A-PHENYLTHIOUREA

There are amines such as A-methylnitroamine, that are too weakly nucleophilic to be able to form covalent adducts with arenediazonium ions. The products of the latter appear to be those of salts ArNJ N(N02)CH3, as found by Baranchik et al. (1957). Amides also appear not to be sufficiently nucleophilic, but thioamides are, as is shown by the reaction of A-phenylthiourea in the presence of NaOH (Scheme 13-12 Nesynov et al., 1970). First a (probably homolytic) phenylation-de-diazoniation takes place, followed by A-coupling. Selenourea also reacts a mixture of products is formed, which indicates a reaction of the same type as with thiourea (Nesynov and Aldokhina, 1976). 

An improved procedure for preparing urea derivatives involves reaction of isocyanates or isothiocyanates with 4(5)-aminoimidazole (25 R = H) in tetrahydrofuran solution [92JCS(P1)2779]. A THF solution of 4(5)-aminoimidazole (25 R=H) generated in situ and then treated with the appropriate reagent gave either lV-imidazole-4-yl-AT-phenylurea (56 X = 0) (32%) or AT-imidazoM-yl-A/ -phenylthiourea (56 X = S) (21%). 

A,TV-Dimethyl-A -phenylthiourea has been shown to coordinate to Rh111 as an N—S bidentate involving four-membered chelate ring formation.154 N-Substituted thioamides also may bond in this manner.155 156 l-Amidino-2-thioureas (44) may behave either as N—S or as N—N bidentates, with this donor choice being dependent mainly on pH and the nature of the metal ion.157 As N—S donors they are known to stabilize lower oxidation states.158 As part of a study on Mo—S-containing complexes as models for redox-active molybdoenzymes, Dilworth et al. have shown that some p-(substituted)phenylhydrazines may coordinate as N—S bidentates in three different ways to one metal atom.159 The three diazenido, diazene and hydrazonido forms vary in their degree of deprotonation and therefore their anionic nature. 

The crystal structure of the dithioacetylacetone (sacsacH) complex of cobalt(n), Co(sacsac)2, shows it to be monomeric square planar,164 in marked contrast to the acacH analogue. Pyridine 2-thiol (LH), which can exist as the thione tautomer (31) forms Co(LH)2X2 (X = Cl, Br, or I) complexes these contain the ligand bonded through the sulphur, as evidenced by the presence of a v(N—H) vibration in the i.r. spectra.165 Morpholine 4-thiocarbonic acid (32) also appears to be S-bonded in the CoL2X2 complexes (X = Cl, Br, or I), since the v(C=S) frequency is lowered upon co-ordination.166 The electronic spectra of the CoL2C12 complexes (L = thiourea, A-phenylthiourea, and TViV -diphenylthiourea) have been recorded.167... 

This reaction takes place in three stages. First, the free amino group of the N-terminal amino acid reacts with phenylisothiocyanate to form a phenylthiourea. Second, the phenylthiourea cyclizes to a thiazolinone and expels the shortened peptide chain. Third, the thiazolinone isomerizes to the more stable phenylthiohydantoin. 

Step 1 Nucleophilic attack by the free amino group on phenyl isothiocyanate, followed by a proton transfer, gives a phenylthiourea. 

The preparation of a-phenylthiourea by the procedure described herein has not been reported, although Douglass and Dains have applied the method to the preparation of various substituted phenyl derivatives. 

O Nucleophilic addition of the peptide terminal amino group to phenyl isothiocyanate (PUC) gives an A/-phenylthiourea derivative. 

Benzoyl chloride added with stirring to NH4-thiocyanate and dry acetone, refluxed 5 min., a soln. of aniline in dry acetone added at such a rate that the soln. refluxes gently, carefully poured into water with stirring, whereby a-ben zoyl-/ -phcnylth iourea precipitates, filtered, and the crystals boiled 5 min. in aq. NaOH —y a-phenylthiourea. Y 76-85%. (R. L. Frank and P. Y. Smith, Org. Synth. 28, 89 (1948).)... 

In this extensive study of thiourea synthesis by coupling isothiocyanates with amines under mechanochemical conditions of neat and LAG, a total of 49 different thiourea derivatives were prepared. Since the supramolecular chemistry of simple synunetrical and nonsymmetrical diarylthiouieas had not previously been studied in detail, the information from the PXRD patterns of the milling products in this work also allowed for a systematic analysis of structural features of diarylthio-ureas. The three main self-assembly motifs were identified. A characteristic supramolecular synthon based on bifurcated N—H - S hydrogen bonds was found in most cases, whereby the individual thiourea molecules were assembled into chains aligned in a head-to-head (parallel molecular dipoles) or head-to-tail (antiparallel molecular dipoles) manner. In the case of slerically hindered thioureas, such as A -(2,6-dimethylphenyl)-A -phenylthiourea, the third motif arising from discrete cen-trosymmetric dimers based on rI(S) supramolecular synthon was found. A detailed look at the measured PXRD patterns for aU diarylthioureas revealed that solid-state structures of these compounds could be classified into two structural families, denoted as family I and family II (Fig. 1.11). 

Mechanism 28.2 illustrates some of the key steps of the Edman degradation. The nucleophilic N-terminal NH2 group adds to the electrophilic carbon of phenyl isothiocyanate to form an A-phenylthiourea, the product of nucleophilic addition (Part [1]). Intramolecular cyclization followed by elimination results in cleavage of the terminal amide bond in Part [2] to form a new peptide with one fewer amino acid. A sulfur heterocycle, called a thiazolinone, is also formed, which rearranges by a multistep pathway (Part [3]) to form an A-phenylthiohydantoin. The R group in this product identifies the amino acid located at the N-terminal end. 

Addition of the free amino group from the N-terminal amino acid to the electrophilic carbon of phenyl isothiocyanate followed by proton transfer forms an A/-phenylthiourea. 

Acetyl-4-phenylpyridine, A-00031 2-Acetyl-6-phenylpyridine, A-00032 A -Acelyl-A-phenylthiourea, in P-00201 A -Acetyl-A -phenylthiourea, in P-00201 Acetylpinacolin, see D-00863 2-Acetylpyrazine, A-00033 2-Acetylpyrazine pyrazinylhydrazone, A-00034 2-Acetylpyrazine 2-pyrimidinylhydrazone,... 

A-Benzoyl-A -phenylthiourea, in P-00201 A-Benzoyl-l-piperidinethioamide, see P-00245 Benzoylpropanone, see P-00107 Benzoylpyrazine, B-00148 2-Benzoylpyrazine 2-quinolylhydrazone,... 

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