With isothiocyanates

Azaindolizine, 5-chloro-nucleophilic substitution, 4, 458 8-Azaindolizine, 7-chloro-nucleophilic substitution, 4, 458 Azaindolizines basicity, 4, 454 electronic spectra, 4, 445 electrophilic substitution, 4, 453 halogenation, 4, 457 hydrogen/deuterium exchange, 4, 458 NMR, 4, 447, 449 nucleophilic attack, 4, 458 protonation, 4, 453 reaction with isothiocyanates, 4, 513 reactions, 5, 267 reviews, 4, 444 UV spectra, 4, 446, 449 Azaindolizines, amino-tautomerism, 4, 452... 

The reaction of enamino ketones with isocyanates and isothiocyanates has not been studied extensively. The enamino ketone (162) has been shown to react with phenyl isothiocyanate to give 163, the product of C acylation 114). Enamino ester derivatives of acetoacetic ester react similarly with isothiocyanates, also giving the C-acylated products 115). 

Substituted 2-mercapto-4(3i/)quinazolinones were prepared by condensing methyl anthranilate with isothiocyanates (see 7c). 

Reactions of unsaturated carbanions with isothiocyanates in synthesis of heterocycles 99JHC1469. 

Free amino acids can be derivatized with isothiocyanates to phenyl- or methyl-thiohydantoin derivatives. The thiohydantoins can be separated on a CSP with poly-[Af-acryloyl-L-phenylalanine ethylester] (Chiraspher ) as a chiral selector [25]. This CSP offers a known selectivity for many five-membered heterocyclic rings. 

Alkylamino)- or 2-(arylamino)-3//-l, 3,4-benzotriazepin-5(4//)-ones 15 are obtained from 2-aminobenzoic acid hydrazide. Treatment with isothiocyanates yields the thiosemicarbazides 14, which readily cyclize under the influence of dieyclohexylcarbodiimide. Selected examples are given.357... 

Reaction of dimsyl anion with isothiocyanates gives a-thioamidosulphoxides 478 in 12-59% yield, whereas with isocyanates it affords a mixture of a-amidosulphoxides 479 and methylsulphinylmalonoamides 480, the products of a double addition549 (equation 289). 

Another main subject of research of Garcia Gonzalez, with the collaboration of J. Femandez-Bolanos, was the reaction of amino sugars with isothiocyanic acid derivatives. 2-Amino-2-deoxy-D-glucose hydrochloride and potassium thiocyanate were shown to give rise to 4-(D-arabino-tetritol-l-... 

The construction of a tricyclic fused system can also be achieved by one-pot intermolecular/intramolecular cyclocondensations as exemplified by the reaction of functionalized amine 250 with isothiocyanate 251 to give 252 (Equation 33) <2005BMC3185>. 

Podhradsky, D., Drobnica, L., and Kristian, P. (1979) Reactions of cysteine, its derivatives, glutathione, coenzyme A, and dihydrolipoic acid with isothiocyanates. Experientia 35, 154. 

Cyclocondensation of pyrido[2,l-/][l,2,4]triazine 789 with phenacyl bromides (84S697) gave 791, whereas reaction of 790 with isothiocyanates gave 792. 

Acylhydrazides reacted with isothiocyanates in a one-pot procedure using microwave irradiation of the starting materials in the presence of either silica or montmorillonite K10 to give the 3-mercapto-l,2,4-triazoles 137a-f in high yields (Equation 42 and Table 26) <2006PS(181)1839>. 

Table 26 Reaction of acylhydrazides with isothiocyanates (Equation 42)...

The reaction of oxaziridines 378 with isothiocyanates has been established as a route to l,2,4-oxadiazolidin-5-thiones 379 (Scheme 64). Two mechanistic possibilities exist via which the products can form, each of which relies upon C-O cleavage, shown as paths a and b in Scheme 64. Interestingly, one of these paths involves the generation of nitrone 380, a species which could be identified as a reaction product <1998H(48)1935>. The nitrone could be generated separately and reacted with isothiocyanates to form identical l,2,4-oxadiazolidin-5-thiones 379. 

Amidines and cyclic amidines are also converted into 1,2,4-thiadiazoles by reaction with isothiocyanates, imino-sulfenyl chlorides, di- and trichloromethyl sulfenyl chlorides, and carbon disulfide in the presence of sulfur. Ureas, thioureas, guanidines, carbodiimides, and cyanimides react with chlorocarbonylsulfenyl chloride to produce 1,2,4-thiadiazol-5-one derivatives in another example of a type B synthesis <1996CHEC-II(4)307>. 

Thiohydrazides react with isothiocyanates to afford 1,3,4-thiadiazoles. The reaction proceeds via a dithioacylhy-drazine intermediate which under the reaction conditions cyclizes with loss of H2S. When the Ar-thiohydrazide pyrazole 143 is refluxed in DMF in the presence of phenyl isothiocyanate the 5-phenylamino-l,3,4-thiadiazol-2-yl pyrazole 144 is formed (Equation 54) <2000JCM544>. 

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>. 

For a related example of a ruthenium(II)-catalyzed cycloaddition of 1,6-diynes with isothiocyanates and carbon disulfide, see Yamamoto, Y. Takagishi, H. Itoh, K. J. Am. Chem. Soc. 2002, 124, 28-29. 

The sodium salts of dialkyl malonates were reacted with isothiocyanates (346) in diethyl ether or in THF at -10°C-0°C. The products were then alkylated with alkyl halides to give mixtures of tautomeric (alkylthio)ami-... 

Diethyl sodiomalonate, prepared from diethyl malonate and sodium hydride, was reacted with isothiocyanate (528) in DMF by dropwise addition at 5°C. The reaction mixture was then stirred at ambient temperature for 1 hr to give (l,3,5-thiadiazepin-2-ylidene)malonate (529) in 76% yield (86S817). 

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