Isothiocyanate formation, amine

K A L U Z A Isothiocyanate synthesis Formation of isothiocyanates from amines. 

In a series of publications and patents,63 64 66"79 Wieniawski and coworkers reported the results of investigations of the reaction of sugar isothiocyanates with amines and various substituted hydrazides of heterocyclic acids. The reaction of isothiocyanate 2 with 2,6-diaminopyridine 81 was described,63 and the formation of dithioureide 82 as the sole product was observed. The... 

Chemical Properties The formation of salts with acids is the most characteristic reaction of amines. Since the amines are soluble in organic solvents and the salts are usually not soluble, acidic products can be conveniendy separated by the reaction with an amine, the unshared electron pair on the amine nitrogen acting as proton acceptor. Amines are good nucleophiles reactions of amines at the nitrogen atom have as a first step the formation of a bond with the unshared electron pair of nitrogen, eg, reactions with acid anhydrides, haUdes, and esters, with carbon dioxide or carbon disulfide, and with isocyanic or isothiocyanic acid derivatives. 

Diamines can also react with only one equivalent of isothiocyanate to form bi-functionnal amine-thiourea ligands 59-68% yields obtained for several alkyl isothiocyanates. However, reaction of phenyhsocyanate with 1,2-diamines could also lead to the formation of the guanidine derivative by cyclisation and elimination of H2S (Scheme 4) [42,43]. 

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... 

NDA derivatization has also been automated for analysis of amino acids in brain tissue and microdialysates (Shah et al, 1999). NDA reacts with primary amines in the presence of cyanide to form a highly stable N-substituted l-cyanobenz[/] isoindole (GBI) derivative. Addition of a nucleophile, such as cyanide, hydrogen sulphite, isothiocyanate, or 2-mercaptoethanol, is essential for the formation of the derivative. 

The interaction of biguanide (CL) and isothiocyanate esters in dimethyl-formamide under mild conditions (376) gives excellent 3delds of 1-sub-stituted hexahydro-4,6-di-imino-s-triazine-2-thiones (CLII), together with small quantities of thioammeline (CLIII) and monosubstituted melamines (CLIV). Under more severe conditions, the latter (CLIV) become the main products. The production of these triazines is explained by a mechanism involving the primary formation of addition products (CLI), followed by their cydisation with loss of either ammonia, hydrogen sulphide, or primary amine (376). 

A comparatively large selection of thioureas can be formed from the reaction of amines with isothiocyanates, hence they are attractive starting materials for formation of guanidines. A common solution-phase approach to this reaction involves abstraction of the sulfur via a thiophillic metal salt, like mercuric chloride.10 For solid-phase syntheses, however, formation of insoluble heavy-metal sulfides can have undesirable effects on resin properties and on biological assays that may be performed on the product. A more relevant strategy, with respect to this chapter, is S-alkylation of thioureas and then reaction of the methyl carbamimidothioates formed (e.g., 5, Scheme 6) with amines. This type of process has been used extensively in solution-phase syntheses.1 Ul4 Two examples are shown in Scheme 6 11 the second is an intramolecular variant, which involves concomitant detrity-lation.15... 

Oligothioureas have been prepared on cross-linked polystyrene from Boc-pro-tected oaminoisothiocyanates, which were synthesized in solution from symmetric diamines [258]. The formation of thioureas from support-bound amines and isothiocyanates is a rather sluggish reaction (e.g. 3 d, 45 °C, mean coupling yield 90% [258]), and only short oligomers can be prepared using this strategy. 

On the other hand, the condensation of isothiocyanates 2, 30, and 31 with 6-aminopenicillamic acid (167), as well as ampicillin (168), in tetrahy-drofuran or N,N-dimethylformamide solution in the presence of triethyl-amine,90 led to formation of only the corresponding thioureides 169-174. 

Khorlin and coworkers92 95 reported that the reaction of isothiocyanates 2 and 53 with acetic acid, as well as benzoic acid, in the presence of triethyl-amine, leads to the formation of N-glycosylacetamides 175 or 176 in 35% yield, and, as coproducts, l,3-bis(glycosyl)ureas (177 and 179) and 1,3-bis(glycosyl)thioureas (178 and 180). This method has been employed in... 

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