Thiouronium salts

Benzylthiouronium salts. Add 0 5 g. of sulphanilic acid to 10 ml. of water and 5 ml. of 10% NaOH solution, zndgently warm the shaken mixture until a clear solution is obtained. Cool, add 1 drop of phenol-phthalein solution, and then add dilute HCl dropwise with shaking until the pink colour is just discharged. Now add very dilute NaOH solution until the pink colour yt/rZ returns. Cool and add with shaking a solution of 0-5 g. of benzylthiouronium chloride in 5 ml. of water. The thiouronium salt rapidly separates filter at the pump, wash with water, drain and recrystallise from ethanol. Colourless crystals, m.p. 185°. (M.ps., p. 548.)... 

When thiourea or thiosemicarbazide are used for substitution of a chlorine atom with a mercapto group, thiouronium salts are formed first, and they are hydrolysed by aqueous base. Other groups, such as alkoxy, alkyl, amino and cyano, if present, are usually not... 

Chlorobenzoic acid [535-80-8] M 156.6, m 154-156°, 158°, dj 1.496, pK 3.82 (5.25 in 50% dimethylacetamide). Crystd successively from glacial acetic acid, aqueous EtOH and pet ether (b 60-80°). It also recrysts from CgH6 or Et20-hexane, and sublimes at 55° in a vacuum. [Anal Chem 26 726 1954] The methyl ester has m 21°, b 231°/atm. The S-benzyl thiouronium salt has m 164-165° (from EtOH) [Acta Chem Scand 9 1425 1955 J Chem Soc 1318 I960],... 

B) Auranofin A cold solution of 1.66g (0.012 mol) of potassium carbonate in 20 ml of distilled water Is added to a solution of 5.3 g (0.011 mol) of S-(2,3,4,6-tetra-0-acetylgluco-pyranosyD-thiopseudourea hydrobromide [Methods in Carbohydrate Chemistry, vol 2, page 435 (1963)1 in 30 ml of water at -10°C. A cold solution of 3.B6 g (0.011 mol) of triethyl-phosphinegold chloride in 30 ml of athanol containing a few drops of methylene chloride is added to the above mixture before hydrolysis of the thiouronium salt is complete. After the eddition is complete, the mixture is stirred in the cold for A hour. The solid that separates... 

The profitable conversion of thiouronium salts into dialkyl thioethers (see Section 4.1) is less successful for synthesis of diaryl thioethers. For example, l-chloro-4-nitrobenzene reacts with bis-thiouronium salts of the type (H2N)2CS(CH2) SC(NH2)2+ under soliddiquid and liquidrliquid conditions to produce the desired bis-thioethers, ArS(CH2) SAr, (20-35%), together with the diaryl sulphide, Ar2S (5-15%). Higher yields of the diaryl sulphide are observed under liquiddiquid conditions whereas, under solidiliquid conditions, the diaryl disulphide, (ArS)2, (20%) is also formed [56], Diaryl disulphides are the sole products (>65%) from the stoichiometric reaction of aryl diazonium salts with benzyltriethylammonium tetrathiomolybdate [57],... 

Compounds of type (XVIII) have been prepared by reduction of a nitroguanidine [199], by reaction of an amine with 5-methylisothiosemicarbazide [131,194,199,200], or by reaction of hydrazine with a substituted S-methyliso-thiouronium salt [131, 193]. 

A special case of SNAr is shown in Fig. 20. It actually involves a tandem 8 2-SNAr process on an Ugi adduct containing both an alkyl and an aryl halide. In 99, the acid-derived alkyl halide behaves therefore as a masked nucleophile. Treatment with thiourea (Sn2) forms an intermediate thiouronium salt which, upon basic hydrolysis, releases the required thiolate that undergoes the SnAt process. A library of benzothiazepinones 100 was produced in this way [92]. 

Methylisothiourea has also been used in place of thiourea to give 2-methylthio-5-cyanopyrimidinone derivatives <2006JME3988>, and polymer-bound thiouronium salts 733 have also been used to prepare derivatives 734 which can be displaced from the solid phase by oxidation of the sulfur atom to give sulfone 735, and subsequent displacement with amines <2002BML667> (Scheme 8). 

The reaction mixture cooled to 12°C upon dissolution of thiouronium salt 3. The checkers, however, found that complete dissolution of 3 was never achieved and that the internal temperature never fell below 15°C. A water bath (ca. 15°C) was therefore used for added temperature control throughout the addition of the NaOH solution. 

JOC1500,6lAK(l8)i5l, 72AJC985). Both the thiocyanopyrroles from the first method and the thiouronium salts from the second can be hydrolyzed to pyrrole-2-thiols. These compounds are evidently quite sensitive to oxidation so that in situ alkylation is frequently done, resulting in isolation of 2-alkylthiopyrroles as indicated in reactions (213) and (214). 2-Methylthiopyrrole is also obtained in low yield by reaction of the magnesium iodide salt of pyrrole with dimethyl disulfide (6lAK(l8)i5i). 

In many cases it is not necessary to prepare the alkyl bromide the S-alkyliso-thiouronium salt may be prepared directly from the alcohol by heating with thiourea and concentrated aqueous hydrobromic acid.236... 

A generally safe sulfur nucleophile is thiourea, giving thiouronium salts which are readily hydrolysed to the thiol, which can be oxidised to the disulphide. Since mishap is associated with separation of an explosive organic phase, an inert organic pick-up solvent, in which decomposition would be more controlled, should lend a measure of safety [14]. 

S -Benzyl derivatives can be formed using the robust synthesis of the appropriately substituted benzyl halide in combination with thiourea (Scheme 4). The tethered thiouronium salts 64-68 are routinely prepared by Sn2... 

The synthesis of thiols 19 is well managed if thiourea 28 is used instead of NaSH or Na2S as the nucleophile. Thiourea is itself highly delocalised but it is still a good nucleophile for saturated carbon through the sulfur atom 29. The product is a thiouronium salt 30 and is not nucleophilic at all, being a cation. Hydrolysis with aqueous base liberates urea 31 and the thiol 19. 

It has been proposed that reaction of / -nitrochlorobenzene with dithiols (such as HSCH2CH2SH, formed in situ from thiouronium salts) under phase transfer conditions to give 4,4 -dinitrodiphenyl sulphide (10%), 4,4 -dinitrodiphenyl disulphide (20%) and l,2-bis(4-nitrophenylthio)ethane (20%) occurs by the S l mechanism in competition with S Ar. These reactions are partially inhibited by /7-benzoquinone and gave ESR signals292. 

A variety of sulfur compounds are converted directly to sulfonyl halides by the action of bromine or chlorine water. The list includes mer-captans, sulfides, disulfides, thiol esters, thiocyanates, alkyl xanthates, and S-alkylthiouronium salts. Chlorination of the thiouronium salts sometimes leads to highly explosive products. Most of the reactions occur at low temperatures and give excellent yields of sulfonyl chlorides. The corresponding bromides are formed in somewhat lower yields (36-67%). Under anhydrous conditions halogenation of disulfides gives sulfenyl halides, viz., RSSR + Xj — 2RSX. 

---