Of isothiocyanates

The 5-acylamino-THISs react with alkynes in a way already exemplified for 5-hydroxy-THISs. Pyrroles are formed under elimination of isothiocyanate (Scheme 29) (37). 5-Acylamino-THISs are readily bromi-nated in the 4-position (21). 

ThiO 4-oxoselenazolidines substituted in the 3-position, have been described in a number of patents, (79, 80). They are used as intermediates in the manufacture of pharmaceuttcal products and color sensitizers in photography. They are obtained by action of isothiocyanates on a-hydroselenoacetic acid in the presence of strong base and in the absence of air (Scheme 77). 

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

As shown by Oliveri-Mandalli,and by Lieber et al., 5-sub-stituted-amino-l,2,3,4-thiatriazoles are also formed by reaction of isothiocyanates with hydrazoic acid. When sodium azide is used instead of the free acid the isomeric mercaptotetrazoles are formed. 

Altanserin (100) is a representative of the thiaquinazolinones. This serotonin antagonist is said to prevent gastric lesions. One method for preparation of this compound involves first preparation of isothiocyanate derivative 99, by reacting 4-fluorobenzoylpiperidine with 2-bromoethylamine and then converting the intermediate to the isothiocyanate with thionyl chloride and base. Condensation of 99 with methyl anthranilate (98) probably proceeds initially to a thiourea. Cyclization by ester-amide interchange leads to altanserin (100) [28]. 

Related to this process is the hydrolysis of isocyanates or isothiocyanates" where addition of water to the carbon-nitrogen double bond would give an N-substituted carbamic acid (3). Such compounds are unstable and break down to carbon dioxide (or COS in the case of isothiocyanates) and the amine ... 

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]. 

Most of the ions in the spectrum of isothiocyanate derivatives of cyclo-phosphazenes are cyclic. The CNS group fragments to give abundant ions M — S, M — S2, and M — CSj. 

Many in vitro studies have been undertaken to explore the relative effectiveness of isothiocyanates, and associated compounds, as inhibitors of cell growth and inducers of apoptosis in cell lines, and some of these are summarised in Table 4.2. Clonal survival studies are often used to determine whether isothiocyanates inhibit initial cell anchorage and subsequent growth of sparsely seeded cells. However, differences in cell number following challenge with the isothiocyanate could be due either to decreased cell division or increased cell loss, and the authors of some in vitro studies have failed to recognise this. Other studies have, however, considered the interacting... 

ZHANG Y, WADE K L, PRESTERA T and TALALAY p (1996) Quantitative determination of isothiocyanates, dithiocarbamates, carbon disulfide, and related thiocarbonyl compounds by cyclocondensation with 1,2-benzenedithioT, Anal Biochem, 239 160-67. 

HONG w K and wu x (2000) Dietary intake of isothiocyanates evidence of a joint effect with glutathione S-transferase polymorphisms in lung cancer risk . Cancer Epidemiol Biomarkers Prev, 9 1017-20. 

NASTRUZZI C, CORTESI R, ESPOSITO E, MENEGATTI E, LEONI O, lORI R and PALMIERI S (2000) In vitro antiproliferative activity of isothiocyanates and nitriles generated hy myrosinase-mediated hydrolysis of glucosinolates from seeds of cruciferous vegetables , JAgric Food Chem, 48 3572-5. 

LUND E K, SMITH T K and JOHNSON I T (2000) The mechanism of isothiocyanate induced death of HT29 adenocarcinoma cells is dependent on the nature of the side chain , Gastroenterology, 118 2895. 

The ImCSIm-method has been used, for instance, in the synthesis of isothiocyanates containing steroid, sugar, and alkaloid components ... 

Amorphanes 38-40 were also isolated from Acanthella cannabina. These are trans-fused and functionalized at C-l rather than C-10 which was the case with the Halichondria metabolites. The carbocyclic skeleton was demonstrated when 39 was dehydrogenated to yield cadalene (37). Relative stereochemistry assignments were secured by extensive 13C- and XH NMR experiments [39], in which 13C data were particularly useful, as illustrated in the case of isothiocyanate 41, one of several isothiocyanates obtained from Acanthella pulcherrima [20]. The ds-fused ring was corroborated by comparing the corresponding chemical shifts with those of enf-epicubenol (42) [20], which has the same relative stereochemistry. 

Along with epi-eudesmanes, 25-27, alloaromadendranes 58-60 were separated from the chloroform solubles of a methanol extract of A. cannabina [36], As was the case with axisonitrile-2 (53), extensive spectroscopic analyses including Eu(fod)3 shift reagent experiments in XH- and 13C NMR permitted assignment of relative stereochemistry. Acanthella pulcherrima was also a source of isothiocyanate 59, although both isonitrile and formamido compounds appear to be absent [20],... 

In analogy to the thiohydantoin synthesis, the PEG-bound diamines have also been treated with various alkyl and aryl isothiocyanates and, after applying traceless cyclative cleavage, the desired thioxotetrahydropyrimidinones were obtained in excellent yields. In contrast to the thiohydantoin synthesis, purification of the products was more complicated if the excess of isothiocyanate amounted to more than 2.2 equivalents [85],... 

The conversion of isothiocyanates to isonitriles under microwave conditions has been studied by Ley and Taylor using a polymer-supported [l,3,2]oxaphospholidine [119]. The use of 3-methyl-2-phenyl-[l,3,2]oxaphospholidine in solution is less favored [120] due to the associated toxicity and instability of the phosphorus-derived reagent, as well as the need to isolate the products from a complex reaction mixture by vacuum distillation. This drawback has been resolved by attaching the active [l,3,2]oxaphospholidine to a polymer matrix. 

Scheme 7.99 Conversion of isothiocyanates to isonitriles utilizing a polymer-supported [1,3,2]oxazaphospholidine.

Reactions of isothiocyanate with nucleophiles give desired thioamides (Scheme 7). 

Reaction of isothiocyanates with resorcinol derivatives in the presence of boron trifluoride-acetic acid complex for overnight at 0-5 °C affords the corresponding thioamides.25... 

Thioureas are most commonly prepared from reaction of isothiocyanates with amines. Also there are some reports on reactions of anime or carbodiimides with several thionating reagents. AA -Disubstituted thioureas bearing double NH groups have been developed as sensors, and as catalysts because of their hydrogen bonding ability. A,A -Disubstituted thiourea-linked sugar chains have been prepared by the reaction of isothiocyanate with amine. 

Reaction of isothiocyanate with amine gives the corresponding thioureas. Many reports are appeared.102 111 The thiourea derivatives have been prepared by reactions of isothiocyanates with arylamines (Scheme 39) and reacted with some substrates to afford heterocyclic compounds, such as 2-amino-4//-ben-zothiazine, 1,3-thiazine, 1,3-thiazinone and l,3-thiazolidin-4-one.112 115... 

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