NO129637B - - Google Patents
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- NO129637B NO129637B NO00484/69A NO48469A NO129637B NO 129637 B NO129637 B NO 129637B NO 00484/69 A NO00484/69 A NO 00484/69A NO 48469 A NO48469 A NO 48469A NO 129637 B NO129637 B NO 129637B
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- Prior art keywords
- sodium
- acid
- methyl
- reaction
- aliphatic
- Prior art date
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- -1 phenoxyphenyl Chemical group 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 13
- 125000001931 aliphatic group Chemical group 0.000 claims description 7
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical class OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 5
- 229940100389 Sulfonylurea Drugs 0.000 claims description 4
- 150000001447 alkali salts Chemical class 0.000 claims description 4
- 150000003948 formamides Chemical class 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 3
- 239000011541 reaction mixture Substances 0.000 claims description 3
- 235000008733 Citrus aurantifolia Nutrition 0.000 claims description 2
- 235000011941 Tilia x europaea Nutrition 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 239000004305 biphenyl Substances 0.000 claims description 2
- 235000010290 biphenyl Nutrition 0.000 claims description 2
- 125000006267 biphenyl group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 239000004571 lime Substances 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- 125000004417 unsaturated alkyl group Chemical group 0.000 claims description 2
- 150000007530 organic bases Chemical group 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- HFFLGKNGCAIQMO-UHFFFAOYSA-N trichloroacetaldehyde Chemical compound ClC(Cl)(Cl)C=O HFFLGKNGCAIQMO-UHFFFAOYSA-N 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 17
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 239000002244 precipitate Substances 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 229910021529 ammonia Inorganic materials 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000000155 melt Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- XWGJFPHUCFXLBL-UHFFFAOYSA-M rongalite Chemical compound [Na+].OCS([O-])=O XWGJFPHUCFXLBL-UHFFFAOYSA-M 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 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 4
- DAULHAZHIILZEA-UHFFFAOYSA-N [Na].NCl.C1(=CC=C(C=C1)S(=O)(=O)O)C Chemical compound [Na].NCl.C1(=CC=C(C=C1)S(=O)(=O)O)C DAULHAZHIILZEA-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- XCTTVNSXEHWZBI-UHFFFAOYSA-N n-(2-methylpropyl)formamide Chemical compound CC(C)CNC=O XCTTVNSXEHWZBI-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- JTDKEDJPCUTMJL-UHFFFAOYSA-N 1-(4-methylphenyl)sulfonyl-3-(2-methylpropyl)urea Chemical compound CC(C)CNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JTDKEDJPCUTMJL-UHFFFAOYSA-N 0.000 description 3
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical class OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 3
- SWGXDLRCJNEEGZ-UHFFFAOYSA-N N-cyclohexylformamide Chemical compound O=CNC1CCCCC1 SWGXDLRCJNEEGZ-UHFFFAOYSA-N 0.000 description 3
- JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- ZJQFAIWMDDWQNS-UHFFFAOYSA-N [Na].NCl.C1(=CC=CC=C1)S(=O)(=O)O Chemical compound [Na].NCl.C1(=CC=CC=C1)S(=O)(=O)O ZJQFAIWMDDWQNS-UHFFFAOYSA-N 0.000 description 2
- DQSCNRIAQYOTPV-UHFFFAOYSA-N [Na].NCl.CC1=C(C(=CC=C1)Cl)S(=O)(=O)O Chemical compound [Na].NCl.CC1=C(C(=CC=C1)Cl)S(=O)(=O)O DQSCNRIAQYOTPV-UHFFFAOYSA-N 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 239000004927 clay Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- DYDNPESBYVVLBO-UHFFFAOYSA-N formanilide Chemical compound O=CNC1=CC=CC=C1 DYDNPESBYVVLBO-UHFFFAOYSA-N 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- JGJLWPGRMCADHB-UHFFFAOYSA-N hypobromite Chemical compound Br[O-] JGJLWPGRMCADHB-UHFFFAOYSA-N 0.000 description 2
- TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- CRWJEUDFKNYSBX-UHFFFAOYSA-N sodium;hypobromite Chemical compound [Na+].Br[O-] CRWJEUDFKNYSBX-UHFFFAOYSA-N 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- DEVUYWTZRXOMSI-UHFFFAOYSA-N (sulfamoylamino)benzene Chemical compound NS(=O)(=O)NC1=CC=CC=C1 DEVUYWTZRXOMSI-UHFFFAOYSA-N 0.000 description 1
- BNZMOMQBYDNFHM-UHFFFAOYSA-N 1-(benzenesulfonyl)-3-(2-methylpropyl)urea Chemical compound CC(C)CNC(=O)NS(=O)(=O)C1=CC=CC=C1 BNZMOMQBYDNFHM-UHFFFAOYSA-N 0.000 description 1
- WJYIUPDCKOYOKO-UHFFFAOYSA-N 1-cyclohexyl-3-(4-methoxyphenyl)sulfonylurea Chemical compound COC1=CC=C(C=C1)S(=O)(=O)NC(=O)NC1CCCCC1 WJYIUPDCKOYOKO-UHFFFAOYSA-N 0.000 description 1
- ZMTSMVZAFDWQRM-UHFFFAOYSA-N 2-phenylethylurea Chemical compound NC(=O)NCCC1=CC=CC=C1 ZMTSMVZAFDWQRM-UHFFFAOYSA-N 0.000 description 1
- ICBQXEWYZVQCFH-UHFFFAOYSA-N 3-(4-bromoanilino)-n,n-dimethylpropanamide Chemical compound CN(C)C(=O)CCNC1=CC=C(Br)C=C1 ICBQXEWYZVQCFH-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- LWNCVRPTMSEJCM-UHFFFAOYSA-N 4-methoxybenzenesulfonamide;sodium Chemical compound [Na].COC1=CC=C(S(N)(=O)=O)C=C1 LWNCVRPTMSEJCM-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- QDHHCQZDFGDHMP-UHFFFAOYSA-N Chloramine Chemical compound ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 description 1
- QQGNLKJAIVSNCO-UHFFFAOYSA-N N-butylformamide Chemical compound CCCCNC=O QQGNLKJAIVSNCO-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- CBSUGLHHVWQEPK-UHFFFAOYSA-N [Na].NBr.C1(=CC=CC=C1)S(=O)(=O)O Chemical compound [Na].NBr.C1(=CC=CC=C1)S(=O)(=O)O CBSUGLHHVWQEPK-UHFFFAOYSA-N 0.000 description 1
- AMIXGQGFDAXFET-UHFFFAOYSA-N [Na].NCl Chemical compound [Na].NCl AMIXGQGFDAXFET-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 235000013405 beer Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229950001336 bromamide Drugs 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000000571 coke Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 230000010030 glucose lowering effect Effects 0.000 description 1
- RIGBPMDIGYBTBJ-UHFFFAOYSA-N glycyclamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NC1CCCCC1 RIGBPMDIGYBTBJ-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- IRAHFWCVGNHHDJ-UHFFFAOYSA-N n-bromo-4-methylbenzenesulfonamide;sodium Chemical compound [Na].CC1=CC=C(S(=O)(=O)NBr)C=C1 IRAHFWCVGNHHDJ-UHFFFAOYSA-N 0.000 description 1
- SJUGPXBWZCQTKM-UHFFFAOYSA-N n-chloro-4-methylbenzenesulfonamide;sodium Chemical compound [Na].CC1=CC=C(S(=O)(=O)NCl)C=C1 SJUGPXBWZCQTKM-UHFFFAOYSA-N 0.000 description 1
- SHIGCAOWAAOWIG-UHFFFAOYSA-N n-prop-2-enylformamide Chemical compound C=CCNC=O SHIGCAOWAAOWIG-UHFFFAOYSA-N 0.000 description 1
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical class O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
- 235000021395 porridge Nutrition 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000001007 puffing effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical class NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical group C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/58—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from fungi
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/38—Products with no well-defined composition, e.g. natural products
- C11D3/386—Preparations containing enzymes, e.g. protease or amylase
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- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Mycology (AREA)
- Biotechnology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Detergent Compositions (AREA)
- Enzymes And Modification Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Fremgangsmåte til fremstilling av sulfonylurinstoffer. Process for the production of sulfonylureas.
For fremstilling av sulfonylurinstoffer, spesielt av benzolsulfonylurlnstoffer, er f or-skjellige fremgangsmåter kjent. Således kan man eksempelvis omsette benzolsulf-amid med alkyl- eller fe>nylisocyanater, idet man fordelaktig går ut fra sulfonsyre-amidenes natriumsalter (sammelign fransk patent na*. 993 465). Flere andra metoder er beskrevet 1 Chemical Reviews nr. 50 For the production of sulfonylureas, especially benzenesulfonylureas, various methods are known. Thus, for example, benzenesulfamide can be reacted with alkyl or phenyl isocyanates, advantageously starting from the sodium salts of sulfonic acid amides (compare French patent no. 993 465). Several other methods are described 1 Chemical Reviews no. 50
(1952), bind IV, side 1 o. f. Disse kjente (1952), volume IV, page 1 et seq. These known
fremgangsmåter er .i nyere tid også benyt-tet til fremstilling av sulfonylurinstoffer med tolodsukkersenkende virkning. methods have recently also been used for the production of sulphonylureas with glucose-lowering effects.
Det er nå blitt funnet en ny teknisk fordelaktig og overfor teknikkens kjemte stand overraskende fremgangsmåte til fremstilling av sulfonylurinstoffer med den generelle formel A new technically advantageous and, compared to the state of the art, surprising process for the production of sulfonylureas with the general formula has now been found
R - SOa - NH - CO - NH - R,, R - SOa - NH - CO - NH - R,,
idet R betyr en, eventuelt en eller flere ganger med alkyl-, alikoksygruppeir eller wherein R means one, optionally one or more times with alkyl, alkyloxy groups or
halogenatomer substituert fenyl- eller naf- halogen atoms substituted phenyl- or naphth-
tylrest, en difenyl-, fenoksyfenyl-, fenylalkyl- eller tetrahydronaftalinrest eller en alifatisk resp. cykloalifatisk resp. blandet cykloalifatisk-lalifatisk rest med inntil 12 kullstoffatomer og R1 betyr en mettet eller umettet alkyl-, cykloailkyl-, cykloalkyl-alkyl, ifenylalkyl- eller fenylrest, idet den alifatiske rest også kan være avbrutt med surstoff, hvor man omsetter alkali-metallsalter av sulfonsyrekiloramid eller sulfonisyrebromamid med formamider med formelen tyl residue, a diphenyl, phenoxyphenyl, phenylalkyl or tetrahydronaphthalene residue or an aliphatic resp. cycloaliphatic resp. mixed cycloaliphatic-laliphatic residue with up to 12 carbon atoms and R1 means a saturated or unsaturated alkyl, cycloalkyl, cycloalkyl-alkyl, ifenylalkyl or phenyl residue, the aliphatic residue can also be interrupted with oxygen, where alkali metal salts of sulfonic acid chloroamide are reacted or sulfonic acid bromamide with formamides of the formula
idet R i har den angitte betydning. where R i has the indicated meaning.
Fremgangsmåten Ifølge oppfinnelsen forløper eksempelviis ved anvendelse av iisobutylformamid og N-(4-metylbenzol-sulfonsyre)-kloramidnatrium som ut-gangsstoffer tilsvarende etterfølgende reaksj onslignlng The method According to the invention proceeds, for example, using isobutylformamide and N-(4-methylbenzenesulphonic acid)-chloramide sodium as starting substances corresponding to the following reaction equation
Formelskjemaet skal ikke bare anskue-liggjøre fremstillingen av N-(4-metyl-benzolsulf onyl) -N'-isObutyl-urinstof f, men ganske generelt vise den allsidige reak-sjons forløp. The formula chart should not only visualize the production of N-(4-methyl-benzenesulfonyl)-N'-isobutylurea, but rather generally show the course of the versatile reaction.
Bortsett fra det overraskende reak-sjonsforløp bestar en spesiell fordel ved fremgangsmåten ifølge oppfinnelsen deri at de nødvendige 'Utgangsmaterialer er til-gjengelige på enkel måte. Eksempelvis kan sulfonsyre-kloramid-natriumsalter utvin-nes fra sulfamider ved omsetning med klorkalik i vandig medium og utfelling med koksalt Ifølge fremgangsmåten angitt i det tyske patent rar. 390 658. Sulfonsyre-bromamid-alkaliforbindelseir fås eksempelvis idet man innbringer tilsvarende sulfamider i form av deres alkalisalter i vandig oppløsning i en vandig hypobromitt-oppløsniing, idet krystallisasjon kan be-virkes resp. fullstendiggjøres eventuelt ved tilsetning av litt konsentrert natronlut, eksempelvis sulfonsyre-otromamidets na-triumsalt. Råproduktet som er fått på den-ne måten lar seg etter avsugning og tør-king ved værelsesteimperatur, for eksempel på leire, anvendes som utgangsstoff for den videre omsetning. Formamidene som benyttes ifølge oppfinnelsen kan fås på enkel måte å fortriinnelig utbytte ved oppvarming av maursyreestere, eksempelvis maursyremetylester med primære alifatiske, cykloalifatiske, aromatiske og aromatisk-alif atiske aminer resp. av slike aminer og kulloksyd. De fremstiller bekvemt forbindelser til bruk. Apart from the surprising course of the reaction, a particular advantage of the method according to the invention is that the necessary starting materials are easily available. For example, sulphonic acid-chloramide-sodium salts can be recovered from sulphonamides by reaction with chloralkali in an aqueous medium and precipitation with coke salt According to the method stated in the German patent rar. 390 658. Sulfonic acid-bromamide-alkali compounds are obtained, for example, by introducing corresponding sulfamides in the form of their alkali salts in aqueous solution in an aqueous hypobromite solution, since crystallization can be effected resp. possibly completed by adding a little concentrated caustic soda, for example the sodium salt of sulfonic acid otromamide. The raw product obtained in this way can, after extraction and drying at room temperature, for example on clay, be used as a starting material for further processing. The formamides used according to the invention can be obtained in a simple way in excellent yield by heating formic acid esters, for example formic acid methyl ester with primary aliphatic, cycloaliphatic, aromatic and aromatic-aliphatic amines resp. of such amines and carbon monoxide. They conveniently prepare compounds for use.
Ved fremgangsmåten Ifølge oppfinnelsen arbeider man ved forhøyede temperaturer, fortrinnsvis ved dåmpbadtempera-tur. Imidlertid kan det også anvendes temperaturer som ligger noe høyere eller lavere. Spesielt er temperaturer mellom 90° C og 130° C aktuelle. Oppvarmimgsti-len utgjør vanligvis ca. en time. Imidlertid kan omsetningen gjennomføres også med en reaksjonstid på 15—120 min. Reaksjonen forløper på en spesiell fordelaktig måte, hvis man tilsetter omsetningskom-ponentenes blanding salter, f. eks. na-triumklorid, kaliumkarbonat eller spesielt natriumbikarbonat og natriumkarbonat. Også en tilsetning iav klorkalk har vist seg gunstig. Den tilblandede saltmengde kan utgjøre inntil 2 mol ved molare tilsetnin-ger. Istedenfor alkalisalter kan man også tilsette reiaksj onskomponentene tertiære aminer, eksempelvis tributylamin. De til-satte sulfonsyre-taalogenamidsalter tilset-tes mest hensiktsmessig i form av deres vanniholdige krystallisater eller i svak fuk-tig tilstand. Under de angitte betingelser (fortynning med salter, vanninnhold, for-holdsvis lav reaksjonstemperatur) behøves det ikke å fryktes for en forpuffing av disse forbindelser. In the method according to the invention, one works at elevated temperatures, preferably at steam bath temperature. However, temperatures that are somewhat higher or lower can also be used. In particular, temperatures between 90° C and 130° C are relevant. The heating style usually amounts to approx. one hour. However, the turnover can also be carried out with a reaction time of 15-120 min. The reaction proceeds in a particularly advantageous way, if one adds salts to the mixture of the reaction components, e.g. sodium chloride, potassium carbonate or especially sodium bicarbonate and sodium carbonate. An addition of chlorinated lime has also proved beneficial. The added amount of salt can amount to up to 2 moles in the case of molar additions. Instead of alkali salts, tertiary amines, for example tributylamine, can also be added to the reaction components. The added sulphonic acid-thalogenamide salts are most suitably added in the form of their water-containing crystallisates or in a slightly moist state. Under the stated conditions (dilution with salts, water content, relatively low reaction temperature) there is no need to fear puffing of these compounds.
Aktuelle reaksj onskomponenter for fremgangsmåten ifølge oppfinnelsen er: alifatiske og cyklo-alifatiske sulfonsyrers halogenamid-alkali-, spesielt -natrlumsal-ter som eksempelvis heptansulfonsyre-kloramid-natrium, heptansulfonsyrebrom-amidsnatrium, cykloheksan-sulfonsyre-kloramidnatrium, cykloheksansulfonsyre-bromamid-niatrium, videre slike aromatiske sulfonsyrer som ibenzolsulfonsyre-kloramidnatoium, benzolsulfonsyrebrom-amid-natrium, p-toluolsulfonsyre-klor-amidnatrium, p-toluol-sulfonsyrebrom-amidnatrium, 2-metyl-6-klorbenzolsulfon-syre-kloramid-natøium, 2- metyl-6-'klor-benzolsulfonsyre-bromamid-natrium, naf-talin-2-sulfonsyre-kloramidniatirium, naf-talin-2-sulfonisyrebromamld-natrium, 5,6, 7,8 -1 e trahydronaftalln- 2 ^sulf onsyre -kloramid-natrium, 5,6,7,8-tetrahydronaftalin-2-sulfonsyrebromamid-natrium, co-benzol-sulfonsyretaromamid-natrium. Relevant reaction components for the method according to the invention are: halogenamide-alkali-, especially -sodium salts of aliphatic and cyclo-aliphatic sulphonic acids, such as for example heptanesulphonic acid-chloramide sodium, heptanesulphonic acid bromide-sodium, cyclohexane-sulphonic acid-sodium chloramide, cyclohexanesulphonic acid-bromide-sodium, further such aromatic sulfonic acids as ibenzenesulfonic acid chloramide sodium, benzenesulfonic acid bromamide sodium, p-toluenesulfonic acid chloroamide sodium, p-toluenesulfonic acid bromoamide sodium, 2-methyl-6-chlorobenzenesulfonic acid chloramide sodium, 2-methyl-6- 'Chloro-benzenesulfonic acid-bromamide-sodium, Naphthalene-2-sulfonic acid-chloramide niathirium, Naphthalene-2-sulfonic acid bromamide sodium, 5,6, 7,8 -1 e trahydronaphthalln- 2 ^sulfonic acid -chloramide sodium, 5,6,7,8-tetrahydronaphthalene-2-sulfonic acid bromamide sodium, co-benzenesulfonic acid taromamide sodium.
Aktuelle formamider er: alifatiske og cyklo-alifatiske primære aminers formyl-forbindelser, eksempelvis N-but3-l- og N-isobutyiformamid, N-cykloheksylform-amid, N-allylformamid, videre aromatiske og aromatisk-alifatiske aminers formyl-forbindelser, eksempelvis N-((3-fenyletyl)-formamid og N-fenylformamid. Relevant formamides are: formyl compounds of aliphatic and cycloaliphatic primary amines, for example N-but3-l- and N-isobutyformamide, N-cyclohexylformamide, N-allylformamide, further aromatic and aromatic-aliphatic amines formyl compounds, for example N -((3-phenylethyl)-formamide and N-phenylformamide.
Fremgangsmåteproduktene har når de blir gitt oralt en antidiabetisk virkning, noe som allerede er kjent eller allerede er blitt foreslått. The process products, when administered orally, have an antidiabetic effect, which is already known or has already been proposed.
Eksempel 1. Example 1.
N- ( 4- metyl- benzolsulfonyl)- N'-isobutyl- urinstoff. N-(4-methyl-benzenesulfonyl)-N'-isobutyl-urea.
144,0 g 4-metyl-benzolsulfonsyre-kloramidnatrium x 3 H20, 60,5 g maursyre-isobutylamid og 71,0 g" Na,CO., med ca. 2 mol krystallvann blandes godt i en skål og oppvarmes i en time i dampbad. Under svak bobledannelse inntrer reaksjonen, Den dannede reaksj oniskake oppløses i 750 cm.3 varmt vann, man tilsetter en dråpe rongalit-oppløsning for å redusere det ikke omsatte 4-metyl-benzolsulfonsyre-kloramidnatriumet og lar den alkaliske oppløsning avkjøle og filtrere. Filtratet,an-syres med fortynnet saltsyre. De dannede krystaller suges fra og behandles med 1 pst.'ig ammoniakk. Etter gjentatt filtrering 144.0 g of 4-methyl-benzenesulfonic acid-chloramide sodium x 3 H20, 60.5 g of formic acid-isobutylamide and 71.0 g" of Na,CO., with about 2 mol of crystal water are mixed well in a bowl and heated for one hour in steam bath Under gentle bubbling the reaction takes place, The reaction cake formed is dissolved in 750 cm.3 of hot water, a drop of rongalite solution is added to reduce the unreacted 4-methyl-benzenesulfonic acid chloramide sodium and the alkaline solution is allowed to cool and filter. The filtrate is acidified with dilute hydrochloric acid. The formed crystals are sucked off and treated with 1% ammonia. After repeated filtration
ansyrer man filtratet med eddiksyre og får en krystallinsk utfelling av N-(4-metyl-benzolsulf onyl) -N'-isobutyl-uriinstoff, som etter avsugingen og tørkingen omkrystalli-seres fra ca. 450 cm3 metanol. Etter opp-arbeidelse av mOderluten får man 76 g N-(4 -metyl-benzolsulf onyl) -N' -isobutyl - the filtrate is acidified with acetic acid and a crystalline precipitate of N-(4-methyl-benzenesulfonyl)-N'-isobutyl-urea is obtained, which after suction and drying is recrystallized from approx. 450 cm3 of methanol. After working up the mother liquor, 76 g of N-(4-methyl-benzenesulfonyl)-N'-isobutyl -
urinstoff (56 pst. av det teoretiske) med smeltepunkt 169—171° C. urea (56 per cent of the theoretical) with a melting point of 169-171° C.
Eksempel 2. Example 2.
16,3 g 4-metyl-ibenzolsulfonsyrebrom-amid-natirium . 3 H20, 5 g N-isobutylform-amid og 7 g natriumkarbonat med ca. 2 mol vann blandes godt. Deretter oppvarmer man blandingen i dampbad og reaksjonen inntrer under bobledannelse. Etter ca. 5 min. avkjøles og oppløses reaksjonsgodset i varmt vann. Man reduserer eventuelt ikke forbrukt toluolsulfonsyrebromamid ved hjelp av litt rongalit-oppløsning, og ansyrer med fortynnet saltsyre. Det erholdte krystallinske bunnfall blir for videre ren-sing oppløst i ca. 1 pst. ammoniak. Man filtrerer og ansyrer filtratet med saltsyre. Bunnfallet av N(-4-metyl-taeinzoJsulfonyl)-N'-isobutyl-urinstoff som således fås i godt utbytte frasuges og tørkes. Substansen er allerede meget ren og smelter etter omkrystallisering fra metanol ved 169— 171° C. 16.3 g of 4-methyl-ibenzenesulfonic acid bromo-amide sodium. 3 H20, 5 g N-isobutylform-amide and 7 g sodium carbonate with approx. 2 moles of water are mixed well. The mixture is then heated in a steam bath and the reaction occurs during bubble formation. After approx. 5 min. cool and dissolve the reaction material in hot water. If not used toluene sulphonic acid bromamide is reduced with the aid of a little rongalite solution, and acidified with dilute hydrochloric acid. For further purification, the obtained crystalline precipitate is dissolved in approx. 1 percent ammonia. The filtrate is filtered and acidified with hydrochloric acid. The precipitate of N(-4-methyl-taeinzoJsulfonyl)-N'-isobutylurea which is thus obtained in good yield is suctioned off and dried. The substance is already very pure and melts after recrystallization from methanol at 169-171°C.
På analog måte får man fra p-toluol-sulfonsyre-ibromamid-natrium og N-for-mylbutylamin N- (4-metyl-benzolsulfonyl) - N'-n-butyl-urinstoff, hvis smeltepunkt etter omkrystalllseringen av eddikester ut-gjør 125 til 127° C. In an analogous way, from p-toluene-sulphonic acid ibromamide sodium and N-for-mylbutylamine N-(4-methyl-benzenesulfonyl)-N'-n-butylurea is obtained, the melting point of which after recrystallization from acetic ester is 125 to 127°C.
Eksempel 3. Example 3.
Analog som i eksempel 1 får man ved 30 min. oppvarming av 14 g 4-metyl-ben-zolsulfonsyre-kloramidnatrlum, 5,0 g maursyre-n-butylamid og 7,0 g Na2CO.( med ca. 2 H.20, en krystallkake som opp-løses i varmt vann. Etter tilsetning av rongalit ansyrer man med fortynnet saltsyre, avsuger den utfelte substans og behandler reaksj onsproduktet med 1 pst.'ig ammoniak. Man klargjør med kull, suger av og får ved ansyring med fortynnet saltsyre en krystallinsk felling av N-(4-metyl-benzolsulfonyl) -N'-n-butyl-urinstoff, som frasuges og tørkes. Råproduktet som fås i et utbytte på 8,8 g (65 pst. av det teoretiske) med smeltepunkt 117° til 119° C gir etter omkrystallisering fra eddikester 7,2 g (53 pst. av det teoretiske) N-(4-metyl-benzolsulf onyl) -N'-n-butyl-urinstof f med smeltepunkt 125° til 127° C. Analogous to example 1, you get at 30 min. heating 14 g of 4-methyl-benzenesulfonic acid-chloramide sodium, 5.0 g of formic acid-n-butylamide and 7.0 g of Na2CO.( with approx. 2 H.20, a crystal cake which dissolves in hot water. After addition of rongalite is acidified with dilute hydrochloric acid, the precipitated substance is filtered off with suction and the reaction product is treated with 1% ammonia. It is clarified with charcoal, suction is obtained and by acidification with dilute hydrochloric acid a crystalline precipitate of N-(4-methyl- benzolsulfonyl)-N'-n-butyl urea, which is filtered off with suction and dried. The crude product which is obtained in a yield of 8.8 g (65 per cent of the theoretical) with a melting point of 117° to 119° C gives after recrystallization from acetic ester 7 .2 g (53 per cent of the theoretical) N-(4-methyl-benzenesulfonyl)-N'-n-butyl-urea with melting point 125° to 127° C.
Eksempel 4. Example 4.
13,3 g benzolsulfonsyre-kloramid-natrium x 3 H20, 5,0 g maursyre-isobutyl-amid og 3,5 g kaliumkarbonat blandes godt. Man oppvarmer blandingen oa. 30 min. i dampbad. Etter ca. 10 min. oppstår en livlig gassutvikling. Man avkjøler og oppløser reaksj onsgodset i vann, filtrerer og ansyrer filtratet med fortynnet saltsyre. Den erholdte krystallinske felling suges 13.3 g of benzenesulfonic acid-chloramide-sodium x 3 H 2 O, 5.0 g of formic acid-isobutyl-amide and 3.5 g of potassium carbonate are mixed well. The mixture is heated, etc. 30 min. in a steam bath. After approx. 10 minutes a lively gas development occurs. The reaction material is cooled and dissolved in water, filtered and the filtrate acidified with dilute hydrochloric acid. The obtained crystalline precipitate is suctioned
fra og omfcrystadliseres fra fortynnet etanol. Man får 6,3 g (50 pst. av det teoretiske) from and recrystallised from dilute ethanol. You get 6.3 g (50 percent of the theoretical)
N-benzol-sulfonyl-N'-isobutyl-urinstoff med smeltepunkt 131 til 133° C. N-benzenesulfonyl-N'-isobutylurea, melting point 131 to 133°C.
Eksempel 5. Example 5.
17,1 g 4-metoksy-benzolsulfonsyre-bromamid-natrium (fremstilt av 4-met-oksy-benzolsulfamld-natrium og natrium-hypobromitt i vann) blandes med 6,3 g N-formylcykloheksylamin og 7 g natriumkarbonat. Man oppvarmer blandingen 10 min. i dampbad, avkj øler og tar opp i vann. Etter reduksjon av ikke omsatt 4-metoksyben-zolsulfoinsyre-bromamid med rongalit ansyrer man. Det oppnådde bunnfall opptas i ca. 1 pst.'lg ammoniakk. Man filtrerer og får ved ansyring av filtratet med fortynnet saltsyre et krystallisat av N-(4-met-oksy-benzolsulfonyl)-N'-cykloheksyl-urinstoff, som man suger fra og tørker. Det fra etanol omkrystalliserte produkt smelter ved 181° til 183° C. 17.1 g of 4-methoxy-benzenesulfonic acid bromamide-sodium (prepared from 4-methoxy-benzenesulfonamide-sodium and sodium hypobromite in water) is mixed with 6.3 g of N-formylcyclohexylamine and 7 g of sodium carbonate. The mixture is heated for 10 min. in a steam bath, cool beers and absorb in water. After reduction of unreacted 4-methoxybenzenesulfonic acid bromamide with rongalite, one acidifies. The precipitate obtained is recorded for approx. 1 pst.'lg ammonia. It is filtered and, by acidifying the filtrate with dilute hydrochloric acid, a crystallisate of N-(4-methoxy-benzenesulfonyl)-N'-cyclohexylurea is obtained, which is sucked off and dried. The product recrystallized from ethanol melts at 181° to 183° C.
Eksempel 6. Example 6.
22,7 g 4-metyl-benzolsulfonsyre-kloramid-natrium og 12,7 g maursyre-cyklo-heksylamid blandes godt og varmes i dampbad. Etter noen minutter har det dannet seg en tyntflytende oppløsning, idet det utvikles gass og stikkende lukt. Etter tilsammen åtte minutter avkjøler man, tilsetter reaksj onsgodset 1 pst.'ig vandig ammoniakk, filtrerer fra uoppløst stoff og ansyrer filtratet med eddiksyre. Etter reaksjonsgodsets gjentatte oppløs-ning og utfelling med ammoniakk respek-tiv eddiksyre, tørker man det oppnådde N- (4-metyl-benzolsulf onyl) -N'-cyklohek-sylurinstoff. Utbyttet utgjør 6,3 g (21 pst. av det teoretiske). Man omikrystalliserer produktet fra fortynnet etanol. Oet således erholdte N- (4 - metyl -b e nzol -sulf onyl) - N' - cykloheksyl-urlnstoff smelter ved 170° til 172° C. 22.7 g of 4-methyl-benzenesulphonic acid-chloramide-sodium and 12.7 g of formic acid-cyclohexylamide are mixed well and heated in a steam bath. After a few minutes, a thin liquid solution has formed, as gas and a pungent odor develop. After a total of eight minutes, cool, add 1% aqueous ammonia to the reaction mixture, filter from undissolved matter and acidify the filtrate with acetic acid. After repeated dissolution and precipitation of the reaction mixture with ammonia or acetic acid, the obtained N-(4-methyl-benzenesulfonyl)-N'-cyclohexylurea is dried. The yield amounts to 6.3 g (21 per cent of the theoretical). The product is recrystallized from diluted ethanol. The N-(4-methyl-benzol-sulfonyl)-N'-cyclohexyl carbon thus obtained melts at 170° to 172° C.
Eksempel 7. Example 7.
15,8 g 2-metyl-6-klorbenzolsulfonsyre-kloramid-natrium, 7,0 g Na2CO;, med ca. 2 H20 og 4,3 g maursyreallyiamid blandes godt og oppvarmes 1 30 min. i dampbad. Det dannes en tynn grøt som etter 20 min. blir flytende. Sporadisk opptrer bob-ler. Etter avkjøling oppløses reaksj onsgodset i varmt vann. Ved tilsetning av noen dråper rongalit-oppløsning blir det over-skytende benzolsulfonsyre-kloramid-natrium redusert og ved tilsetning av fortynnet saltsyre fås en felling som suges fra. Substansen behandles med 1 pst.'ig ammoniakk. Man filtrerer fra uoppløst og ansyrer filtratet med fortynnet saltsyre. Man får en felling av 4 g N-(2-metyl-6-klorbenzolsulfonyl) -N'-allyl-urinstoff som smeltepunkt 184° til 187° C, som etter omkrystallisering av eddikester smelter ved 192° til 194° C. 15.8 g 2-methyl-6-chlorobenzenesulfonic acid chloramide sodium, 7.0 g Na2CO;, with approx. 2 H 2 O and 4.3 g of formic acid allyamide are mixed well and heated for 1 30 min. in a steam bath. A thin porridge is formed which after 20 min. becomes liquid. Bubbles occasionally appear. After cooling, the reaction material is dissolved in hot water. By adding a few drops of rongalite solution, the excess benzolsulfonic acid-chloramide sodium is reduced and by adding dilute hydrochloric acid, a precipitate is obtained which is sucked off. The substance is treated with 1 percent ammonia. One filters from undissolved and acidifies the filtrate with dilute hydrochloric acid. A precipitate of 4 g of N-(2-methyl-6-chlorobenzenesulfonyl)-N'-allylurea is obtained as melting point 184° to 187° C, which after recrystallization from acetic ester melts at 192° to 194° C.
Eksempel 8. Example 8.
33 g 3-metyl-4-metoksy-benzolsulfon-syrebromamid-natrlum (fremstilt av 3-metyl-4-metoksy-atenzolsulfamid-natrium og en ekvivalent . natriumhypo-bromittoppløsning i vann, idet det nevnte salt ved tilsetning av natronlut bringes til krystallisasjon), 14 g natriumkarbonat og 18 g N-formyl-(3-fenyietylamin blandes. Blandingen oppvarmes i en rundkolbe i dampbad. Etter ca. 5 min. inntrer livlig reaksjon. Man avkjøler, oppløser reaksj onsgodset i vann og ansyrer med fortynnet saltsyre. Det erholdte bunnfall frasuges, oppløses i ca. 1 pst.'lg ammoniakk og etter filtrering fra filtratet utfelles ved ny ansyring. De erholdte krystaller av N-(3-metyl-4-metoksy-faenzolBurfonyl)-N'-p- 33 g 3-methyl-4-methoxy-benzenesulfonic acid bromide-sodium (prepared from 3-methyl-4-methoxy-atenzolsulfamide-sodium and an equivalent sodium hypobromite solution in water, the aforementioned salt being brought to crystallization by adding caustic soda ), 14 g of sodium carbonate and 18 g of N-formyl-(3-phenylethylamine) are mixed. The mixture is heated in a round flask in a steam bath. After approx. 5 min. a lively reaction occurs. The reaction material is cooled, dissolved in water and acidified with dilute hydrochloric acid. The resulting precipitate is suctioned off, dissolved in approx. 1 pst.'lg of ammonia and, after filtration from the filtrate, is precipitated by further acidification.
fenyletyl-urinstoff avsuges og omkrystal-liseres av etanol etter tørking på leire. Substansen smelter ved 148—150° C. phenylethylurea is suctioned off and recrystallized from ethanol after drying on clay. The substance melts at 148-150° C.
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO385369A NO131940C (en) | 1968-02-08 | 1969-09-27 |
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|---|---|---|---|
| JP786368 | 1968-02-08 | ||
| JP1697068 | 1968-03-15 |
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| NO129637B true NO129637B (en) | 1974-05-06 |
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| FR (1) | FR2001575A1 (en) |
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| NO (1) | NO129637B (en) |
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| DK564086A (en) * | 1986-11-25 | 1988-06-17 | Novo Industri As | ENZYMATIC DETERGENT ADDITIVE |
| DK563986A (en) * | 1986-11-25 | 1988-06-17 | Novo Industri As | PREPARATION OF A LOW-TEMPERATURE-ACTIVE PROTEASE |
| US4711739A (en) * | 1986-12-18 | 1987-12-08 | S. C. Johnson & Son, Inc. | Enzyme prespotter composition stabilized with water insoluble polyester or polyether polyol |
| DK571587D0 (en) * | 1987-11-02 | 1987-11-02 | Novo Industri As | ENZYMATIC DETERGENT COMPOSITION |
| DE68924654T2 (en) * | 1988-01-07 | 1996-04-04 | Novonordisk As | Specific protease. |
| US5156761A (en) * | 1988-07-20 | 1992-10-20 | Dorrit Aaslyng | Method of stabilizing an enzymatic liquid detergent composition |
| CA2069147A1 (en) * | 1991-05-22 | 1992-11-23 | Kazuaki Kitano | Dna and its use |
| US20070010416A1 (en) * | 2004-10-22 | 2007-01-11 | Novozymes A/S | Protease with improved stability in detergents |
| FR3115901B1 (en) | 2020-11-05 | 2022-11-18 | Commissariat Energie Atomique | System-on-chip binary tree summation of floating-point values |
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1969
- 1969-02-03 US US795951A patent/US3655570A/en not_active Expired - Lifetime
- 1969-02-06 BE BE728027D patent/BE728027A/xx not_active IP Right Cessation
- 1969-02-06 NL NL6901889.A patent/NL157657B/en not_active IP Right Cessation
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- 1969-02-07 NO NO00484/69A patent/NO129637B/no unknown
- 1969-02-07 DK DK66069AA patent/DK130190B/en unknown
- 1969-02-07 ES ES363379A patent/ES363379A1/en not_active Expired
- 1969-02-07 DE DE1906001A patent/DE1906001C3/en not_active Expired
- 1969-02-07 FR FR6902949A patent/FR2001575A1/fr not_active Withdrawn
- 1969-02-08 FI FI690391A patent/FI47205C/en active
- 1969-02-10 GB GB1231150D patent/GB1231150A/en not_active Expired
-
1970
- 1970-06-15 ES ES380768A patent/ES380768A1/en not_active Expired
-
1971
- 1971-11-19 SE SE14869/71A patent/SE409335B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US3655570A (en) | 1972-04-11 |
| NL6901889A (en) | 1969-08-12 |
| DE1906001B2 (en) | 1978-04-06 |
| DK130190C (en) | 1975-06-30 |
| DE1906001C3 (en) | 1978-12-07 |
| ES363379A1 (en) | 1971-02-16 |
| DK130190B (en) | 1975-01-13 |
| SE368028B (en) | 1974-06-17 |
| FI47205B (en) | 1973-07-02 |
| NL157657B (en) | 1978-08-15 |
| ES380768A1 (en) | 1973-04-01 |
| BE728027A (en) | 1969-07-16 |
| FR2001575A1 (en) | 1969-09-26 |
| DE1906001A1 (en) | 1969-09-11 |
| GB1231150A (en) | 1971-05-12 |
| FI47205C (en) | 1973-10-10 |
| SE409335B (en) | 1979-08-13 |
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