G. Zigeuner

Über Tetrahydro-6-methyl- bzw. 6-phenyl-2-oxopyrimidin-5-carbonsäuren und ihre Derivate Über Heterocyclen, 48 Mitt

Tetrahydro-6-methyl- and-6-phenyl-2-oxopyrimidine-5-carboxylic acids5, 8 resp are obtained on hydrogenolysis of the corresponding benzyl esters4, 7; 1-methyl compounds (5, 8) are also formed by hydrolysis of the ethyl and benzyl esters (3, 4, 6, 7) in alcoholic KOH. Benzyl esters4 which are unsubstituted at position1 are converted by alcoholic KOH into ethyl esters3. Phenols convert3, 4, 5, depending on the substituent in position 1, into 6-hydroxyphenyltetrahydro-2(1H)-pyrimidinones (10) or di(tri)phenylalkanes11, 12. Bromination of the pyrimidine-carboxylic acids5 or of the tert butyl esters18 leads to the 6-bromomethyl- and dibromomethyl derivatives15, 16, which are easily transformed into furo-[3,4-d]pyrimidines17. Thermal decarboxylation of carboxylic acids5 c, f, g lead to dihydro-2(1H)-pyrimidinones13 a, c, d.

Über Heterocyclen, 12. Mitt.: Zur Bromierung der 2-Oxo-6-methyltetrahydropynimidine

Die Bromierung von 2-Oxo-6-methyl- bzw. 2-Oxo-5-carbathoxy-6-methyltetrahydropyrimidinen verlauft unter Substitution an der CH3-Gruppe am C-6. 2-Oxo-5-carbathoxy-6-brommethyl-bzw.-dibrommethyltetrahydropyrimidine konnen in 2-Oxo-6-hydroxymethyl-tetrahydropyrimidin-5-carbonsaurelactone umgewandelt werden. Im Gegensatz zu Brom reagiert Chlor mit 2-Oxo-5-carbathoxy-6-methyltetrahydropyrimidinen unter Addition.

Über 4-Alkylamino-bzw. 4-Arylamino-5,6-dihydro-2(1H)-pyridinthione

Heating 1-alkyl- or 1-aryldihydro-6-methyl-2(1H)-pyrimidinethiones5, 6 in an inert medium causes rearrangement to 4-alkylamino-(4-arylamino-)-5,6-dihydro-2(1H)-pyridinethiones11, 12, probably via the methylene form29, by thermal heterolysis of the N1/C2 bond and exchange of the alkylamino (arylamino) group 1 through the carbon atom of the methylene group 6. The aminodihydropyridinethiones11, which can be regarded as cyclic derivatives of 3-aminothiocrotonamide, react with bistrichlorophenylmalonate under diacylation, and with formaldehyde and primary amines to yield aminodialkylation products of the enamine system, tetrahydro-4-hydroxy-7,7-dimethyl-5-thioxopyrido[4,3-b]pyridine-2(1H)-ones13, 14 and hexahydro-7,7-dimethylpyrido[4,3-d]pyrimidine-5(6H)-thiones18, 19, 21 respectively. H2O2 converts11 to the corresponding 4-aminodihydro-2(1H)-pyridones22, which can be reconverted into11 with P4S10.11 reacts with alkyl halides to 2-alkylthiodihydropyridines23, 24, 25. The mechanism of the methylpyrimidine-pyridine rearrangement is discussed.

Über kondensierte Heterocyclen aus β-Isothiocyanatoketonen und Aminoalkoholen bzw. Diaminen

Abstract2- and 3-aminoalcohols, o-aminobenzylalcohol, o-hydroxybenzylamine and o-amino(thio)-phenol react with 4-isothiocyanato-4-methyl-2-pentanone (1) to yield derivatives of condensed heterocycles (oxazolopyrimidines7, pyrimidooxazine8, pyrimidobenzoxazines9, 10, pyrimidobenzoxazole11 a and pyrimidobenzothiazole11 c respectively). Ethylenediamine or 1,3-diaminopropane react with1 to yield either imidazo-pyrimidine13 and pyrimidopyrimidine14 respectively or the 1,2-ethylene- and trimethylenebisdihydro-2(1H)-pyrimidinethione15 a, b respectively, according to the molar ratio of the reactants. o-Phenylenediamine gives pyrimidobenzimidazole11 d. 11a undergoes ring cleavage in boiling dimethylformamide followed by methylpyrimidine-pyridine rearrangement to dihydrohydroxyphenylamino-2(1H)-pyridinethione12, while15 a is converted into the bis-4-(ethanediimino)-pyridinthione16.

Über das 4-Hydroxy-6,6-dimethyl-5,6-dihydro-2(1H)-pyridinthion bzw.-on und die entsprechenden Tautomeren

The tautomers, 4-hydroxy-5,6-dihydro-6,6-dimethyl-2(1H)-pyridinethione (1) and 6,6-dimethyl-2-thioxo-4-piperidone (2) resp., and 4-hydroxy-5,6-dihydro-6,6-dimethyl-2(1H)-pyridone (9) and 6,6-dimethyl-2,4-piperidinedione (10) resp. were synthesized by hydrolysis of 4-amino-5,6-dihydro-6,6-dimethyl-2(1H)-pyridinethiones (4, 5) and-ones (11, 12).1, 2 and9, 10 undergo an aminolysis in amines to the corresponding 4-aminodihydro-2(1H)-pyridinethiones4, 5 and-ones11, 12 resp.

Kondensierte Heterocyclen aus β-Isothiocyanatoketonen und Aminocarbonsäuren

On reaction of glycine, anthranilic acid and anthranilamide respectively with 4-isothiocyanato-4-methyl-2-pentanone (1), derivatives of condensed heterocycles (oxazolopyrimidine5, pyrimidobenzoxazine7 a, pyrimidobenzodiazine7 c) are formed. The same holds for the reaction of dithiocarbamates, prepared from glycine and CS2 in aqueous NaOH, with 4-methyl-3-penten-2-one and cinnamaldehyde respectively (12 a, b). The reaction of hot dimethylformamide with7 a leads under initial aminolysis to pyrimidine-anthranildimethylamide2 i; this is subsequently transformed partly through methylpyrimidine-pyridine rearrangement into the N-4′-pyridine-anthranil-N,N-dimethylamide10 d, partly under further aminolysis byDMF followed by rearrangement to the dimethylaminodihydro-2(1H)-pyridinethione10 c. 5 is converted to dihydro-4-methylamino-2(1H)-pyridinethione (10 a) in boiling hexanol and2 c to n-hexyl-3-(tetrahydrothioxo-pyridylamino)-propionate (10 b).

Zur Synthese der 4-Dialkylamino-5,6-dihydro-2(1H)-pyridinthione sowie entsprechender 4-Alkylamino- bzw. 4-Arylaminoverbindungen

The rearrangement of 1-alkyl- and 1-aryldihydro-6-methyl-2(1H)-pyrimidinethiones (1 a) or-ones (1 b) and of methylene compounds (2a, 2b) resp., to 4-alkylamino- and 4-arylaminodihydro-2(1H)-pyridinethiones (4 a) or-ones (4 b) takes place via the corresponding 3-alkylamino- and 3-aryl-amino-3-butenylisothiocyanates (3 a) or-isocyanates (3 b). Dialkylamino-dihydro-2(1H)-pyridinethiones (10) are formed by heating dihydro-6-methyl-2(1H)-pyrimidinethiones (6 a) and 3,4-dihydro-6-methyl-1,3-thiazin-2-thiones (6 b) with dialkylformamides and by the reaction of secondary amines with tetrahydro-6-hydroxy-6-methyl-1,3-thiazin-2-thiones (5 a), with N,N-dialkyl-N′-(3-oxobutyl)-thioureas (7) and 3-oxobutyl isothiocyanates (8). A general method for the preparation of10 is the reaction of dialkylammoniumrhodanides12, N,N-dialkylthioureas13 and dialkylammonium chlorides and KCNS, resp., with 3-alken-2-ones14 and 4-hydroxy-2-alkanones15, resp. Methyl ketones such as acetone, which readily undergo the aldol condensation, behave analogously. The reactions described take place via the intermediate aminoalkenyl isothiocyanates (9).

Über Dihydro-6-methyl- bzw.-6-styryl-4-phenyl-2(1H)-pyrimidinone (-thione) sowie Hexahydro-5-benzoyl- bzw.-cinnamoyl-4,7-diphenyl-2(1H)-chinazolinone (-thione)

ZusammenfassungDihydro-6-methyl-4-phenyl-2 (1H)-pyrimidinone (-thione) (1) reagieren als α-Methylalkenylharnstoffe bzw.-thioharnstoffe mit Säuren zu Hexahydro-4,4′-methylendi-2(1H)-pyrimidinonen (-thionen) (3), mit Phenolen zu Tetrahydro-6-hydroxyphenyl-2(1H)-pyrimidinonen (-thionen) (2), mit Benzaldehyd zu 6-Styrylverbindungen (1 d, e, g) und mit α,β-ungesättigten Ketonen zu Tetrahydro-2(1H)-chinazolinonen (7). Aus 1,5-Diphenyl-1,4-pentadien-3-on und Harnstoffen, Thioharnstoffen bzw. Ammonrhodanid entstehen Diphenyl-1,3,7,9-tetraazaspiro-5,5-undecan-2,8-dione (9) bzw. Hexahydrotriphenyl-6-cinnamoyl-2(1H)-chinazolinthione (10). Hexahydro-6-benzoyl-bzw.-6-cinnamoyl-2(1H)-chinazolinone (-thione) (10) bilden sich allgemein bei Einwirkung von α,β-ungesättigten Ketonen auf Dihydro-4-phenyl-6-styryl-2(1H)-pyrimidinone (-thione) (1 d, e, g).AbstractDihydro-6-methyl-4-phenyl-2(1H)-pyrimidinones (-thiones) (1) react as α-methylalkenylureas (-thioureas) with acids to hexahydro-4.4′-methylenedi-2(1H)-pyrimidinones (-thiones) (3), with phenols to tetrahydro-6-hydroxyphenyl-2(1H)-pyrimidinones (-thiones) (2), with benzaldehyde to 6-styryl compounds (1 d, e, g) and with α,β-unsaturated ketones to tetrahydro-2(1H)-quinazolinones (7).On reacting 1.5-diphenyl-1.4-pentadien-3-one with ureas, thioureas or ammonium thiocyanate, the products formed are diphenyl-1.3.7.9-tetraazaspiro-5.5-undecane-2.8-diones (9) and hexahydrotriphenyl-6-cinnamoyl-2(1H)-quinazolinethiones (10), resp. Hexahydro-6-benzoyl- (or-6-cinnamoyl-)-2(1H)-quinazolinones (-thiones) (10) are formed generally by the action of α,β-unsaturated ketones on dihydro-4-phenyl-6-styryl-2(1H)-pyrimidinones (-thiones) (1 d, e, g).

Notiz zur Struktur des Umsetzungsproduktes von 4-Isothiocyanato-4-methyl-2-pentanon mit Hydrazin —Über das 2,4,5,6-Tetrahydro-5,5,7-trimethyl-3H-1,2,4-triazepin-3-thion

On reaction of 4-isothiocyanato-4-methyl-2-pentanone (1) with hydrazine 2,4,5,6-tetrahydro-5,5,7-trimethyl-3H-1,2,4-triazepine-3-thione (4 a) is formed not 1-aminodihydro-2(1H)-pyrimidinethione (3 a) [1-aminodihydro-2-pyrimidinethiol (2 a)].

Über Dihydro-2(1H)-pyrimidinthione

Zusammenfassung6-Alkyl-3,4-dihydro-2(1H)-pyrimidinthione sind als cyclische Alkenylthioharnstoffe der Addition von Phenolen zu 6-Hydroxyphenyltetrahydro-2(1H)-pyrimidinthionen bzw. derMannich-reaktion zu 6-Dialkylaminoäthylidentetrahydro-bzw. 6-Dialkylaminoäthyldihydro-2(1H)-pyrimidinthionen sowie zu Hexahydro-2(1H)-pyrido[4,3—d]pyrimidinthionen zugänglich. 6-Methylderivate können auch in Dihydro-6-styryl-2(1H)-pyrimidinthione bzw., in einem Fall, in ein Hexahydro-4,4-methylendi-2(1H)-pyrimidinthion umgewandelt werden.Abstract6-Alkyl-3,4-dihydro-2(1H)-pyrimidinethiones (cyclic alkenylthio carbamides) add phenoles to give 6-hydroxyphenyltetrahydro-2(1H)-pyrimidinethiones and undergoMannich reaction, to give 6-dialkylaminoethylidentetrahydro-and 6-dialkylaminoethyldihydro-2(1H)-pyrimidinethiones and hexahydro-2(1H)-pyrido[4,3—d]pyrimidinethiones, resp. 6-Methyl derivatives can also be transformed into dihydro-6-styryl-2(1H)-pyrimidinethiones resp., in one case, into a hexahydro-4,4-methylendi-2(1H)-pyrimidinethione.