SE435376B - SET TO PREPARE 1,2,3-THIADIAZOL-5-YL CARBAMIDES - Google Patents
SET TO PREPARE 1,2,3-THIADIAZOL-5-YL CARBAMIDESInfo
- Publication number
- SE435376B SE435376B SE7907841A SE7907841A SE435376B SE 435376 B SE435376 B SE 435376B SE 7907841 A SE7907841 A SE 7907841A SE 7907841 A SE7907841 A SE 7907841A SE 435376 B SE435376 B SE 435376B
- Authority
- SE
- Sweden
- Prior art keywords
- formula
- general formula
- carboxylic acid
- thiadiazole
- azide
- Prior art date
Links
- -1 1,2,3-THIADIAZOL-5-YL CARBAMIDES Chemical class 0.000 title claims description 20
- 238000000034 method Methods 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 11
- 150000001412 amines Chemical class 0.000 claims description 10
- 150000001540 azides Chemical class 0.000 claims description 10
- 239000011541 reaction mixture Substances 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 5
- UDSVLKOSDHNDNJ-UHFFFAOYSA-N thiadiazole-5-carbonyl azide Chemical compound [N-]=[N+]=NC(=O)C1=CN=NS1 UDSVLKOSDHNDNJ-UHFFFAOYSA-N 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 4
- 235000013877 carbamide Nutrition 0.000 claims description 4
- 239000007795 chemical reaction product Substances 0.000 claims description 4
- BXCZJWHJYRELHY-UHFFFAOYSA-N thiadiazole-5-carboxylic acid Chemical compound OC(=O)C1=CN=NS1 BXCZJWHJYRELHY-UHFFFAOYSA-N 0.000 claims description 4
- 238000009835 boiling Methods 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- HYLDNDBHUFKUSG-UHFFFAOYSA-N 1,2,5-thiadiazole-3-carbonyl azide Chemical compound S1N=C(C=N1)C(=O)N=[N+]=[N-] HYLDNDBHUFKUSG-UHFFFAOYSA-N 0.000 claims 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
- HFCYZXMHUIHAQI-UHFFFAOYSA-N Thidiazuron Chemical compound C=1C=CC=CC=1NC(=O)NC1=CN=NS1 HFCYZXMHUIHAQI-UHFFFAOYSA-N 0.000 claims 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 125000006501 nitrophenyl group Chemical group 0.000 claims 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 239000012442 inert solvent Substances 0.000 description 5
- 239000003513 alkali Substances 0.000 description 4
- 235000019439 ethyl acetate Nutrition 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000052 vinegar Substances 0.000 description 3
- 235000021419 vinegar Nutrition 0.000 description 3
- HWOZXDJQTCTHNJ-UHFFFAOYSA-N 2h-1,2,5-thiadiazole-5-carboxylic acid Chemical compound OC(=O)N1SNC=C1 HWOZXDJQTCTHNJ-UHFFFAOYSA-N 0.000 description 2
- 101100298295 Drosophila melanogaster flfl gene Proteins 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical class [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 239000012286 potassium permanganate Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 150000003672 ureas Chemical class 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- PJBPUBIFRFCYHE-UHFFFAOYSA-N 1,2,3-Thiadiazole, 5-methyl- Chemical compound CC1=CN=NS1 PJBPUBIFRFCYHE-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-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
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102100038803 Somatotropin Human genes 0.000 description 1
- 108050007673 Somatotropin Proteins 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 150000001731 carboxylic acid azides Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 239000012045 crude solution Substances 0.000 description 1
- ZQKKGHXDMUVUFH-UHFFFAOYSA-N cyclohexanone;propan-2-one Chemical compound CC(C)=O.O=C1CCCCC1 ZQKKGHXDMUVUFH-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- IVZZCUPPIUETNY-UHFFFAOYSA-N ethyl thiadiazole-5-carboxylate Chemical compound CCOC(=O)C1=CN=NS1 IVZZCUPPIUETNY-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 210000002837 heart atrium Anatomy 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000002641 lithium Chemical group 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002826 nitrites Chemical class 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 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
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000011403 purification operation Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- DHTBORBAEQJWLZ-UHFFFAOYSA-N thiadiazole-5-carbohydrazide Chemical compound NNC(=O)C1=CN=NS1 DHTBORBAEQJWLZ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/06—1,2,3-Thiadiazoles; Hydrogenated 1,2,3-thiadiazoles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
naveln-e à -180°C, företrädesvis 50-120°C, varefter reaktionsprodukten isoleras på i och för sig känt sätt och varvid R1 och R2 har den i krav 1 angivna betydelsen. the navel-e at -180 ° C, preferably 50-120 ° C, after which the reaction product is isolated in a manner known per se and wherein R1 and R2 have the meaning given in claim 1.
Speciella utföringsformer av sättet enligt uppfinningen består i att omsättningen genomföres vid koktemperaturen för reaktions- blandningen, _ att man omsätter ekvimolära mängder av aziden med formeln II och aminen med den allmänna formeln III, att omsättningen av aziden med formeln II med aminen med den allmänna formeln III sker i ett steg och att man använder en 1,2,3-tiadiazol-5-karbonsyraazid med for- meln II, som framställts på i och för sig känt sätt och inte isoleras ur den erhållna reaktionsblandningen, så att även ett kontinuerligt förfaringssätt blir möjligt. 1,2,3-tiadiazol-5-karbonsyraaziden med formeln II kan framställas enligt i och för sig kända förfaranden genom att a) 1,2,3-tiadiazol-5-karbonsyra med formelng q H å C - COOH _ IV \\ 1' får reagera med klcrmyrsyraestrar med den allmänna formeln Cl - CO - OR3 V 790784146 3 i ett inert lösningsmedel l närvaro av syraölndande medel till den blandade anhydríden med den allmänna formeln fi-ífl N;\ I/--CO-O-CO-OR3 VI S varefter man omsätter med lösningar av alkaliazider med den allmänna formeln MeN3 VII eller b) 4,2,5-tiadiazo1-5-karbonsyrahalogenider med den allmänna formeln fi r Nxs/ ”°°"X VIII omsättes i ínerta organiska lösningsmedel med vattenhaltiga lösningar av alkaliazider med den allmänna formeln NeN3 VII eller c) 1,2,5-tiadiazol-5-karbonsyrahydrazid med formeln f"'°“ Ä -CO-NH-NH \SJ 2 IX i inerta lösningsmedel omsättes med lösningar av alkalinitri- ter med den allmänna formeln MeNO2 X eller med alkylnitríter med den allmänna formeln R5-O-NO XI i närvaro av syra till 1,2,5-tiadiazol-5-karbonsyraazid med formeln ' N"'CH E I-GO N xs/ 'B II varvid R5 betecknar en G1-G6-alkylrest, Me betecknar en en- värd metallekvivalent, företrädesvis en natrium-, kalium- eller litiumatom och X betecknar en halogenatom, företrädes- vis en kloratom. 7 9 9 7 8 41- 6 *I Den härefter erhållna” 'azhiïfden med formeln II Behöver enligt ett fördelaktigt arbetssätt inte isoleras ur den erhåll- na reaktionsblandningen utan används med tillämpning av nämnda blandningar direkt för sättet enligt uppfinningen.Particular embodiments of the process according to the invention are that the reaction is carried out at the boiling temperature of the reaction mixture, that equimolar amounts of the azide of the formula II and the amine of the general formula III are reacted, that the reaction of the azide of the formula II with the amine of the general formula III takes place in one step and that a 1,2,3-thiadiazole-5-carboxylic acid azide of the formula II is used, which is prepared in a manner known per se and is not isolated from the reaction mixture obtained, so that even a continuous process becomes possible. The 1,2,3-thiadiazole-5-carboxylic acid azide of the formula II can be prepared according to methods known per se by a) 1,2,3-thiadiazole-5-carboxylic acid of the formula q H å C - COOH - IV 1 'is reacted with chloroformic acid esters of the general formula C1 - CO - OR3 V 790784146 3 in an inert solvent in the presence of acid solvents to the mixed anhydride of the general formula fi- í fl N; \ I / - CO-O-CO -OR3 VI S then reacting with solutions of alkali azides of the general formula MeN3 VII or b) 4,2,5-thiadiazol-5-carboxylic acid halides of the general formula fi r Nxs / "°°" X VIII are reacted in inert organic solvents with aqueous solutions of alkali azides of the general formula NeN3 VII or c) 1,2,5-thiadiazole-5-carboxylic acid hydrazide of the formula f "'°" Ä -CO-NH-NH 2 SJ 2 IX in inert solvents alkali nitrites of the general formula MeNO2 X or of alkyl nitrites of the general formula R5-O-NO XI in the presence of acid to 1,2,5-thiadiazole-5- carbonic acid azide of the formula 'N "' CH E I-GO N xs / 'B II wherein R5 represents a G1-G6 alkyl radical, Me represents a monovalent metal equivalent, preferably a sodium, potassium or lithium atom and X represents a halogen atom , preferably a chlorine atom. 7 9 9 7 8 41- 6 * I The hereinafter obtained '' azhiifden of formula II Need according to an advantageous mode of operation need not be isolated from the obtained reaction mixture but be used with application of said mixtures directly for the method according to the invention.
De som utgàngsprodukter erforderliga' 1,2,5-tiadiazol-5- -karbonsyran och dess derivat kan framställas på i och för sig; känt sätt, genom att exempelvis a) acylhydrazoner av propienaldehyd med den allmänna formeln GH5-GH2-G-:N-NH-CO-R4 ' XII får reagera med tionylklorid med formeln S°°12 XIII till E-metyl-'MEJ-tiadiazol med formeln Nr*- GH Il J i N\s _0153 XIV varefter denna oxideras med vanliga oxidatíonsmedel såsom krom-(VI) -oxid, kaliumpermanganat och salpetersyra till 'I ,2,5..-tiadiazol-š-karbonsyra med formeln IV i Niu- II I :Ks /æoon IV eller b) aeylhydrazoner av formylittiksyraester med den allmänna formeln _ H-C-Cflz-CGOR; N-EH-COfi-R4 XV omsättes med tionylklorid mediformeln 50312 XIII till 1,2,5-tiadiazol-S-kartonsyraestrar med den allmänna for- meln N*- GH N.\S /'-G0OR5 XVI Dessa kan därefter, eventdïellt i iaolära organiska lösningsmedel, omsättas med hydrazin medf formeln _: 7907841-6 _ . XVI-I . , till 1,2,5-tiadiazol-5-karbonsyrahydrazid med formeln ïïfi” N\\S -CO-NH-NH2 IX eller på i och för sig känt sätt förtvålas med lämpade oorga- niska baser såsom oxider, hydroxider eller karbonater av al- kali- eller jordalkalimetaller eller företrädesvis alkoholater, eventuellt i organiska lösningsmedel, vilken reaktion sker på i och för sig känt sätt odh man därvid erhåller 1,2,5-tiadia- zol-5-karbonsyra med formeln N\\S -OOOH . IV som därefter enligt kända förfaranden omsättes på nytt med van- liga halogeneringsmedel såsom tionglklorid odh fosforpenta- klorid till 4,2,5-tiadiazol-5-karbonsyrahalogenid med den all- männa formeln uni-_- "e I, lkxs -CO-X VIII RB och X har härvid ovan angiven betydelse och R4 beteck- nar en alkoxigrupp, företrädesvis en G1-04-alkoxigrupp, en aminogrupp eller en alkylaminogrupp, företrädesvis en 01-04- alkylaminogrupp.The starting materials required for the 1,2,5-thiadiazole-5-carboxylic acid and its derivatives can be prepared per se; known method, by reacting, for example, a) acyl hydrazones of propienaldehyde of the general formula GH5-GH2-G-: N-NH-CO-R4 'XII with thionyl chloride of the formula S °° 12 XIII to E-methyl-'MEJ- thiadiazole of the formula Nr * - GH II J i N \ s _0153 XIV after which it is oxidized with common oxidizing agents such as chromium (VI) -oxide, potassium permanganate and nitric acid to 'I, 2,5 ..- thiadiazole-š-carboxylic acid of the formula IV i Niu-II I: Ks / æoon IV or b) aylhydrazones of formylitic acid ester of the general formula - HC-Cflz-CGOR; N-EH-CO fi-R 4 XV is reacted with thionyl chloride of the formula 50312 XIII to 1,2,5-thiadiazole-S-carboxylic acid esters of the general formula N * - GH N. \ S / '- GOR5 XVI These can then, optionally, in organic organic solvents, is reacted with hydrazine of the formula _: 7907841-6 _. XVI-I. , to 1,2,5-thiadiazole-5-carboxylic acid hydrazide of the formula η 2 -N 2 -CO-NH-NH 2 IX or in a manner known per se saponified with suitable inorganic bases such as oxides, hydroxides or carbonates of alkali or alkaline earth metals or preferably alcoholates, optionally in organic solvents, which reaction takes place in a manner known per se and 1,2,5-thiadiazole-5-carboxylic acid of the formula N . IV which is then reacted again according to known procedures with customary halogenating agents such as thionyl chloride or phosphorus pentachloride to give 4,2,5-thiadiazole-5-carboxylic acid halide of the general formula uni -_- "e I, lkxs -CO- X VIII RB and X have the meaning given above and R4 represents an alkoxy group, preferably a G1-04 alkoxy group, an amino group or an alkylamino group, preferably a 01-04 alkylamino group.
Vid sättet enligt uppfinningen använder man sig alltså av lättillgängliga utgàngssubstanser och förfarandet möjliggör en tekniskt enkel ooh ofarlig framställning av de önskade pro- dnkterna.The method according to the invention thus uses readily available starting substances and the process enables a technically simple and harmless production of the desired products.
En stor teknisk fördel är härvid att 1,2,5-tiadiazol-5- -karbonsyraaziden med formel II inte behöver isoleras ur reak- tionsblandningarna för dess framställning utan enligt ett en- kärlsförfarande under användning av dessa blandningar kan om- sättas direkt med en amin med den allmänna formeln III.A major technical advantage here is that the 1,2,5-thiadiazole-5-carboxylic acid azide of formula II does not have to be isolated from the reaction mixtures for its preparation but according to a single-vessel method using these mixtures can be reacted directly with a amine of the general formula III.
Speciellt överraskande är det att vid detta förfarings- sätt den önskade förfaringsprodukten bildas ooh inte, såsom man kunde förvänta sig, en substitution av azidresten sker medelst aminen till 4,2,5-tiadiazol-5-karbonsyraamid. 7907841-6 é Genomföringen av sättet uppfinningen kan exempel- vis ske så att den råa lösningen av aziden i blandning med ekvimolär mängd av aminen »får rinna droppvis till ett inert lösningsmedel för aminen vid återflödestemperatur eller även genom att azidlösningen sättas till den med lösningsmedel ut- gspädda aminen vid återflödestemperaturen för blandningen. Återflödesintensiteten möjliggör en kontroll av det spontana reaktionsförloppet.It is particularly surprising that in this process the desired process product is formed and, as might not be expected, a substitution of the azide residue takes place with the amine for 4,2,5-thiadiazole-5-carboxylic acid amide. The process of the invention can be carried out, for example, so that the crude solution of the azide in admixture with an equimolar amount of the amine »is allowed to flow dropwise to an inert solvent for the amine at reflux temperature or even by adding the azide solution to it with solvent. dilute the amine at the reflux temperature of the mixture. The reflux intensity enables a control of the spontaneous reaction process.
Aziden kan emellertid även' värmas i blandning med aminen i i närvaro av ett inert lösningsmedel. e ä Temperaturerna uppgår lämpligen till 20-'180°C, företrä-l desvis till 50-120°C. Mest fördelaktigt genomföres dock om- sättningen vid koktemperaturen för reaktionsblandningen.However, the azide can also be heated in admixture with the amine in the presence of an inert solvent. The temperatures suitably amount to 20-180 ° C, preferably to 50-120 ° C. Most advantageously, however, the reaction is carried out at the boiling temperature of the reaction mixture.
Såsom gentemot reaktanterna inerta lösningsmedel kan nämnas följande: alifatiska och aromatiska kolväten såsom cyklohexan, heptan, ligroin, bensen, klorbensen, toluen och acylen, etrar såsom dioxan, tetrahydrofuran, diisopropyleter, estrar såsom ättikester och malonester, ketoner såsom aceton, metylisobutylketon, isoforon och cyklohexanon, halogenerade kolväten såsom metylenklorid, kloroform och koltetraklorid samt karbonsyranitriler såsom acetonitril.As inert to the reactants inert solvents may be mentioned the following: aliphatic and aromatic hydrocarbons such as cyclohexane, heptane, ligroin, benzene, chlorobenzene, toluene and acylene, ethers such as dioxane, tetrahydrofuran, diisopropyl ether, esters such as acetic ester and malone ester, ketones, isobutonyl acetone cyclohexanone, halogenated hydrocarbons such as methylene chloride, chloroform and carbon tetrachloride and carboxylic acid nitriles such as acetonitrile.
Efter avslutad reaktion upparbetas reaktionsblandningen på i och för sig känt sätt, exempelvis genom avdestillering av det insatta lösningsmedlet vid normaltryck eller vid mins- kat tryck, genom utfällning med vatten eller' i flertalet fall genom endast avfiltreringlav de önskade reaktionsprodukterna.After completion of the reaction, the reaction mixture is worked up in a manner known per se, for example by distilling off the solvent inserted at normal pressure or at reduced pressure, by precipitating with water or in most cases by filtering only the desired reaction products.
Man erhåller på detta sätt 'I,2,3-ftiadiazoI-S-yl-karbamider i mycket ren form och med i' det närmaste kvantitativa utbyten och man behöver för den fortsatta användningen inga ytterli- gare reningsoperationer. :Separationsproblem såsom uppträder t.ex. vid reaktionen mellan å-amalno-'LEJ-tiadiazol och iso- cyanater i form av de somšbiprodukter bildade symmetriska karbamiderna bortfaller härvid på ett fördelaktigt sätt.In this way, 1,2,3-phthiadiazol-5-yl ureas are obtained in a very pure form and in almost quantitative yields, and no further purification operations are required for further use. : Separation problems such as occur e.g. in the reaction between α-amalno-'LEJ-thiadiazole and isocyanates in the form of the symmetrical ureas formed by the by-products, this is advantageously eliminated.
Nedan följande exempel belysergenomförámgen av sättet enligt uppfinningen.The following examples illustrate the implementation of the method according to the invention.
Exempel 'l Framställning av *l-fenyl-š-(fl ßß-tiadiazol-E-yl) -karbamid från 1,2,æeiaaiazeï-s-kai-benßyrarieria.Example 1 Preparation of * 1-phenyl-β- (β-β-thiadiazol-E-yl) -urea from 1,2, ε-α
I en 250 ml rundkolv med' tre öppningar, försedd med om-J 7907841-6 ? rörare och termometer, försattes en lösning av 5,1 g (0,14 mol) natriumazid i 40 ml vatten med 40 ml toluen. Därefter till- satte man under loppet av 15 minuter vid en temperatur av 15- 2000 en lösning av 14,8 g (0,1 mol) 1,2,5-tiadiazol-5-karbon- syraklorid i 80 ml toluen under intensiv omrörning och varvid tillsatsen skedde droppvia.Man efterrörde sedan 1,5 timme vid -20°C, avskilde toluenfasen och torkade denna över magnesium- sulfat. Den torkade 1,2,5-tiadiazo1-5-karbonsyraazidlösningen försattes vid rumstemperatur med 9,14 ml (0,1 mol) anilin.In a 250 ml round-bottomed flask with three openings, equipped with om-J 7907841-6? stirrer and thermometer, a solution of 5.1 g (0.14 mol) of sodium azide in 40 ml of water was added with 40 ml of toluene. Then, a solution of 14.8 g (0.1 mol) of 1,2,5-thiadiazole-5-carboxylic acid chloride in 80 ml of toluene was added over 15 minutes at a temperature of 15-2000 with intense stirring. and the addition took place dropwise. The mixture was then stirred for 1.5 hours at -20 ° C, the toluene phase separated off and dried over magnesium sulphate. The dried 1,2,5-thiadiazol-5-carboxylic acid azide solution was added at room temperature with 9.14 ml (0.1 mol) of aniline.
Under tiden värmde man i en annan 250 ml rundkolv med tre öpp- ningar, försedd med omrörare, ternoieter och återflödeskylare, 80 ml toluen till 11000. Härtill tillsattes karbonsyraazid/ anilinlösningen droppvis under loppet av 10 minuter på sådant sätt, att innertemperaturen hölls vid 100-11000. Under stark gasutveckling utskildes genast svagt gulfärgade kristaller.Meanwhile, in another 250 ml round-bottomed flask, equipped with a stirrer, ternoites and reflux condenser, heat 80 ml of toluene to 11000. To this was added the carboxylic acid azide / aniline solution dropwise over 10 minutes so as to keep the internal temperature at 100 ° C. -11000. During strong gas evolution, pale yellow crystals were immediately separated.
Man efterrörde ytterligare 5 minuter under àterflöde, kylde till 5°C och avfiltrerade kristallerna, vilka torkades i vakuum vid Lto°c till ktnstnnt vikt.The mixture was stirred for a further 5 minutes under reflux, cooled to 5 [deg.] C. and the crystals were filtered off, which were dried in vacuo at 100 DEG C. to room weight.
Utbyte; 495 e (8s,e 96 av att teoretiska) snäitpnnkt: 24 7°c (eönaetaelning DG: medbringare = ättikester Rf-värde: 0,25.Exchange; 495 e (8s, e 96 of that theoretical) snäitpnnkt: 24 7 ° c (eönaetaelning DG: bringer = vinegar ester Rf value: 0.25.
Exempel 2 Framställning av 1-fenyl-5-(1,2,3-tiadiazol-5-yl)-karbamid från 1,2,5--tiadiazol-5-karbonsyrahydrazid.Example 2 Preparation of 1-phenyl-5- (1,2,3-thiadiazol-5-yl) -urea from 1,2,5-thiadiazole-5-carboxylic acid hydrazide.
I en 500 ml rundkolv med tre öppningar, försedd med ter- mometer och omrörare, löstes 14,4 g (0,1 mol) 1,2,3-tiadiazol- -5-karbonsyrahydrazid i 100 ml vatten och 12 ml koncentrerad saltsyra. Lösningen försattes sedan med 200 ml toluen. Till _ blandningen sattes under loppet av 50 minuter vid O-5°C dropp- vis en lösning av 7,25 g (O,105 mel) natriumnitrit i 20 ml ~ vatten. Man ont-örat 15 minuter v1<1so-5°c, evkylae tnlnenfasen och torkade denna över magneeiumsulfat. Den torkade 1,2,3- -tiadiazol-5-karbonsyraazidlösningen försattes vid rumstempe- ratur med 9,14 ml (0,1 mol) anilin.In a 500 ml three-hole round bottom flask equipped with a thermometer and stirrer, 14.4 g (0.1 mol) of 1,2,3-thiadiazole-5-carboxylic acid hydrazide were dissolved in 100 ml of water and 12 ml of concentrated hydrochloric acid. The solution was then added with 200 ml of toluene. To the mixture was added dropwise over 50 minutes at 0 DEG-5 DEG C. a solution of 7.25 g (0.65 ml) of sodium nitrite in 20 ml of water. The mixture was stirred for 15 minutes at 1.5 DEG-50 DEG C., evaporated to dryness and dried over magnesium sulfate. The dried 1,2,3-thiadiazole-5-carboxylic acid azide solution was added at room temperature with 9.14 ml (0.1 mol) of aniline.
I en 500 ml trehalskolv, rundkolv, försedd med omrörare, termometer och àterflödeskylare, värmdes under tiden 50 ml to- luen till 110°C. Den torkade karboneyraazid/anilin-löaningen tillsattes droppvis under loppet av 10 minuter på sådant sätt att innertemperaturen hölls vid 100-110°C. Gulfärgade kristal- 79Û7841¿6 8 eler utskildes genast_u§der~stÄrk gasutvecklinà. *Man omrörde ytterligare 5 minuter under àterriöae, kyiae sedan till 5°c och avsög kristallerna, vilka torkades till konstant vikt i vakuum vid ÅLOOC. , .Meanwhile, in a 500 ml three-necked, round-bottomed flask equipped with a stirrer, thermometer and reflux condenser, 50 ml of the toluene was heated to 110 ° C. The dried carbonaceous azide / aniline solution was added dropwise over 10 minutes so as to maintain the internal temperature at 100-110 ° C. Yellow-colored crystals were immediately separated by strong gas evolution. The mixture was stirred for a further 5 minutes under the atrium, then cooled to 5 DEG C. and the crystals were filtered off with suction, which were dried to constant weight in vacuo at 80 DEG C. ,.
Utbyte: 16,2 g (?3,6 % av det teoretiska) sms1epunke= 217°c (söneeraeining) DC: medbringare = ättikester Br-värde: 0,25.Yield: 16.2 g (? 3.6% of theory) sms1epunk = 217 ° c (sonar unit) DC: carrier = vinegar ester Br value: 0.25.
Följande exempel 'belyser framställningen av utgàngspro- duktyerna. ' Exemgel 3 _ _ 1 , 2 , 3-tiadiaz ol-S-karbonsyrahydrazid .The following examples illustrate the preparation of the starting materials. Exemgel 3 - 1,2,3-thiadiazole-S-carboxylic acid hydrazide.
I en 100 ml rundkolv med tre öppningar, försedd med-ome- rörare och termometer, försattes 31,6 g (0,2 mol) 1,2,3-tia- diaàol-5-karbonsyraetylester, löst i 50 ml etanol, med 11,0 g (O,22 mol) hydrazinhydrat vid rumstemperatur under loppet av minuter. Under långsam temperaturstegring till 50°C utskil- des gula kristaller. Man efterrörde 1 timme vid rumstemperatur och avsög därefter bildade kristaller, vilka torkades till konsten: vikt via 4o°c_1 vekuun.In a 100 ml round-bottomed flask equipped with a stirrer and thermometer, add 31.6 g (0.2 mol) of 1,2,3-thiadiazole-5-carboxylic acid ethyl ester, dissolved in 50 ml of ethanol, with 11.0 g (0.22 mol) of hydrazine hydrate at room temperature over minutes. During a slow rise in temperature to 50 ° C, yellow crystals separated. The mixture was stirred for 1 hour at room temperature and then crystals were filtered off, which were dried to give the art: weight via 40 DEG C. for 1 week.
Utbyte: 27,4 s (95 % av det teoretiska) smäifpunke: flus-1ue9c ' 5 I DC: medbringare =ättikester RI-värde: 0,195.Yield: 27.4 s (95% of theory) melting point: fl us-1ue9c '5 I DC: carrier = acetic ester RI value: 0.195.
Exemgel 1-l-_ 3 1,2,3-tiadiazol-5~karbonsyraklqrid I en 250 ml rundkolv med. tre öppningar, försedd med om- rörare, kylare, termometer odh avloppsledning i avdragsöppning- en, värmdes 30,0 g (0,23 mel) 1,2,3-tiadiazol-5-karbonsyra i 125 ml tionylklorid 2 timmar-under återflödeskylning. Den kla- ra brunaktiga lösningen indunstades vid 40°G och 15 torr och återstoden fraktiensdestillerades.Example 1 1-1 1,2,3-Thiadiazole-5-carbonic acid chloride In a 250 ml round bottom flask with. three orifices, equipped with stirrer, condenser, thermometer and drain line in the outlet orifice, 30.0 g (0.23 ml) of 1,2,3-thiadiazole-5-carboxylic acid were heated in 125 ml thionyl chloride for 2 hours - under reflux. . The clear brownish solution was evaporated at 40 ° C and 15 torr and the residue was fractionally distilled.
Utbyte: 25,00 3 (?3,4 % av det teoretiska) Kp11= 75-7e°c _ ~ » Exemgel 5 0 1,2,3-tiadiazol-54karbonsyraetylester.Yield: 25.00 3 (? 3.4% of theory) Kp11 = 75-7e ° c _ ~ »» Example gel 1,2,3-thiadiazole-54-carboxylic acid ethyl ester.
I en 500 ml rundkolv med tre öppningar, försedd med omrö- rare, termometer, återflödeskylare, torkrör och gasavloppsled- ningi avioppsänaen, kyidee 50,4 mi tionyrkieria (o,s9 moi) till -1500 och försattes därefter under loppet av 30 minuter under svagt minskat tryck med 36,2 g (0,21 mol) formylättiksyraetyls q 7907841-6 estersemikarbazon vid en inneftemperatur av från -15 till -10°C. Den bruna lösningen efterrördes 1 timme vid -10°C och utspäddes därefter med 130 ml kloroform. överskottet av tionylklorid försattes försiktigt med 130 ml av en mättad kaliumvätekarbonatlösning, varvid temperaturen hölls mellan ~10°C och 20°C. Kloroformfasen avskildes, tvättades med 50 ml av en mättad kaliumvätekarbonatlösning, torkades över magnesiumsulfat och indunstades vid 40oC i vakuum från en vattenstrålpump. Återstoden fraktionsdestillerades.In a 500 ml three-orifice round-bottomed flask equipped with a stirrer, thermometer, reflux condenser, dryer, and gas drain line in the aviopsaena, kyidee 50.4 ml thionyrkieria (o, s9 moi) to -1500 and then continued for 30 minutes under slightly reduced pressure with 36.2 g (0.21 mol) of formyl acetic acid ethyl ester ester semicarbazone at an inner temperature of from -15 to -10 ° C. The brown solution was stirred for 1 hour at -10 ° C and then diluted with 130 ml of chloroform. the excess thionyl chloride was carefully added with 130 ml of a saturated potassium bicarbonate solution, keeping the temperature between ~ 10 ° C and 20 ° C. The chloroform phase was separated, washed with 50 ml of a saturated potassium bicarbonate solution, dried over magnesium sulphate and evaporated at 40 ° C in vacuo from a water jet pump. The residue was fractionally distilled.
Utbyte: 28,6 g (86 % av det teoretiska) Kp11= 95-1oo°c DC: medbringare=ättikester, Rf-värde: 0,600.Yield: 28.6 g (86% of theory) Kp11 = 95-100 ° C DC: carrier = acetic ester, Rf value: 0.600.
Exempel 6 1,2,3-tiadiazol-5-karbonsyra.Example 6 1,2,3-Thiadiazole-5-carboxylic acid.
I en 4 l rundkolv med tre öppningar, försedd med omrö- rare, termometer och återflödeskylare, värmdes 152 g (1,1 mol) kaliumkarbonat i 1 l vatten till 90°C och försattes med 50 g (0,5 mol) 5-metyl-1,2,3-tiadiazol. Därefter tillsattes dropp- vis under loppet av 1 timme en lösning av 158 g (1,0 mol) ka- liumpermanganat i 1,5 l vatten vid 95-100°C. Man värmde ytter- ligare 30 minuter under återflöde tills reaktionslösningen fullständigt avfärgats, varefter den utfällda mangandioxiden avsögs och tvättades med 1 1 varmt vatten. Filtratet induns- tades därefter i vakuum vid 50°C till ca 1 l och surgjordes vid 20°C med 80 ml koncentrerad svavelsyra. Därefter extrahe- rade man omsorgsfullt fem gånger med 300 ml ättikester varje gång. Ättikesterextraktentorkades över magnesiumsulfat och indunstades till torrhet i vakuum från en vattenstrålpump vid 4o°c.In a 4 L round-bottomed flask equipped with a stirrer, thermometer and reflux condenser, 152 g (1.1 mol) of potassium carbonate in 1 L of water were heated to 90 ° C and charged with 50 g (0.5 mol) of 5- methyl-1,2,3-thiadiazole. Then a solution of 158 g (1.0 mol) of potassium permanganate in 1.5 l of water at 95-100 ° C was added dropwise over the course of 1 hour. The mixture was heated for a further 30 minutes under reflux until the reaction solution was completely decolorized, after which the precipitated manganese dioxide was filtered off with suction and washed with 1 l of hot water. The filtrate was then evaporated in vacuo at 50 ° C to about 1 L and acidified at 20 ° C with 80 ml of concentrated sulfuric acid. Thereafter, it was carefully extracted five times with 300 ml of ethyl acetate each time. Vinegar ester extract was dried over magnesium sulfate and evaporated to dryness in vacuo from a water jet pump at 40 ° C.
Utbyte: 21,7 g (33,3 % av det teoretiska) Smältpunkt: 106°C (sönderdelning).Yield: 21.7 g (33.3% of theory) Melting point: 106 ° C (decomposition).
Exempel 7-29 Analogt med exempel 2 framställdes följande 1,2,3-tia- diazol-5-yl-karbamider, varvid molförhållandet för 1,2,3- -tiadiazol-5-karbonsyraazid (0,1 mol) och reaktionsbetingel- serna var desamma som i exempel 2: TO 79978 41-6 Uflñmflumx = = = w m_mm ««.o~ «~_w mw.wm ”.znw |^H>;m=HoNmflwmH»|m_~ = uowm, m «_m_ ß~_o~ mw.m m«~@m “.H@n _fv|m|H>=ww|P|H>»:n|F .QP UAENQHNM _. : ._ N u-.SHU IÃAKÜIMlHÛNNHÜMHUÉIM~N = .uoomf w ~.>, wm._~ mm.m «m.«m ".Hwn _PV|m|H»mo»m|P|H»smm|_ .wF øflsm = = = w m_>> >«_- m~.m mm.mm ".num |n~mx|^Hm|m|Ho~mfimwflw«m = . oooøw m w.nF wm.- >w.« o~.mm ”.~wn .~.P.|m|Hænwm|~|H>uw|P .NP ¶ wfism = = = w ~_~w w@.m~ m«_« °m._m «.nuw |nHmx|.fi>|m|HoNmHw«fl@|m = uo«m_ m °.@_ fm_- °m.« w~.Pm “.umn .~.P.|m|H>:ww|P:H>»ws|~ .wF wfiem _ = = = w Q_ow m>~m~ «~_m °>.f« “.;~w |nH@x|.H>|m|Ho~mflwmfi»|m = oo~m~ m m.m. °@.w~ ww.~ m>.o« ".HwQ .~_~v|m|.H>nwmoH»fl=|m.|F .wF _ - wflam _. = = = W ~_æm mw.w~ f>_~ >>~.« ".;Hw |nH~x|^H»|m|~o~mfiw«fl»|~ = uomwfl w «.m. =«_w~ mw_~ m>.°« “.nwn .N_P.|m|.fl>nw«oHufi=|~.|. .wF ¶ _ wflam . = = = W w.wm mm@w~ Pf~m ~P.~« ".a~w |n»mx|^H>»m|Honmflwmfi»|m = uo~m~ w o.mf °«.w~ @m.~ m>~Q« ".nwn .~__.|~|^~>nwwo~»fln:«,|_ .MP . uflšmnnmx . = = = W °_@w f«.m, P>.~ ~@_,« ".nHw |^H>=@«H>»waHoøHmflH»|m.|m = uoqmw m °.m_ ««_@f m«_~ @@__« ".»mp 1^H>|m»Ho~mfl@mfl»|m_~_+.|_ .NF = = = w m_mm f~.~m ~m.« °~_mm ".=H@ wflsfln~mx|.H>»m|Ho~mfiwmfi» = uo-~ w ~.@ «m.~m @@_« >@.«m ".H@n |m.~_P.|m|H»»mafiw»~_. .FP _ = = = w N.fm wo_@m @~\« ~>.m~ ".;nw wfiamnHmx|.H>|m|Ho~m uo«>F . w f_w ~«.mm ~w.m >m_°m “.»wp |flwmfl»|m.~.P.|m|H>»wa|F .of = = = w m.>> ~w.m~ mw~« o«_om ".;Hw wfismn~mx|.H>|m|HoNmflwmH» = uow- m ~_æf f@.m~ °m_w @~_,m “.Hmn 1m.~_FV:m|A~>nw«~>»ws|«.|P .m = = = w m.m« °m.«~_ mw.w «m_w« ".n~w wflamnHmxfAH>|m|Ho~mflwmfl@ = uemfw m ~.°_ >æ.«~ %w.m wm_>« ".HwQ |m.w_FV|m|H>xmQ@Hg>u|P .w . .»m~0w» www >m w f.m> «m__~ f@_~ @f.m« ".;H@ wfismn~mg|^H>|m|fio~wH@øfi» .cflmuflwwamm uommm m ~.@F °o_- >>.~ ««_~« “.Hwn |m_~_F.|m|^H»n@wHoHx|v.|f .ß ^.m;Ewv Hwucwvmnox mu>QvD Z m U _ mcflcmuwm mxmflflmxflmäm w fl cwwum>w>Hm:4 799784146 ll .UHEQ = = = w ~_«> mw_Pm «~.m @w_m« «.;Hw |nnmx|^H>|m|~oNwflwm«» = uo>- m w.@_ >w_Pm m«_m P«.m« ".Hwn |m_~__v|m|_HæwflH>m|N.|_ .mm .THEN = = = w m.mm ww.m wQ_m« “.pnw |n»mx|^H>|m|Ho-fløwfl» = oowfw w ~_~P mf.m _«_m« ".Hwn |m.~_f,|~|.H>wflH»m|~.|f .w~ øfiam = = = w m.~m mm_m @«_m« “.§uw |numx|^H>|m|Ho~mfiømfl» = uomF~ m ~.mP mF.m P«_m« ".~wn |m.~.P.|~|.H>wflH>@|«V1F .ßw wHemnu~x|.H> = = = w w.mw ~w.o~ ~w.> «w_mm «.suw |m|flo~mfiømfl»|~.~.f.|m uommw m w.>, ww~°~ ~m.> ww_mm “.Hwn |H>mo~momfl|F|H>xwno~xwu|F .ww Uflämnnwxl Äæcwu = = = W ~.°> m@.°~ m«.~ mw.Q« “.ßHw |H>»ws»oøH«fiu»|~.|m».H» = uom- w ~.°~ m«.m~ m«.~ «w.«« “.Hmn |m|Ho~mfiumfi»|m.~_,V|P .m~ wflamnnmxnfifim = = = w m.N« «_.°~ ~æ.w Q~.Nm “.§Hm |m|Ho~mflumflp|m.~.f«|~ ._ uoowf m m.,f @w_o~ ~m\> ww.mm ".Hwn |fi>moHm|f|H>xw;oHx>u|F .«~ = = = w m.om _>.>~ o~.w >w_f« “.a~w wfism@~mx|^H>|m|fioNmflø _. . uoowf v P.oF mm.>~ «o_m >m_F« ".Hwn |mfi»|m.~.f.|m|H>»øn|F .MN = = = w m.«m ~«.m~ @>_m m°_m~ ".nHw wfiemn~mg|.H>|m»Ho~««w uoowf m f.oF °P.om F«.m >@.mm ".Hmn |mfi»|m.~.P,|~nfi>moHm|F .NN .TMEMQHMÅ : : = M n-Ä-HÜ låfiälm|flONflflflflflfllm~N~wfl = uomfm m ~.w- >m.f~ wm.m m@.«m ".HmQ |m|Hwuw«|«|H>moumowfl|P .FN ¶ wflam .ßwuowß »mv >m w o.Qm >>_>~ o@.m m>.f« ".@»w |n~mx|.H»|m|HoN«fiwmfl« .nflwwwmvamw uowmfmwf m @~of m@-~ «°.@ @m_~@ ".H@n |m_-Fv=m|H>»mfiø|P__ .ON A .m .Ewv uwßfimvwcox muænub Z m U mflflnwußm mxmflfimvflmmm w fl cmwnfifmæfimcmExamples 7-29 In analogy to Example 2, the following 1,2,3-thiadiazol-5-yl ureas were prepared, the molar ratio of 1,2,3-thiadiazole-5-carboxylic acid azide (0.1 mol) and reaction conditions were the same as in Example 2: TO 79978 41-6 U fl ñm fl umx = = = w m_mm «« .o ~ «~ _w mw.wm” .znw | ^ H>; m = HoNm fl wmH »| m_ ~ = uowm, m« _m_ ß ~ _o ~ mw.mm «~ @ m“ .H @ n _fv | m | H> = ww | P | H> »: n | F .QP UAENQHNM _. : ._ N u-.SHU IÃAKÜIMlHÛNNHÜMHUÉIM ~ N = .uoomf w ~.>, Wm._ ~ mm.m «m.« M ".Hwn _PV | m | H» mo »m | P | H» smm | _ .wF ø fl sm = = = w m _ >>> «_- m ~ .m mm.mm" .num | n ~ mx | ^ Hm | m | Ho ~ m fi mw fl w «m =. oooøw m w.nF wm.-> w. «o ~ .mm”. ~ wn. ~ .P. | m | Hænwm | ~ | H> uw | P .NP ¶ w fi sm = = = w ~ _ ~ ww @ .m ~ m «_« ° m._m «.nuw | nHmx |. fi> | m | HoNmHw« fl @ | m = uo «m_ m °. @ _ fm_- ° m.« w ~ .Pm “. umn. ~ .P. | m | H>: ww | P: H> »ws | ~ .wF w fi em _ = = = w Q_ow m> ~ m ~« ~ _m °> .f «“.; ~ w | nH@x|.H> | m | Ho ~ m fl wm fi »| m = oo ~ m ~ m mm ° @ .w ~ ww. ~ M> .o «" .HwQ. ~ _ ~ V | m | .H> nwmoH »fl = | m. | F .wF _ - w fl am _. = = = W ~ _æm mw .w ~ f> _ ~ >> ~. «".; Hw | nH ~ x | ^ H »| m | ~ o ~ m fi w« fl »| ~ = uomw fl w« .m. = «_ W ~ mw_ ~ m>. °« “.nwn .N_P. | M |. Fl> nw« oHu fi = | ~. |. .wF ¶ _ w fl am. = = = W w.wm mm @ w ~ Pf ~ m ~ P. ~ «" .a ~ w | n »mx | ^ H>» m | Honm fl wm fi »| m = uo ~ m ~ w o.mf °« .w ~ @ m. ~ m> ~ Q «" .nwn. ~ __. | ~ | ^ ~> nwwo ~ »fl n:«, | _ .MP. u fl šmnnmx. = = = W ° _ @ wf «.m, P>. ~ ~ @ _,« ".NHw | ^ H> = @« H> »waHoøHm fl H» | m. | M = uoqmw m ° .m_ «« _ @fm «_ ~ @@ __« ".» mp 1 ^ H> | m »Ho ~ m fl @ m fl» | m_ ~ _ +. | _ .NF = = = w m_mm f ~. ~ m ~ m. « ° ~ _mm ". = H @ w fl s fl n ~ mx | .H>» m | Ho ~ m fi wm fi »= uo- ~ w ~. @« M. ~ M @@ _ «> @.« M ".H @ n | m. ~ _P. | m | H »» ma fi w »~ _. .FP _ = = = w N.fm wo_ @ m @ ~ \ «~> .m ~".; Nw w fi amnHmx | .H> | m | Ho ~ m uo «> F. W f_w ~« .mm ~ wm > m_ ° m “.» wp | fl wm fl »| m. ~ .P. | m | H>» wa | F .of = = = w m. >> ~ wm ~ mw ~ «o« _om ".; Hw w fi smn ~ mx | .H> | m | HoNm fl wmH »= uow- m ~ _æf f @ .m ~ ° m_w @ ~ _, m“ .Hmn 1m. ~ _FV: m | A ~> nw «~>» ws | «. | P .m = = = w mm« ° m. «~ _ Mw.w« m_w «" .n ~ w w fl amnHmxfAH> | m | Ho ~ m fl wm fl @ = uemfw m ~. ° _> æ. «~ % wm wm_> «" .HwQ | m.w_FV | m | H> xmQ @ Hg> u | P .w. . »M ~ 0w» www> mw fm> «m__ ~ f @ _ ~ @fm« ".; H @ w fi smn ~ mg | ^ H> | m | fi o ~ wH @ ø fi» .c fl mu fl wwamm uommm m ~. @ F ° o_- >>. ~ «« _ ~ «“ .Hwn | m_ ~ _F. | M | ^ H »n@wHoHx|v.|f .ß ^ .m; Ewv Hwucwvmnox mu> QvD Z m U _ mc fl cmuwm mxm flfl mx fl mäm w fl cwwum> w> Hm: 4 799784146 ll .UHEQ = = = w ~ _ «> mw_Pm« ~ .m @w_m ««.; Hw | nnmx | ^ H> | m | ~ oNw fl wm «» = uo> - m w. @ _> w_Pm m «_m P« .m «" .Hwn | m_ ~ __v | m | _Hæw fl H> m | N. | _ .mm .THEN = = = w m.mm ww.m wQ_m « “.Pnw | n» mx | ^ H> | m | Ho- fl øw fl »= oowfw w ~ _ ~ P mf.m _« _ m «" .Hwn | m. ~ _F, | ~ | .H> w fl H »m | ~. | f .w ~ ø fi am = = = w m. ~ m mm_m @ «_ m« “.§uw | numx | ^ H> | m | Ho ~ m fi øm fl» = uomF ~ m ~ .mP mF.m P «_M« ". ~ Wn | m. ~ .P. | ~ | .H> w fl H> @ |« V1F .ßw wHemnu ~ x | .H> = = = w w.mw ~ wo ~ ~ w.> « w_mm «.suw | m | fl o ~ m fi øm fl» | ~. ~. f. | m uommw m w.>, ww ~ ° ~ ~ m.> ww_mm “.Hwn | H> mo ~ mom fl | F | H> xwno ~ xwu | F .ww U flämnnwxl Äæcwu = = = W ~. °> m @. ° ~ m «. ~ mw.Q« “.ßHw | H>» ws »oøH« fi u »| ~. | m» .H »= Uom- w ~. ° ~ m« .m ~ m «. ~« W. «« “.Hmn | m | Ho ~ m fi um fi» | m. ~ _, V | P .m ~ w fl amnnmxn fifi m = = = w mN «« _. ° ~ ~ æ.w Q ~ .Nm “.§Hm | m | Ho ~ m fl um fl p | m. ~ .f« | ~ ._ uoowf m m., f @ w_o ~ ~ m \> ww .mm ".Hwn | fi> moHm | f | H> xw; oHx> u | F. «~ = = = W m.om _>.> ~ O ~ .w> w_f« “.a ~ w w fi sm @ ~ mx | ^ H> | m | fi oNm fl ø _. . uoowf v P.oF mm.> ~ «o_m> m_F« ".Hwn | m fi» | m. ~ .f. | m | H> »øn | F .MN = = = w m.« m ~ «.m ~ @> _ m m ° _m ~ ".nHw w fi emn ~ mg | .H> | m» Ho ~ «« w uoowf m f.oF ° P.om F «.m> @. mm" .Hmn | m fi »| m. ~ .P, | ~ n fi> moHm | F .NN .TMEMQHMÅ:: = M n-Ä-HÜ lå fi älm | fl ON flflflflflfl lm ~ N ~ w fl = uomfm m ~ .w-> mf ~ wm.mm @. «m ".HmQ | m | Hwuw« | «| H> moumow fl | P .FN ¶ w fl am .ßwuowß» mv> mw o.Qm >> _> ~ o @ .mm> .f «". @ »W | n ~ mx | .H »| m | HoN« fi wm fl «.n fl wwwmvamw uowmfmwf m @ ~ of m @ - ~« °. @ @ m_ ~ @ ".H @ n | m_-Fv = m | H>» m fi ø | P__. ON A .m .Ewv uwß fi mvwcox muænub Z m U m flfl nwußm mxm flfi mv fl mmm w fl cmwn fi fmæ fi mcm
Claims (6)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19782841825 DE2841825A1 (en) | 1978-09-22 | 1978-09-22 | METHOD FOR THE PRODUCTION OF 1,2,3-THIADIAZOL-5-YL UREA |
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| Publication Number | Publication Date |
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| SE7907841L SE7907841L (en) | 1980-03-23 |
| SE435376B true SE435376B (en) | 1984-09-24 |
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| Application Number | Title | Priority Date | Filing Date |
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| SE7907841A SE435376B (en) | 1978-09-22 | 1979-09-21 | SET TO PREPARE 1,2,3-THIADIAZOL-5-YL CARBAMIDES |
Country Status (35)
| Country | Link |
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| JP (1) | JPS5545683A (en) |
| AR (1) | AR223349A1 (en) |
| AT (1) | AT373593B (en) |
| AU (1) | AU533137B2 (en) |
| BE (1) | BE878925A (en) |
| BG (1) | BG30930A3 (en) |
| BR (1) | BR7905614A (en) |
| CA (1) | CA1131224A (en) |
| CH (1) | CH641792A5 (en) |
| CS (1) | CS209936B2 (en) |
| DD (1) | DD146184A5 (en) |
| DE (1) | DE2841825A1 (en) |
| DK (1) | DK361579A (en) |
| EG (1) | EG14167A (en) |
| ES (1) | ES483788A1 (en) |
| FI (1) | FI69838C (en) |
| FR (1) | FR2436783A1 (en) |
| GB (1) | GB2031889B (en) |
| GR (1) | GR73092B (en) |
| HU (1) | HU182999B (en) |
| IE (1) | IE48944B1 (en) |
| IL (1) | IL58274A (en) |
| IT (1) | IT1123731B (en) |
| LU (1) | LU81704A1 (en) |
| NL (1) | NL7905355A (en) |
| NZ (1) | NZ191603A (en) |
| PH (1) | PH15388A (en) |
| PL (1) | PL123956B1 (en) |
| PT (1) | PT70178A (en) |
| RO (1) | RO77754A (en) |
| SE (1) | SE435376B (en) |
| SU (1) | SU921466A3 (en) |
| TR (1) | TR20895A (en) |
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| DE2909991A1 (en) * | 1979-03-12 | 1980-10-02 | Schering Ag | 1,2,3-THIADIAZOL-5-CARBONIC ACID DERIVATIVES, METHOD FOR THE PRODUCTION OF THESE COMPOUNDS, AND THEIR CONTAINING AGENTS WITH HERBICIDAL AND GROWTH REGULATORY AND FUNGICIDAL EFFECT |
| JPS55150238U (en) * | 1980-04-03 | 1980-10-29 | ||
| DE3139506A1 (en) * | 1981-10-01 | 1983-04-21 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | 1,2,3-THIADIAZOL-5-YL-UREA DERIVATIVES, METHOD FOR THE PRODUCTION OF THESE COMPOUNDS AND THEIR CONTAINING AGENTS WITH GROWTH REGULATIVE AND DEFOLIATING EFFECT |
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| DE2636994C2 (en) | 1976-08-13 | 1984-10-18 | Schering AG, 1000 Berlin und 4709 Bergkamen | Process for the preparation of 5-amino-1,2,3-thiadiazole |
-
1978
- 1978-09-22 DE DE19782841825 patent/DE2841825A1/en not_active Withdrawn
-
1979
- 1979-07-09 NL NL7905355A patent/NL7905355A/en not_active Application Discontinuation
- 1979-08-20 YU YU2027/79A patent/YU40759B/en unknown
- 1979-08-29 DK DK361579A patent/DK361579A/en not_active Application Discontinuation
- 1979-08-31 BR BR7905614A patent/BR7905614A/en unknown
- 1979-08-31 ES ES483788A patent/ES483788A1/en not_active Expired
- 1979-09-06 FI FI792770A patent/FI69838C/en not_active IP Right Cessation
- 1979-09-06 ZA ZA00794722A patent/ZA794722B/en unknown
- 1979-09-11 CA CA335,363A patent/CA1131224A/en not_active Expired
- 1979-09-14 PT PT70178A patent/PT70178A/en unknown
- 1979-09-14 BG BG044862A patent/BG30930A3/en unknown
- 1979-09-17 TR TR20895A patent/TR20895A/en unknown
- 1979-09-18 EG EG555/79A patent/EG14167A/en active
- 1979-09-18 NZ NZ191603A patent/NZ191603A/en unknown
- 1979-09-19 IL IL58274A patent/IL58274A/en unknown
- 1979-09-19 DD DD215645A patent/DD146184A5/en unknown
- 1979-09-20 CH CH850479A patent/CH641792A5/en not_active IP Right Cessation
- 1979-09-20 GR GR60083A patent/GR73092B/el unknown
- 1979-09-20 IT IT25880/79A patent/IT1123731B/en active
- 1979-09-20 LU LU81704A patent/LU81704A1/en unknown
- 1979-09-20 PH PH23049A patent/PH15388A/en unknown
- 1979-09-20 PL PL1979218429A patent/PL123956B1/en unknown
- 1979-09-20 SU SU792811707A patent/SU921466A3/en active
- 1979-09-21 SE SE7907841A patent/SE435376B/en not_active IP Right Cessation
- 1979-09-21 IE IE1789/79A patent/IE48944B1/en unknown
- 1979-09-21 HU HU79SCHE691A patent/HU182999B/en unknown
- 1979-09-21 CS CS796380A patent/CS209936B2/en unknown
- 1979-09-21 AR AR278157A patent/AR223349A1/en active
- 1979-09-21 RO RO7998731A patent/RO77754A/en unknown
- 1979-09-21 AU AU51075/79A patent/AU533137B2/en not_active Ceased
- 1979-09-21 GB GB7932815A patent/GB2031889B/en not_active Expired
- 1979-09-21 AT AT0622779A patent/AT373593B/en not_active IP Right Cessation
- 1979-09-21 BE BE0/197257A patent/BE878925A/en not_active IP Right Cessation
- 1979-09-21 JP JP12093079A patent/JPS5545683A/en active Pending
- 1979-09-24 FR FR7923681A patent/FR2436783A1/en active Granted
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