Bromine reaction with thiourea

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. - ... 

Two types of derivatives of 1,2-cyclohexadiene with two heteroatoms were proposed as reactive intermediates more than 20 years ago. Lloyd and McNab [168] observed the reaction of the 5-bromo-l,2-dihydropyrimidinium ions 411 with thiourea in refluxing ethanol to give the bromine-free cations 413. Suspected as intermediates, the 5d2-dihydropyrimidines 412 were initially considered as zwitterions of the type 414-Zj. However, quantum-chemical calculations on the parent systems suggested an unambiguous preference of the allene structure 414 over the zwitterion 414-Za [169]. 

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. 

The evidence available suggests that, in a general way, steric factors affect the course of the reaction. Increase in the size of substituents at positions 5 or 7 or in the size of the nucleophile appears to favor protode-bromination over nucleophilic substitution, Furthermore it appears that 6-iododihydrodiazepines undergo protodeiodination rather than nucleophilic substitution irrespective of the size of the nucleophile or of 5(7)-substituents, whereas 6-chlorodihydrodiazepines are less susceptible to protodchalogenation.64 Thus with thiourea 6-bromodihydrodiazepines undergo protodebromination, whereas 6-chlorodihydrodiazepines form 6-isothiouronium salts, in contrast to the normally more ready formation of isothiouronium salts from bromo compounds than from chloro compounds. It is not unreasonable that protodehalogenation should be favored for more bulky dihydrodiazepines or nucleophiles since this reaction has less steric demands than nucleophilic substitution. Similarly, both for... 

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... 

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. 

Azido-terminated polymers can also be used in dick chemistry modifications with acetylene derivatives to incorporate various functional groups. Polymers with phosphonium end-groups were prepared from bromine-terminated PS or polyacrylates and BusP. Mercapto-terminated PS was prepared by the reaction of the corresponding bromo-compound with either thiodimethylformamide or thiourea followed by reaction with a nucleophile. ... 

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. 

A related reaction is the bromine-induced oxidative cyclization of l-acyI-3-(3-thienyl)-thioureas to 2-acylaminothieno[3,2-d]thiazoles the reaction probably proceeds through the formation of the sulfenyl bromide (Scheme 23) (78JHC81). The corresponding 2-thienyl derivatives, however, gave only bromo substituted products (Scheme 23). A similar cyclization is brought about on treatment of /3-(3-benzo[6]thienyl)-a-mercaptoacrylic acids (129) with iodine in THF, when the tricyclic compounds (130) are formed (70AHC(ll)l77>. 

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). 

Of all the methods described for the synthesis of thiazole compounds, the most efficient involves the condensation of equimolar quantities of thiourea and a-halo ketones or aldehydes to yield the corresponding 2-aminothiazoles (Scheme 167) (l888LA(249)3l). The reaction occurs more readily than that of thioamides and can be carried out in aqueous or alcoholic solution, even in a distinctly acid medium, an advantage not shared by thioamides which are often unstable in acids. The yields are usually excellent. A derived method condenses the thiourea (2 mol) with the non-halogenated methylene ketone (1 mol) in the presence of iodine (1 mol) or another oxidizing agent (chlorine, bromine, sulfuryl chloride, chlorosulfonic acid or sulfur monochloride) (Scheme 168) (45JA2242). 

Elemental chlorine, bromine, and iodine, sulfuryl chloride and thionyl chloride convert diorgano ditellurium compounds to organo tellurium trihalides (p. 314). The reactions are carried out in inert organic solvents with stoichiometrically required amounts of reagents. Dialkyl ditellurium compounds may lose alkyl halides if the halogenolysis is not performed under mild conditions at low temperatures. When equimolar amounts of halogens and diaryl ditellurium derivatives are combined in appropriate solvents, aryl tellurium halides are formed (p. 239). The formation of aryl tellurium halides is facilitated by stabilizing substituents in the orf/to-position to the tellurium atom or by the presence of thioureas or selenoureas in the reaction mixture. 

Reaction of an amino-substituted heterocyclic thiol such as 84 with acylating agents gives compounds 85, which are cyclized by POCl3 to form the respective imidazo[2,l- ][l,3,4]thiadiazoles 86 (Scheme 51) (for a review see <1998CHE1003>). Bromine oxidation of the cyclic thiourea 87 forms 2,3,5,6-tetrahydroimidazo[l,2- /][l,2,4]thiadia-zol-3-ones 88 (Scheme 52) <1973JPR539>. 

The preparations of 1,2,4-thiadiazoles and 1,2,4-thiadiazolidines from thioureas are well known and have been summarized in three reviews those of Bambas, Sherman, and Kurzer. Contained in these reviews are discussions of the controversies that surrounded some of the products, notably Hector s bases, which resulted from oxidation of substituted thioureas.Subjects covered in the above reviews, but too extensive to outline in detail here, are the oxidation of amidinothioureas to 3,5-diamino-l,2,4-thiadiazoles (71), the oxidation of phenylthiourea and of substituted amidinothioureas to 3,5-diimino-1,2,4-thiadiazolidines (72, Hector s bases), the reaction of thiopseudoureas with trichloromethanesulfenyl chloride to form 3-alkylthio-5-chloro-l,2,4-thiadiazoles (73), the reaction of thiopseudoureas with sodium thiocyanate and bromine and the oxidation... 

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