Thiophosgene reaction with amines

Bis(benzotriazol-lyl)methanethione 974 is easily prepared from thiophosgene and l-(trimethylsilyl)benzotriazole <1978JOC337>. In reactions with thiols and triethylamine, thiones 974 are converted to derivatives 973 in modest yields the main side products result from nucleophilic attacks of the thiolate anions on the thione sulfur atom to produce disulfides <2005JOC7866>. In reactions with amines, compounds 974 are smoothly converted to l-(thiocarbamoyl)benzotriazoles 975 <2004JOC2976>. Substitution of one of the benzotriazolyl groups in 974 by phenolate anions yields l-(aryloxythioacyl)benzotriazoles 978 (Scheme 161) <2005JOC7866>. 

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 ... 

Saccharidic templates bearing an amino group in C-2, C-6, C-3, C-5. Generally, an amine located on non-anomeric position reacts similarly through the condensation reaction with carbon disulfide or thiophosgene, the preliminary formed isothiocyanate leads to spontaneous or base-induced cyclization into 1,3-oxazolidine- or l,3-oxazine-2-thiones, as previously mentioned. Several extensive studies are reported about the selective introduction of thionocarbamate moieties on carbohydrate scaffolds.3 22 23 320 34 38... 

Symmetrical dialkyl and diaryl thioureas have been prepared in generally good yield (60-90%) from the reaction of the amine with thiophosgene, formed in situ from the catalysed reaction of carbon tetrachloride with sodium sulphide [5], Reaction with diamines yields cyclic ureas. 

The dibromo derivatives 125a and 126a have been prepared by reaction of the unsubstituted amine 125c and the methanesulphonate salt of 126c with excess bromine in acetic acid. Amines 125b and 126b have been converted to the isothiocyanates 125 and 126 by reaction with thiophosgene in a biphasic chloroform-bicarbonate system. The radiochemical purity and the specific radioactivity of the isothiocyanate 125 were 99.9% and 27.4 Ci mmol -1, respectively. The benzimidazole isothiocyanate 126 has been prepared with >95% radiochemical purity and with specific activity of 16.3 Ci mmol -1. 

Wagner and Nuhn19 also detailed treatment of the l-seleno-/3-o-glucoside1112 with thiophosgene, a reaction which yielded a thiocyanato derivative after reaction with various classes of amine. 

Other preparative routes to isothiocyanates involve reaction of amines with carbon disulfide and alkali and subsequent treatment of the dithiocarbamate (112) with phosgene or ethyl chloroformate. Alternatively, the dithiocarbamate may be reacted with mercury(II) chloride or lead tetranitrate (Scheme 61). Amines can also be reacted with thiophosgene or N,N-diethyl thiocarbamoyl chloride (113) (Scheme 61). 

This compound, 223, a potent and selective iXj-adrenoceptor agonist used also in studies of vasoconstriction , has been obtained according to the reaction sequence of equation 93. This involves oxidation of high-specific-activity paraldehyde-with selenous acid to ethanedial-l,2- C2 which was condensed directly with 1,2,4-benzenetriamine dihydrochloride to 6-quinoxalin-2,3- C2-amine in 56% yield, bromi-nation of 224 and conversion of 225 to its isocyanate 226 by reaction with thiophosgene, and finally the reaction of 226 with ethylenediamine in refluxing 1 1 methanol-toluene. The overall radiochemical yield of 223 was 11% starting from paraldehyde-The radiochemical purity of the tartrate 227 was 98.2%, specific activity 101.5 mCi mmor ... 

Like 2-aminopyridines and 2-aminopyrimidine, 2-aminopyrazine (39) (Scheme 29) has been converted into the nitroso compound (121) by reaction with dimethyl sulfide and NCS followed by deprotonation of the resulting sulfonium salt with sodium methoxide to the 5, 5-dimethylsulfilimine and then oxidation with MCPBA <82JOC552>. The extremely reactive nitrosopyrazine (121) condenses with 1,3-dienes to give 3,6-dihydro-1,2-oxazines and with aromatic amines in the presence of acid to gives azo compounds, and is smoothly oxidized with ozone or sodium hypochlorite to 2-nitropyrazine (122). Methyl 3-aminopyrazinecarboxylate reacts with thiophosgene to produce the... 

In carbohydrate chemistry, the most described method for the preparation of saccharidic thionocarbamates involves preliminary introduction of the amine function on a partially or non-protected saccharidic template. The condensation of amino sugars with carbon disulfide or thiophosgene leads to cyclization in 1,3-oxazolidine- or l,3-oxazine-2-thiones. This reaction involves the formation of an intermediate isothiocyanate, which reacts further with a 3- or y-located hydroxyl group. The viability and facility of this process depends on the saccharidic ring size and the inherent strain. Some major rules can be put into light from the cases studied 30... 

Condensation of ethyl anthranHates with isothiocyanates provides entry to a closely related compound in which the carbonyl at the 2 position is replaced by a thione. The sequence starts with the alkylation of pyrrolidine nitrogen in (92-1) with 2-bromoethylamine. Reaction of the primary amine in the product (92-2) with thiophosgene leads to the isothiocyanate derivative (92-3). Reaction of that reactive intermediate with methyl anthranilate (92-4) leads initially to the transient... 

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