Reactions of Isothiocyanates

Reactions of Isothiocyanates.— Pyrolysis of but-3-enyl and l-methylprop-2-enyl isothiocyanates gives buta-1,3-diene and HNCS in the primary reaction eventual products include the thiocyanate formed by re-addition of HNCS and pyrolysis products of the hydrocarbon. 

Benzoyl isothiocyanate reacts with Grignard reagents R R CHMgX at isothiocyanate carbon, giving N-benzoylthioamides, from which keten S,N-acylals R R C=C(SCOR )NHCOPh are formed by further acylation.  

Sonoda, G. Yamamoto, and S. Tsutsumi, Bull. Chem. Soc. Japan, 1972, 45, 2937. 

Further examples of multifunctional isothiocyanates include aryl for-mamidinoyl-isothiocyanates RiNC(=NR )NCS, which may be isomerized into 3H-quinazoline-4-thiones and which undergo well-known amine addition and cycloaddition reactions associated with simpler isothiocyanates ° and sulphonyl isothiocyanates, for which 1,3-dipolar cycloaddition to alkyl azides has been demonstrated,thermolysis of the resulting thiatriazolines giving sulphonyl carbodi-imides ArS02N=O=NR. 

Conversion of trityl isoselenocyanate into the isocyanide can be brought about by treatment with various tervalent phosphorus compounds/  

---

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. 

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... 

Cyclic thiourea derivatives having three different types of cyclophane structure (ortho-meta, meta-meta and meta-para) and a lariat-type thiourea have been synthesized, using reaction of isothiocyanate with amine.230 Cyclic thioureas have been obtained from formaldehyde aminals and sulfur (Sg) (Scheme 77).231... 

A further variation is the reaction of isothiocyanates (e.g., 162f) with hydrazine that has been solidified by inclusion into the host hydroquinone (163). Ball-milling of the solids leads to a quantitative reaction and the auxiliary 165 is washed away with water [79] (Scheme 20). 

Reaction of isothiocyanate 135 with aminopyrazole 136 in the presence of ZnClj gives the pyrazolo[3,4-d]pyrimidine 138, probably via the intermediate thiocyanate derivative 137 (79CPB1143). 

The reaction of isothiocyanate 2 and 30 with 2-amino-4-picoline has also been reported.55 Dorn and coworkers56"59 reported the synthesis of a number of substituted thioureido derivatives by treatment of isothiocyanates 2 and 5 with 2-phenylethylamine, bis(2-chloroethyl)amine, and 2-(4-ethoxyphenyl)-1 -phenylethylamine. 

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... 

Reaction of isothiocyanates 2, 30, and 31 with the acyl- or aroyl- and alkyl-hydrazine derivatives82 123a, 123b, 124a and 124b has also been... 

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... 

L abb6 and co-workers have found that 4-alkyl-5-sulfonylimino-A2-l,2,3,4-thiatriazolines 165 can be easiliy prepared by reaction of the highly reactive arylsulfonyl isothiocyanates 166 with alkyl azides (Equation 15). Kinetic experiments indicate that the reaction between picryl isothiocyanate and alkyl azides is probably concerted since no significant solvent effect has been observed <1973JOC2916, 1974JA3973>. This is in support of the postulated mechanism involving the intermediate 5-imino-A2-l,2,3,4-thiatriazolines 164 in the reaction of isothiocyanates with hydrazoic acid. 

The [2+2] cycloaddition reaction of isothiocyanates with carbodiimides generally proceeds across the C=S bond of the isothiocyanate to give thiazetidine derivatives 218. However, in the reaction of methyl isothiocyanate with N-(4-dimethylaminophenyl)-N -methylcarbodiimide a mixture of the thiazetidine derivative 218 and the isomeric iminodi-azetidinethione derivative 219 is obtained. The structure of 219 was confirmed by X-ray crystallography. ... 

Treatment of 3-amino-6-methoxypyridine or the corresponding thiourea 471 with thiophosgene gives the l,3-thiazetidine-2-thione 472. 1,3-Thiazetidine-2-thiones are possible intermediates in the reaction of carbon disulfide or isothiocyanates with isothioureas,in the reaction of carbon disulfide with imines, " and in the reaction of salts of dithiocarbamic acids with a,/3-unsaturated acid chlorides. 4-Imino-l,3-thiazetidine-2-thione is suggested as an intermediate in reactions of isothiocyanic acid (HNCS). ... 

N-vinylic phosphazenes react with isocyanates to yield N-vinylic carbodiim-ides. The reaction of isothiocyanates and an N = P moiety has been used to prepare oxazole derivatives The reactivity of the — N = P moiety in synthetic procedures has also been demonstrated by the aza-Wittig reaction with aldehydes " ... 

With aromatic isothiocyanates, triazolium-4-(acetyl)imide displays both 1,3- and 1,5-dipolar activity, depending on reaction conditions, mainly solvent polarity. In nonpolar solvents such as benzene, concerted 1,3-additions occur across both the C=N (113) and C=S (114) bonds of the isothiocyanate (84CCC1713) this is unlike the reaction of isothiocyanates with azomethinimines of the dihydroisoquinoline series, in which 1,3-ad-... 

Thiiranimine is prepared by the reaction of isothiocyanate with diphenyl-diazomethane at 0°C in 67% yield (Equation (34)) <78AG(E)195>. 

The 2-imino-l,3-oxathiolanes (43) may be prepared by reaction of isothiocyanates, RNCS, with either (310) <77BCJ3271> or (311) <74JOM(72)103>, and reaction of the latter with CSj gives 1,3-oxathiolane-2-thione (42). 

Particularly significant is the extension to the S5mthesis of enantioenriched oxazolidin-2-thiones of the reaction of isothiocyanate 189 with aromatic aldehydes. This reaction is catalysed by Mg(C104) and the asymmetric induction is provided by a pybox ligand <05AG(E)1543>. A different approach to enantioenriched oxazolidin-2-thione was provided by a kinetic resolution of racemic substrate with an organic catalyst. Compound 192 efficiently catalysed the methanolysis of iV-acyl oxazolidinethiones 191 and afforded an efficient kinetic resolution of 191 with an s-factor up to 32 <05JA13502>. 

Sulfonyl imides(RN=S02), generated from alkylsulfamoyl chloride (RNHSOjCl) and triethylamine, react with enamines in the same way as sulfenes do, to give four-membered heterocycloadducts such as 210 Phenyl isocyanate undergoes [2 -t- 2] cycloaddition with enamines affording azetidinones (211) whereas azetidinothiones (212) have been obtained from the reaction of isothiocyanates with enamines without j8-hydrogens . ... 

Thiocarbamoyl isothiocyanate reacts with cyclic enamines to form a fused thiazinethione under mild conditions a mechanism has been suggested for this unusual cyclization. The reactions of isothiocyanates have been reviewed [3990]. 

---