Thiourea with bromine

The preparation and spectroscopic properties (infrared, ultraviolet, NMR) of iV-alkoxycarbonyl-N -(2-thiazolyl)thioureas (268) have been studied by the Nagano group (78, 264). These compounds react with bromine in acetic acid or chloroform to give 2--alkoxycarbonylimino-thiazolo[3,2-h]thiadiazolines (Scheme 162), whose structures were established by mass spectroscopy, infrared, NMR, and reactivity patterns (481). 

As demonstrated above, nitro derivatives of five-membered heterocycles have found extensive use as antiinfective agents. It is therefore of interest that the nitro derivative of a substituted thiazole was at one time used as an antitrichomonal agent. Bro-mination of 2-aminothiazole (136) (obtained from condensation of thiourea with chloroacetaldehyde) gives the 4-bromo derivative (138) this is then acetylated to 139. Treatment of 139 with nitric acid leads to an interesting displacement of bromine by a nitro group to afford aminitrazole (140)... 

A series of 3-substituted 2-nitrosiminobenzothiazohnes (35a-e) as well as the disub-stituted analog 35f were prepared (Scheme 3.24) [198]. The reaction of an arylamine hydrochloride with potassium thiocyanate gave the corresponding unsymmetrical thiourea [199]. Oxidative cyclizations with bromine provide the iminobenzothia-zolines [191, 200], which on treatment with sodium nitrite in acetic acid afforded the nitrosiminobenzothiazoline (35a-f). The nitrosiminobenzoselenazoline (42) was similarly prepared. 

Treatment of l- 6-[(/>-nitrophenyl)thio]-benzothiazol-2-yl thiourea 298 with bromine in chloroform yields 2-amino-7-[(/>-nitrophenyl)thio][l,2,4]thiadiazolo[3,2-/)]benzothiazolium bromide 299 (Equation 44) <2002MI15>. 

Isothiocyanate sulfides, (RNCS)2S, arise similarly from isothiocyanates by successive treatment with bromine in anhydrous chloroform, and hydrogen sulfide158,160 or ethanol.161 The phenyl homolog has also been obtained by the action of thiophosgene on diphenyl-thiourea,162 or aluminum chloride on phenyl isothiocyanate.103... 

Freund and Wolf10 reported that 2,4-diphenyl-l,2,4-thiadiazolidine-3,5-dithione was formed by heating l,3-diphenyl-2-thiourea with thiophosgene in benzene whereas, a 1,3-thiazetidine was produced at lower temperatures in ether (see Section II). Ohande181 has reported that 3,5-diamino-l,2,4-thiadiazoles are formed by the reaction of thiopseudoureas with carbon disulfide in the presence of bromine. Use has also been made of thioureas in the synthesis of 1,3,4-thiadiazolines (79) via reaction with the halohydrazones 78.185,186 The analogous reaction with solenoureas was recently reported by Bulka and Ehlers187 to yield 1,3,4-selenadiazolines. 

Bond formation between oxygen and sulfur occurs when the AM2-hydroxyethyl)thiourea (155) is oxidatively cyclized with bromine to give the 1,2,4-oxathiazine (3) (77TL4245), and when the intermediate (183), from reaction of ketones with fluorosulfonyl isocyanate (FSI), is cyclized with base to give (184) <80AG(E)13l). 

Two modifications of the well-knonm benzothiazole preparation have been employed to prepare unusual heteropolycycles. Konig et treated l-thiocarbamoyl-l,2,3,4-tetrahydroquinoline (236) with bromine in chloroform to give the thiazolo[3,4,5-J,i]quinoline derivative 237. In a process which requires disruption of the resonance stabilization of the pyridine ring, Harrisreported that treatment of l-(2-pyridyl)-2-thioureas with sulfuryl chloride or with bromine gives the hydrohalide salts of 2-imino-2//-[l,2,4]thiadiazolo[2,3-a]pyridines (238). 

Bromination is usually performed with bromine in a suitable solvent, but in a few cases where this is ineffective (e.g., 415 and 414 ), N-bromosuccinimide has been employed. In the case of 414, bromination was found to be successful only when R = Me. Chlorination of 410 has been achieved with sulfuryl chloride (Table III). Thiocyanations have been carried out either with bromine and ammonium thiocyanate or bromine and thiourea -though the structures of the products (thiocyanates or isothiocyanates) have not been established with certainty. Kano showed that imidazo[2,l-6]-l,3,4-thiadiazole 411 undergoes bromination and thiocyanation preferentially at C-5 (position a, Scheme 18) when this position is free. C-5-substituted derivatives are brominated at C-6 (position b), but thiocyanation fails. Electrophilic substitution reactions in l//-pyrrolo[l,2-6]-s-triazole have also been studied. ... 

S-Unsubstituted 2-thiohydantoins are brominated with bromine in acetic acid to give S-bromo derivatives, which are intermediates in several reactions. Thus by refluzing with either thiourea or thioacetamides, thiazolothiohy-dantoin derivatives (108) are obtained.276... 

Thiazole derivatives are obtained from ethyl 3-amino-3-acylhydrazinopropenoate 21 in good yields <04H(63)259>. Treatment of 21 with thiourea and bromine in acetic acid... 

Bi(alkyl xanthates) [dithiodi(thioformates)], (RO—CS—S—)2, and thiuram disulfides [dithiodi(formamides)], (NH2—CS—S—)2, are formed by oxidation of xanthates and salts of dithiocarbamic acid, respectively. Thioureas can be dehydrogenated analogously to di(amidino) disulfide salts, [+NH2=C(NH2)—S—)2 2X , by a wide variety of oxidizing agents. Reaction with bromine in chloroform is particularly satisfactory for these reactions.799... 

Similarly, a-bromination of the 5-acetyl group of 231 with bromine afforded 5-(2-bromoacetyl) 232, which upon cyclocondensation with thiourea yielded 5-(2-aminothiazol-4-yl)-3,4-dihydropyrimidin-2(lH)-one/ thione 233 (Scheme 89) (09IJC(B)1732). 

A rather detailed study of the reaction between thiourea and bromine in the pH range 1.5-4 has appeared/ and the mechanism is set out in reactions (55)-(58). Three separate intermediates are postulated. In addition to this, reaction (57) can occur by an additional pathway catalyzed by bromide ion. This is certainly a much more complex system than the reaction of I2 with thiourea, where the established product is (NH2 CSSC(NH2)i. Buxton has published a study of the oxidation of SCN and of 1 by H to form (SCN)2 and IJ, respectively. The species HSCN" is a precursor in the former case. The spectrum of HP could not be detected. In concluding this section, we note a theoretical study of the regioseleCtive addition of dicyanoacetylene to S4N4. 

An iodine-KI-soln. added to a soln. of startg. pyrrole and thiourea in aq. ethanol isothiouronium iodide. Y 85-95%. F. e., also bromides with bromine, s. R. L. N. Harris, Tetrah. Let. 1968, 4045. 

Cyanamide, HjNCN, has been prepared by (1) desulfurizing thiourea with mercury(II) oxide, lead acetate, or bromine, (2) passing gaseous cyanogen chloride into ammonia dissolA in anhydrous ether, and (3) oxidizing thiourea with alkaline permanganate. The method described below is an adaptation for laboratory use of a commercial procedure that uses calcium cyanamide as a starting material. 

Application of the Hugershoff cyclization (of arylthioureas with bromine) to pyrrolylthioureas and to A-acyl-iST -(3-thienyl)thioureas gave pyrrolothiazoles... 

Aminolhtazoles were synthetized from thiourea by three methods Method A, from a-haloketones or aldehydes designated as (Cl) or (Br) Method B, from ketones and iodine (fj) or bromine (Btj) Method C, from iodomercuriketones. Method D consists in condensing ketones with cyanamid and sulfur. 

Tropolone has been made from 1,2-cycloheptanedione by bromination and reduction, and by reaction with A -bromosuccinimide from cyolo-heptanone by bromination, hydrolysis, and reduction from diethyl pimelate by acyloin condensation and bromination from cyclo-heptatriene by permanganate oxidation from 3,5-dihydroxybenzoic acid by a multistep synthesis from 2,3-dimethoxybenzoic acid by a multistep synthesis from tropone by chlorination and hydrolysis, by amination with hydrazine and hydrolysis, or by photooxidation followed by reduction with thiourea from cyclopentadiene and tetra-fluoroethylene and from cyclopentadiene and dichloroketene. - ... 

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