DE1811973A1 - 4-alkylthio pyridine-3-carbonitriles - Google Patents
4-alkylthio pyridine-3-carbonitrilesInfo
- Publication number
- DE1811973A1 DE1811973A1 DE19681811973 DE1811973A DE1811973A1 DE 1811973 A1 DE1811973 A1 DE 1811973A1 DE 19681811973 DE19681811973 DE 19681811973 DE 1811973 A DE1811973 A DE 1811973A DE 1811973 A1 DE1811973 A1 DE 1811973A1
- Authority
- DE
- Germany
- Prior art keywords
- carbonitrile
- hydroxy
- methylthio
- pyridine
- dihydro
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 12
- 150000001875 compounds Chemical class 0.000 claims abstract description 11
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 7
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 4
- -1 2-Chloro-6,7-dihydro-4-methylthio-5H-1-pyrindine-3-carbonitrile Chemical compound 0.000 claims description 73
- 150000003222 pyridines Chemical class 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 6
- 239000012442 inert solvent Substances 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- BBFZXHSWLXPJFP-UHFFFAOYSA-N 4-methylsulfanyl-2-oxo-1,5,6,7-tetrahydrocyclopenta[b]pyridine-3-carbonitrile Chemical compound OC1=NC=2CCCC2C(=C1C#N)SC BBFZXHSWLXPJFP-UHFFFAOYSA-N 0.000 claims description 2
- ARDXJKISLUSLHZ-UHFFFAOYSA-N CCC(C(SC)=C1C#N)=CN=C1O Chemical compound CCC(C(SC)=C1C#N)=CN=C1O ARDXJKISLUSLHZ-UHFFFAOYSA-N 0.000 claims description 2
- INLMUTQTXGLFRN-UHFFFAOYSA-N 4-methylsulfanyl-2-oxo-5,6,7,8-tetrahydro-1h-quinoline-3-carbonitrile Chemical compound C1CCCC2=C1C(SC)=C(C#N)C(=O)N2 INLMUTQTXGLFRN-UHFFFAOYSA-N 0.000 claims 1
- JXYLBLPCSFUBFZ-UHFFFAOYSA-N CSC=1C=CNC(=O)C=1C#N Chemical compound CSC=1C=CNC(=O)C=1C#N JXYLBLPCSFUBFZ-UHFFFAOYSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 4
- 239000011814 protection agent Substances 0.000 abstract description 3
- 239000003963 antioxidant agent Substances 0.000 abstract description 2
- 230000003385 bacteriostatic effect Effects 0.000 abstract description 2
- 239000000417 fungicide Substances 0.000 abstract description 2
- 239000004009 herbicide Substances 0.000 abstract description 2
- 239000002917 insecticide Substances 0.000 abstract description 2
- 230000001069 nematicidal effect Effects 0.000 abstract description 2
- 239000005645 nematicide Substances 0.000 abstract description 2
- 239000005648 plant growth regulator Substances 0.000 abstract description 2
- 230000001857 anti-mycotic effect Effects 0.000 abstract 1
- 239000000543 intermediate Substances 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 16
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 13
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 229910001868 water Inorganic materials 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 238000001816 cooling Methods 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 3
- 239000003610 charcoal Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000000575 pesticide Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 239000007832 Na2SO4 Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 150000002081 enamines Chemical class 0.000 description 2
- CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-tetralone Chemical compound C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- KCKZIWSINLBROE-UHFFFAOYSA-N 3,4-dihydro-1h-naphthalen-2-one Chemical compound C1=CC=C2CC(=O)CCC2=C1 KCKZIWSINLBROE-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- GUUCCZXZHBJWHQ-UHFFFAOYSA-N 4-methylsulfanyl-2-oxo-5,6-dihydro-1h-benzo[h]quinoline-3-carbonitrile Chemical compound C1CC2=CC=CC=C2C2=C1C(SC)=C(C#N)C(=O)N2 GUUCCZXZHBJWHQ-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical class [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- YGINSNYIDWWASM-UHFFFAOYSA-N C1=CC=C2C3=NC(N)=C(C#N)C(SC)=C3CCC2=C1 Chemical compound C1=CC=C2C3=NC(N)=C(C#N)C(SC)=C3CCC2=C1 YGINSNYIDWWASM-UHFFFAOYSA-N 0.000 description 1
- YBZBSNZNEMXLLX-UHFFFAOYSA-N CC(C)CC(C(SC)=C1C#N)=CN=C1O Chemical compound CC(C)CC(C(SC)=C1C#N)=CN=C1O YBZBSNZNEMXLLX-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-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
- 239000005977 Ethylene Substances 0.000 description 1
- VGGSQFUCUMXWEO-DICFDUPASA-N Ethylene-1,1-d2 Chemical compound [2H]C([2H])=C VGGSQFUCUMXWEO-DICFDUPASA-N 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 235000019568 aromas Nutrition 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
- 229940106681 chloroacetic acid Drugs 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- CGZZMOTZOONQIA-UHFFFAOYSA-N cycloheptanone Chemical compound O=C1CCCCCC1 CGZZMOTZOONQIA-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
- 150000002440 hydroxy compounds Chemical class 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229940116315 oxalic acid Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- QCCDLTOVEPVEJK-UHFFFAOYSA-N phenylacetone Chemical compound CC(=O)CC1=CC=CC=C1 QCCDLTOVEPVEJK-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229940065287 selenium compound Drugs 0.000 description 1
- 150000003343 selenium compounds Chemical class 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/84—Nitriles
- C07D213/85—Nitriles in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
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Abstract
Description
Pyridinderivate und Verfahren zu ihrer Herstellung Die Erfindung betrifft Pyridinderivate der allgemeinen Formel I worin R1 Alkyl mit 1 - 4 C-Atomen, R2 II oder Alkyl mit 1 - 4 C-Atomen oder zusammen mit R³ eine -(CH2)n- oder -o-06H4-CH2CH2-Kette, R3 H, Benzyl oder zusammen mit R2 eine (CH2)n- oder -o-C6H4CH2CH2-Kette, n 3,4 oder 5 und X C1, Er, J, OH oder bedeuten Es wurde gefunden, dap die Verbindungen der Formel I in guten Ausbeuten erhalten werden können, wenn man ein 1,1-Dicyan-2-alkylthio-4-amino-l,3-alkadien der allgemeinen Formel II (CN)2C=C(SR1)-CR2=CR3-NR4R5 II worin R4 und R5 jeweils Alkyl mit 1 - 4 C-Atomen oder zusammen (CH2)m-oder -(CH2)2-O-(CH2)2- und m 4 oder 5 bedeuten, mit einer Verbindung der Formel X gegebenenfalls in Gegenwart eines inerten Lösungsmittels umsetzt.Pyridine derivatives and processes for their preparation The invention relates to pyridine derivatives of the general formula I wherein R1 is alkyl with 1-4 carbon atoms, R2 II or alkyl with 1-4 carbon atoms or together with R3 a - (CH2) n or -o-06H4-CH2CH2 chain, R3 is H, benzyl or together with R2 is a (CH2) n or -o-C6H4CH2CH2 chain, n 3, 4 or 5 and X is C1, Er, J, OH or It has been found that the compounds of the formula I can be obtained in good yields if a 1,1-dicyan-2-alkylthio-4-amino-1,3-alkadiene of the general formula II (CN) 2C = C (SR1) -CR2 = CR3-NR4R5 II where R4 and R5 are each alkyl with 1 - 4 carbon atoms or together (CH2) m- or - (CH2) 2-O- (CH2) 2- and m are 4 or 5, with a compound of the formula X, optionally in the presence of an inert solvent.
Die erfindungsgemäße Bildung vo ryridinderivaten aus den Dinitrilen II und selen Verbindungen HX ist neu und aus den Angaben der Literatur nicht herzuleiten. Sie eröffnet einen neuen, einfachen Syntheseweg in die Pyridinreihe, der unter milden Bedingungen aus leicht und billig herstellbaren Ausgangsstoffen in guter Ausbeute bisher unbekannte Pyridinderivate liefert, die nach herkömmlichen Methoden eniger leicht oder überhaupt nicht erhältlich sind.The inventive formation of ryridine derivatives from the dinitriles II and selenium compounds HX is new and cannot be derived from the information in the literature. It opens up a new, simple synthetic route into the pyridine series, the one under mild Conditions from starting materials which can be prepared easily and cheaply in good yield supplies previously unknown pyridine derivatives that eniger by conventional methods are easily or not available at all.
Die Verbindungen der Formel I können als Pflanzenschutzmittel (Nematozide; ferner Herbizide, Insektizide, Fungizide) als Pflanzenwachstumsregulatoren, als Arzneimittel und vor allem als Zwischenprodukte für die Herstellung weiterer Pflanzenschutzmittel, Arzneimittel, Galvanisationsbeschleuniger und Antioxydantien verwendet werden.The compounds of the formula I can be used as crop protection agents (nematocides; also herbicides, insecticides, fungicides) as plant growth regulators, as Medicines and, above all, as intermediate products for the manufacture of other pesticides, Medicines, galvanization accelerators and antioxidants are used.
Gegenstand der Erfindung sind demnach Pyridinderivate der oben angegebenen Formel I sowie ein Verfahren zu ihrer Herstellung, das dadurch gekennzeichnet ist, daß man ein Dinitril der Formel II mit einer Verbindung der Formel, HX, gegebenenfalls in Gegenwart eines inerten Lösungsmittels, umsetzt.The invention accordingly relates to pyridine derivatives of the above Formula I and a process for their preparation, which is characterized in that that a dinitrile of the formula II with a compound of the formula, HX, optionally in the presence of an inert solvent.
Gegenstand der Erfindung sind ferner die folgenden bevorzugten Verfahrensprodukte der Formeln aa bis Ii worin R7 Methyl oder Aethyl, R8 H oder Alkyl mit 1 - 4 0-Atomen 9 und R10 zusammen eine -(CH2)m- oder -o-06H40H20H2 -Kette und X1 Cl, Br oder J bedeuten: In den angegebenen Formeln bedeutet Alkyl vorzugsweise Methyl oder Aethyl; es kann aber auch Propyl, Isopropyl, n-Butyl, Isobutyl, sek.Butyl oder tert.Butyl bedeuten.The invention also relates to the following preferred process products of the formulas aa to Ii in which R7 is methyl or ethyl, R8 is H or alkyl having 1-4 0 atoms, and R10 together is a - (CH2) m or -o-06H40H20H2 chain and X1 Cl, Br or J mean: In the formulas given, alkyl is preferably methyl or ethyl; but it can also mean propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl.
Die Dinitrile der Die Dinitrile der Formel II sind in der Regel nach den Angaben des DBP . (deutsche Patentanmeldung aus Ketenmercaptalen der Formel (CN)C=C(SR1)2 und Einaminen der Formel CHR²=CR³-NR4R5 unter Abspaltung von R SH erhältlich.The dinitriles of the The dinitriles of the formula II are usually according to the information of the DBP. (German patent application for ketene mercaptals of the formula (CN) C = C (SR1) 2 and one amines of the formula CHR² = CR³-NR4R5 with cleavage of R SH available.
Die Ketenmercaptale und die Enamine der angegebenen Formeln sind größtenteils bekannt. Die Enamine leiten sich insbesondere ab von folgenden Carbonylverbindungen: Acetaldehyd, Propionaldehyd, Butyraldehyd, Cyclopentanon, Cyclohexanon, Cycloheptanon, Phenylaceton, 1-Tetralon oder 2-Tetralon, und von folgenden Aminen: Dimethylarnin, Diäthylamin, Pyrrolidin, Piperidin, Morpholin.The ketene mercaptals and the enamines of the formulas given are for the most part known. The enamines are derived in particular from the following carbonyl compounds: Acetaldehyde, propionaldehyde, butyraldehyde, cyclopentanone, cyclohexanone, cycloheptanone, Phenylacetone, 1-tetralone or 2-tetralone, and of the following amines: dimethylamine, Diethylamine, pyrrolidine, piperidine, morpholine.
Allgemein sind als Dinitrile solche der nachstehenden Formeln II a bis II i bevorzugt (worin Q Pyrrolidino, Piperidino oder Morpholino bedeutet): *) diese Patentanrneldung "1-Cyan-2-alkylthio-4-amino-1,3-alkadiene "wurde am 14. 11. 1968 an das Deutsche Patentamt geschicht; ihr Aktenzeichen ist der Anmelderin noch nicht Als Verbindungen HX dienen Chlorwasserstoff, Bromwasserstoff, Jodwasserstoff, Wasser oder Ammoniak.In general, preferred dinitriles are those of the following formulas II a to II i (in which Q is pyrrolidino, piperidino or morpholino): *) this patent application "1-cyano-2-alkylthio-4-amino-1,3-alkadiene" was filed with the German Patent Office on November 14, 1968; The applicant has not yet had its file number. The compounds HX are hydrogen chloride, hydrogen bromide, hydrogen iodide, water or ammonia.
Erfindungsgemäp werden vorzugsweise 1 Mol des jeweiligen Dinitrils II mit 1 - 10 Mol der Verbindung EZ in Abwesenheit oder (vorzugsweise) in Gegenwart eines inerten Lösungsmittels umgesetzt. Als inerte Lösungsmittel sind beispielsweise geeignet: Kohlenwasserstoffe, wie Benzol oder Toluol; Aether, wie Diäthyläther, Diisopropyläther, Tetrahydrofuran, Dioxan; Nitrile, wie Acetonitril; Amide, wie Formamid, Dimethylformamid, N-Methylpyrrolidon; Alkohole, wie Methanol, Aethanol, Isopropanol, Propanol, Butanol; Sulfoxide, wie Dimethylsulfoxid; tertiäre Amine wie Pyridin oder Picolin (bevorzugt füt HX = NH); Wasser oder auch Gemische dieser Lösungsmittel untereinander. Besonders bevorzugt sind Wasser, Methanol und Acetonitril. Die Reaktionstemperaturen liegen zwischen -30 und +1500, vorzugsweise zwischen 50 und 1000, die Reaktionszeiten zwischen 10 Minuten und 6 Tagen, vorzugsweise zwischen 1 und 24 Stunden. Man läßt das Reaktionsgemisch vorzugsweise stehen oder rührt gegebenenfalls, insbesondere beim Vorliegen eines heterogenen Systems.According to the invention, 1 mol of the respective dinitrile is preferably used II with 1-10 mol of the compound EZ in the absence or (preferably) in the presence an inert solvent implemented. Examples of inert solvents are suitable: hydrocarbons such as benzene or toluene; Ethers, such as diethyl ether, Diisopropyl ether, tetrahydrofuran, dioxane; Nitriles such as acetonitrile; Amides, like Formamide, dimethylformamide, N-methylpyrrolidone; Alcohols such as methanol, ethanol, Isopropanol, propanol, butanol; Sulfoxides such as dimethyl sulfoxide; tertiary amines such as pyridine or picoline (preferably for HX = NH); Water or mixtures of these Solvents among themselves. Water, methanol and acetonitrile are particularly preferred. The reaction temperatures are between -30 and +1500, preferably between 50 and 1000, the reaction times between 10 minutes and 6 days, preferably between 1 and 24 hours. The reaction mixture is preferably left to stand or optionally stirred, especially when there is a heterogeneous system.
Bei dem erfindungsgemäßen Verfahren kann Wasser einerseits als Reagens HX (X = OH), andererseits als Lösungsmittel dienen. Zur Herstellung der Pyridinderivate I (X = OH) setzt man zweckmäßig die Dinitrile II mit verdünnten wässerigen Säuren um, deren Konzentration sich vorzugsweise zwischen 0,5 und 4, insbesondere um 2, Moläquivalent/Liter bewegt. Die Anwesenheit von Säure ist zum Zweck der Neutralisation des abgespaltenen Amins HNR4R5 empfehlenswert; man kann z. B. verdünnte Fluorwasserstoffsäure, Chlorwasserstoffsäure, Bromwasserstoffsäure, Jodwasserstoffsäure, Schwefelsäure, Phosphonsäure, Perchlorsäure, Essigsäure, Chloressigsäure, Oxalsäure, p-Toluolsulfonsäure verwenden. Die Verfahrensprodukte I (X = Cl, Br oder J) entstehen dagegen überwiegend, wenn man die entsprechenden Säuren HX in wasserfreiem Medium (insbesondere in Acetonitril, Aether, Methanol, Aethanol oder Isopropanol) zur Einwirkung kommen läßt. Beim Arbeiten in z. B. wässerig-alkoholischer halbkonzentrierter oder in wässeriger konzentrierter Halogenwasserstoffsäure entstehen beide Produkte I (X = OH und X = Cl, Br oder J) nebeneinander.In the method according to the invention, on the one hand, water can be used as a reagent HX (X = OH), on the other hand, serve as a solvent. For the preparation of the pyridine derivatives I (X = OH) it is expedient to use the dinitriles II with dilute aqueous acids around, the concentration of which is preferably between 0.5 and 4, in particular around 2, Molecular equivalent / liter moved. The presence of acid is for the purpose of neutralization of the cleaved amine HNR4R5 recommended; you can z. B. dilute hydrofluoric acid, Hydrochloric acid, hydrobromic acid, hydriodic acid, sulfuric acid, Phosphonic acid, perchloric acid, acetic acid, chloroacetic acid, oxalic acid, p-toluenesulfonic acid use. Process products I (X = Cl, Br or J) develop on the other hand, predominantly, if one uses the corresponding acids HX in an anhydrous medium (especially in acetonitrile, ether, methanol, ethanol or isopropanol) for action lets come. When working in z. B. aqueous-alcoholic semi-concentrated or Both products I are formed in aqueous concentrated hydrohalic acid (X = OH and X = Cl, Br or J) next to each other.
Zur Verwendung als Schädlingsbekämpfungsmittel können die neuen Verbindungen der Formel I zusammen mit festen und/oder flüssigen Trägerstoffen, gegebenenfalls unter Zusatz von Füll- und/oder Hilfsstoffen und/oder weiteren Schädlingsbekämpfungsmitteln z. B. zu Spritz- oder Stäubemitteln, Granulaten, Lösungen, Emulsionen oder Suspensionen verarbeitet werden.For use as pesticides, the new compounds of the formula I together with solid and / or liquid carriers, if appropriate with the addition of fillers and / or auxiliaries and / or other pesticides z. B. to spray or dust, granules, solutions, emulsions or suspensions are processed.
Die neuen Verbindungen zeigen ferner interessante biologische Wirkungen. Insbesondere treten Wirkungen auf das Zentralnervensystem, ferner bakteriostatische und antimykotische Wirkungen auf. Die Substanzen können im Gemisch mit festen und/oder flüssigen Arzneimittelträgern in der Human- oder Veterinärmedizin eingesetzt werden. Als Trägersubstanzen kommen solche organischen oder anorganischen Stoffe in Frage, die für die parenterale, enterale oder topikale Applikation geeignet sind und die mit den neuen Verbindungen nicht in Reaktion treten, wie beispielsweise Wasser, pflanzliche Oele, Polyäthylenglykole, Gelatine, Milchzucker, Stärke, Magnesiumstearat, Talk, Vaseline, Cholesterin. Zur parenteralen Applikation dienen insbesondere Lösungen, vorzugsweise ölige oder wässerige Lösungen sowie Suspensionen oder Emulsionen.The new compounds also show interesting biological effects. In particular, there are effects on the central nervous system, as well as bacteriostatic ones and antifungal effects. The substances can be mixed with solid and / or liquid pharmaceutical carriers are used in human or veterinary medicine. Such organic or inorganic substances are suitable as carrier substances, which are suitable for parenteral, enteral or topical application and which do not react with the new compounds, such as water, vegetable oils, polyethylene glycols, gelatine, lactose, starch, magnesium stearate, Talc, petroleum jelly, cholesterol. Solutions are especially used for parenteral administration, preferably oily or aqueous solutions and suspensions or emulsions.
Für die enterale Applikation eignen sich ferner Tabletten, Dragees, Sirupe und Säfte, für die topikale Anwendung Salben, Cremes oder Puder. Die angegebenen Zubereitungen können gegebenenfalls sterilisiert oder mit Hilfsstoffen, wie Konservierungs -, Stabilisierungs- oder Netzmitteln, Salzen zur Beeinflussung des osmotischell Druckes, Puffersubstanzen, Farb-, Geschmacks- und/oder Aromastoffen versetzt werden.Tablets, coated tablets, Syrups and juices, for topical application ointments, creams or powders. The specified Preparations can optionally be sterilized or with auxiliaries such as preservatives -, Stabilizing or wetting agents, salts to influence the osmotic pressure, Buffer substances, colors, flavors and / or aromas are added.
Beispiel 1 20 g 4-Diäthylamino-2-methylthio-1,3-butadien-1,1-dicarbonitril werden in 200 ml 2n HC1 und 50 ml Aethanol unter Rühren 3,5 Stunden bei 90° gehalten. Nach dem Erkalten wird das erhaltene 2-IIydroxy- 4 -methylthiopyridin- 3- carboni-t;ril abgesaugt, mit Aether gewaschen und aus Aethanol/Wasser unter Zusatz von Kohle umkristallisiert; F.<250°.Example 1 20 g of 4-diethylamino-2-methylthio-1,3-butadiene-1,1-dicarbonitrile are kept in 200 ml of 2N HCl and 50 ml of ethanol with stirring for 3.5 hours at 90 °. After cooling, the 2-hydroxy-4-methylthiopyridine-3-carbonate obtained becomes ril suctioned off, washed with ether and recrystallized from ethanol / water with the addition of charcoal; F. <250 °.
Analog erhält man mit 2-Aet;hylthio-lt-diät-hylamino-1,3-butadien-1,1-dicarbonitril, 2-n-Pyrolthio-4-diäthylamino-1,3-butadien-1,1-dicarbonitril, 2-n-Butylthio-4-diäthylamino-1,3-butadien-1,1-dicarbonitril bzw. 2-isobutyl-4-diäthylamino-1,3-butadien-1,1-dicarbonitril: 2-Hydroxy-1-äthylthio-pyridin-3-carbonitril 2-Hydroxy-4-n-propylthio-pyridin-3-carbonitril 2-Hydroxy-4-n-butylthio-pyridin-3-carbonitril 2-Hydroxy-4-isobutylthio-pyridin-3-carbonitril.Analogously with 2-eth, one obtains hylthio-lt-diet-hylamino-1,3-butadiene-1,1-dicarbonitrile, 2-n-Pyrolthio-4-diethylamino-1,3-butadiene-1,1-dicarbonitrile, 2-n-butylthio-4-diethylamino-1,3-butadiene-1,1-dicarbonitrile or 2-isobutyl-4-diethylamino-1,3-butadiene-1,1-dicarbonitrile: 2-hydroxy-1-ethylthio-pyridine-3-carbonitrile 2-Hydroxy-4-n-propylthio-pyridine-3-carbonitrile, 2-Hydroxy-4-n-butylthio-pyridine-3-carbonitrile 2-Hydroxy-4-isobutylthio-pyridine-3-carbonitrile.
Beispiel 2 In eine siedende Lösung von 24,2 g 2-Methylthio-2-(2-pyrrolidinocyclopenten-1-yl)-äthylen-1,1-dicarbonitril in 75 ml Acetonitril wird 2 Stunden lang HCl-Gas eigenleitet. Darauf wird eingedampft, der Rückstand mit Aether extrahiert, die Aetherphase eingedampft und das Zurückbleibende 2-Chlor-6,7-dihydro-4-methylthio-5H-1-pyridin-3-carbonitril aus Cyclohexan umkristallisiert, F. 85 - 87°.Example 2 In a boiling solution of 24.2 g of 2-methylthio-2- (2-pyrrolidinocyclopenten-1-yl) -ethylene-1,1-dicarbonitrile in 75 ml of acetonitrile, HCl gas is passed in for 2 hours. It is evaporated on, the residue extracted with ether, the ether phase evaporated and the residue 2-chloro-6,7-dihydro-4-methylthio-5H-1-pyridine-3-carbonitrile recrystallized from cyclohexane, F. 85-87 °.
Analog erhält man aus 2-Aethylthio-, 2-n-Propylthio-, 2-n-Butylthio- bzw. 2-Isobutylthio-2-(2-pyrrolidinocyclopenten-1-yl)-äthylen-l,l-dicarbonitril: 2-Chlor-4-äthylthio-5H-6,7-dihydro-l-pyrindin-3" carbonitril 2-Chlor-4-n-protylthio-5H-6,7-dihydro-l-pyrindin-3-carbonitril 2-Chlor-4-n-butylthio-5H-6,7-dihydro-1-pyridin-3-carboniltril 2-Chlor-4-isobutylthio-5H-6,7-dihydro-l-pyrindin-3-carbonitril Durch Einleiten von HBr an Stelle von HCl erhält man aus den gleichen Ausgangsstoffen: 2-Brom-4-methylthio-5H-6,7-dihydro-1-pyridin-3-carbonitril 2-Brom-4-äthylthio-5H-6,7-dihydro-1-pyridin-3 carbonitril 2-Brom-4-n-propylthio-5H-6,7-dihydro-l-pyrindin-3-carbonitril 2-Brom-4-n-butylthio-5H-6,7-dihydro-1-pyridin-3-carbonitril 2-Brom-4-isobutylthio-5H-6,7-dihydro-1-pyridin-3-carbonitril Analog wurden aus 2-n-Butylthio-2-(2-morpholino-cyclopentenl-yl)-athylen-l,l-dicarbonitril unter Einleiten von HCl bzw.Analogously from 2-ethylthio, 2-n-propylthio, 2-n-butylthio- or 2-isobutylthio-2- (2-pyrrolidinocyclopenten-1-yl) -ethylene-l, l-dicarbonitrile: 2-chloro-4-ethylthio-5H-6,7-dihydro-1-pyrindine-3 "carbonitrile 2-chloro-4-n-protylthio-5H-6,7-dihydro-1-pyrindine-3-carbonitrile 2-chloro-4-n-butylthio-5H-6,7-dihydro-1-pyridine-3-carbonitrile, 2-chloro-4-isobutylthio-5H-6,7-dihydro-1-pyrindine-3-carbonitrile By introducing HBr instead of HCl one obtains from the same starting materials: 2-Bromo-4-methylthio-5H-6,7-dihydro-1-pyridine-3-carbonitrile, 2-Bromo-4-ethylthio-5H-6,7-dihydro-1-pyridine-3 carbonitrile 2-bromo-4-n-propylthio-5H-6,7-dihydro-l-pyrindine-3-carbonitrile 2-bromo-4-n-butylthio-5H-6,7-dihydro-1-pyridine-3- carbonitrile 2-Bromo-4-isobutylthio-5H-6,7-dihydro-1-pyridine-3-carbonitrile Analogously from 2-n-butylthio-2- (2-morpholino-cyclopentenl-yl) -ethylene-l, l- dicarbonitrile with the introduction of HCl resp.
HBr gewonnen: 2-Chlor-6,7-dihydro-4-butylthio-5H-l-pyrindin-3-carbonitril 2-Brom-6,7-dihydro-4-butylthio-5H-l-pyrindin-3-carbonitril.HBr recovered: 2-chloro-6,7-dihydro-4-butylthio-5H-1-pyrindine-3-carbonitrile 2-Bromo-6,7-dihydro-4-butylthio-5H-1-pyrindine-3-carbonitrile.
Beispiel 3 14,8 g 2-Methylthio-2- (2-pyrrolidinocyclopenten-l-yl)-äthylen l,l-dicarbonitril werden in 50 ml 2n HC1 2 Stunden bei 1000 erwärmt. Das nach dem Erkalten abgesaugte 6,7-Dihydro-2-hydroxy-4-methylthio-5H-l-pyrindin-3-carbonitril wird aus Eisessig umkristallisiert; F. 279 - 2800.Example 3 14.8 g of 2-methylthio-2- (2-pyrrolidinocyclopenten-1-yl) ethylene 1,1-dicarbonitrile are heated in 50 ml of 2N HCl for 2 hours at 1000. That after 6,7-dihydro-2-hydroxy-4-methylthio-5H-1-pyrindine-3-carbonitrile which is suctioned off when cooled is recrystallized from glacial acetic acid; F. 279-2800.
Analog erhält man aus den entsprechenden 2-Alkylthio-2-(2-pyrrolidinocyclopenten-l-yl)-äthylen-1,1-dicarbonitrilen: 2-Hydroxy-4-åthylthio-5H~6,7-dShydro-1-pyrindin-3-carbonitril 2-Hydroxy-4-n-propylthio-5H-6, 7-dihydro-l-pyrindin-3-carbonitril 2-Hydroxy-4-n-butylthio-5H-6, 7-dihydro-l-pyrindin-3-carbonitril 2-Hydroxy-4-isobutylthio-5H-6,7-dihydro-1-pyrindin-3-carbonitril.Analogously, from the corresponding 2-alkylthio-2- (2-pyrrolidinocyclopenten-l-yl) -ethylene-1,1-dicarbonitriles: 2-Hydroxy-4-ethylthio-5H ~ 6,7-d-Hydro-1-pyrindine-3-carbonitrile 2-hydroxy-4-n-propylthio-5H-6, 7-dihydro-1-pyrindine-3-carbonitrile, 2-hydroxy-4-n-butylthio-5H-6, 7-dihydro-1-pyrindine-3-carbonitrile 2-Hydroxy-4-isobutylthio-5H-6,7-dihydro-1-pyrindine-3-carbonitrile.
Entspreehend wird aus 2-Methylthio-2- (morpholinocyclohepten 1-yl)-äthylen-1,1-dicarbonitril gewonnen: 2-Hydroxy-4-methylthio-6,7,8,9-tetrahydro-5H-cyclohepta(b)pyridin-3-carbonitril.Correspondingly, 2-methylthio-2- (morpholinocyclohepten 1-yl) -ethylene-1,1-dicarbonitrile becomes recovered: 2-hydroxy-4-methylthio-6,7,8,9-tetrahydro-5H-cyclohepta (b) pyridine-3-carbonitrile.
Beispiel 4 13,8 g rohes 3-Aethyl-4-morpholino-2-methylthio-1,3-butadienl,l-dicarbonitril werden in einem Gemisch von 50 ml 2n HC1 und 20 ml konzentrierter HC1 6 Stunden auf dem Dampfbad gerührt.Example 4 13.8 g of crude 3-ethyl-4-morpholino-2-methylthio-1,3-butadienl, l-dicarbonitrile are in a mixture of 50 ml of 2N HCl and 20 ml of concentrated HCl for 6 hours stirred on the steam bath.
Nach den Erkalten und Absaugen wird das erhaltene 5-Aethyl-2-hydroxy-4-methylthiopyridin-3-carbonitril aus Isopropanol unter Zusatz von Kohle umkristallisiert; B. 192 - 1950.After cooling and filtration with suction, the 5-ethyl-2-hydroxy-4-methylthiopyridine-3-carbonitrile obtained is obtained recrystallized from isopropanol with the addition of charcoal; B. 192 - 1950.
Analog erhält man mit 2-Aethylthio-3-äthyl-4-morpholino-1,3-butadien-1,1-dicarbonitril, 2-n-Propylthio-3-äthyl-4-morpholino-1,3-butadien-1,1-dicarbonitril, 2-n-Butylthio-3-äthyl-4-morpholino-1,3-butadien-1,1-dicarbonitril bzw.Analogously with 2-ethylthio-3-ethyl-4-morpholino-1,3-butadiene-1,1-dicarbonitrile, 2-n-propylthio-3-ethyl-4-morpholino-1,3-butadiene-1,1-dicarbonitrile, 2-n-butylthio-3-ethyl-4-morpholino-1,3-butadiene-1,1- dicarbonitrile respectively.
2-Inol)utylthio-3-äthyl-4-morpholino-1,3-butadienz diw carbonitril: 2-Hydroxy-4-äthylthio-5-äthyl-pyridin-3-carbonitril 2-Hydroxy-4-n-propylthio-5-äthyl-pyridin-3-carbonitril 2-Hydroxy-4-n-butylthio-5-äthyl-pyridin-3-carbonitril 2-Hydroxy-4-isoAutylthio-5-äthyl-pyridin-3-carbonitril sowie unter Verwendung der entsprechenden 3-Methyl-, 3-n-Propyl-, 3-n-Butyl- bzw. 3-Isobutyl-2-alkylthio-4-morpholino 1,3-butadien-1,1-dicarbonitrile: 2-Hydroxy- 4-methylthio- 5-methyl-pyridin 3- carbonitril 2-Hydroxy-4-äthylthio-5-methyl-pyridin-3-carbo-nitril 2-Hydroxy-4-n-propylthio-5-methyl-pyridin-3-carbonitril 2-Hydroxy-4-n-butylthio-5-methyl-pyridin-3-carbonitril 2-Hydroxy-4-isobutylthio-5-methyl-pyridin-3-carbonitril 2-Hydroxy-4-methylthio-5-n-propyl-pyridin-3-carbonitril 2-Hydroxy-4-äthylthio-5-n-propyl-pyridin-3-carbonitril 2-Hydroxy-4-n-propylthio-5-n-propyl-pyridin-3-carbonitril 2-Hydroxy-4-n-butylthio-5-n-propyl-pyridin-3-carbo:nitril 2-Hydroxy-4-isobutylthio-5-n-propyl-pyridin-3-carbonitril 2-Hydroxy-4-methylthio-5-n-butyl-pyridin-3-carbonitril 2-Hydroxy-4-äthylthio-5-n-butyl-pyridin-3-carbonitril 2-Hydroxy-4-n-propylthio-5-n-butyl-pyridin-3-carboitril 2-Hydroxy-4-n-butylthio-5-n-butyl-pyridin-3-carbonitril 2-Hydroxy-4-isobutylthio-5-n-butylwpyridin-3~carbonitril 2~Hydroxy-4-methylthio-5-isobutyl~pyridin 3-carbonitril 2-Hydrocy-4-äthylthio-5-isotutyl-pyridin-3-carbonitril 2-Hydroxy-4-n-propylthio-5-isobutyl-pyridin-3-carbonitril 2-Hydroxy-4-n-butylthio-5-isobutyl-pyridin-3-carbonitril 2-Hydroxy-4-isobutylthio-5-isobutyl-pyridin-3-carbonitril.2-ynol) utylthio-3-ethyl-4-morpholino-1,3-butadiene diw carbonitrile: 2-Hydroxy-4-ethylthio-5-ethyl-pyridine-3-carbonitrile 2-Hydroxy-4-n-propylthio-5-ethyl-pyridine-3-carbonitrile, 2-hydroxy-4-n-butylthio-5-ethyl-pyridine-3-carbonitrile 2-Hydroxy-4-isoAutylthio-5-ethyl-pyridine-3-carbonitrile and using the corresponding 3-methyl-, 3-n-propyl-, 3-n-butyl- and 3-isobutyl-2-alkylthio-4-morpholino 1,3-butadiene-1,1-dicarbonitrile: 2-hydroxy-4-methylthio-5-methyl-pyridine 3-carbonitrile 2-Hydroxy-4-ethylthio-5-methyl-pyridine-3-carbo-nitrile, 2-hydroxy-4-n-propylthio-5-methyl-pyridine-3-carbonitrile 2-Hydroxy-4-n-butylthio-5-methyl-pyridine-3-carbonitrile, 2-hydroxy-4-isobutylthio-5-methyl-pyridine-3-carbonitrile 2-Hydroxy-4-methylthio-5-n-propyl-pyridine-3-carbonitrile, 2-hydroxy-4-ethylthio-5-n-propyl-pyridine-3-carbonitrile 2-Hydroxy-4-n-propylthio-5-n-propyl-pyridine-3-carbonitrile, 2-hydroxy-4-n-butylthio-5-n-propyl-pyridine-3-carbo: nitrile 2-Hydroxy-4-isobutylthio-5-n-propyl-pyridine-3-carbonitrile, 2-hydroxy-4-methylthio-5-n-butyl-pyridine-3-carbonitrile 2-Hydroxy-4-ethylthio-5-n-butyl-pyridine-3-carbonitrile, 2-hydroxy-4-n-propylthio-5-n-butyl-pyridine-3-carboitrile 2-Hydroxy-4-n-butylthio-5-n-butyl-pyridine-3-carbonitrile, 2-hydroxy-4-isobutylthio-5-n-butylwpyridine-3-carbonitrile 2-hydroxy-4-methylthio-5-isobutyl-pyridine 3-carbonitrile 2-hydrocy-4-ethylthio-5-isotutyl-pyridine-3-carbonitrile 2-Hydroxy-4-n-propylthio-5-isobutyl-pyridine-3-carbonitrile, 2-Hydroxy-4-n-butylthio-5-isobutyl-pyridine-3-carbonitrile 2-Hydroxy-4-isobutylthio-5-isobutyl-pyridine-3-carbonitrile.
Beispiel 5 In eine Lösung von 13,8 g In eine Lösung von 13,8 g rohem 3-Aethyl-4-morpholino-2- rohem 3-Aethyl-4-morpholino-2-methylthio-1,3-butadien-1,1-dicarbonitril in 200 ml Aether wird 48 Stunden lang bei Raumtemperatur HCl-Gas geleitet.Example 5 In a solution of 13.8 g In a solution of 13.8 g of crude 3-ethyl-4-morpholino-2-crude 3-ethyl-4-morpholino-2-methylthio-1,3-butadiene-1,1-dicarbonitrile HCl gas is passed into 200 ml of ether at room temperature for 48 hours.
Darauf wird eingedampft, der Rückstand mit Wasser und Chloroform gectchüttelt, die Chloroformphase mit Na2SO4 getrocknet und eingedampft;. Der Rückstand wird bei 110 - 130° (Luftbadtemperatur) / 0,6 mm destilliert, das erhaltene 5-Aethyl-2-chlor-4-methylthiopyridin-3-carbonitril aus Cyclohexan u?-nkristallisiert; F. 56 - 58°.It is then evaporated, the residue is shaken with water and chloroform, the chloroform phase dried with Na2SO4 and evaporated ;. The residue is at 110-130 ° (air bath temperature) / 0.6 mm distilled, the 5-ethyl-2-chloro-4-methylthiopyridine-3-carbonitrile obtained crystallized from cyclohexane; F. 56 - 58 °.
Analog erhält man unter Verwendung der in Beispiel 4 genannten Ausgangestoffe die entsprechendc-n 2-Chlor-4-alkylthio-pyridin-3-caronitrile.Using the starting materials mentioned in Example 4, one obtains analogously the corresponding c-n 2-chloro-4-alkylthio-pyridine-3-caronitriles.
Beim Einleiten von HBr an Stelle von HC1 erhält man 2-Brom-4-methylthio-5-äthyl-pyridin-3-carbonitril bzw.When HBr is introduced instead of HCl, 2-bromo-4-methylthio-5-ethyl-pyridine-3-carbonitrile is obtained respectively.
die entsprechenden 2-Brom-4-alkylthio-pyridin-3-carbonitrile.the corresponding 2-bromo-4-alkylthio-pyridine-3-carbonitriles.
Analog erhält man aus 3-n-Butyl-2-methylthio-4-piperidino-1,3-butadien-1,1-dicarbonitril: 5-n Butyl- -chlor-4-methylthiopyridin-3-carbonitril.Similarly, from 3-n-butyl-2-methylthio-4-piperidino-1,3-butadiene-1,1-dicarbonitrile: 5-n butyl-chloro-4-methylthiopyridine-3-carbonitrile.
Beispiel ö 3 g 2-Methylthio-2-(2-pyrrolidinocyclohexen-1-yl)-äthylen-1,1-dicarbonitril oder 2-Methylthio-2-(2-morpholinocyclohexen-1-yl)-äthylen-1,1-dicarbonitril werden in 15 ml 2n Salzsäure 2 Stunden unter Rühren auf 100° erwärmt. Nach dem Erkalten wird abgesaugt, das erhaltene 2-Hydroxy-4-methylthio-5,6,7,8-tetrahydro-chilolin-3-carbonitril mit Wasser, Methanol und Aether gewaschen und getrocknet. F. >250°.Example ö 3 g of 2-methylthio-2- (2-pyrrolidinocyclohexen-1-yl) -ethylene-1,1-dicarbonitrile or 2-methylthio-2- (2-morpholinocyclohexen-1-yl) -ethylene-1,1-dicarbonitrile heated in 15 ml of 2N hydrochloric acid with stirring to 100 ° for 2 hours. After cooling down is suctioned off, the 2-hydroxy-4-methylthio-5,6,7,8-tetrahydro-chiloline-3-carbonitrile obtained washed with water, methanol and ether and dried. F.> 250 °.
An Stellc der Salzsäure kann man auch Essigsäure, Phosphorsäure, Schwefelsäure, fiF, HBr oder HJ verwenden.Instead of hydrochloric acid, acetic acid, phosphoric acid, sulfuric acid, Use fiF, HBr or HJ.
Analog erhält man: aus 2-Aethylthio-2- (2-pyrrolidinocyclohexen-1-y1)-äthylen 1,l-dicarbonitril bzw. den entsprechenden höheren 2-Alkylthiohomologen: 2-Hydroxy-4-athylthio-5,6,7,8-tetrahydro-chinolin-3-carbonitril 2-Hydroxy-4-n-propylthio-5,6,7,8-tetrahydro-chinolin-3-carbonitril 2-Hydroxy-4-n-butylthio-5,6,7,8-tetrahydro-chinolin-3-carbonitril 2-Hydroxy-4-isobutylthio-5,6,7,8-tetrahydro-chinolin-3-carbonitril; aus 2-Methylthio-2- (3 ,4-dihydro-1-pyrrolidino-2-naphthy1) äthylen-1,1-d'icarbonitril bzw. den entsprechenden höheren 2-Alkylthio-homologen: 2-Hydroxy-4-methylthio-5,6-dihydro-benzo(h)chinolin-3-carbonitril, F. 275 - 2780; 2-Hydroxy-4-äthylthio-5,6-dihydro-benzo(h)chinolidin-3-carbonitril 2-Hydroxy-4-n-propylthio-5,6-dihydro-benzo(h)chinolidin-3 carbonitril 2-Hydroxy-4-n-butylthio-5,6-dihydro-benzo(h)chinolin-3-carbonitril 2-Hydroxy-4-isobutylthio-5, 6-dihydro-benzo(h)chinolin-3 carbonitril.The following is obtained analogously: from 2-ethylthio-2- (2-pyrrolidinocyclohexen-1-y1) -ethylene 1,1-dicarbonitrile or the corresponding higher 2-alkylthiohomologues: 2-hydroxy-4-ethylthio-5,6,7,8-tetrahydroquinoline-3-carbonitrile 2-hydroxy-4-n-propylthio-5,6,7,8-tetrahydro-quinoline-3-carbonitrile 2-hydroxy-4-n-butylthio-5,6,7,8-tetrahydro-quinoline-3-carbonitrile 2-hydroxy-4-isobutylthio-5,6,7,8-tetrahydroquinoline-3-carbonitrile; from 2-methylthio-2- (3, 4-dihydro-1-pyrrolidino-2-naphthy1) ethylene-1,1-d'icarbonitrile or the corresponding higher 2-alkylthio homologues: 2-hydroxy-4-methylthio-5,6-dihydro-benzo (h) quinoline-3-carbonitrile, F. 275-2780; 2-Hydroxy-4-ethylthio-5,6-dihydro-benzo (h) quinolidine-3-carbonitrile 2-Hydroxy-4-n-propylthio-5,6-dihydro-benzo (h) quinolidine-3-carbonitrile, 2-hydroxy-4-n-butylthio-5,6-dihydro-benzo (h) quinoline-3-carbonitrile 2-Hydroxy-4-isobutylthio-5, 6-dihydro-benzo (h) quinoline-3 carbonitrile.
Beispiel 7 In eine Lösung von 13,6 g 2-Methylthio-2-(2-pyrrolidinocyclohexen-1-yl)-äthylen-1,1-dicarbonitril in 50 ml Acetonitril(oder 100 ml Isopropanol)wird 2 Stunden bei 70 - 800 HC1-Gas eingeleitet. Nach dem Eindampfen wird das erhaltene 2-Chlor-4-methylthio-5,6,7,8-tetrahydrochinolin-3-carbonitril mit Wasser gewaschen und aus Cyclohexan unter Zusatz von Kohle umkristallisiert; F. 114 - 1160.Example 7 In a solution of 13.6 g of 2-methylthio-2- (2-pyrrolidinocyclohexen-1-yl) ethylene-1,1-dicarbonitrile in 50 ml acetonitrile (or 100 ml isopropanol) is 2 hours with 70-800 HC1 gas initiated. After evaporation, the 2-chloro-4-methylthio-5,6,7,8-tetrahydroquinoline-3-carbonitrile obtained is obtained washed with water and recrystallized from cyclohexane with the addition of charcoal; F. 114 - 1160.
Analog erhält man aus den in Beispiel 6 genannten Ausgangs verbindungen: 2-Chlor-4-äthylthio-5,6,7,8-tetrahydro-chinolin-3-carbonitril 2-Chlor-4-n-propylthio-5, 6, 7,8-tetrahydro-ehinolin-3-carbonitril 2-Chlor-4-n-butylthio-5,6,7,8-tetrahydro-chinolin-3-carbonitril 2-Chlor-4-isobutylthio-5,6,7,8-tetrahydro-chinolin-3-carbonitril.Analogously, one obtains from the starting compounds mentioned in example 6: 2-chloro-4-ethylthio-5,6,7,8-tetrahydroquinoline-3-carbonitrile 2-chloro-4-n-propylthio-5, 6, 7,8-tetrahydro-quinoline-3-carbonitrile, 2-chloro-4-n-butylthio-5,6,7,8-tetrahydro-quinoline-3-carbonitrile 2-chloro-4-isobutylthio-5,6,7,8-tetrahydroquinoline-3-carbonitrile.
Analog lassen sich aus den gleichen Ausgangsstoffen durch Einleiten von HBr erhalten: 2-Brom-4-methylthio-5, 6,7,8-tetrahydro-chinolin-3 carbonitril; Fo 106 - 107°; 2-Brom-4-äthylthio-5,6,7,8-tetrahydro-chinolin-3 carbonitril 2-Brom-4-n-propylthio 5,6,7,8- tetrahydro- chinolin- 3-carbonitril 2-Brom-4-n-butylthio-5,6,7,8-tetrahydro-chinolin-3-carbonitril 2-Brom-4-isobutylthio-5,6,7,8-tetrahydro-chinolin-3-carbonitril.Analogously, the same starting materials can be introduced by introducing them Obtained from HBr: 2-bromo-4-methylthio-5, 6,7,8-tetrahydroquinoline-3 carbonitrile; Fo 106-107 °; 2-Bromo-4-ethylthio-5,6,7,8-tetrahydro-quinoline-3-carbonitrile 2-Bromo-4-n-propylthio 5,6,7,8-tetrahydro-quinoline-3-carbonitrile, 2-bromo-4-n-butylthio-5,6,7,8-tetrahydro-quinoline-3-carbonitrile 2-Bromo-4-isobutylthio-5,6,7,8-tetrahydroquinoline-3-carbonitrile.
Chlor- und Bromverbindungen lassen sich auch neben der Hydroxyverbindung erhalten, indem man je 5 g 2-Methylthio-2-(pyrrolidinocyclohexen-l-yl)-äthylen-l,l-dicarbonitril in 10 ml Methanol mit 10 ml wässeriger konzentrierter HC1 bzw. 10 ml wässeriger konzentrierter HBr 10 Minuten kocht, eine Stunde bei Raumtemperatur stehen läßt, absaugt, mit Wasser wäscht und dann mit Aether extrahiert. Die verbleibenden Kristalle bestehen aus 2-fiydroxy-4-methy1thio-5,6,7 ,8-tetrahydrochinolin-3-carbonitril; die Aetherphase liefert nach dem Eindampfen und Umkristallisieren 2-Chlor- bzw. 2-Brom-4-methylthio-5,6,7,8-tetrahydrochinolin-3-carbonitril.Chlorine and bromine compounds can also be found in addition to the hydroxy compound obtained by adding 5 g of 2-methylthio-2- (pyrrolidinocyclohexen-l-yl) -ethylene-l, l-dicarbonitrile in 10 ml of methanol with 10 ml of aqueous concentrated HCl or 10 ml of aqueous concentrated HBr boils for 10 minutes, leaves to stand for one hour at room temperature, suctioned off, washed with water and then extracted with ether. The remaining crystals consist of 2-hydroxy-4-methy1thio-5,6,7,8-tetrahydroquinoline-3-carbonitrile; after evaporation and recrystallization, the ether phase yields 2-chloro or 2-Bromo-4-methylthio-5,6,7,8-tetrahydroquinoline-3-carbonitrile.
Beispiel 8 5,4 g 2-Methylthio-2- (2-pyrrolidinocyclohexen-1-yl)-äthylenl,l-dicarbonitril werden in 70 ml Methanol und 60 ml konzentrierter wässeriger Ammoniaklösung 12 Stunden gekocht. Das nach dem Erkalten abgeschiedene 2-Amino-4-methylthio-5, 6,7,8-tetrahydrochinolin-3-carbonitril wird aus Benzol umkristallisiert; P. 206 - 2080.Example 8 5.4 g of 2-methylthio-2- (2-pyrrolidinocyclohexen-1-yl) -ethylenel, l-dicarbonitrile are in 70 ml of methanol and 60 ml of concentrated aqueous ammonia solution for 12 hours cooked. The 2-amino-4-methylthio-5,6,7,8-tetrahydroquinoline-3-carbonitrile deposited after cooling is recrystallized from benzene; P. 206-2080.
Entsprechend läßt sich aus 2-Methylthio-2-(2-pyrrolidinocyc lopentenyl)-äthylen-1,1-dicarbonitril erhalten: 2-Amino-6,7-dihydro-4-methylthio-5H-1-pyrindin-3-carbonitril.Correspondingly, from 2-methylthio-2- (2-pyrrolidinocyc lopentenyl) -ethylene-1,1-dicarbonitrile obtained: 2-amino-6,7-dihydro-4-methylthio-5H-1-pyrindine-3-carbonitrile.
Beispiel 9 In eine siedende Lösung von 20 g 2-Methylthio-5-phenyl-4-piperidino-1,3-pentadien-1,1-dicarbonitril, das durch Reaktion von l-Phenyl-2-piperidinopropen-(1) mit 2,2-Bis-(methylthio)-äthylen-l,l-dicarbonitril unter gleichzeitiger Verschiebung der Doppelbindung hergestellt werden kann, in 100 ml Acetonitril wird 4 Stunden HCl-Gas eingeleitet. Nach dem Einengen wird das erhaltene 2-Benzyl-6-chlor-4-methylthiopyridin-5-carbonitril mit Wasser digeriert, abgesaugt und aus Methanol umkristallisiert; F. 125 - 1270.Example 9 In a boiling solution of 20 g of 2-methylthio-5-phenyl-4-piperidino-1,3-pentadiene-1,1-dicarbonitrile, the reaction of l-phenyl-2-piperidinopropen- (1) with 2,2-bis- (methylthio) -ethylene-l, l-dicarbonitrile can be produced with simultaneous shifting of the double bond, in 100 ml of acetonitrile are passed in HCl gas for 4 hours. After narrowing it will 2-benzyl-6-chloro-4-methylthiopyridine-5-carbonitrile obtained digested with water, suctioned off and recrystallized from methanol; F. 125-1270.
Beispiel 10 16,6 g 2-Methylthio-5-phenyl-4-piperidino-1,3-pentadien-1,1-dicarbonitril werden mit 10 ml Methanol und 30 ml konzentrierter wässeriger HBr-Lösung 5 Minuten auf dem Dampfbad erwärmt.Example 10 16.6 g of 2-methylthio-5-phenyl-4-piperidino-1,3-pentadiene-1,1-dicarbonitrile with 10 ml of methanol and 30 ml of concentrated aqueous HBr solution for 5 minutes warmed up on the steam bath.
Darauf wird mit Chloroform/Wasser durchgeschüttelt, die mit Na2S04 getrocknete Chloroformphase eingedampft und das erhaltene 2-Benzyl-6-brom-4-methylthiopyridin-5-carbonitril aus Isopropanol umkristallisiert; P. 113 - 1150.Then it is shaken with chloroform / water, which with Na2S04 evaporated dried chloroform phase and the resulting 2-benzyl-6-bromo-4-methylthiopyridine-5-carbonitrile recrystallized from isopropanol; P. 113-1150.
Beispiel 11 10 g 2-Methylthio-5-phenyl-4-piperidino-1,3-pentadien-1,1-dicarbonitril werden mit 30 ml Methanol und 40 ml konzentrierter wässeriger HJ-Lösung unter Schütteln auf dem Dampfbad erwärmt. Darauf wird mit Chloroform/Wasser durchgeschüttelt, die Chloroformphase nach dem Trocknen mit Na2SO4 eingedampft und der Rückstand über 300 g Kieselgel mit CfiCl3/, Hexan (9:1) filtriert. Das Eluat wird eingedampft und das erhaltene 2-Benzyl-6- jod-4-methylthiopyridin-5-carbonitril aus Isopropanol umkristallisiert; F. 135 - 1370.Example 11 10 g of 2-methylthio-5-phenyl-4-piperidino-1,3-pentadiene-1,1-dicarbonitrile are mixed with 30 ml of methanol and 40 ml of concentrated aqueous HJ solution with shaking warmed up on the steam bath. Then it is shaken with chloroform / water, the Chloroform phase evaporated after drying with Na2SO4 and the residue over 300 g of silica gel with CfiCl3 /, hexane (9: 1) filtered. The eluate is evaporated and the 2-benzyl-6-iodo-4-methylthiopyridine-5-carbonitrile obtained from isopropanol recrystallized; F. 135-1370.
Beispiel 12 5 g 2-Methylthio-5-phenyI-4-piperidino-1,3-pentadien-1,1-dicarbonitril werden mit 20 ml Methanol und 4 ml konzentrierter wässeriger HF-Bösung 20 Minuten auf dem Dampfbad erwärmt.Example 12 5 g of 2-methylthio-5-phenyI-4-piperidino-1,3-pentadiene-1,1-dicarbonitrile with 20 ml of methanol and 4 ml of concentrated aqueous HF solution for 20 minutes warmed up on the steam bath.
Nach dem Abkühlen wird der Niederschlag abgesaugt und das erhaltene 2-Benzyl-6-hydroxy-4-methylthiopyridin-5-carbonitril aus Methylglykol umkri-talltsiert. F. 270 - 2740.After cooling, the precipitate is filtered off and the one obtained 2-Benzyl-6-hydroxy-4-methylthiopyridine-5-carbonitrile recrystallized from methyl glycol. F. 270-2740.
Beispiel 13 13,5 g 2-Methylthio-5-phenyl-4-piperidino-1,3-pentadien-1,1-dicarbonitril werden mit 10 ml Methanol und 25 ml 25 %iger wässeriger NI13-Lösung 15 Stunden am Rückfluß erwärmt. Darauf wird eingedampft, das erhaltene 6-Amino-2-benzyl-4-methylthiopyridin-5-carbonitril mit Isopropanol digeriert und aus Methanol umkristallisiert; F. 171 - 1730.Example 13 13.5 g of 2-methylthio-5-phenyl-4-piperidino-1,3-pentadiene-1,1-dicarbonitrile are with 10 ml of methanol and 25 ml of 25% aqueous NI13 solution for 15 hours Heated to reflux. It is then evaporated, the 6-amino-2-benzyl-4-methylthiopyridine-5-carbonitrile obtained digested with isopropanol and recrystallized from methanol; F. 171-1730.
Entsprechend wird aus 2-Methylthio-2-(3,4-dihydro-1-pyrrolidino- 2-naphthyl)-äthylen-l , l-dicarbonitril erhalten: 2-Amino-5,6-dihydro-4-methylthio-benzo(h)chinolin-3-carbonitril.Correspondingly, from 2-methylthio-2- (3,4-dihydro-1-pyrrolidino-2-naphthyl) -ethylene-l , l-dicarbonitrile obtained: 2-amino-5,6-dihydro-4-methylthio-benzo (h) quinoline-3-carbonitrile.
Beispiel 14 In eine Lösung von 3 g rohem 2-Methylthio-2-(3,4-dihydro-1-pyrrolidino-2-naphthyl)-äthylen-1,1-dicarbonitril in Methanol wird unter Rückfluß 3 Stunden HCl-Gas eingleitet. Darauf wird eingedampft und das erhaltene 2-Chlor-5,6-dihydro-4-methyl thio-benzo(h) chinolin-3-carbonitril aus Methanol umkristallisiert; P. 172 - 1730.Example 14 In a solution of 3 g of crude 2-methylthio-2- (3,4-dihydro-1-pyrrolidino-2-naphthyl) ethylene-1,1-dicarbonitrile HCl gas is passed in under reflux for 3 hours in methanol. It is then evaporated and the obtained 2-chloro-5,6-dihydro-4-methylthio-benzo (h) quinoline-3-carbonitrile recrystallized from methanol; P. 172-1730.
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| US4395555A (en) * | 1981-01-30 | 1983-07-26 | Basf Aktiengesellschaft | Preparation of 2-aminopyridine derivatives |
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