(Cl)(=O)=O.[O-][N+](=O)C1=CC=CC=C1 HKTBRYQNVRPBCF-UHFFFAOYSA-N 0.000 description 1
- 239000003538 oral antidiabetic agent Substances 0.000 description 1
- 238000006400 oxidative hydrolysis reaction Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 201000004518 sulfonamide allergy Diseases 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
Classifications
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01Q—ANTENNAS, i.e. RADIO AERIALS
- H01Q1/00—Details of, or arrangements associated with, antennas
- H01Q1/08—Means for collapsing antennas or parts thereof
- H01Q1/10—Telescopic elements
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01Q—ANTENNAS, i.e. RADIO AERIALS
- H01Q1/00—Details of, or arrangements associated with, antennas
- H01Q1/12—Supports; Mounting means
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01Q—ANTENNAS, i.e. RADIO AERIALS
- H01Q1/00—Details of, or arrangements associated with, antennas
- H01Q1/48—Earthing means; Earth screens; Counterpoises
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Aerials With Secondary Devices (AREA)
- Support Of Aerials (AREA)
Description
Fremgangsmåte ved fremstilling av sulfonylurinstoffer med antidiabetisk virkning. Process for the production of sulfonylureas with antidiabetic action.
Det er kjent at p-aminobenzensulfonyl-urinstoffer har en virkning som senker sukkerinnholdet i blodet og at de er egnet for oral anvendelse av diabetes mellitus. It is known that p-aminobenzenesulfonylureas have an effect that lowers the sugar content in the blood and that they are suitable for oral use in diabetes mellitus.
Det har nu vist seg at m-aminobenzen-sulfonyl-urinstoffer med den generelle formel: It has now been shown that m-aminobenzenesulfonylureas with the general formula:
i hvilken R betegner en alkyl- eller cycloalkylrest med fra 4 til 6 carbonatomer, uten å ha noen antibakteriell virkning har en utmerket blodsukkersenkende virkning og god tålbarhet, slik at de også kan brukes som orale antidiabetiske midler. Denne opp-dagelse er meget overraskende når man tar i betraktning at sulfonamidene mister sin bakteriostatiske virkning når aminogruppen forskyves fra p-stillingen til Bi-stillingen. De nye forbindelser utmerker seg først og fremst ved at de som følge av at aminogruppen befinner seg i m-stillingen, også kan gis diabetikere som reagerer allergisk mot aminogruppen i p-stillingen (sulfon-amid-allergi), jfr. Angewandte Chemie 71, 1959; Nachrichten aus Chemie und Tech-nik, side 391 (blå sider). Fremgangsmåten ifølge oppfinnelsen til fremstilling av de nevnte forbindelser består i at benzensulfonylurinstoffer med den generelle formel: in which R denotes an alkyl or cycloalkyl residue with from 4 to 6 carbon atoms, without having any antibacterial effect have an excellent blood sugar-lowering effect and good tolerability, so that they can also be used as oral antidiabetic agents. This discovery is very surprising when one takes into account that the sulfonamides lose their bacteriostatic effect when the amino group is displaced from the p-position to the Bi-position. The new compounds are distinguished primarily by the fact that, as a result of the amino group being in the m-position, they can also be given to diabetics who react allergically to the amino group in the p-position (sulfonamide allergy), cf. Angewandte Chemie 71, 1959; Nachrichten aus Chemie und Tech-nik, page 391 (blue pages). The process according to the invention for producing the aforementioned compounds consists in benzenesulfonylureas with the general formula:
i hvilken R har den ovenfor angitte betyd-ning og W betegner en acylamino- eller en nitrogruppe, på i og for seg kjent måte hydroliseres i alkalisk miljø eller hydreres. in which R has the meaning given above and W denotes an acylamino or a nitro group, is hydrolysed in an alkaline environment or hydrated in a manner known per se.
De nedenfor oppførte resultater av sammenligningsforsøk mellom eksempler på forbindelser fremstilt ifølge nærværende fremgangsmåte og de lignende, kjente forbindelser «Nadisan» og «Artosin» viser de fordeler som oppnåes ved hjelp av oppfinnelsen. 1. Sammenligning av den blodsukkersenkende virkning. The below listed results of comparison tests between examples of compounds produced according to the present method and the similar, known compounds "Nadisan" and "Artosin" show the advantages achieved by means of the invention. 1. Comparison of the blood sugar-lowering effect.
Kaniner ble ved intravenøs injeksjon gitt de nedenfor oppførte forbindelser i forskjellige doser, og den mengde av hver forbindelse som førte til påvisning av den første tydelige senkning av blodsukker-innholdet (grensedosen) ble bestemt. N, -sulf anilyl-N2- (n-butyl) -urin- Rabbits were given by intravenous injection the compounds listed below in various doses, and the amount of each compound which led to the detection of the first clear lowering of the blood sugar content (limiting dose) was determined. N, -sulfanilyl-N2-(n-butyl)-urine-
stoff («Nadisan») 200 mg/kg substance ("Nadisan") 200 mg/kg
Nj-metanilyl-N.,- (n-butyl) -urin - Nj-methanylyl-N,-(n-butyl)-urine -
stoff 250 » fabric 250 »
N, -metanilyl-Ng-cyclohexyl- N, -methanylyl-Ng-cyclohexyl-
' urinstoff ................. 50 » N, -metanilyl-N2- (2-pentyl) - ' urea ................. 50 » N, -methanilyl-N2-(2-pentyl) -
urinstoff ................. 150 » urea ................. 150 »
De nye forbindelser oppviser således en blodsukkersenkende virkning som er om-trent fra 1 til 4 ganger så stor som virk-ningen av handelspreparatet «Nadisan». 2. Sammenligning av giftigheten. The new compounds thus exhibit a blood sugar-lowering effect which is roughly from 1 to 4 times as great as the effect of the commercial preparation "Nadisan". 2. Comparison of the toxicity.
Dosis letalis LD 50 ble bestemt ved sub-cutan injeksjon på mus. The lethal dose LD 50 was determined by subcutaneous injection in mice.
N, - (p-toluensulf onyl) -N2-(n-butyl) -urinstoff ........ 0,78 g/kg N, - (p-toluenesulfonyl)-N2-(n-butyl)-urea ........ 0.78 g/kg
[ = D 860 = «Artosin»] [ = D 860 = "Artosin"]
N, -metanilyl-N,- (n-butyl) -urinstoff " 0,99 » N,-metanilyl-N3-cyclohexyl-urinstoff 1,02 » N,-metanilyl-N.,-(2-pentyl -urinstoff '. 0,95 » N, -methanylyl-N,-(n-butyl)-urea " 0.99 » N,-methanylyl-N3-cyclohexyl-urea 1.02 » N,-methanylyl-N,-(2-pentyl -urea ' .0.95 »
De nye forbindelser er således mindre giftige enn handelspreparatet «Artosin». Deres giftighet relativt til «Artosin» («Artosin» — 1) er ca. %. The new compounds are thus less toxic than the commercial preparation "Artosin". Their toxicity relative to "Artosin" ("Artosin" — 1) is approx. %.
De som utgangsmaterialer anvendte N^m-acylamino-benzensulfonyl-urinstoffer og ^-(m-nitrobenzensulfony^-urinstoffer kan fremstilles på de vanlige måter til fremstilling av sulfonylurinstoffer. Således kan man omsette et isocyanat med formelen 0=N=C-R (eller en forbindelse som under reaksjonsbetingelsene kan om-dannes til et sådant isocyanat, f. eks. det tilsvarende carbaminsyreklorid) med et m-acylaminobenzensulfonamid eller et m-ni-trobenzensulfonamid, eller deres alkalisal-ter eller omsette et m-acylaminobenzen-sulfonyl-isocyanat eller et m-nitrobenzensulfonyl-isocyanat (eller en forbindelse som under reaksjonsbetingelsene kan om-dannes til et sådant isocyanat, f. eks. det tilsvarende sulfonylurethan) med et amin med formelen H,NR, eller omsette en iso-urinstoffalkylether med formelen H9N-C(0-Alk)=N-R med et m-acylaminoben-zensulfonylhalogenid eller et m-nitroben-zensulfonylhalogenid og omdanne det erholdte sulfonyl-isourinstoffderivat til sulfonyl-urinstoffet ved behandling med ha-logenhydrogensyre, eller ved alkalisk eller oxydativ hydrolyse omdanne m-acylamino-benzensulfonyl-guanidiner eller -thiourinstoffer eller m-nitrobenzensulfonyl-guani-diner eller -thiourinstoffer til de tilsvarende sulfonyl-urinstoffer. The N^m-acylamino-benzenesulfonylureas and ^-(m-nitrobenzenesulfony^-ureas used as starting materials can be prepared in the usual ways for the production of sulfonylureas. Thus, one can react an isocyanate with the formula 0=N=C-R (or a compound which under the reaction conditions can be converted into such an isocyanate, e.g. the corresponding carbamic acid chloride) with an m-acylaminobenzenesulfonamide or an m-nitrobenzenesulfonamide, or their alkali salts or react with an m-acylaminobenzenesulfonyl isocyanate or an m-nitrobenzenesulfonyl isocyanate (or a compound which under the reaction conditions can be converted into such an isocyanate, e.g. the corresponding sulfonylurethane) with an amine of the formula H,NR, or react an iso-urea alkyl ether with the formula H9N-C (O-Alk)=N-R with an m-acylaminobenzenesulfonyl halide or an m-nitrobenzenesulfonyl halide and convert the obtained sulfonyl isourea derivative into the sulfonyl urea by treatment with halo genhydrogen acid, or by alkaline or oxidative hydrolysis convert m-acylamino-benzenesulfonyl-guanidines or -thioureas or m-nitrobenzenesulfonyl-guanidines or -thioureas into the corresponding sulfonylureas.
De nedenstående eksempler illustrerer noen utførelsesformer for fremgangsmåten ifølge oppfinnelsen. The following examples illustrate some embodiments of the method according to the invention.
Eksempel 1. Nl-( m- amino- benzensulfonyl)-N.,-( n- butyl- urinstoff). Example 1. Nl-(m-amino-benzenesulfonyl)-N.,-(n-butyl-urea).
a) 160 g di-(acetylmetanilyl-urinstoff (fremstilt av acetylmetanilsyreamid og a) 160 g of di-(acetylmethanilyl urea) (produced from acetylmethanilic acid amide and
fosgen, (smeltepunkt 202—205° C, spaltning) føres inn i 640 cm:! vann på 80° C og tilsettes under omrøring 37 cm'<!> n-butylamin. Ved omrøring utkrystalliserer n-bu-tylaminsaltet av di-(acetylmetanilyl)-urinstoffet. Utbytte 156 g. Smeltepunkt 166— 169° C (spaltning). phosgene, (melting point 202—205° C, cleavage) is introduced into 640 cm:! water at 80° C and add, while stirring, 37 cm'<!> of n-butylamine. Upon stirring, the n-butylamine salt of the di-(acetylmethanilyl)urea crystallizes out. Yield 156 g. Melting point 166—169° C (decomposition).
b) n-butylamin-saltet av di-(acetyl - metanilyl)-urin-stoffet opphetes i 3 timer b) the n-butylamine salt of the di-(acetyl-methanylyl)-urea is heated for 3 hours
til 142° C. Det erholdte spaltningsprodukt omrøres med 500 cm3 0,5 n natronlut og det uoppløste acetyl-metanilamid suges av. Filtratet bringes derpå ved innføring av C02 på en pH-verdi av 8,8 og filtreres påny. Ved surgj øring av dette filtrat med 6n saltsyre utfelles N,-acetyl-metanilyl-N2-butyl-urinstoff med et utbytte på 61 g. Smeltepunkt 160—163° C (fra vandig methanol). to 142° C. The cleavage product obtained is stirred with 500 cm3 of 0.5 N caustic soda and the undissolved acetyl methanilamide is sucked off. The filtrate is then brought to a pH value of 8.8 by introducing CO 2 and filtered again. When this filtrate is acidified with 6N hydrochloric acid, N,-acetyl-methanilyl-N2-butyl-urea is precipitated with a yield of 61 g. Melting point 160-163° C (from aqueous methanol).
c) Acetylmetanilyl-butyl-urinstoffet opphetes i en time til 95° C med 123 cm<3>c) The acetylmethanilyl-butyl urea is heated for one hour to 95° C with 123 cm<3>
5n kalilut. Derpå fortynnes reaksjonsblandingen med vann og pH-verdien innstilles med iseddik på 8,5. Ef ter klaring med aktivt kull og frafiltrering gjøres reaksjonspro-duktet svakt surt overfor congorødt med fortynnet saltsyre, hvorved metanilyl-butyl-urinstoffet utfelles i krystallinsk form. Utbytte 41 g. Smetlepunkt 115—117° C (spaltning). 5n kali lute. The reaction mixture is then diluted with water and the pH value is adjusted to 8.5 with glacial acetic acid. After clarification with activated charcoal and filtration, the reaction product is made weakly acidic to Congo red with dilute hydrochloric acid, whereby the methanilyl-butyl urea is precipitated in crystalline form. Yield 41 g. Melting point 115-117° C (decomposition).
Eksempel 2. Nr( m- amino- benzensulfonyl)-N9- cyclohexyl- urinstoff. Example 2. Nr(m-amino-benzenesulfonyl)-N9-cyclohexyl-urea.
a) 77 g acetylmetanilyl-ethylurethan (fremstilt av acetylmetanil-syreamid og a) 77 g of acetylmethanyl ethylurethane (produced from acetylmethanyl acid amide and
klormaursyreester, smeltepunkt 116° C) omrøres med 100 cm<3> dimethylformamid og 33 cm<:1> cyclohexylamin i to timer i et olje-bad på 105° C. Derpå tilsettes 100 cm<8> vann til reaksjonsblandingen og surgj øres med fortynnet saltsyre. Det dannede bunnfall avsuges og omrøres med 500 cm<3> vann og 20 cm<3> konsentrert ammoniakk-oppløsning. chloroformic acid ester, melting point 116° C) is stirred with 100 cm<3> dimethylformamide and 33 cm<:1> cyclohexylamine for two hours in an oil bath at 105° C. Then 100 cm<8> water is added to the reaction mixture and acidified with dilute hydrochloric acid. The formed precipitate is filtered off and stirred with 500 cm<3> of water and 20 cm<3> of concentrated ammonia solution.
Efter at det uoppløste er suget bort, surgj øres filtratet. Derved fåes 53 g av acetyl - metanilyl-cyclohexyl-urinstoffet med et smeltepunkt på 158—162° C (spaltning). After the undissolved has been sucked away, strain the filtrate. Thereby 53 g of the acetyl-methanilyl-cyclohexyl-urea with a melting point of 158-162° C (decomposition) are obtained.
b) 41 g av acetylforbindelsen oppvarmes med 92 cm<3> 10n kalilut i 70 minutter i b) 41 g of the acetyl compound is heated with 92 cm<3> 10n potassium hydroxide for 70 minutes in
et vannbad på 95° C. Derpå oppløses den erholdte blanding i 150 cm:) vann på 60° C, avstumpes med HC1 til en pH-verdi 8,0 og gjøres klart med aktivt kull. Efter frafiltrering kan metanilyl-cyclohexyl-urinstoffet a water bath at 95° C. The resulting mixture is then dissolved in 150 cm:) of water at 60° C, blunted with HC1 to a pH value of 8.0 and made clear with activated charcoal. After filtration, the metanilyl-cyclohexyl-urea can
utfelles med fortynnet saltsyre ved 50° C. Utbytte 30 g. Smeltepunkt 162—165° C (spaltning). precipitated with dilute hydrochloric acid at 50° C. Yield 30 g. Melting point 162-165° C (decomposition).
På analog måte fåes N1-(m-amino-benzensulfonyl) -N2- (pentyl) -urinstoff med et smeltepunkt på 128—130° C (spaltning). Den tilsvarende acetylforbindelse smelter ved 140—143° C. In an analogous manner, N1-(m-amino-benzenesulfonyl)-N2-(pentyl)-urea is obtained with a melting point of 128-130° C (decomposition). The corresponding acetyl compound melts at 140-143° C.
Eksempel 3. N-( 3- amino- benzensulfonyl)-N'- 7i- butyl- urinstoff. Example 3. N-(3-amino-benzenesulfonyl)-N'-7i-butylurea.
a) 151,5 g (7,5/10 mol) 3-nitro-benzen-sulfonamid suspenderes i 250 cm<3> aceton og a) 151.5 g (7.5/10 mol) of 3-nitro-benzene-sulfonamide are suspended in 250 cm<3> of acetone and
oppløses med 500 cm<3> vandig natronlut med et innhold av 30 g NaOH. Til denne opp-løsning dryppes der under omrøring inn 75 g n-butyl-isocyanat ved 10—15° C. Reaksjonsblandingen omrøres i ca. 30 minutter ved romtemperatur, hvorpå små meng-der bunnfall frafiltreres. Filtratet surgj ø-res med fortynnet eddiksyre, det utfelte N- (3-nitrobenzensulfonyl) -N'-n-butyl-urinstoff suges bort og oppløses i fortynnet etanol. Forbindelsen smelter ved 175— 177° C. dissolve with 500 cm<3> of aqueous caustic soda with a content of 30 g of NaOH. 75 g of n-butyl isocyanate is dripped into this solution while stirring at 10-15° C. The reaction mixture is stirred for approx. 30 minutes at room temperature, after which small amounts of sediment are filtered off. The filtrate is acidified with dilute acetic acid, the precipitated N-(3-nitrobenzenesulfonyl)-N'-n-butyl urea is sucked off and dissolved in dilute ethanol. The compound melts at 175-177° C.
b) 100 g N-(3-nitro-benzensulfonyl)-N'-n-butyl-urinstoff suspenderes i 350 cm<8>b) 100 g of N-(3-nitro-benzenesulfonyl)-N'-n-butyl urea is suspended in 350 cm<8>
methanol og reduseres ved romtemperatur med hydrogen i nærvær av palladium. Ved reduksjonen finner der sted en fullstendig oppløsning. Fra oppløsningen som suges av fra katalysatoren, utkrystalliseres N-(3-amino-benzensulfonyl) -N'-n-butyl-urinstoffet ved tilsetning av vann. Efter opp-løsning i fortynnet ethanol smelter forbindelsen ved 116° C. methanol and is reduced at room temperature with hydrogen in the presence of palladium. In the case of reduction, a complete dissolution takes place. From the solution sucked off from the catalyst, the N-(3-amino-benzenesulfonyl)-N'-n-butylurea is crystallized by adding water. After dissolution in dilute ethanol, the compound melts at 116°C.
Eksempel 4. Metanilyl- butyl- urinstoff. 12 g n-butyl-isourinstoff-methylether-methylsulfat (fremstilt av n-butyl-urinstoff og dimethylsulfat) oppløses i 50 ml vann, og oppløsningen tilsettes under om-røring først 55 g vannfritt kaliumcarbonat og derpå 18 g m-nitrobenzen-sulfoklorid, hvorved blandingen oppvarmes. Man hol-der temperaturen på 60° C i 30 minutter. Der avkjøles derpå, og det bunnfall som danner seg fraskilles, suspenderes i 50 ml vann og surgj øres. Efter fraskillelse av den olje som herved dannes, oppvarmer man denne med 30 ml konsentrert saltsyre til 65° C inntil utviklingen av methylklorid er opphørt. Man omrører reaksjonsblandingen med 100 ml vann, hvorved der dannes et bunnfall som oppløses i svakt ammoniak-alsk vann. Oppløsningen behandles med aktivt kull og surgj øres derpå. Der utfelles 10 g Nj-m-nitrobenzensulfonyl-No-butyl-urinstoff med smeltepunkt 175—177° C. Denne forbindelse overføres ved katalytisk reduksjon (således som angitt i eksempel 3b) til metanilyl-butyl-urinstoff. Produk-tets smeltepunkt er 116° C. Example 4. Metanylyl-butyl-urea. 12 g of n-butyl-isourea-methylether-methylsulphate (made from n-butyl-urea and dimethylsulphate) is dissolved in 50 ml of water, and to the solution is added, while stirring, first 55 g of anhydrous potassium carbonate and then 18 g of m-nitrobenzene sulphochloride, whereby the mixture is heated. The temperature is kept at 60° C for 30 minutes. It is then cooled, and the precipitate that forms is separated, suspended in 50 ml of water and filtered. After separation of the oil which is thereby formed, this is heated with 30 ml of concentrated hydrochloric acid to 65° C until the development of methyl chloride has ceased. The reaction mixture is stirred with 100 ml of water, whereby a precipitate is formed which dissolves in slightly ammoniacal water. The solution is treated with activated charcoal and then cured. 10 g of Nj-m-nitrobenzenesulfonyl-No-butyl urea with a melting point of 175-177° C are precipitated. This compound is transferred by catalytic reduction (as indicated in example 3b) to metanilyl-butyl urea. The product's melting point is 116° C.
Eksempel 5. N j- metanilyl- N 9-( n- butyl) - Example 5. N j- methanilyl- N 9-( n- butyl) -
urinstoff. urea.
210 g N,-acetylmetanilyl-N2-(n-butyl) - thiourinstoff (erholdt ved omsetning av acetyl-metanilamid-natrium med butyl-sennepsolje) oppløses under oppvarmning i 1400 ml aceton. Den erholdte oppløsning blandes med 500 ml vann og tilsettes under omrøring og avkjøling til 15—20° C i løpet av 45 minutter en oppløsning av 63 g NaNO, i 120 ml vann. Der dannes en krystallsu-spensjon som i løpet av 30 minutter tilsettes 240 ml 25 pst.s iseddik. Blandingen omrøres i 6 timer, hvorpå man suger væsken bort fra det dannede butylacetyl-metanilyl-urinstoff som er blandet med svovel. Rå-produktet suspenderes i 1 liter vann og gjøres svakt alkalisk overfor fenolfthalein. Uoppløst svovel fraskilles. Av filtratet får man ved surgjøring 150 g ^-(acetylmetanilyl)-N2-(-butyl) -urinstoff med smeltepunkt 160—163° C. Denne forbindelse oppvarmes i 2 timer under omrøring til 92° C med 500 ml 5 N-kaliumhydroxy-oppløsning. Det faste reaksjonsprodukt bringes i opp-løsning ved oppvarmning med 750 ml vann, og den erholdte oppløsning renses med aktivt kull. Oppløsningen oppvarmes derpå til 60° C og surgjøres, hvorved man får 117 g Nt-metanilyl-NP- (n-butyl) -urinstoff med smeltepunkt 115—117° C. 210 g of N,-acetylmethanylyl-N2-(n-butyl)-thiourea (obtained by reacting acetyl-methanilamide sodium with butyl mustard oil) are dissolved while heating in 1400 ml of acetone. The resulting solution is mixed with 500 ml of water and a solution of 63 g of NaNO in 120 ml of water is added while stirring and cooling to 15-20° C over the course of 45 minutes. A crystal suspension is formed to which 240 ml of 25% glacial acetic acid is added within 30 minutes. The mixture is stirred for 6 hours, after which the liquid is sucked away from the formed butylacetyl-methanilyl urea which is mixed with sulphur. The crude product is suspended in 1 liter of water and made slightly alkaline to phenolphthalein. Undissolved sulfur is separated. The filtrate is acidified to yield 150 g of ^-(acetylmethanylyl)-N2-(-butyl)-urea with a melting point of 160-163° C. This compound is heated for 2 hours while stirring to 92° C with 500 ml of 5 N-potassium hydroxy- resolution. The solid reaction product is brought into solution by heating with 750 ml of water, and the resulting solution is purified with activated charcoal. The solution is then heated to 60° C and acidified, thereby obtaining 117 g of Nt-methanylyl-NP-(n-butyl) urea with a melting point of 115-117° C.
Claims (1)
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
NO437172A NO128892B (en) | 1972-11-29 | 1972-11-29 | |
GB5538173A GB1448999A (en) | 1972-11-29 | 1973-11-29 | Portable antenna |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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NO437172A NO128892B (en) | 1972-11-29 | 1972-11-29 |
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NO128892B true NO128892B (en) | 1974-01-21 |
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NO437172A NO128892B (en) | 1972-11-29 | 1972-11-29 |
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NO (1) | NO128892B (en) |
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DE3201067C2 (en) * | 1981-01-28 | 1988-04-14 | Salzgitter Maschinen Und Anlagen Ag, 3320 Salzgitter | Telescopic mast |
FR2527013A1 (en) * | 1982-05-14 | 1983-11-18 | Thomson Csf | DEPORTABLE ANTENNA FOR PORTABLE OR PORTABLE ELECTROMAGNETIC ELECTROMAGNETIC WAVE TRANSMITTER STATION |
EP2112711A1 (en) * | 2008-04-23 | 2009-10-28 | R.A. Miller Industries, INC. | Field antenna |
DK2946436T3 (en) * | 2012-12-24 | 2022-10-10 | Leonardo UK Ltd | Personal portable antenna unit |
-
1972
- 1972-11-29 NO NO437172A patent/NO128892B/no unknown
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1973
- 1973-11-29 GB GB5538173A patent/GB1448999A/en not_active Expired
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