Hexahydropyrimidine-2-ones

Hexafluoroacetylacetone reacts with urea and thiourea to yield 4,6-bis(hydroxy)-4,6-bis(trifluoromethyl)hexahydropyrimidine-2-one and -2-thione (01ZOR915, 00JFC(103)17), respectively (Scheme 54). The dehydration of the products and also the reaction of unsymmetric fluoroalkylcontaining 1,3-diketones with urea and thiourea afford substituted pyrimidines. 

Putilova ES, Troitskii NA, Zlotin SG, Khudina OG, Burgart YV, Saloutin VI, Chupakhin ON (2006) One-step solvent-free synthesis of fluoroalkyl-substituted 4-hydroxy-2-oxo(thioxo) hexahydropyrimidines in the presence of l-butyl-3-methylimidazolium tetrafluoroborate. Russ J Org Chem 42 1392-1395... 

Cyclobutane-fused hexahydropyrimidine-2,4-dione 569 was converted to the corresponding l,3-oxazin-2-one derivative 571 in a two-step procedure (Scheme 109). Compound 569 was reduced with NaBH4 to give ureidoalco-hol 570 in excellent yield, the diazotization of which provided the cyclic carbamate derivative 571 <2006TL5981>. 

Emphasis is placed on simply substituted free bases. The problems of conformational equilibria in /V-alkylpiperidinium salts and N-quaternization reactions and the relationships of these to conformational equilibria in the free bases are not covered, since this area is a large one requiring separate treatment. In other relevant previous reviews, the topics include heterocyclic conformational analysis,3-7 interactions in azacyclic systems,8 the conformational analysis of piperidine,9 hexahydropyrimidines,10,11 hexahydropyri-dazines,12 quinolizidines,13 the conformational analysis of bi- and polycyclic... 

Luknitskii et nl.2i5 reported preparation of the hexahydropyrimidin-4-one-2-thione 110 hy fusion of thiourea with 4-trichloromethyl-2-oxetanone (111) at 110-130°. Performing the reaction in ethanolic triethylamine gave an oxazine product instead. With selenopseudoureas, 111 gives 1,3-selenazines.246... 

Wamhoff and Huang obtained alkyl 2,3,4,9-tetrahydro-6-oxo-67/-pyrido[l,2-a]pyrimidine-9-carboxylates 237 in the reaction of 3-(hexahy-dropyrimidin-2-ylidene)-2(3.//)-furanones 235 (R3 = H) and methyl propi-olate in a refluxing alcohol in excellent yields (Scheme 17) (84CB1856). When the reactions were carried out in benzene or dioxane, addition products 236 could be isolated, which then were transformed in quantitative yields to tetrahydro-6-oxo-6//-pyrido[ 1,2-a ]pyrimidine-9-carboxyl-ates 237 by stirring in an alcohol at ambient or elevated temperature. When 3-(hexahydropyrimidin-2-ylidene)-2(3//)-furanones 235 (R3 = Me) were reacted with methyl acrylate or with dimethyl acetylenedicarboxy-late, hexahydro- and tetrahydropyridopyrimidin-6-ones 238 and 239, respectively, were obtained in good yields (84CB1926). 

Cyclic ketene acetals can also react with amines to give 1,1-enediamines with elimination of ethylene glycol76. Treatment of 2-[(methoxycarbonyl)cyanomethylene]-1,3-dioxolane (38) with 1,3-diaminopropane or with 4,5-dimethyl-1,2-phenylenediamine gives the hexahydropyrimidine and the benzimidazoline derivatives 39 and 40, respectively (equation 11). Similarly to the reaction of ketene dithioacetals with amines, the reaction between ketene acetals and amines proceeds via monoamino-substituted intermediates and ketene 7V,Oacetals can be isolated when one molar amine is used72. 

Agricultural pesticides were found to be effective insect resist agents when applied in emulsion form to wool dyebaths. Dieldrin (Fig. 16.2a), one of the original nerve poisons, is also highly toxic to mammals and aquatic life and its use has been banned in most countries. Products based on permethrin (Fig. 16.2b), a synthetic pyrethroid, are very effective against moth larvae, but have less effect on Anthrenus beetles. To overcome this disadvantage, combination products of permethrin and hexahydropyrimidine derivatives (Fig. 16.2c) have been introduced. 

The first hypothesis of an in-situ reduction of acetonitrile and propionitrile in the presence of 1 to 4 and 5 suggested that one might be able to use this approach as a new synthetic route to this class of heterocyclics. Hexahydropyrimidines are conventionally prepared by condensation of aldehydes or ketones with 1,3-diamines (4). Water is a by-product in these reactions and must be removed either to favor the imine or enamine equilibrium or for product purification. Generally, the condensation is acid or base catalyzed and run in solvents (6). In some cases... 

Reaction of disecondary amines and carbonyl compounds affords cyclic aminals if the amino groups are in suitable positions relative to one another (1,2-, 1,3-, or 1,4-). For example, 1,3-diamines condense readily with aldehydes or ketones to give hexahydropyrimidine derivatives,966 967 and disecpndary ethylenediamine derivatives give imidazolidines.968... 

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