Thiocarbamylation

Sulfenamides. Sulfenamides (4) are often produced by oxidising an equimolar mixture of MBT and an aliphatic amine. Alternatively, the /V-ch1oroamine can react with the sodium salt of MBT. One sulfenamide, OTOS (S), uses a thiocarbamyl functionaUty in place of the ben2othia2ole group. 

Thiophosgene reacts with alcohols and phenols to form chlorothionoformates or thiocarbonates. The most studied reactions of thiophosgene are with primary amines to give isothiocyanates and with secondary amines to give thiocarbamyl chlorides ... 

Carbamyl and thiocarbamyl fluorides are obtained from hydrogen fluoride and cyanic acid or alkali metal cyanates or thiocyanates [/, 54] Nitnles give iraidofluoride salts with hydrogen fluoride [7] whereas hydrogen cyanide affords difluoromethylamine, which can be isolated as its hexafluoroarsinate salt [55) (equation II)... 

Quinazoline-2-thione-4-one (522) and its 3-phenyl derivative coordinate to Ni11 after deprotonation via the S and the NI donor resulting in a square planar complex.1372 The related 2-isopropylquinoline-8-thiolate (523) forms a distorted tetrahedral complex.1 73 For deprotonated 2-thiocarbamyl-thiazoline (HL = (524)) the octahedral complex [NiL(H20)4]+ is favored over the square planar [NiL2] complex.1374... 

Sweedler reported a two-dimensional separation, where fluorescein thiocarbamyl derivatives of peptides were separated by capillary zone electrophoresis in the first dimension (Liu and Sweedler, 1996). The outlet of the capillary was wiped across the top of an SDS-PAGE gel, where peptides were then separated based on their size. 

Obviously, the main purpose for the introduction of CL detection coupled to CE separations is inherent to the development and improvement of sensitive and uncomplicated devices to achieve a decrease of the band broadening caused by turbulence at the column end, together with the attractive separation efficiency of CE setups. With this purpose in mind, Zhao et al. [83] designed a postcolumn reactor for CL detection in the capillary electrophoretic separation of isoluminol thiocarbamyl derivatives of amino acids, because, like other isothiocyanates, isoluminol isothiocyanate has potential applications in the protein-sequencing area. 

The elimination of turbulent mixing in the flow chamber and the short residence time of the reaction mixture in the detection chamber provided a high separation efficiency of 100,000 theoretical plates for labeled amino acids, obtaining good resolution in comparison with previous CL detectors [79, 82], For the isoluminol thiocarbamyl derivative of valine, a detection limit of 500 amol was reported however, it was not possible to separate all 20 isoluminol-deriva-tized amino acids. 

Di(thiocarbomyi)-hydrazine. See N,Nf-Bis-(thiocarbamyl)-hydrazine In Vol 2 of Encycl, pp B158-R B159-L... 

Crysts, mp 232—237° very si sol in w dissolves in bases from which solas it may be repptd by addition of acid. It was obt in yields up to 60% by deamination of bis-thiocarbamyl-hydrazide, HaN CS.NH-NH CS NHa, in the presence of polyphosphoric acid concg 82—84% P2Os as the deaminating and cycliz-ing agent. This compd seems to be identical with the 234° mp form described in Beil... 

Di (thiocarbamyl)-hydrazine see N. N -Bis (thio-carbamyl)-hydrazine 2 B158-B159... 

The submitters have prepared the following thiocarbamyl chlorides by the chlorination of the corresponding disulfides dimethylthiocarbamyl chloride, b.p. 90-95°/0.5 mm., m.p. 42.5-43.5°, carbon tetrachloride reaction medium diisopropylthio-carbamyl chloride, m.p. 69-71°, benzene reaction medium diiso-butylthiocarbamyl chloride, m.p. 46-48°, no solvent. 

The procedure is essentially similar to that described for the preparation of 5-amino-l,2,3,4-thiatriazole. Freund and Hempel6,7 have reported observing that the initial diazotization products of 4-aryl-substituted thiosemicarba-zides lead to the formation of tetrazoles, while the corresponding 4-alkyl-substituted thiosemicarbazides were considered by Freund and Schwarz8 to be thiatriazoles. However, Oliveri-Mandala,9 on the basis of his study of the reaction of alkyl and aryl isothiocyanates with hydrazoic acid, concluded that the initial diazotization product of either 4-aryl or 4-alkyl thiosemicarbazides were open-chain thiocarbamyl azides, RNHC( S)N3. Lieber, Pillai, and Hites10 have recently clarified this situation and have shown... 

Selenium and tellurium dioxides react with alkali xanthates and dithiocarbamates to give xanthates and dithiocarbamates of selenium(IV) and tellurium(IV).1,2 Russell1 states that the product formed by sodium diethyldithio-carbamate and selenium dioxide sometimes appears as an equimolar mixture of selenium (II) dithiocarbamate and the corresponding bis(thiocarbamyl) disulfide, (R2NCS)2S2. The commercial selenium dithiocarbamates, prepared by the above-mentioned method, usually consist of such mixtures. The disulfide can, in most cases, be extracted from selenium (II) dithiocarbamate by means of cold benzene or chloroform. 

Similar reactions have been carried out with amidines (67NEP6610627). Thus tri-chloroacetamidine (309) reacts with chlorothioformate esters to produce thioacyl products (310) which are readily oxidized to 5-alkoxy-3-trichloromethyl-l,2,4-thiadiazoles (311). The yields in both steps are about 80% (Scheme 111). The bromine oxidation of N-thiocarbamyl derivatives (312) of cyclic amidines (2-aminopyridine, 2-aminothiazole, 2-aminopyrimidine) yields thiadiazolium salts (313) (71JPR1148). In the 2-aminopyridine series, products of type (230 Scheme 81) are obtained in 20-73% yield when R is an ethoxycar-bonyl group (750PP55). 

The only known compound of this type is a thiocarbamyl derivative. Bromomagnesium ethenetellurolate combined with /V.TV-dimethylamino-Lhiocarbonyl chloride to give orange-red, solid N,N-dimethylaminothiocarbonyl ethenyl tellurium, which is stable at 20° under an atmosphere of argon, but is decomposed by acids1. 

Difficulty finding conditions that would allow both efficient sequencing and suppression of the O-to-N shift led us to investigate tertiary amine catalysis of thiocarbamylation. Complete reaction of ONCS showed little effect of solvent on coupling. Adding 1.5 to 2.5 equivalents of acetic acid, however, decreased the fraction of the desired product (Table HI). 

Table III. Tertiary-amine catalysis of thiocarbamylation with ONCS...

When MNCS was used instead of ONCS, there was a greater tendency for the reaction to form multiple products (greater sensitivity to reaction conditions), so MNCS was used for subsequent tests. Formation of multiple products as pH was lowered is consistent with the results obtained using ONCS and HSA at different pHs (Table II). Examination of coupling in the presence of one equivalent each of M6N and A demonstrated that thiocarbamylation in ethanol does not follow pseudo-first order kinetics, showing instead a long lag before the reaction mixture becomes effective. Of six solvents tested, mSO gave the fastest reaction and the best ratio of products. 

Various amines were tested near neutrality for thiocarbamylation catalysis (Table IV). Amine pKa varied directly with reaction rate, and inversely with the percentage of correct product. Rapid reaction in the absence of tertiary amine suggested another activation pathway for thiocarbamylation. 

That coupling could be catalyzed without tertiary amines led to examination of non-tertiary amine catalysis of thiocarbamylation. Tests with sodium salts revealed a moderate catalysis by acetate, and weaker effect of formate (data... 

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