Thioureido compounds

Goodman and Christensen i( >> first noted this type of aziridine formation in the conversion of the dithiocarbamate (207) into the substituted ethylenimine (209) by means of hot, methanolic sodium methoxide. Subsequently, the conversions of the ureido sugars (168) and (204) into the aziridines (203) and (205), respectively, and of the thioureido compound (206) into (208), by using similar reaction conditions, was reported. 

The conformationally mobile thioureido compound (210) also gave an... 

Decisive progress in stepwise degradation was brought about by Pehr Edman (Plate 15) in 1950 [11], who found that phenylisothiocyanate, the sulfur analog of Bergmann s reagent, reacts with the N-terminal amino group at pH 9 even at room temperature, and that the thioureido compound hereby formed is readily split by weak acids, e.g. trifluoroacetic acid, to yield a 2-anilinothiazolin-5-one. 

The sulfur atom of the thiocarbonyl group is a good nucleophile, and reaction between benzyl bromide and l-(2-thiazolyl)thiourea yields the isothiouronium salt (496). The sulfur atom may also be engaged in a chelate, as exemplified by the Cu chelate of 2-thioureido-4-methylthiazole (491). These chelates with metal ions were thoroughly studied in acidic, neutral, and alkaline media for 66 metal ions in order to define their analytical use. They are formed in the molar ratio of 1 2 for metal II compounds (498). 

Undoubtedly these reactions proceed via an intermediate ureido or thioureido derivative. These compounds have been obtained by Dornow and Hahmann by the action of potassium cyanate or ammonium isothiocyanate on 2-amino-4,6-dimethylnicotinic acid (11), but whereas the urea (12, X = 0) was converted into the pyrido[2,3-li]-pyrimidine-2,4(lI/,3/7)-dione (13, X = 0) by the action of heat, the thiourea (12, X = S) was unchanged after similar treatment. 

The 6-methyl derivative (98, R = Me) was an important intermediate in the synthesis of analogs (e.g., 183) of folic acid. Korte has shown that 2-aminopyrido[3,2-guanidine carbonate with 3-aminopicolinic acid and that treatment of the same acid with ammonium thiocyanate or potassium cyanate yields the thioureido and ureido derivatives (100, X = S and X = 0). In contrast to the pyrido[2,3-d]pyrimidine system bsoth of these compounds could be cyclized by heat and the latter (100, X = O) is a likely intermediate in the synthesis of the dione (98) by the fusion with urea. 

Reaetion of l,3-benzoxazin-4-ones (43, 44) or trithioisatoie anhydride (45) with amidrazones (46, 47) or thiosemiearbazide (48) resulted in the formation of 3-(l-amidino)- (49-51) and 3-(l-thioureido)pyrimidines (52) respeetively. Compounds 49-52 underwent thermal intramoleeular ey-elization to the eorresponding l,2,4-triazolo[l,5-c]quinazolines (53-56) [68CB2106 76MI1 80PHA582 83MI1 85H(23)2357] (Seheme 18). 

The amino group of 3-amino-1,2,4-oxadiazoles shows little nucleophilic character. For example, addition to phenyl isothiocyanate to give 3-(phenylthioureido) compounds requires heating of the components without solvent at 120-130 °C or the use of polar aprotic solvents (DMSO, DMF) and long reaction times (30 days at 23°C) <77JCS(P1)1616>. 3-(Thioureido)-1,2,4-oxadiazoles undergo fast ring transformations to thiadiazoles (see Section 4.04.5.1.1). 

The mild reaction of the thioureido derivative 153 with methanol produces the compound 154 with migration of the acetyl group. On heating, this compound isomerizes into the cw-fused cyclic 155 [129] (O Scheme 37). 

As we can see, every kind of parameters have limitations thus, the combination of several kinds of parameters is advantageous. The combination of several kinds of parameters can often completely reflect the properties of compounds. Wang et al. [9] conducted some studies in this field. They introduced several structural parameters to study the correlation between the molecular structures of O-ethyl-O-aryl-A-iso-propylphosphoroamidothioates, O-ethyl, O-isopropyl phosphoro(thioureido) thioates, and their retention factors in high-performance TLC (HPTLC), respectively. 

Thin-layer Chromatography. - Fourteen newly-synthesised organophos-phorus compounds have been separated by TLC, and a study made of their Rf values and structures for the aryloxyphenylthiophosphonyl hydrazides. When electron-donor solvents were used as mobile-phase, there were carbonyl displacement effects and the order of Rf values was reversed. In another study (by HPTLC), a correlation between the molecular structures of sixteen O-ethyl, N-isopropyl phosphoro(thioureido)thioates and their observed Rf values has been checked against a computer-assisted Rf prediction system for these... 

Sequences that allow combinatorial variations to be introduced in immediate succession may also be verified by starting from compounds with functional groups that can be transformed independently. As an example, 4-amino-benzylamine was first selectively ac-ylated at the aliphatic amino group. Subsequently the aromatic amino group was converted to a thioureido or a secondary amino group (Scheme 3.8, [9]). 

Oxidative cyclization occurs in high yield when a compound containing lactam thiocarbonyl and thioureido functions is treated with bromine-TEA at ambient temperature. 

All of these derivatives are 1,2-disubstituted benzenes, which are converted by chemical reaction, for example, in aqueous medium with sodium hydroxide or with dimethyl sulfate, into alkyl N-benzimidazol-2-yl-carbamates (Koyamada et ai, 1969 Adams and Wommack, 1970). Thiophanate derivatives themselves are inactive (Nogutsi et al., 1971), but in plants they are converted into benzimidazole derivatives, exerting their effect in this form (Selling et ai, 1970 Vonk and Kaars Sijpesteijn, 1971 Soeda et al., 1972). The lack of activity of 1,3- and l,4-bis(3-alkoxycarbonyl-l-thioureido)benzenescan be explained by their inability to cyclise the benzimidazole ring. Thioallophanic acid derivatives are thus the precursors of alkyl N-benzimidazol-2-yl-carbamates. Further substitutions on the benzene ring decrease the fungitoxicity of the compounds. 

The adduct of Hector s base with carbon disulfide,1,3 first regarded as 21,37 has the solid state structure 22.40 With isothiocyanate esters, simple 5-thioureido derivatives (23, 24) are obtained (see also Refs. 35, 41). The structure of the addition compound with methyl isothiocyanate, for example, is 23 (R = Me) in both the crystalline and dissolved (DMSO) state, as determined by X-ray analysis, and 15N- and 13C-NMR measurements.31... 

Aryl-2-(carboxymethyl)(or carboxyethyl)thiazolo[3, 4 2,3]-l,2,4-triazolo[5,4-3]-l,3,3-thiadiazines 234 are obtained from 2-aryl-3-thioureido-4-thiazolidinones 235, which are formed by the addition-condensation of aldehyde thiosemi-carbazones 237 and mercaptoacetic acid. Compounds 235 undergo chemoselective intramolecular heterocyclizations to 5-aryl-2-mercapto-l,5-dihydrothiazolo[3,4- ]-l,2,4-triazoles 236, which in turn undergo condensation with a-amino acids to yield 1,3,5-thiadiazines 234 (Scheme 44) <1994JFA811>. 

HI El-Subbagh et al. [76] S3mthesized a sequence of 2,4-disubstituted thiazole compounds containing N-n-butyl or N-cyclohexyl thioureido synthon at position-2 and N-substituted thiosemicarbazone moiety 25 at position-4 and verified for antitumor activity. All of the established derivatives revealed antineoplastic activity at concentrations less than 10 pM. 

The nucleophilic reactivity of the nitrogen atoms in thioureas towards carbonyl compounds has been further exemplified by some recently described addition and addition-elimination reactions of thioureas with aldehydes. The same reactivity also played an important part in recent syntheses of heterocyclic compounds containing the thioureido-grouping. ... 

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