Isothiocyanates primary

Primary or secondary aminopyrazines may be converted directly into ureido- or thioureidopyrazines by treatment with isocyanates or isothiocyanates primary aminopyrazines may also be converted into such products indirectly via the corresponding isocyanato- or isothiocyanatopyrazines piperazines may be converted into 1/4-carbamoyl- or thiocarbamoylpiperazines by treatment with isocyanates, A-nitrourea, or isothiocyanates and aminopyrazines may be converted into guani-dinopyrazines by treatment with. S -methylisothiourcas or cyanamide. These processes (and some subsequent intramolecular cyclizations or other reactions) are illustrated in the following examples ... 

Isothiocyanates. Primary aliphatic amines react with carbon disulfide and DCC in ether at 0° to give isothiocyanates and dicyclohexylthiourea.5 The reaction can also be applied to the less basic primary arylamines if the reaction is carried out in pyridine (in a few cases one molar equivalent of triethylamine is also added).6 Yields of isothiocyanates are in the range 70-95%. 

Isothiocyanates. Primary amines are converted into isothiocyanates by combining with carbon disulfide and decomposing the dithiocarbamic acid salts with TsCl. ... 

Keywords Ninhydrin, malononitrile, aryl isothiocyanates, primary aliphatic amines, ethanol, triethylamine, room temperature, one-pot multicomponent synthesis, thio-Michael and Knoevenagel reactions, sulfur-nitrogen heterocycles, oxathiaaza[3.3.3]-propellanes, che-moselectivity, regioselectivity... 

Phenylthioureas. Primary and secondary amines react with phenyl isothiocyanate to yield phenylthioureas ... 

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 ... 

Bazureau et al. have reported a similar protocol to that described in Sect. 8.1 for the rapid synthesis of 2-thioxo tetrahydropyrimidin-4-(lH)-ones via cycli-zation of a primary amine with an isothiocyanate and a /1-dielectrophile (Fig. 35) [138]. First a j6-amino ester was linked to the ionic hquid support... 

When the reagent is the thiocyanate ion, S-alkylation is an important side reaction (10-43), but the cyanate ion practically always gives exclusive N-alkylation. ° Primary alkyl halides have been converted to isocyanates by treatment with sodium nitrocyanamide (NaNCNN02) and m-chloroperoxybenzoic acid, followed by heating of the initially produced RN(N02)CN. ° When alkyl halides are treated with NCO in the presence of ethanol, carbamates can be prepared directly (see 16-7). ° Acyl halides give the corresponding acyl isocyanates and isothiocyanates. For the formation of isocyanides, see 10-111. 

Ammonia and primary and secondary amines can be added to isocyanates to give substituted ureas. Isothiocyanates give thioureas. This is an excellent method for the preparation of ureas and thioureas, and these compounds are often used as derivatives for primary and secondary amines. Isocyanic acid (HNCO) also gives the reaction usually its salts (e.g., NaNCO) are used. Wohler s famous synthesis of urea involved the addition of ammonia to a salt of this acid. "... 

Salts of dithiocarbamic acid can be prepared by the addition of primary or secondary amines to carbon disulfide. This reaction is similar to 16-9. Hydrogen sulfide can be eliminated from the product, directly or indirectly, to give isothiocyanates (RNCS). Isothiocyanates can be obtained directly by the reaction of primary amines and CS2 in pyridine in the presence of DCC. ° In the presence of diphenyl phosphite and pyridine, primary amines add to CO2 and to CS2 to give, respectively, symmetrically substituted ureas and thioureas ... 

Analogous to the synthesis of isocyanates, isothiocyanates are obtained in good yield by reacting AyV -thiocarbonyldiimidazole (ImCSIm) with primary aliphatic or aromatic amines in equimolar amount. In chloroform at room temperature the dissociation equilibrium of imidazole-A-thiocarboxamides is shifted completely to isocyanates. 

Biological specificity is a paramount consideration if one considers two examples, Acanthella pulcherrima [20] and Pseudaxinyssa sp. [68], That thiocyanate ion may be the precursor to marine isothiocyanates should be tested on these organisms since isothiocyantes were the primary representative of the triad. Also, should incorporation of thiocyanate ion by Phycopsis terpnis yield 81 and 82 [48], rather than the unreported corresponding isothiocyanates, the biospecificity of marine organisms will be demonstrated. 

Isothiocyanates react with nucleophiles such as amines, sulfhydryls, and the phenolate ion of tyrosine side chains (Podhradsky et al., 1979). The only stable product, however, is with primary amine groups, and so TRITC is almost entirely selective for modifying s- and N-terminal amines in proteins. The reaction involves attack of the nucleophile on the central, electrophilic... 

Richter utilized a reductive amination in their synthesis of the natural product (+)-hapalindole Q [294], Employing 10 equivalents of sodium cyanoborohydride and 40 equivalents of ammonium acetate in a methanol/THF mixture (150 °C, 2 min), the primary amine was obtained as a 6 1 mixture of diastereomers. Transformation to the isothiocyanate completed the total synthesis of (+)-hapalindole Q (Scheme 6.150). 

The soluble polymer support was dissolved in dichloromethane and treated with 3 equivalents of chloroacetyl chloride for 10 min under microwave irradiation. The subsequent nucleophilic substitution utilizing 4 equivalents of various primary amines was carried out in N,N-dimethylformamide as solvent. The resulting PEG-bound amines were reacted with 3 equivalents of aryl or alkyl isothiocyanates in dichloromethane to furnish the polymer-bound urea derivatives after 5 min of micro-wave irradiation (Scheme 7.75). After each step, the intermediates were purified by simple precipitation with diethyl ether and filtration, so as to remove by-products and unreacted substrates. Finally, traceless release of the desired compounds by cyclative cleavage was achieved under mild basic conditions within 5 min of micro-wave irradiation. The 1,3-disubstituted hydantoins were obtained in varying yields but high purity. 

Other approaches to tetrazoles were also recently published. Primary and secondary amines 195 were reacted with isothiocyanates to afford thioureas 196, which underwent mercury(II)-promoted attack of azide anion, to provide 5-aminotetrazoles 197 . A modified Ugi reaction of substituted methylisocyanoacetates 198, ketones, primary amines, and trimethylsilyldiazomethane afforded the one-pot solution phase preparation of fused tetrazole-ketopiperazines 200 via intermediate 199 <00TL8729>. Microwave-assisted preparation of aryl cyanides, prepared from aryl bromides 201, with sodium azide afforded aryl tetrazoles 202 . 

In analogous fashion to isocyanate chemistry, isothiocyanates like 125 can be utilized to produce the corresponding quinazoline-2-thioxo-4-ones. Makino and co-workers reported the solid phase synthesis of quinazoline derivatives 126 through the reaction of polymer-bound primary amines 124 with isothiocyanates 125 <00TL8333>. 

Thus, (dimorpholinophosphoryl)formonitrile oxide undergoes 1,3-addition reactions with HC1, HI, primary and secondary amines, acylhydrazines, and even with thiourea or thiosemicarbazide (Scheme 1.13) (98). The former gives (dimor-pholinophosphoryl)isothiocyanate and urea. Those products might arise from a retro destruction of the unstable 1,3,5-oxathiazoline. The latter transforms to the isothiocyanate, the product of addition of a second molecule of thiosemicarbazide. (98). 

Dipolar cycloaddition reactions, of nitrones to olefins, 46, 97 of 3-phenylsydnone, 46, 98 Dispiro[5.1.5.1]tetradecane-7,14-dione, photolysis to cyclohexylidene-cyclohexane, 47, 34 preparation from cyclohexanecarbonyl chloride and triethylamine, 47, 34 Displacement of bromine from 1-bromo-2-fluoroheptane to give 2-fluoro-heptyl acetate, 46, 37 N,N -Disubstituted formamidines from triethyl orthoformate and primary amines, 46, 41 N,N-Disubstituted thioureas from secondary amines and silicon tetra-isothiocyanate, 45, 69 N,N-Disubstituted ureas from secondary amines and silicon tetraiso-cyanate, 45, 69... 

The present procedure2 describes the conversion of resin-bound, primary aliphatic amines into isothiocyanates and the conversion of the latter into 3-aminothiophenes. The generation of isothiocyanates is related to known procedures,3 in which amines are first treated with carbon disulfide and the resulting dithiocarba-mates are desulfurized by treatment with a condensing agent (alkyl chloroformates, carbodiimides, lead or mercury salts, etc.). The presence of resin-bound isothiocyanates on the polystyrene support could be qualitatively ascertained by infrared spectroscopy (KBr-pellet strong absorption at 2091 cm-1). 

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