2-substituted derivatives, from thioureas

Moreau and co-workers have also prepared (ll ,2K)-l,2-diaminocyclo-hexane amino-urea and thiourea derivatives [43]. Diphenylethylenediamine-substituted monothioureas are more stable than the cyclohexyldiamine counterpart, but they can also rearrange to guanidine derivatives, especially at high temperature or in the presence of metal [43]. Under the same conditions, thioureas also rearrange to guanidines in the presence of amines. Selective formation of substituted guanidines from thiourea derivatives of diaminocy-clohexane or diphenylethylenediamine were also reported in a recent paper from Ishikawa [44]. 

Though dental afflictions constitute a very significant disease entity, these have received relatively little attention from medicinal chemists. (The fluoride toothpastes may form an important exception.) This therapeutic target Is, however, sufficiently Important to be the focus of at least some research. A highly functionalized piperazine derivative that has come out of such work shows prophylactic activity against dental caries. Condensation of the enol ether 1 of thiourea with ji-pentylisocyanate gives the addition product 1J. Reaction of this with diamine 78, derived from piperazine, leads to substitution of the methylthio moiety by the primary amine, in all likelihood by an addition-elimination sequence. There is thus obtained ipexidine (79). ... 

The synthesis of 2-substituted pyrimidines from 1,3-dicarbonyl compounds and urea derivatives was first described by Evans2 and was later improved by Hunt, McOmie, and Sayer3 for the preparation of 2-mercapto-4,6-dimethylpyrimidine. Burness4 employed 3-ketobutyraldehyde acetal in this procedure to give 2-mercapto-4-methylpyrimidine. 2-Mercaptopyrimidine has been prepared from 1,1,3,3-tetraethoxypropane and thiourea by variations of this basic method 3 6 6 as well as by the reaction of 2-chloropyrimidine with thiourea 1 or sodium hydrosulfide.8... 

The reaction of thiourea derivatives with a metal complex to form NHC complexes is a combination of the NHC formation from thioureas with potassium or sodium [Eq. (23)] and the cleavage of electron rich olefins. For example, a lO-S-3-tetraazapentalene derivative is cleaved by Pd(PPh3)4 and [(Ph3P)3RhCl], respectively [Eq. (35)]. Other substitution patterns in the carbene precursor, including selenium instead of sulfur can also be used. ... 

Typically, thioxonium salts (32) are stable compounds, and the deprotonation is performed at low temperatures. This method has been used to synthesize reactive thiocarbonyl yhdes as well as stable and isolable ones (56-60). Arduengo and Burgess (3) prepared differently substituted thiocarbonyl ylides from thiourea derivatives, and in the case of 33, the structure has been established by X-ray crystallography. 

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... 

Formation of imidazoles from thiourea derivatives has been limited largely to the 2-alkylthio or 2-aralkylthio-substituted rings (unsubstituted 2-mercaptoimidazoles will be classified as 4-imidazoline-2-thiones in this review). 

In special cases the reaction of the anions of carbon acids at the enaminone carbonyl group in a 1,2-addition can be forced by acetalization. For example, a tertiary amino-methylenelactone can thus be attacked by the anion derived from cyanoacetamide. Substitution of the tertiary amine in a second step yields tetrahydrofuropyridone in good yield. Reaction of thiourea or guanidine leads to fused pyrimidines247 (equation 179). 

There are some literature reports on the reactions of 1,2,4-triazoles. 2-Amino-4-aryl-5-( I //-l, 2,4-triazol-1 -yl)thiazolc derivatives were synthesized from the reaction of a-bromo substituted acetophenone and thiourea <07SC199>. 5-Amino-l-methyl-l//-[l,2,4]triazole-3-carboxylic acid were employed as precursors in peptide synthesis <07SC1917>. 3-... 

Aiiiino-4-phenylthiazoles, from o-diazo-acetophenone and thiourea, 231 2-Amino-5-phenylthiazole, diuretic prope ties of Schiffs bases of, 167 synthesis of, by condensation of ammonia with At(ary 1-1,3-oxathiol-2-yIidine) tertiary iminium salts. 300 2-(p-Ammophenyl) thiazoles, syntheses of, 4,5-disubstituted derivatives of, 191 2-Amino5-substituted thiazoles, from o-haloaiddiydes and thiourea, 224, 225 /V,At -bis (2-Amino-4 substituted thiazolyl)-p biphenylene, from p-biphenylene dithiourea and o-halocarbonyl compounds, 243... 

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