With thiourea

This preparation illustrates the ready formation of the thiazole ring by the condensation of an ot-halogeno-ketone and a thioamide. Thus chloroacetone, which may conveniently be represented in the enol form (I), condenses with thiourea (II) to give 2-amino-4-methylthiazolc (III). 

S-Alkyl-iso-thiuronium picrates. Alkyl bromides or iodides react with thiourea in alcoholic solution to produce S-alkyl-iso-thiuronium salts, which yield picrates of sharp melting point ... 

Aminotliiazole (III) is prepared by the condensation of chloroacetalde-hyde (II) with thiourea (I). The reaction may be represented as follows ... 

Benzyl chloride reacts with thiourea in dilute alcohohc solution to give iS-benzyl-iso-thiuronium chloride ... 

Glycosidic thiol groups can be introduced into glycosyl bromides by successive reactions with thiourea and aqueous sodium disulfite (D. Horton, 1963 M. Cemy, 1961, 1963). Such thiols are excellent nucleophiles in weakly basic media and add to electrophilic double bonds, e.g., of maleic esters, to give Michael adducts in high yields. Several chiral amphiphiles have thus been prepared without any need for chromatography (J.-H. Fuhrhop, 1986 A). 

As in the case of the thiazoles, a variation on the Hantzsch s method has been used. This consists of using a nonhalogenated carbonyl derivative directly in the presence of iodine in the reaction with selenourea (Scheme 7) (20). However, in this case the reaction with selenourea is slower than with thiourea, and normally an excess of carbonyl compound is used. 

In 1877, Maly (45) discussing formula 34 applied to thiohydantoine found it unable to explain the basic properties of the compound. He preferred a structure in which the -CH2-CO- group would be bonded to only one nitrogen atom. Meyer (46) prepared a monophenyl thiohydantoin (m.p. 178°C) by condensing diloroacetanilide with thiourea and proposed 42 for its structure. 

In 1882, Nencki and Sieber (98), condensing dibromopyruvic acid with thiourea, obtained a compound they named sulfuvinuric acid (Sulfuvinursaure), which was later demonstrated (99) to be a derivative of 2-aminothiazole. The same year Will (100) observed that the sulfur atom of 56 is masked to Pb(N03)2 and to alkalis. 

Arylamino-2-chloroprop-2- enoic esters (72) obtained from 2-chloroaceto acetic ester (71) and arylamines, react with thiourea to yidd substituted 2-aminothiazoles (73), probably by initial nucleophilic substitution of the chloro atom of 72, followed by cyclization with loss of aniline (Scheme 33) (729). 

II. Thiazoles from -Halocarbonyl Compounds and Derivatives 213 3. Reaction with Thiourea... 

Similarly, by condensing y-bromoacetoacetic esters with thiourea, 4-carboxy-2-aminothiazoles (104a), Rj = C02H, R2 = H, were obtained after hydrolysis (183, 185, 221, 441), These compounds can be decarbox-ylated by heating (158). 

The a-halogenated acids or their esters (105) also react with thiourea to give 2-amino-4-hydroxythiazoles (106a) or their 2-amino-4-thiazolone (106b) (1, 247, 254, 530) or 2-imino-4-oxathia2olidine (106c) tautomers (Scheme 47). 

Bis (meta or para haloacetyl) benzenes (C1CH2C0)2C6H4 condensed with thiourea yield the corresponding meta or para bis(4-thiazolyl-2-amino)phenylene (573, 574), analogous to 36 with R=NH2-By refluxing in alcohol solution m- or p-2-thiazolylphenacyl bromide (37) with thiourea, compound 111, in which R = H, Ph, P-CIC6H4, and p-OjNC H, was obtained (569). 

Similarly, the ether and thioether (112), with X = O or S, were prepared in 80 to 90% yield by condensing 39 with thiourea (410). 

Bromo-4-piperidone hydrochloride condensed with thiourea 3 days at 20°C give the 2-amino-4,5,6,7-tetrahydrothiazolo[5,4c]pyridine (119) (Scheme 55) (648). 

Compounds other than a-halocarbonyls and thiourea can lead to 2-aminothiazoles. Thus 3-halogenoalkynes (120) condensed with thiourea in absolute alcohol give 2-aminothiazoles (Scheme 56a) (497), with Rj = Me, Et, n-Bu, H CPh, and HjCCgH tR-p R2 = H, Ph, CgH4R, and Q-naphthyl. Yields ranged from 20 to 80% (497). 

Similarly, 2,4-dichloro-2,3-epoxyalkanoates react with thiourea in methanol to yield 2-amino-4-niethoxycarbonyl-5-(l-inethoxyalkyl)-thiazoles (Scheme 56b) (755). 

But the reaction with aliphatic a-halocarbonyl compounds is usually complex, and a variety of compounds can be formed depending on the reactants and the reaction conditions. With chloroacetone in neutral medium (alcohol) the acyclic intermediate (144) analogous to those obtained with thiourea and thioamides was isolated (Scheme 70). 

Other sulfur compounds such as thiourea, ammonium dithiocarbamate, or hydrogen sulfide also lead to 2-mercaptothiazoles. Thus thiourea has been used in the syntheses of 4,5-dimethyl (369) and 4-aryl-2-mercapto-thiazoles (Table 11-30) (519). The reactions were carried out by condensing the ia -thiocyanatoketones with thiourea in alcohol and water acidified with hydrochloric acid. By this procedure, 4-aryl-2-mercaptothiazoles were obtained in yields of 40 to 80% with bis-(4-aryl-2-thiazolyl) sulfides as by-products (519). These latter products (194) have also been observed as a result of the action of thiourea on 2-chloro-4-arylthiazole under the same experimental conditions. They can be separated from 2-mercaptothiazoles because of their different degrees of solubility in sodium hydroxide solution at 5%. In this medium bis-(4-phenyl-2-thiazolyl)sulfide is... 

Reactions were carried out by condensing a-thiocyanatokeiones with thiourea in alcohol and water acidified with hydrochloric acid. 

DiaminO 4,4-dimethyl-l,3,5-thiadiazine hydrobromide was isolated as by-product (418). Benzene sulfonates of cyanohydrin prepared from sodium cyanide and an halobenzoaldehyde, when treated with thiourea or its derivatives, afford 2,4-diamino-5-(p-halogenophenyl)-thiazole benzene sulfonates (447). Similarly, cyanoamido thiocarbamates obtained from cyanamide and isothiocyanates yield substituted 2,4-diaminothiazoles (598). 

Another approach to 2-aminothiazole derivatives was recently developed by Zbiral and Hengstberger (667, 700) thus the condensation of )3-acylvinylphosphonium salts (248) with thiourea affords the thiazolyl-methylphosphonium salt (249) via an acyclic intermediate analogous to the Hantzsch s synthesis. Final alkaline hydrolysis of 249 furnishes the 2-aminothiazoles (250) (Scheme 127) (700). 

Sulfur Complexes. Silver compounds other than sulfide dissolve in excess thiosulfate. Stable silver complexes are also formed with thiourea. Except for the cyanide complexes, these sulfur complexes of silver are the most stable. In photography, solutions of sodium or ammonium thiosulfate fixers are used to solubilize silver hahdes present in processed photographic emulsions. When insoluble silver thiosulfate is dissolved in excess thiosulfate, various silver complexes form. At low thiosulfate concentrations, the principal silver species is Ag2(S203) 2j high thiosulfate concentrations, species such as Ag2(S203) 3 are present. Silver sulfide dissolves in alkaline sulfide solutions to form complex ions such as Ag(S 2 Ag(HS) 4. These ions are... 

Chemical Properties. Ammonium thiocyanate rearranges upon heating to an equiHbrium mixture with thiourea 30.3 wt % thiourea at 150°C, 25.3 wt % thiourea at 180°C (373,375). At 190—200°C, dry ammonium thiocyanate decomposes to hydrogen sulfide, ammonia, and carbon disulfide, leaving guanidine thiocyanate [56960-89-5] as a residue. Aqueous solutions of ammonium thiocyanate are weakly acidic a 5 wt % solution has a pH of 4—6. 

The primary synthesis of alkoxypyrimidines is exemplified in the condensation of dimethyl malonate with O-methylurea in methanolic sodium methoxide at room temperature to give the 2-methoxypyrimidine (854) (64M207) in the condensation of diethyl phenoxymalonate with formamidine in ethanolic sodium methoxide to give the 5-phenoxypyrimidine (855) (64ZOB1321) and in the condensation of butyl 2,4-dimethoxyacetoacetate with thiourea to give 5-methoxy-6-methoxymethyl-2-thiouracil (856) (58JA1664). 

Because of the structural requirements of the bielectrophile, fully aromatized heterocycles are usually not readily available by this procedure. The dithiocarbamate (159) reacted with oxalyl chloride to give the substituted thiazolidine-4,5-dione (160) (see Chapter 4.19), and the same reagent reacted with iV-alkylbenzamidine (161) at 100-140 °C to give the 1 -alkyl-2-phenylimidazole-4,5-dione (162) (see Chapter 4.08). Iminochlorides of oxalic acid also react with iV,iV-disubstituted thioureas in this case the 2-dialkylaminothiazolidine-2,4-dione bis-imides are obtained. Thiobenzamide generally forms linear adducts, but 2-thiazolines will form under suitable conditions (70TL3781). Phenyliminooxalic acid dichloride, prepared from oxalic acid, phosphorus pentachloride and aniline in benzene, likewise yielded thiazolidine derivatives on reaction with thioureas (71KGS471). 

A variation of this idea utilizes the glycidic ester (175). This underwent condensation with thioureas and phenyl dithiocarbamate to give (176 R =NR2, SPh, respectively) (71BSF4021). 

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