Thioureas, cyclocondensation with

In a standard method, 1,3-diketones are cyclocondensed with amidines, ureas, thioureas and guanidines giving 4,6-di- and 2,4,6-trisubstituted pyrimidines 4, 2-pyrimidones 5, 2-thiopyrimidones 6 and 2-aminopyrimidines 7 respectively Pinner synthesis) [140] ... 

Similarly, a-bromination of the 5-acetyl group of 231 with bromine afforded 5-(2-bromoacetyl) 232, which upon cyclocondensation with thiourea yielded 5-(2-aminothiazol-4-yl)-3,4-dihydropyrimidin-2(lH)-one/ thione 233 (Scheme 89) (09IJC(B)1732). 

N-Substituted thioamides cyclocondense with (a-halogeno) carbonyl compounds to give N-substituted thiazolium salts 21, salts (or esters) of dithiocarbamic acid yield 2-sulfanylthiazoles 22, and thiourea affords 2-aminothiazoles 23 ... 

Analogously, a-hydroxy ketones cyclocondense with amidines (to give imidazoles (36)), guanidines (to give 2-aminoimidazoles), and urea or thiourea (to give imidazole-2(3H)-ones or -thiones, respectively). Imidazoles unsubstituted at the 2-position are obtained from a-hydroxyketones and formamide (Brederek synthesis) ... 

Ethyl cyanoacetate is cyclocondensed with thiourea under base catalysis giving 4-amino-2-thiouracil 26, onto which the second amino group is introduced (— 27). Oxidative desulfurization yields a sulfinic acid, which ehminates 802( 28) condensation with orthoformic ester transforms 28 into hypoxanthin (25). 

Regioselective cyclocondensation of N-(l-chlorobenzyl) benzimidoylchlorides with thioureas yields 1,3,5-triazine-2(lJ )-thiones 4 but if the reaction is carried out in the presence of triethylamine thiadiazines 5 are obtained <95ZOB1246 96CA(124)317108>. 

Substantial MW rate enhancements have been reported in the Biginelli synthesis of dihydropyrimidines [50, 51] under homogeneous conditions. The synthesis involves a one-pot cyclocondensation of a /i-ketoester with an aryl aldehyde and urea or thiourea in the presence of a catalytic amount of HC1 in ethanol solution. An example of this synthesis is shown in Scheme 4.17. 

The cyclizations to obtain cyclic thioureas have been performed using thiocarbonyldiimidazole.232 Reaction of methyl acetoacetate, thiourea and an aliphatic aldehyde in the presence of the zinc iodide (Znl2) was studied. Under the normal pressure, reaction has not been occurred whereas at high pressure (300 MPa) conditions 3,4-dihydropyrimidine-2-thione was obtained only in 10% yield.233 The same one-pot three-component cyclocondensation reaction in the presence of iodide (I2) provides a variety of 3,4-dihydropyrimi-dine-2-thione in high yields.234 Condensation reaction of thioureas with a,p-unsaturated ketones in the presence of the sodium methoxide in methanol affords 3,4-dihydropyrimidine-2-thione derivatives.235,236 Acylation of N,N -disubstituted thioureas with methyl malonyl chloride followed by base-catalysed cyclization leads in the formation of l,3-disubstituted-2-thiobarbituric acids (Scheme 78).237... 

A series of 4-heteroaryl-5,6-di(2,5-dimethyl-3-thienyl)-2-phenyM//-l,6-thiazines 54 with photochromic properties was prepared by reacting 3-(2-(2,5-dimethylthiophen-3-yl)ethynyl)-2,5-di ethylthiophene with thiobenzamide and aldehydes <2005CHE86, 2005PS1503>. The acid-catalyzed cyclocondensation of cyclopentanone, aromatic aldehydes, ArCHO, and thiourea affords the cyclopenta[t ]l,3-thiazines 37 <2006PS1655>. Two equivalents of the aldehyde are required. The same products are isolated when 2,5-dibenzylidenecyclopentanones are treated with thiourea under the same conditions. 2-Amino-4i/-l,3-thiazines 184 are easily synthesized in one pot by the reaction of aromatic alkynes, R feCH, aromatic aldehydes, R CHO, and thiourea in the presence of TFA/acetic acid <2005OL3797>. 

Most reported solid-phase thiazole syntheses have been based on the cyclocondensation of thioamides or thioureas with a-halo ketones (Table 15.18). These reactions generally proceed smoothly under basic or acidic conditions, and are compatible with most common linkers. 

Pyrimidopyridazinethione and -dithione are obtained by cyclocondensation of aminodiphenyl-pyridazinecarbonitrile with phenyl isocyanate and CS2 <91ZN(B)835>. The cyclocondensation of 4,5-dibenzylidentetrahydropyridazine-3,6-dione (54) with thiourea in boiling ethanolic potassium... 

Formal substitution of the carbonyl group of enaminones by an imino group leads to enamino imines. In the reaction with isocyanates or isothiocyanates they result in urea or thiourea derivatives, which can be transformed to pyrimidines or pyrimidones depending on substitution340 (equation 258). Treatment of similar enaminoimines with hydroxylamine gives regiospecifically isoxazoles by thermal cyclocondensation of the isolated oximes341 (equation 259). 

S-methylisothiourea (which is more correctly termed a substituted amidine) has already been mentioned above and elsewhere <8uoci30l>. Pyruvaldehyde reacts with ureas to form 4,5-dihydroxyimidazolin-2-ones which dehydrate to hydantoins <86JHCii25>, while benzil gives 4,5-diphenyl-4-imidazolin-2-ones ((241) R R = Ph) when heated with thioureas in acidic solution (Scheme 173) <9UCS(P2)1501>. Direct cyclocondensation of an a-bromoketone with urea forms around 50% of 2-imidazolinone when refluxed in ethylene glycol in the presence of an excess of... 

The cyclocondensation of l-alkynyl(phenyl)-Aiodanes with thioureas and thioamides is also a useful method for thiazole synthesis <05AG(E)6896>. For instance, reaction of iodane 36 with thiourea in the presence of triethylamine affords 2-aminophenylthiazole 38. When the same reaction is carried out in the absence of triethylamine, thiazole 38 is not formed instead the isothiouronium mesylate 37 MsOH is isolated in 82% yield. Exposure of this mesylate to an aqueous solution of sodium bicarbonate produces 38 through an intramolecular 5-endo digonal cyclization. Presumably, methanesulfonic acid, generated... 

A novel construction of 2-imino-1,3-benzothiazin-4(3//)-ones (208) utilizes the cyclocondensation of thioureas and 2-iodobenzamides (209) in the presence of a nickel catalyst (Equation (26)) <90CL2205>, and dithiocarbamic acid reacts with 2-benzylidenecyclohexanone to form stereoisomeric perhydro-3,l-benzothiazine-2-thiones (210) (Equation (27)) <87TL571>. 

Standard approach is the cyclocondensation of 1,3-diketones with N-C-N systems like amidines, ureas, thioureas and guanidines, which gives rise to 4,6- or 2,4,6-substituted pyrimidines 13, 2-pyrimidinones 14, 2-thiopyrimidinones 15, and 2-arninopyrimidines... 

Phenyl-3H-thiazol-2-yhdene)malononitrile 133, was obtained by cyclocondensation of l-phenyl-2-thiocyanatoethanone with malononitrile, on the reaction with thiourea or guanidine (Scheme 60) led to the formation of thiazolo[3,2-c]pyrimidine 134[86],... 

Hydroxylations of fatty acids by cytochrome P450119 compound increase in rate with chain length and show no intermolecular KE in buffer. With glycerol, the rate of reaction of lauric acid increases, and a KIE is observed. Reversible formation of a non-reactive complex of a fatty acid with the cytochrome and its isomerization to a reactive one is proposed. A tandem oxidative cyclocondensation process is reported for the synthesis of 3,4-dihydropyrimidin-2(l//)-one or -thione derivatives from primary aryl alcohols, -keto esters, and urea or thiourea in the presence of aluminium nitrate nonahydrate as oxidant catalyst. ... 

---