Nitrogen acyl isothiocyanates

Other thietane derivatives have been obtained by isomerization of nitrogen-containing heterocycles. The reaction of an acyl isothiocyanate (RCONCS) with diphenyldiazomethane gave 20 and this isomerized in solution to the tetraphenyl-3-thietanone 21 <96BSB253>. Additionally, the isoxazolidine 22 was converted into 23 by the action of trimethylsilyl iodide and zinc iodide <96H1211>. 

In this case, the acidic species RCOX is a hard acid and reacts with the nitrogen end of SCN to form an acyl isothiocyanate. The soft methyl group bonds to the S atom and forms methyl thiocyanate. Consider the reactions of NC)2 ... 

Aryl and acyl isothiocyanates were also found to react with alkyl azides, but yield thiatriazoline-5-imines only as elusive intermediates which are transformed in situ into a series of bisadducts after loss of nitrogen. Interestingly, L abbe et al. have found that picryl isothiocyanate is an exception to this and reacts smoothly with alkyl azides to yield 4-alkyl-5-picrylimino-l,2,3,4-thiatriazolines (177) which are stable below 100°C <90JHC1059>. Kinetic experiments indicate that the reaction between picryl isothiocyanate and alkyl azides most likely is concerted as no significant solvent effect was observed. 

Acyl isothiocyanates have been shown to participate in [4 + 2] cycloadditions with enamines,98 imines," ketenimines,100 and hydrazones.101 Similar reports have detailed the [4 + 2] cycloadditions of thioacyl isothiocyanates with the carbon-carbon double bond of ketenes, ketenimines, and enamines as well as the carbon-nitrogen double bond of imines, carbodii-mides, and isocyanates.102... 

Azoles containing a free NH group react comparatively readily with acyl halides. N-Acyl-pyrazoles, -imidazoles, etc. can be prepared by reaction sequences of either type (66) -> (67) or type (70)->(71) or (72). Such reactions have been carried out with benzoyl halides, sulfonyl halides, isocyanates, isothiocyanates and chloroformates. Reactions occur under Schotten-Baumann conditions or in inert solvents. When two isomeric products could result, only the thermodynamically stable one is usually obtained because the acylation reactions are reversible and the products interconvert readily. Thus benzotriazole forms 1-acyl derivatives (99) which preserve the Kekule resonance of the benzene ring and are therefore more stable than the isomeric 2-acyl derivatives. Acylation of pyrazoles also usually gives the more stable isomer as the sole product (66AHCi6)347). The imidazole-catalyzed hydrolysis of esters can be classified as an electrophilic attack on the multiply bonded imidazole nitrogen. 

Acylations at nitrogen include N-acetylation using acetic anhydride (82H1595) and N-mesylation (84TL4223), as well as the N-carboxyalk-ylation of 81 and reaction of 82 with isocyanates or isothiocyanates to afford 83 (Scheme 2) (76JAP76-65757). Alkylations include methylation to yield N-methyl and N,N -dimethyl-l,2-diazocines (69JOC3237). An in-... 

Amidines with a more complicated substitution pattern have been prepared from amidines by alkylation—either at nitrogen or at nitrogen substituents. - Variations at these positions have been achieved by heteroarylation, acylation,vinylation or carboxylation with phosgene, thio-phosgene, isocyanide dichlorides or isothiocyanates. Some interesting amidines, e.g. (347)-(3S2) (Scheme 59), have been prepared in this manner. The amidine skeleton can also be varied by halogen-ation, - hydrolysis, isomerization or catalytic hydrogenation or other addition reactions if there are C=—C double bonds present as in (353 equation 173) for example. ... 

The reactions of 2-aminobenzimidazoles have been reviewed <83S86l>. The compounds form Schiffs bases with carbonyl compounds, with isocyanates and isothiocyanates they give ureas and thioureas, they are subject to 1,3-dipolar addition reactions, and to the formation of carbamates on acylation and aroylation. When aminoimidazoles are acylated there is frequently competition between the annular and exocyclic nitrogen (see above). Add chlorides and anhydrides (soft) acylate the amino group chlorocarbonic acid esters (hard) are specific for the heteroatom <84CHE204>. When heated, the A -acyl products isomerize (Scheme 91). 

Addition reactions of 2-chloro-3-pyridylcarbonyl isothiocyanate with primary amines yield acylated thioureas 1. Because of the ambident character of the thiocarbamoyl group, in the following cyclization step the 2-chloro substituent of the pyridine may react either with the sulfur or the nitrogen center, depending on the reaction conditions. In the example below, heating under reflux in toluene yields 2-aminopyrido[3,2-e][l,3]thiazin-4-ones, whereas the anion prepared by metalation with lithium hydride in dimethylformamide at room temperature leads to 2-thioxo-l,2-dihydropyrido[2,3-c/]pyrimidin-4(3//)-ones 2.6... 

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