DE1248056B - Process for the preparation of hexahydropyrimidine-2,4-diones - Google Patents
Process for the preparation of hexahydropyrimidine-2,4-dionesInfo
- Publication number
- DE1248056B DE1248056B DEF45312A DEF0045312A DE1248056B DE 1248056 B DE1248056 B DE 1248056B DE F45312 A DEF45312 A DE F45312A DE F0045312 A DEF0045312 A DE F0045312A DE 1248056 B DE1248056 B DE 1248056B
- Authority
- DE
- Germany
- Prior art keywords
- isocyanate
- hexahydropyrimidine
- isocyanates
- enamines
- diones
- 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
- OIVLITBTBDPEFK-UHFFFAOYSA-N 5,6-dihydrouracil Chemical class O=C1CCNC(=O)N1 OIVLITBTBDPEFK-UHFFFAOYSA-N 0.000 title claims description 7
- 238000000034 method Methods 0.000 title claims description 7
- 238000002360 preparation method Methods 0.000 title claims description 4
- -1 alkyl radicals Chemical group 0.000 claims description 15
- 239000012948 isocyanate Substances 0.000 claims description 12
- 150000002513 isocyanates Chemical class 0.000 claims description 11
- 150000002081 enamines Chemical group 0.000 claims description 9
- 150000003254 radicals Chemical class 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 4
- XPCJYQUUKUVAMI-UHFFFAOYSA-N cyclohex-2-ene-1-carbaldehyde Chemical compound O=CC1CCCC=C1 XPCJYQUUKUVAMI-UHFFFAOYSA-N 0.000 claims description 3
- KVFDZFBHBWTVID-UHFFFAOYSA-N cyclohexanecarbaldehyde Chemical compound O=CC1CCCCC1 KVFDZFBHBWTVID-UHFFFAOYSA-N 0.000 claims description 3
- 150000003335 secondary amines Chemical class 0.000 claims description 3
- 125000003435 aroyl group Chemical group 0.000 claims description 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 238000009833 condensation Methods 0.000 claims description 2
- 230000005494 condensation Effects 0.000 claims description 2
- 230000004048 modification Effects 0.000 claims 1
- 238000012986 modification Methods 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 125000003107 substituted aryl group Chemical group 0.000 claims 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 150000001875 compounds Chemical class 0.000 description 13
- 239000000203 mixture Substances 0.000 description 12
- PAXNHQZTZQFBPC-UHFFFAOYSA-N 1-(2-methylprop-1-enyl)pyrrolidine Chemical compound CC(C)=CN1CCCC1 PAXNHQZTZQFBPC-UHFFFAOYSA-N 0.000 description 8
- 239000002904 solvent Substances 0.000 description 7
- ZQZUJFQBFGFJMM-UHFFFAOYSA-N 1-(2-methylprop-1-enyl)piperidine Chemical compound CC(C)=CN1CCCCC1 ZQZUJFQBFGFJMM-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- LURYMYITPCOQAU-UHFFFAOYSA-N benzoyl isocyanate Chemical compound O=C=NC(=O)C1=CC=CC=C1 LURYMYITPCOQAU-UHFFFAOYSA-N 0.000 description 6
- 238000001816 cooling Methods 0.000 description 5
- ADAKRBAJFHTIEW-UHFFFAOYSA-N 1-chloro-4-isocyanatobenzene Chemical compound ClC1=CC=C(N=C=O)C=C1 ADAKRBAJFHTIEW-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- VMVZGGPZNHFGKS-UHFFFAOYSA-N ethyl n-(oxomethylidene)carbamate Chemical compound CCOC(=O)N=C=O VMVZGGPZNHFGKS-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- RSEUOMWVYSLIKM-UHFFFAOYSA-N 4-(2-methylprop-1-enyl)morpholine Chemical compound CC(C)=CN1CCOCC1 RSEUOMWVYSLIKM-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-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
- 238000009835 boiling Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 2
- GFNKTLQTQSALEJ-UHFFFAOYSA-N 1-isocyanato-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(N=C=O)C=C1 GFNKTLQTQSALEJ-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- XYUCULXRVSQDCG-UHFFFAOYSA-N 1,2,3,4,5-pentachloro-6-isocyanatobenzene Chemical compound ClC1=C(Cl)C(Cl)=C(N=C=O)C(Cl)=C1Cl XYUCULXRVSQDCG-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- HXNJPHHNZNLQRP-UHFFFAOYSA-N 1-methyl-2-(2-methylprop-1-enyl)piperazine Chemical compound C(=C(C)C)C1N(CCNC1)C HXNJPHHNZNLQRP-UHFFFAOYSA-N 0.000 description 1
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- NJBCRXCAPCODGX-UHFFFAOYSA-N 2-methyl-n-(2-methylpropyl)propan-1-amine Chemical compound CC(C)CNCC(C)C NJBCRXCAPCODGX-UHFFFAOYSA-N 0.000 description 1
- HEBTZZBBPUFAFE-UHFFFAOYSA-N 2-methyl-n-(oxomethylidene)benzenesulfonamide Chemical compound CC1=CC=CC=C1S(=O)(=O)N=C=O HEBTZZBBPUFAFE-UHFFFAOYSA-N 0.000 description 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
- MFUVCHZWGSJKEQ-UHFFFAOYSA-N 3,4-dichlorphenylisocyanate Chemical compound ClC1=CC=C(N=C=O)C=C1Cl MFUVCHZWGSJKEQ-UHFFFAOYSA-N 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- VLJQDHDVZJXNQL-UHFFFAOYSA-N 4-methyl-n-(oxomethylidene)benzenesulfonamide Chemical compound CC1=CC=C(S(=O)(=O)N=C=O)C=C1 VLJQDHDVZJXNQL-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 150000005840 aryl radicals Chemical group 0.000 description 1
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- LDUOHXCVIFQGBK-UHFFFAOYSA-N carbonisocyanatidic acid Chemical class OC(=O)N=C=O LDUOHXCVIFQGBK-UHFFFAOYSA-N 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 1
- WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- HTVHSOYSKFBUGY-UHFFFAOYSA-N isocyanato(methoxy)methane Chemical compound COCN=C=O HTVHSOYSKFBUGY-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 125000004401 m-toluyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C(*)=O 0.000 description 1
- IHSJXWLJYTXOCL-UHFFFAOYSA-N n,n,2-trimethylprop-1-en-1-amine Chemical compound CN(C)C=C(C)C IHSJXWLJYTXOCL-UHFFFAOYSA-N 0.000 description 1
- KKGSBWUFOPDBGS-UHFFFAOYSA-N n-butyl-n-(2-methylprop-1-enyl)butan-1-amine Chemical compound CCCCN(C=C(C)C)CCCC KKGSBWUFOPDBGS-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000005441 o-toluyl group Chemical group [H]C1=C([H])C(C(*)=O)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 125000005440 p-toluyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C(*)=O)C([H])([H])[H] 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- FSZKLYCUEQGCKW-UHFFFAOYSA-N phenyl n-(oxomethylidene)carbamate Chemical compound O=C=NC(=O)OC1=CC=CC=C1 FSZKLYCUEQGCKW-UHFFFAOYSA-N 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 239000004476 plant protection product Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/20—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D239/22—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to ring carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
Description
Verfahren zur Herstellung von Hexahydropyrimidin-2,4-Dionen Es wurde gefunden, daß man Hexahydropyrimidin-2,4-dione erhält, wenn man tertiäre Enamine, deren ß-ständiges Kohlenstoffatom durch Alkylrest substituiert ist, oder Enamine, die durch Kondensation von Hexa- oder Tetrahydrobenzaldehyd oder Tetrahydrotolylaldehyd mit sekundären Aminen erhalten worden sind, mit Isocyanaten der allgemeinen Formel RNCO, worin R einen Aroyl-, gegebenenfalls alkylierten Arylsulfonyl-, gegebenenfalls chlorierten Carbalkoxy- oder Carboaryloxyrest, den Methoxymethylrest oder einen mit elektrophilen Resten substituierten Arylrest bedeutet, - oder mit Isocyanatothioestern in einem organischen Lösungsmittel bei 10 bis 100"C im Molverhältnis 1: 2, wobei die Isocyanate in einem Uberschuß bis zu etwa 10°/o vorliegen können, umsetzt. Der Reaktionsverlauf sei am Beispiel der Umsetzung von Isobutenyl-piperidin mit Benzoylisocyanat erläutert: Als Aroylisocyanat wird vorzugsweise Benzoylisocyanat verwendet. Als elektrophile Reste der Arylgruppe (vorzugsweise Phenyl oder Naphthyl) seien genannt: Fluor-, Chlor-, Brom-, Nitro-, Carbo- methoxy-, Carboäthoxy- sowie die Trifluormethylgruppe.Process for the preparation of hexahydropyrimidine-2,4-diones It has been found that hexahydropyrimidine-2,4-diones are obtained if tertiary enamines whose ß-carbon atom is substituted by alkyl radicals, or enamines which are obtained by condensation of hexa- or tetrahydrobenzaldehyde or tetrahydrotolylaldehyde have been obtained with secondary amines, with isocyanates of the general formula RNCO, in which R is an aroyl, optionally alkylated arylsulfonyl, optionally chlorinated carbalkoxy or carboaryloxy radical, the methoxymethyl radical or an aryl radical substituted by electrophilic radicals, - Isocyanatothioesters in an organic solvent at 10 to 100 "C in a molar ratio of 1: 2, whereby the isocyanates can be present in an excess of up to about 10%. The course of the reaction is illustrated using the example of the reaction of isobutenyl piperidine with benzoyl isocyanate: Benzoyl isocyanate is preferably used as the aroyl isocyanate. The following electrophilic radicals of the aryl group (preferably phenyl or naphthyl) may be mentioned: fluorine, chlorine, bromine, nitro, carbomethoxy, carboethoxy and trifluoromethyl groups.
Als für das Verfahren Verwendung findende Isocyanate seien beispielsweise genannt: 2-Chlorphenyl-, 3-Chlorphenyl-, 4-Chlorphenyl-, 2-Bromphenyl-, 4-Fluorphenyl-, 2-Nitrophenyl-, 3 - Nitrophenyl-, 4Nitrophenyl-, 3,4-Dichlorphenyl-, 3,4,6-Trichlorphenyl-, Pentachlorphenyl-, 4-Chlor-3-(trifluormethyl)-phenyl-, a- oder fl-Naphthoyl-, l-Chlor-2-naphthyl-, o-, m- oder p-Toluoyl-, Benzolsulfonyl- oder o- oder p-Toluolsulfonylisocyanat sowie die gemäß einem eigenen älteren Vorschlag erhältlichen Isocyanato-ameisensäureester bzw. Thioester, z. B. Carbäthoxy-, Carbo-,B-chloräthoxy-, Carbophenoxy-, Carbo-thiophenoxy- oder Carbo-o-chlorphenoxyisocyanat. Das hier nicht beanspruchte Verfahren zur Herstellung dieser Isocyanatoameisensäureester sei am Beispiel des Carbäthoxyisocyanats erläutert: In eine Mischung aus 160g Oxalylchlorid und 250ml trockenem o-Dichlorbenzol trägt man bei 0 bis +10°C im Verlauf von einer Stunde 89 g Carbaminsäureäthylester portionsweise ein. Hierbei wird eine schwache Gasabspaltung beobachtet. Man rührt noch 1/2 Stunde bei Raumtemperatur nach und steigert dann die Temperatur innerhalb von 2 Stunden auf 60"C, wobei unter starker Gasentwicklung eine klare Lösung entsteht. Man heizt noch kurze Zeit bei 60 bis 70"C nach, bis die Gasentwicklung vollständig aufhört. Nach Beseitigung der leichtflüchtigen Bestandteile können bei einem Siedepunkt von 1140 C 89 g reines Carbäthoxyisocyanat ab destilliert werden. Isocyanates used for the process are, for example named: 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-bromophenyl, 4-fluorophenyl, 2-nitrophenyl, 3 - nitrophenyl, 4nitrophenyl, 3,4-dichlorophenyl, 3,4,6-trichlorophenyl, Pentachlorophenyl-, 4-chloro-3- (trifluoromethyl) -phenyl-, a- or fl-naphthoyl-, l-chloro-2-naphthyl-, o-, m- or p-toluoyl, benzenesulfonyl or o- or p-toluenesulfonyl isocyanate and the isocyanato-formic acid esters available according to an older proposal of our own or thioesters, e.g. B. Carbethoxy, Carbo, B-chloroethoxy, Carbophenoxy, Carbo-thiophenoxy or carbo-o-chlorophenoxy isocyanate. The manufacturing method not claimed here this isocyanatoformic acid ester is explained using the example of carbethoxy isocyanate: In a mixture of 160g oxalyl chloride and 250ml dry o-dichlorobenzene carries 89 g of ethyl carbamate are added in portions at 0 to + 10 ° C. in the course of one hour a. A slight elimination of gas is observed here. The mixture is stirred for another 1/2 hour at room temperature and then increases the temperature within 2 hours to 60 "C, with vigorous evolution of gas forming a clear solution. The heating is carried out a short time at 60 to 70 "C until the evolution of gas completely ceases. After removing the volatile constituents, a boiling point of 1140 C 89 g of pure carbethoxy isocyanate are distilled off.
Die sonstigen Verbindungen dieses Typs können in analoger Weise erhalten werden. The other compounds of this type can be obtained in an analogous manner will.
Für das Verfahren vorzugsweise in Betracht kommende Enamine sind beispielsweise : Isobutenylmorpholin, Isobutenyl-piperidin, Isobutenyl-pyrrolidin, Isobutenyl-N-methylpiperazin, Isobutenyl-dimethylamin, Isobutenyl-di-n-butylamin. Enamines which are preferred for the process are for example: isobutenylmorpholine, Isobutenyl piperidine, isobutenyl pyrrolidine, Isobutenyl-N-methylpiperazine, isobutenyl-dimethylamine, isobutenyl-di-n-butylamine.
Weiterhin können Enamine verwendet werden, die aus Hexa- oder Tetrahydrobenzaldehyd oder Tetrahydrotolylaldehyd mit vorzugsweise nachstehenden sekundären Aminen hergestellt worden sind: Dimethylamin, Di-n-propylamin, Di-isopropylamin, Din-butylamin, Di-isobutylamin, Piperidin, Morpholin, Pyrrolidin, Hexamethylenimin, N-Methyl-piperazin. It is also possible to use enamines derived from hexa- or tetrahydrobenzaldehyde or tetrahydrotolylaldehyde with preferably the following secondary amines have been: dimethylamine, di-n-propylamine, di-isopropylamine, din-butylamine, di-isobutylamine, Piperidine, morpholine, pyrrolidine, hexamethyleneimine, N-methyl-piperazine.
Im allgemeinen führt man die Reaktion so durch, daß man in eine Lösung des Enamins in einem organischen Lösungsmittel bei Temperaturen zwlschen etwa +10 und etwa +100°C, vorzugsweise zwischen +20 und +80°C, die oben angegebene Menge des Isocyanats eintropft. - Mitunter kann es zweckmäßig sein, in Lösung zunächst das 1:1-Addukt von Enamin und Isocyanat herzustellen und dieses dann mit einem weiteren Mol bzw. einem geringen Uberschuß desselben oder eines anderen Isocyanats zum Hexahydropyrimidin-2,4-dion umzusetzen. Man kann somit auch Hexahydropyrimidin-2,4-dione herstellen, die in 1- und 3-Stellung verschiedene Substituenten tragen. Als organische Lösungsmittel können Kohlenwasserstoffe, wie Hexan, Cyclohexan, Benzol, Toluol oder Xylol, Ketone, wie Aceton, Methyläthylketon oder Cyclohexanon, chlorierte Kohlenwasserstoffe, wie Chloroform, Tetrachlorkohlenstoff oder Chlorbenzol, sowie Acetonitril, Dimethylformamid oder Pyridin verwendet werden. In general, the reaction is carried out in such a way that one is in a solution of the enamine in an organic solvent at temperatures between about +10 and about + 100 ° C, preferably between +20 and + 80 ° C, the amount indicated above of the isocyanate is added dropwise. - Sometimes it can be useful in solution initially the 1: 1 adduct of enamine and isocyanate to produce and then this with another Mol or a slight excess of the same or of another isocyanate to the hexahydropyrimidine-2,4-dione to implement. One can thus also produce hexahydropyrimidine-2,4-diones, which in 1- and 3-position carry different substituents. As an organic solvent can hydrocarbons such as hexane, cyclohexane, benzene, toluene or xylene, ketones, such as acetone, methyl ethyl ketone or cyclohexanone, chlorinated hydrocarbons, such as Chloroform, carbon tetrachloride or chlorobenzene, as well as acetonitrile, dimethylformamide or pyridine can be used.
Die neuen Verbindungen sind Zwischenprodukte zur Herstellung von Pharmazeutika und Pflanzenschutzmitteln. The new compounds are intermediates for the production of Pharmaceuticals and plant protection products.
Beispiel 1 In eine Lösung von 14,1 g Isobutenyl-piperidin in 25 ccm Acetonitril läßt man unter Rühren 29,4 g Benzoylisocyanat, gelöst in 25 ccm Acetonitril, eintropfen. Durch Kühlen hält man die Temperatur zwischen 30 und 35"C. Man rührt 30 Minuten nach und saugt die beim Erkalten ausgefallenen Kristalle ab. Man erhält 38 g einer Verbindung der Formel Nach Umlösen aus Benzol: F. 164"C.EXAMPLE 1 29.4 g of benzoyl isocyanate, dissolved in 25 cc of acetonitrile, are added dropwise with stirring to a solution of 14.1 g of isobutenylpiperidine in 25 cc of acetonitrile. The temperature is maintained between 30 and 35 ° C. by cooling. The mixture is subsequently stirred for 30 minutes and the crystals which have precipitated out on cooling are filtered off with suction. 38 g of a compound of the formula are obtained After dissolving from benzene: F. 164 "C.
Analyse: C25H27N304 (433,5).Analysis: C25H27N304 (433.5).
Berechnet... C69,2, H6,3, N9,70/o; gefunden . . C 69,09, H 6,21, N 9,790/o; Beispiel 2 Wie unter Beispiel 1 beschrieben, werden 28,2 g Isobutenyl-morpholin und 58,8 g Benzoylisocyanat umgesetzt. Nach dem Erkalten wird der kristalline Niederschlag abgesaugt. Man erhält 74 g einer Verbindung der Formel Nach Umlösen aus Benzol: F. 186 bis 187"C.Calculated ... C69.2, H6.3, N9.70 / o; found . . C 69.09, H 6.21, N 9.790 / o; Example 2 As described in Example 1, 28.2 g of isobutenyl morpholine and 58.8 g of benzoyl isocyanate are reacted. After cooling, the crystalline precipitate is filtered off with suction. 74 g of a compound of the formula are obtained After dissolving from benzene: F. 186 to 187 "C.
Analyse: C24H2sN3Os (435,4).Analysis: C24H2sN3Os (435.4).
Berechnet ... C 66,2, H 5,8, N9,650/o; gefunden . . C66,62, H6,16, N9,93°/o. Calculated ... C 66.2, H 5.8, N 9.650 / o; found . . C66.62, H6.16, N9.93%.
Beispiel 3 Wie unter Beispiel 1 beschrieben, werden 12,5 g Isobutenyl-pyrrolidin und 29,4 g Benzoylisocyanat umgesetzt. Beim Erkalten erstarrt der Kolbeninhalt. Example 3 As described under Example 1, 12.5 g of isobutenylpyrrolidine are used and 29.4 g of benzoyl isocyanate reacted. The contents of the flask solidify on cooling.
Man digeriert mit Methanol und saugt ab. Man erhält 28 g einer Verbindung der Formel Nach Umlösen aus Benwl-Leichtbennn: F. 145 bis 146"C.It is digested with methanol and filtered off with suction. 28 g of a compound of the formula are obtained After dissolving from Benwl-Leichtbennn: F. 145 to 146 "C.
Analyse: C2aH25N304 (419,4).Analysis: C2aH25N304 (419.4).
Berechnet ... C68,7, H6,0, N 10,00/0; gefunden ... C 68,18, H 6,0, N 10,350/0. Calculated ... C68.7, H6.0, N 10.00 / 0; found ... C 68.18, H 6.0, N 10.350 / 0.
Beispiel 4 Wie unter Beispiel 1 beschrieben, werden 14,1 g Isobutenyl-piperidin und 32,6 g Carbophenoxyisocyanat umgesetzt. Man destilliert das Lösungsmittel im Vakuum ab, suspendiert den kristallinen Rückstand in Methanol und saugt ab. Man erhält 38 g einer Verbindung der Formel ausgefallene Produkt ab. Man erhält 41 g einer Verbindung der Formel Nach Umlösen aus Benzol-Leichtbenzin: F. 143 bis 144"C.Example 4 As described under Example 1, 14.1 g of isobutenylpiperidine and 32.6 g of carbophenoxy isocyanate are reacted. The solvent is distilled off in vacuo, the crystalline residue is suspended in methanol and filtered off with suction. 38 g of a compound of the formula precipitated product are obtained. 41 g of a compound of the formula are obtained After dissolving from benzene-light gasoline: F. 143 to 144 "C.
Analyse: CwHz7N306 (465,3).Analysis: CwHz7N306 (465.3).
Berechnet .. C 64,5, H 5,8, N 9,00/0; gefunden ... C64,51, H5,84, N9,170/o. Calculated .. C 64.5, H 5.8, N 9.00 / 0; found ... C64.51, H5.84, N9,170 / o.
Beispiel. 5 Wie unter Beispiel 1 beschrieben, werden 14,1 g Isobutenylpiperidin und 23,0 g Carbäthoxyisocyanat umgesetzt. Anschließend destilliert man das Lösungsmittel im Vakuum ab und löst den öligen Rückstand in Petroläther. Nach Zugabe von Aktiv-Kohle filtriert man und destilliert das Lösungsmittel im Vakuum ab. Man erhält 31 g eines gelblichen Ols der Formel Analyse: C17H27N306 (369,4).Example. 5 As described in Example 1, 14.1 g of isobutenylpiperidine and 23.0 g of carbethoxy isocyanate are reacted. The solvent is then distilled off in vacuo and the oily residue is dissolved in petroleum ether. After the addition of activated charcoal, the mixture is filtered and the solvent is distilled off in vacuo. 31 g of a yellowish oil of the formula are obtained Analysis: C17H27N306 (369.4).
Berechnet ... C 55,3, H 7,4, N 11,40/0; gefunden . . C 54,41, H 7,20, N 12,230/o. Calculated ... C 55.3, H 7.4, N 11.40 / 0; found . . C 54.41, H 7.20, N 12.230 / o.
Beispiel 6 12,5 g Isobutenyl-pyrrolidin werden zusammen mit 30,8 g 4-Chlorphenylisocyanat in 50 ccm Acetonitril vereinigt. Dabei steigt die Temperatur auf 50"C an. Example 6 12.5 g of isobutenylpyrrolidine, together with 30.8 g of 4-chlorophenyl isocyanate combined in 50 cc of acetonitrile. The temperature rises to 50 "C.
Man erhitzt 1/2 Stunde zum Sieden und saugt das Nach Umlösen aus Dimethylformamid: F. 234 bis 236"C.It is heated to the boil for 1/2 hour and sucks it off After redissolving from dimethylformamide: m.p. 234 to 236 "C.
Analyse: C22H2sCl2N302 (432).Analysis: C22H2sCl2N302 (432).
Berechnet ... C 61,5, H 5,33, N 9,75, Cl 16,40/o; gefunden ... C 61,2, H 5,5, N 9,9, C116,30/o. Calculated ... C 61.5, H 5.33, N 9.75, Cl 16.40 / o; found ... C 61.2, H 5.5, N 9.9, C 116.30 / o.
Beispiel 7 12,5 g Isobutenyl-pyrrolidin werden mit 38,0 g 3,4-Dichlorphenylisocyanat in 50 ccm Acetonitril gegeben. Dabei steigt die Temperatur auf 70"C an. Example 7 12.5 g of isobutenylpyrrolidine are mixed with 38.0 g of 3,4-dichlorophenyl isocyanate given in 50 cc of acetonitrile. The temperature rises to 70.degree. C. during this process.
Man erhitzt 1/2 Stunde zum Sieden und destilliert dann das Lösungsmittel ab. Der Rückstand wird aus Methanol umgelöst. Man erhält 25 g einer Verbindung der Formel F. 168 bis 171"C.The mixture is heated to boiling for 1/2 hour and then the solvent is distilled off. The residue is redissolved from methanol. 25 g of a compound of the formula are obtained F. 168 to 171 "C.
Analyse: C22H2lCl4N302 (501).Analysis: C22H2lCl4N302 (501).
Berechnet ... C 52,7, H 4,2, N 8,40/0; -gefunden ... C 52,9; H 4,3, N 8,60/0. Calculated ... C 52.7, H 4.2, N 8.40 / 0; - found ... C, 52.9; H 4.3, N 8.60 / 0.
Beispiel 8 13,9 g Isobutenyl-piperidin werden zusammen mit 15,4 g 4-Chlorphenylisocyanat in 50 ccm Acetonitril gelöst. Die Temperatur steigt auf 40"C an. Man rührt 10 Minuten nach und gibt dann weitere 15,4 g 4-Chlorphenylisocyanat hinzu. Anschließend wird 1 Stunde zum Sieden erhitzt. Beim Abkühlen kristallisieren 30 g einer Verbindung der Formel F. 204 bis 206"C.Example 8 13.9 g of isobutenylpiperidine are dissolved together with 15.4 g of 4-chlorophenyl isocyanate in 50 cc of acetonitrile. The temperature rises to 40 ° C. The mixture is stirred for 10 minutes and then a further 15.4 g of 4-chlorophenyl isocyanate are added. The mixture is then heated to the boil for 1 hour. On cooling, 30 g of a compound of the formula crystallize F. 204 to 206 "C.
Analyse: C23H2sN3Cl202 (446).Analysis: C23H2sN3Cl202 (446).
Berechnet... C61,5, H5,62, N9,40/o; gefunden ... C61,7, H5,7, N9,40/0. Calculated ... C61.5, H5.62, N9.40 / o; found ... C61.7, H5.7, N9.40 / 0.
Beispiel 9 6,25 g Isobutenyl-pyrrolidin werden zusammen mit 29,1 g Pentachlorphenylisocyanat in 100 ccm Chloroform gelöst. Dabei steigt die Temperatur auf 40°C an. Man rührt 1/2 Stunde bei dieser Temperatur nach und versetzt dann mit 100 ccm Acetonitril. Dabei scheiden sich 18 g einer farblosen Verbindung der Formel ab. F. 213 bis 215"C.Example 9 6.25 g of isobutenylpyrrolidine are dissolved together with 29.1 g of pentachlorophenyl isocyanate in 100 cc of chloroform. The temperature rises to 40 ° C. The mixture is stirred for 1/2 hour at this temperature and then treated with 100 cc of acetonitrile. This separates 18 g of a colorless compound of the formula away. F. 213 to 215 "C.
Analyse: C22H25Cl10NO2 (708).Analysis: C22H25Cl10NO2 (708).
Berechnet ... C 37,3, H 2,1, N 5,940/0; gefunden ... C 36,7, H 2,3, N 6,10/0. Calculated ... C 37.3, H 2.1, N 5.940 / 0; found ... C 36.7, H 2.3, N 6.10 / 0.
Beispiel 10 12,5 g Isobutenyl-pyrrolidin werden zusammen mit 17,4 g Methoxymethylisocyanat in 50 ccm Acetonitril gelöst. Die Temperatur steigt'auf 32"C an. Example 10 12.5 g of isobutenylpyrrolidine are used together with 17.4 g of methoxymethyl isocyanate dissolved in 50 cc of acetonitrile. The temperature rises 32 "C at.
Anschließend erhitzt man 3 Stunden ziim Sieden und destilliert dann alle flüchtigen Bestandteile im Va- kuum ab. Man erhält 28 g eines gelblichen Ols der Formel Analyse des Rohprodukts: Cl3H2404N3 (286).The mixture is then heated to the boil for 3 hours and then all volatile constituents are distilled off in vacuo. 28 g of a yellowish oil of the formula are obtained Analysis of the crude product: Cl3H2404N3 (286).
Berechnet ... C 54,5, H 8,4, N 14,7°/o; gefunden ... C 53,4, H 8,0, N 16,20/o. Calculated ... C 54.5, H 8.4, N 14.7 ° / o; found ... C 53.4, H 8.0, N 16.20 / o.
Beispiel 11 12,5 g Isobutenyl-pyrrolidin werden zusammen mit 15,3 g 4-Chlorphenylisocyanat in 50 ccm Acetonitril vereinigt. Dabei steigt die Temperatur auf 50"C an. Example 11 12.5 g of isobutenyl-pyrrolidine are used together with 15.3 g of 4-chlorophenyl isocyanate combined in 50 cc of acetonitrile. The temperature rises to 50 "C.
Nach dem Abklingen der Umsetzung fügt man 14,7 g Benzoylisocyanat hinzu und rührt 1/2 Stunde bei 50"C nach. Dann filtriert man von wenig Ungelöstem und destilliert das Lösungsmittel ab. Der Rückstand wird mit Methanol verrieben und dann aus Äthanol umkristallisiert. Man erhält 17 g einer Verbindung der Formel F. 163 bis 167"C.After the reaction has subsided, 14.7 g of benzoyl isocyanate are added and the mixture is stirred at 50 ° C. for 1/2 hour. A little undissolved material is then filtered off and the solvent is distilled off. The residue is triturated with methanol and then recrystallized from ethanol receives 17 g of a compound of the formula F. 163 to 167 "C.
Analyse: C23H27C1N305 (425,5).Analysis: C23H27C1N305 (425.5).
Berechnet . . . C 65,0, H 5,65, N 9,850/0; gefunden . . C 65,7, H 5,7, N 10,2°/o. Calculated . . . C 65.0, H 5.65, N 9.850 / 0; found . . C 65.7, H 5.7, N 10.2%.
Beispiel 12 14,1 g Isobutenyl-morpholin und 23,0 g Carbäthoxyisocyanat werden gemäß Beispiel 1 umgesetzt. Example 12 14.1 g of isobutenyl morpholine and 23.0 g of carbethoxy isocyanate are implemented according to Example 1.
Anschließend destilliert man das Lösungsmittel im Vakuum ab und löst den harzigen Rückstand in 50 ccm Benzol. Nach Zugabe von 50ccm Leichtbenzin filtriert man wenig Ungelöstes ab und versetzt die Lösung mit weiteren 150 ccm Leichtbenzin.The solvent is then distilled off in vacuo and dissolved the resinous residue in 50 cc benzene. After adding 50ccm light petrol, it is filtered a little undissolved material is removed and the solution is mixed with a further 150 cc of light petrol.
Nach mehrstündigem Stehen erstarrt das sich primär abscheidende Ol zu einem kristallinen Produkt, das abgesaugt und mit Leichtbenzin gewaschen wird. Man erhält 23 g der Verbindung der Formel F. 84 bis 85"C.After standing for several hours, the primary oil that separates out solidifies to a crystalline product, which is filtered off with suction and washed with light gasoline. 23 g of the compound of the formula are obtained F. 84 to 85 "C.
Analyse: C16H25N307 (371,4).Analysis: C16H25N307 (371.4).
Berechnet ... C 51,8, H 6,8, N 11,30/o; gefunden ... C 52,17, H 6,89, N 11,48°/o. Calculated ... C 51.8, H 6.8, N 11.30 / o; found ... C 52.17, H 6.89, N 11.48%.
Beispiel 13 In eine Lösung von 6,3 g Isobutenyl-pyrrolidin in 25 ccm Benzol läßt man unter Rühren 8,2 g 4-Nitrophenylisocyanat, gelöst in 20 ccm Benzol, eintropfen. Example 13 In a solution of 6.3 g of isobutenylpyrrolidine in 25 ccm of benzene is left with stirring 8.2 g of 4-nitrophenyl isocyanate, dissolved in 20 ccm Benzene, drop in.
Dabei steigt die Temperatur auf 38"C an. Man rührt 15 Minuten bei
dieser Temperatur, gibt weitere 8,2 g 4-Nitrophenylisocyanat, gelöst in 20 ccm Benzol,
hinzu und erhitzt 11/2 Stunden zum Sieden. Anschließend filtriert man wenig Ungelöstes
ab, destilliert das Lösungsmittel im Vakuum ab, suspendiert den kristallinen Rückstand
in Methanol und saugt ab, Man erhält 13 g der Verbindung der Formel
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEF45312A DE1248056B (en) | 1965-02-20 | 1965-02-20 | Process for the preparation of hexahydropyrimidine-2,4-diones |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEF45312A DE1248056B (en) | 1965-02-20 | 1965-02-20 | Process for the preparation of hexahydropyrimidine-2,4-diones |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1248056B true DE1248056B (en) | 1967-08-24 |
Family
ID=7100438
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEF45312A Pending DE1248056B (en) | 1965-02-20 | 1965-02-20 | Process for the preparation of hexahydropyrimidine-2,4-diones |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1248056B (en) |
-
1965
- 1965-02-20 DE DEF45312A patent/DE1248056B/en active Pending
Non-Patent Citations (1)
| Title |
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| None * |
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