Amines thiophosgene

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 ... 

Treatment of a chiral amine with phosgene is the cheapest way to prepare symmetrical ureas [29]. Nevertheless, due to the toxicity and reactivity of that reagent, it can advantageously be replaced by triphosgene [30] or l,l -carbonyldiimidazole [31-34] or other derivatives such as l,l -carbonyldi-2(lH)-pyridinone [35]. This procedure can be extended to thiophosgene (Scheme 1) and its thio-analogues, such as l,l -thiocarbonyldi-2(lH)-pyridinone to produce thioureas [36] chiral diamines can thus be transformed into the corresponding monoureas or monothioureas. 

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>. 

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... 

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. 

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... 

Isothiocyanates can be prepared from support-bound primary amines by treatment with thiophosgene [14] or synthetic analogs thereof (Entry 5, Table 14.2). In an alternative two-step procedure, the amine is first treated with CS2 and a tertiary amine to yield an ammonium dithiocarbamate, which is subsequently desulfurized with TsCl or a chloroformate (Entry 6, Table 14.2 Experimental Procedure 14.1). Highly reactive acyl isothiocyanates have been prepared from support-bound acyl chlorides and tetra-butylammonium thiocyanate (Entry 7, Table 14.2). These acyl isothiocyanates react with amines to give the corresponding 7V-acylthiourcas, which can be used to prepare guanidines on insoluble supports (Entry 6, Table 14.3). 

Billeter prepared diethylthiocarbamyl chloride2 and other carbamyl chlorides by the reaction of the appropriate amine as amine hydrochloride with thiophosgene. The present preparation represents an adaptation of the Ritter process.6... 

Pteridine synthesis from pyrazine precursors are usually applied in such cases where the formation of special derivatives cannot be achieved easily by the pyrimidine approach. Methyl 3-amino-2-pyrazinecarboxylate (362) reacts with thiophosgene to give the corresponding 3-isothiocyanato derivative (363) which cyclizes with primary amines, arylalkylamines, aminoalcohols, amino acids,... 

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. 

---