N-substituted thiourea

The cyclization of N-substituted thioureas (123) with halocarbonyl compounds gives 2-monosubstituted aminothiazoles (124) (Scheme 58)... 

In contrast to the Michaelis-Arbuzov reaction, triaryl phosphites prove to be quite useful for addition to a,(3-unsaturated carbonyl compounds in this type of reaction. A wide variety of unsaturated compounds have been utilized successfully as substrates for such additions, including condensation products of the simple carbonyl compounds with urea,229 thiourea,230-233 N-substituted thioureas,232 234 235 ethyl carbamate,236 2-imidazolidinone,237 2-imidazoli-dinethione,237 and benzyl carbamate.238-240... 

Thiourea and its /V-substituted derivatives readily reacted with EMME in hot ethanolic sodium ethoxide to yield 2-thiopyrimidine-5-carboxylates (219) (42JA794 56JA5294), With N-substituted thiourea, as in the case of -substituted urea, the primary amino group was first involved in the reaction. 

Aldehydo nitriles are readily available and can be used to prepare 4-amino-6-unsubstituted pyrimidines carrying one or more substituents in any of the other positions. Equivalents of the formyl group are also often used, for example, a 3-ethoxy-, 3-amino-, or 3-haloacrylonitrile. Most syntheses with /3-keto nitriles are carried out with equivalents thereof Such equivalents are /3-substituted /3-alkoxy-, /3-amino-, or /3-haloacrylonitriles. /3 -Ester nitrile reactions are also well established. Malononitriles and substituted malononitriles react readily with thiourea and N-substituted thioureas in refluxing ethanolic sodium ethoxide to form pyrimidine-4,6-diamines. An example is the reaction of N2-malononitrile 680 with N2-thiourea 681 to give N4- 4,6-diamino-2-(l//)-pyrimidinethione 682 which was then used in the synthesis of Ns-labeled adenine derivatives <2001JOC5463>. 

The preparation of pyrido[5,4-< ][l,3]thiazines by coupling of 4-halopyrimidine-5-pyrimidinecarboxylates with N-substituted thioureas was recorded in CHEC-II(1996) <1996CHEC-II(7)780>. A related approach has since been used to prepare a series of heteroannulated derivatives from the aldehyde 146, as summarized in Scheme 93... 

The protonation of N-substituted thioureas (B) occurs on the thiocarbonyl sulphur atom158-160 and it has been found157,164 to follow the //(" acidity function see equation 3516. 

Because of the presence of three nucleophilic centers in thiourea, an alternative direction of its reactions with a,(3-unsaturated carbonyls with the formation of dihydrothiazines was found in several cases (Scheme 3.15). This trend is usually observed in cases of N-substituted thioureas or cyclic a, 3-unsaturated ketones using an acidic catalyst [62, 63, 64, 65]. 

A number of methods of 2-imino-TA synthesis are based on the cycliza-tion of acylthioureas containing an a,/ -unsaturated acid fragment. In the case of reactions of acryloyl chloride with thiourea (72MI1) or with N-substituted thioureas (73MI2), no A-acryloylthioureas were isolated and hydrochlorides of 3-substituted 5,6-dihydro-TAs 128 were obtained (Scheme 42). 

In the reaction of acylhydrazines with isothiocyanates, N-substituted thiourea derivatives 14 are formed, which react with a polystyrene based polymeric carbodiimide (PCD) to generate the nitrogen substituted carbodiimide 15, which cyclizes to form 2-amino-1,3,4-oxazoles 16. ... 

This kind of redox system leads also to other free-radical species and the obtained polymers are not purely hydroxytelechelic. Hydroxylamine/mineral acid (HC1, H2S04)/H202 55 59,60), NaHS03/H202 55), ascorbic acid/H202 61), thiourea (or N-substituted thiourea)/H202 62 -64) systems have been suggested. The last one yields mostly hydroxyl-terminated polymers. 

The parent compound 45, R = H has been prepared from TFAE and thiourea as early as in 1948 (ref. 48) but N-substituted thioureas do not seem to react (ref. 47). 

Alkylation of pyrimidinethiols/thiones is almost exclusively on sulfur. V-Alkyl as well as N-arylpyrimidinethiones are therefore prepared by primary syntheses from the corresponding N-substituted thiourea in the 2-position, or in any of the electrophilic positions by thiation of the corresponding V-substituted pyrimidinone. 

Copper complexes of thioureas and N-substituted thioureas have also been suggested to account for the effectiveness of the parent compounds as antitubercular agents [537]. On the other hand, Ueno [538] suggested that the parent thioureas acted by removing copper from some M. tuberculosis copper-dependent enzyme and that the antitubercular activity was dependent on the relative stabilities of the enzyme complex and thiourea complex. However, the activities of two series of N-substituted (2-pyridyl and 4-pyryl) thioureas [539] could not be correlated with copper complex stability [540]. 

Nickel(II) complexes with thiourea (tu) (Table 93 307 R = R" = H) and either N- or iV,N -substituted thioureas are very numerous and have in most cases been known for a long time. ... 

Reactions with N-substituted Thiourea 3.1.2.1. N-monosubstituted thioureas... 

The 2-monosubstituted or disubstituted aminothiazoles obtained reaction between Halo carbonyl and N-substituted thiourea compounds [38]. 

Reviews.— Two papers, surveying the progress in the chemistry of simple aliphatic and aromatic thioketones during the period 1964—1972, have appeared recently. Two other comprehensive reviews deal with the chemistry of thiocarbonyl halides and the synthesis of N-substituted thioureas." Synthesis, co-ordination chemistry, and analytical application of monothio- 3-diketones, synthesis and properties of transition-metal... 

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