Benzoyl isothiocyanate

A similar regiospecific [2 -I- 2] cycloaddition across a C=S group occurred when benzoyl isothiocyanate (436) and 2,3-diphenyl-1-azirine were heated in refiuxing benzene for 12 hours. The product obtained was shown to be (438) and an intermediate such as (437) could also be involved in this cycloaddition (74JOC3763). In contrast, thiobenzoyl isocyanate added in a [4-1-2] fashion, and after ring expansion gave a thiadiazepine derivative. 

Amino-4-arylazopyrazole 338 reacted with benzoyl isothiocyanate to give the expected pyrazol-5-ylthioureas 339, which on heating with acetic acid-hydrochloric acid afforded (76JOC3781) pyrazolo[3,4-e][l,2,41-... 

Formate esters behave as typical carbonyl compounds in reactions with a number of ylides, eliminating phosphine oxide and forming vinyl ethers, e.g. (33).35 Stabilized phosphoranes are able to condense with the carbonyl group of cyclic thioanhydrides (34).38 Quinoline derivatives, e.g. (35), are obtained from the condensation of dicar-boalkoxy-ylides with isocyanates.37 Benzoyl isothiocyanates and keto-phosphoranes give quantitative yields of (36), which are unreactive in Wittig reactions but can be readily oxidized by selenous acid.38 The products obtained from reactions (Scheme 9) with the triazolinedione (37) depend upon the stability of the ylide used.39... 

In the 1,2,4-dithiazolidine series, 4-phenyl-3-aroylimino-5-methylimino-1,2,4-dithiazolidine (15) rearranges under the influence of benzoyl isothiocyanate into the 3-aroylimino-4-methyl-5-phenylimino-l,2,4-dithiazolidine (16) (78JOC4951). The Dimroth rearrangement is suggested to occur via a betaine as intermediate (Scheme IV.IO). It is of interest to mention that the isomerization of 15 into 16 was not observed with the Lewis acids aluminum trichloride or benzoyl chloride. 

Pyrazolo[l,5-a]-l,3,5-triazines are also obtained from acyclic intermediates. Thus, treatment of cyanoethanoic acid hydrazide with benzoyl isothiocyanate affords the corresponding benzoylthiosemicarbazide, which cyclizes into 4-thioxo-2-phenyl-3,4,6,7-tetrahydropyrazolo[l,5-a]-l,3,5-triazine-7-one upon treatment with 5% potassium hydroxide (84JHC781). 

In the reactions of benzoyl isothiocyanate 324 and dialkyl acetylenedicarboxylates 325 in the presence of triphenyl-phosphine, 2-phenyl-4-thioxo-47/-l,3-oxazine-5,6-dicarboxylates 326 and dialkyl 2-(benzoylimino)-5-phenyM//-[l,3]dithiolo[4,5- ]pyrrole-4,6-dicarboxylates 327 were formed in a ratio of 1 3 (Equation 30) <2006TL2953>. 

The manner in which a carbene was generated was found to be critical to the product distribution in a synthesis of 4(5//)-thiooxazolones (Scheme 6.9). Treatment of diethyl bromomalonate with excess triethylamine in the presence of benzoyl isothiocyanate afforded a mixture of the 4(5//)-thiooxazolone 25 (44%) and the 1,3-oxathiole 26 (minor). However, if the carbene was generated via copper-catalyzed decomposition of diethyl diazomalonate, then 26 was isolated as the major product, albeit in low yield (22%). 

Compound 100 reacts with benzoyl isothiocyanate or ammonium thiocyanate to yield 101 (76JOC378I). 

Only two classes appear to be known. The 1,2,5,6-system (599) is said to result from the treatment of the semicarbazide (598) with iron(III) chloride (28JIC439), and more recently it has been shown that benzoyl isothiocyanate adds to the phenylhydrazones of benzaldehyde and several ketones to give the l,3,4,6-oxatriazepine-5-thione system (600) (67JCS(C)952, 76JCS(P1)2243). The products rearrange to give (601) quantitatively on treatment with acid. 

When acrylonitrile or ethyl acrylate was used as the dipolarophile, the azomethine adducts (134) and (135) were formed no thiocarbonyl ylide addition products were isolable in refluxing toluene or xylene, although the isoindoles (136a) and (136b) derived from them were isolated. In contrast to the reactions with fumaronitrile or AT-phenylmaleimide, the azomethine adducts (134) and (135) were still present at higher reaction temperatures — almost 50% in toluene and 4-5% in xylene. Under the same reaction conditions other electron-deficient dipolarophiles like dimethyl fumarate, norbornene, dimethyl maleate, phenyl isocyanate, phenyl isothiocyanate, benzoyl isothiocyanate, p-tosyl isocyanate and diphenylcyclopropenone failed to undergo cycloaddition to thienopyrrole (13), presumably due to steric interactions (77HC(30)317). 

Only a few examples of the formation of 1,2,4-triazines by this fragment combination have been published, all cases being 1,2,4-benzotriazine syntheses. 2-Nitroaniline reacts with cyanamides to give 2-nitrophenylguanidines (601) which cyclize under basic conditions to 3-amino-l,2,4-benzotriazine 1-oxides (602) <78HC(33)189, p.699). With benzoyl isothiocyanate it affords Ar-(2-nitrophenyl)-N -benzoylthiourea (603), which cyclizes to l,2,4-benzotriazine-3-thione 1-oxide (604) (80MI21900).. 

Brown et al. have patented (90EUP404356) a short route to potassium thieno[3,4-d]pyrimidin-4(l//)-one-2-thiolate 308 which involves heating aminoester 292 (Y = Me) with benzoyl isothiocyanate in refluxing toluene and then cyclizing the resulting thiourea 307 by heating with methanolic potassium hydroxide. 

The calcined OMSs used in post-synthesis modification possessed a hexagonal (MCM-41 and SBA-15) or cubic (MCM-48) arrangement of mesopores. Benzoyl isothiocyanate was reacted with aminopropyl-modified surfaces of MCM-41 and MCM-48 to give the OMM-1 and OMM-2 samples, respectively.15,44... 

Ethoxycarbonyl isothiocyanate, as well as benzoyl isothiocyanate, interacts with 2-amino-2-thiazoIine at the ring nitrogen atom (509). The initial adducts react further to form fused 1,3,5-triazines (75JOC2000). 

Reaction of tertiary enaminones with benzoyl isothiocyanate gives substituted 2-pyridinethiones in moderate yields, indicating the reactivity of enaminones at a-methyl group6 (equation 2). Phenylisothiocyanate reacts simply at the -position7 (equation 3). 

In the case of phenyl isothiocyanate, however, the reaction directly leads to cyclic products the corresponding pyrimidinethiones are obtained in satisfactory yields. Benzoyl isothiocyanate immediately gives mercaptopyrimidines by hydrolysis, caused by formation of water during the cyclization244 (equation 175). 

Treatment of the / -nitroenamines 361 (R = Me or Ph) with benzoyl isothiocyanate gives / -(benzoylthiocarbamoyl)-/ -nitroenamines 362, which are transformed into pyr-imidine-4-thiones 363 on heating with ammonium acetate (equation 147)179. 

Several condensed 5-nitropyrimidine derivatives have also been prepared from appropriate nitro-containing precursors. 2-Nitromethylene hexahydro-azepine (127) forms an adduct with benzoyl isothiocyanate which, during recrystallization from acetic acid, cyclizes to the pyrimido[3,4-a] azepine 128 (Scheme 25).119 This seems to be the only example of the use of a type 2 synthon for the synthesis of a 5-nitropyrimidine. 

The RNAse model compound of Hamilton was constructed in a few steps (Scheme 15) [30]. Benzoyl isothiocyanate was allowed to react with diamine 59 to yield bis(thiourea) 61 after deprotection. S-methylation activated the urea moieties for guanidine formation with Af,A -dimethyl-ethy-lenediamine 62 to reach the desired compound 53. 

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