Iodine‐Catalyzed Synthesis of Spiro[1,3,4‐benzotriazepine‐2,3′‐indole]‐2′,5(1H,1′H)‐diones under Mild Conditions

The I₂‐catalyzed preparation of spiro[1,3,4‐benzotriazepine‐2,3′‐indole]‐2′,5(1H,1′H)‐diones from 2‐aminobenzohydrazide and isatins in MeCN at room temperature in good‐to‐excellent yields is described. The structure of 3 was corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS data). A plausible mechanism for this type of reaction is proposed (Scheme 2).     

Unexpected Thermal Transformation of Aryl 3‐Arylprop‐2‐ynoates: Formation of 3‐(Diarylmethylidene)‐2,3‐dihydrofuran‐2‐ones

A number of aryl 3‐arylprop‐2‐ynoates 3 has been prepared (cf. Table 1 and Schemes 3 – 5). In contrast to aryl prop‐2‐ynoates and but‐2‐ynoates, 3‐arylprop‐2‐ynoates 3 (with the exception of 3b ) do not undergo, by flash vacuum pyrolysis (FVP), rearrangement to corresponding cyclohepta[b]furan‐2(2H)‐ones 2 (cf. Schemes 1 and 2). On melting, however, or in solution at temperatures >150°, the compounds 3 are converted stereospecifically to the dimers 3‐[(Z)‐diarylmethylidene]‐2,3‐dihydrofuran‐2‐ones (Z)‐ 11 and the cyclic anhydrides 12 of 1,4‐diarylnaphthalene‐2,3‐dicarboxylic acids, which also represent dimers of 3 , formed by loss of one molecule of the corresponding phenol from the aryloxy part (cf. Scheme 6). Small amounts of diaryl naphthalene‐2,3‐dicarboxylates 13 accompanied the product types (Z)‐ 11 and 12 , when the thermal transformation of 3 was performed in the molten state or at high concentration of 3 in solution (cf. Tables 2 and 4). The structure of the dihydrofuranone (Z)‐ 11c was established by an X‐ray crystal‐structure analysis (Fig. 1). The structures of the dihydrofuranones 11 and the cyclic anhydrides 12 indicate that the 3‐arylprop‐2‐ynoates 3 , on heating, must undergo an aryl O→C(3) migration leading to a reactive intermediate, which attacks a second molecule of 3 , finally under formation of (Z)‐ 11 or 12 . Formation of the diaryl dicarboxylates 13 , on the other hand, are the result of the well‐known thermal Diels‐Alder‐type dimerization of 3 without rearrangement (cf. Scheme 7). At low concentration of 3 in decalin, the decrease of 3 follows up to ca. 20% conversion first‐order kinetics (cf. Table 5), which is in agreement with a monomolecular rearrangement of 3 . Moreover, heating the highly reactive 2,4,6‐trimethylphenyl 3‐(4‐nitrophenyl)prop‐2‐ynonate ( 3f ) in the presence of a twofold molar amount of the much less reactive phenyl 3‐(4‐nitrophenyl)prop‐2‐ynonate ( 3g ) led, beside (Z)‐ 11f , to the cross products (Z)‐ 11fg , and, due to subsequent thermal isomerization, (E)‐ 11fg (cf. Scheme 10), the structures of which indicated that they were composed, as expected, of rearranged 3f and structurally unaltered 3g . Finally, thermal transposition of [¹⁷O]‐ 3i with the ¹⁷O‐label at the aryloxy group gave (Z)‐ and (E)‐[¹⁷O₂]‐ 11i with the ¹⁷O‐label of rearranged [¹⁷O]‐ 3i specifically at the oxo group of the two isomeric dihydrofuranones (cf. Scheme 8), indicating a highly ordered cyclic transition state of the aryl O→C(3) migration (cf. Scheme 9).     

Unexpected Formation of Dimethylthioketene Cycloadducts in the Reaction of 1,3‐Diphenylaziridine‐2,2‐dicarboxylate with Cyclobutanethione Derivatives

The reaction of 2,2,4,4‐tetramethyl‐3‐thioxocyclobutanone ( 1 ) with cis‐1‐alkyl‐2,3‐diphenylaziridines 5 in boiling toluene yielded the expected trans‐configured spirocyclic 1,3‐thiazolidines 6 (Scheme 1). Analogously, dimethyl trans‐1‐(4‐methoxyphenyl)aziridine‐2,3‐dicarboxylate (trans‐ 7 ) reacted with 1 and the corresponding dithione 2 , respectively, to give spirocyclic 1,3‐thiazolidine‐2,4‐dicarboxylates 8 (Scheme 2). However, mixtures of cis‐ and trans‐derivatives were obtained in these cases. Unexpectedly, the reaction of 1 with dimethyl 1,3‐diphenylaziridine‐2,2‐dicarboxylate ( 11 ) led to a mixture of the cycloadduct 13 and 5‐(isopropylidene)‐4‐phenyl‐1,3‐thiazolidine‐2,2‐dicarboxylate ( 14 ), a formal cycloadduct of azomethine ylide 12 with dimethylthioketene (Scheme 3). The regioisomeric adduct 16 was obtained from the reaction between 2 and 11 . The structures of 6b , cis‐ 8a , cis‐ 8b, 10 , and 16 have been established by X‐ray crystallography.     

One‐Pot Synthesis of 4‐(2,3‐Dihydro‐2‐hydroxy‐1,3‐dioxo‐1H‐inden‐2‐yl)‐Substituted 1‐Aryl‐1H‐pyrazole‐3‐carboxylates via a Tandem Three‐Component Reaction

The hitherto unreported, highly functionalized 1H‐pyrazole‐3‐carboxylates 3 have been synthesized in good yields via a one‐pot three‐component domino reaction of phenylhydrazines, dialkyl acetylenedicarboxylates, and ninhydrin under mild conditions for the first time. No co‐catalyst or activator is required for this multicomponent reaction, and the reaction is, from an experimental point of view, simple to perform (Scheme 1). The structures of compounds 3 were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses. A plausible mechanism for this type of cyclization/addition reaction is proposed (Scheme 2).     

Synthesis of 2‐Aryl‐5‐oxo‐4‐[2‐(phenylmethylidene)hydrazino]‐2,5‐dihydro‐1H‐pyrrole‐3‐carboxylates by the Reaction between Hydrazones,Acetylenedicarboxylates, and 1‐Aryl‐N,N′‐bis(arylmethylidene)methanediamines

An efficient approach for the preparation of functionalized 2‐aryl‐2,5‐dihydro‐5‐oxo‐4‐[2‐(phenylmethylidene)hydrazino]‐1H‐pyrroles is described. The four‐component reaction between aldehydes, NH₂NH₂?H₂O, dialkyl acetylenedicarboxylates, and 1‐aryl‐N,N′‐bis(arylmethylidene)methanediamines proceeds in EtOH under reflux in good‐to‐excellent yields (Scheme 1). The structures of 4 were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS, and, in the case of 4f , by X‐ray crystallography). A plausible mechanism for this type of reaction is proposed (Scheme 2).     

Über Umlagerungen bei der Cyclialkylierung von Arylpentanolen zu 2,3‐Dihydro‐1H‐inden‐Derivaten, 4. Mitteilung

On Rearrangements by Cyclialkylations of Arylpentanols to 2,3‐Dihydro‐1 H ‐indene Derivatives. Part 4. The Acid‐Catalyzed Cyclialkylation of 2,4‐Dimethyl‐2‐phenyl[3‐ ¹³ C]pentan‐3‐ol The cyclialkylation of 2,4‐dimethyl‐2‐phenyl[3‐¹³C]pentan‐3‐ol ( 4 ) gives only 2,3‐dihydro‐1,1,2,3‐tetramethyl‐1H‐[3‐¹³C]indene ( 6 ) (cf. Scheme 2) and not a trace of the isotopomeric 2,3‐dihydro‐1,1,2,3‐tetramethyl‐1H‐[2‐¹³C]indene ( 5 ). The mechanism proposed in [3] for the cyclialkylation of 4 (cf. Scheme 2, Path A) has, therefore, to be abandoned. The mechanism of Scheme 2, Path B, is proposed and may be considered as definitively established.     

One‐Pot Synthesis of 4‐(Alkylamino)‐1‐(arylsulfonyl)‐3‐benzoyl‐1,5‐ dihydro‐5‐hydroxy‐5‐phenyl‐2H‐pyrrol‐2‐ones via a Multicomponent Reaction

An effective route to novel 4‐(alkylamino)‐1‐(arylsulfonyl)‐3‐benzoyl‐1,5‐dihydro‐5‐hydroxy‐5‐phenyl‐2H‐pyrrol‐2‐ones 10 is described (Scheme 2). This involves the reaction of an enamine, derived from the addition of a primary amine 5 to 1,4‐diphenylbut‐2‐yne‐1,4‐dione, with an arenesulfonyl isocyanate 7 . Some of these pyrrolones 10 exhibit a dynamic NMR behavior in solution because of restricted rotation around the C? N bond resulting from conjugation of the side‐chain N‐atom with the adjacent α,β‐unsaturated ketone group, and two rotamers are in equilibrium with each other in solution ( 10 ? 11 ; Scheme 3). The structures of the highly functionalized compounds 10 were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS), by elemental analyses, and, in the case of 10a , by X‐ray crystallography. A plausible mechanism for the reaction is proposed (Scheme 4).     

One‐Pot Four‐Component Synthesis of N2‐Alkyl‐N3‐[2‐(1,3,4‐oxadiazol‐2‐yl)aryl]benzofuran‐2,3‐diamines

A simple synthesis of N²‐alkyl‐N³‐[2‐(1,3,4‐oxadiazol‐2‐yl)aryl]benzofuran‐2,3‐diamines 5 via a one‐pot four‐component reaction is described (Scheme 1). A mixture of N‐(isocyanoimino)triphenylphosphorane ( 1 ), a 2‐aminobenzoic acid 2 , a 2‐hydroxybenzaldehyde 3 , and an isocyanide 4 in absolute EtOH at room temperature undergoes a smooth reaction to afford 5 in excellent yields (Table).     

1,3‐Thiazolidine‐dicarboxylates from Thioketones and Thermally Generated Azomethine Ylides

The reaction of 9H‐fluorene‐9‐thione ( 1 ) with the cis‐ and trans‐isomers of dimethyl 1‐(4‐methoxyphenyl)aziridine‐2,3‐dicarboxylate (cis‐ and trans‐ 2 , resp.) in xylene at 110° yielded exclusively the spirocyclic cycloadduct with trans‐ and cis‐configurations, respectively (trans‐ and cis‐ 3 , resp.; Scheme 1). Analogously, less‐reactive thioketones, e.g., thiobenzophenone ( 5 ), and cis‐ 2 reacted stereoselectively to give the corresponding trans‐1,3‐thiazolidine‐2,4‐dicarboxylate (e.g., trans‐ 8 ; Scheme 2). On the other hand, the reaction of 5 and trans‐ 2 proceeded in a nonstereoselective course to provide a mixture of trans‐ and cis‐substituted cycloadducts. This result can be explained by an isomerization of the intermediate azomethine ylide. Dimethyl 1,3‐thiazolidine‐2,2‐dicarboxylates 14 and 15 were formed in the thermal reaction of dimethyl aziridine‐2,2‐dicarboxylate 11 with aromatic thioketones (Scheme 3). On treatment of 14 and 15 with Raney‐Ni in refluxing EtOH, a desulfurization and ring‐contraction led to the formation of azetidine‐2,2‐dicarboxylates 17 and 18 , respectively (Scheme 4).     

Thermal [2+3]‐Cycloadditions of trans‐1‐Methyl‐2,3‐diphenylaziridine with CS and CC Dipolarophiles: An Unexpected Course with Dimethyl Dicyanofumarate

The thermal reaction of trans‐1‐methyl‐2,3‐diphenylaziridine (trans‐ 1a ) with aromatic and cycloaliphatic thioketones 2 in boiling toluene yielded the corresponding cis‐2,4‐diphenyl‐1,3‐thiazolidines cis‐ 4 via conrotatory ring opening of trans‐ 1a and a concerted [2+3]‐cycloaddition of the intermediate (E,E)‐configured azomethine ylide 3a (Scheme 1). The analogous reaction of cis‐ 1a with dimethyl acetylenedicarboxylate ( 5 ) gave dimethyl trans‐2,5‐dihydro‐1‐methyl‐2,5‐diphenylpyrrole‐3,4‐dicarboxylate (trans‐ 6 ) in accord with orbital‐symmetry‐controlled reactions (Scheme 2). On the other hand, the reactions of cis‐ 1a and trans‐ 1a with dimethyl dicyanofumarate ( 7a ), as well as that of cis‐ 1a and dimethyl dicyanomaleate ( 7b ), led to mixtures of the same two stereoisomeric dimethyl 3,4‐dicyano‐1‐methyl‐2,5‐diphenylpyrrolidine‐3,4‐dicarboxylates 8a and 8b (Scheme 3). This result has to be explained via a stepwise reaction mechanism, in which the intermediate zwitterions 11a and 11b equilibrate (Scheme 6). In contrast, cis‐1,2,3‐triphenylaziridine (cis‐ 1b ) and 7a gave only one stereoisomeric pyrrolidine‐3,4‐dicarboxylate 10 , with the configuration expected on the basis of orbital‐symmetry control, i.e., via concerted reaction steps (Scheme 10). The configuration of 8a and 10 , as well as that of a derivative of 8b , were established by X‐ray crystallography.     

Chemoselective Route for Synthesis of N‐Aryl‐3‐oxochromeno[2,3‐c]pyrazole‐2(3H)‐carbothioamide Derivatives

A chemoselective route for the synthesis of chromeno[2,3‐c]pyrazole‐2(3H)‐carbothioamide derivatives by a five‐component reaction of salicylaldehyde, malononitrile, NH₂NH₂?H₂O, aryl isothiocyanate, and H₂O in EtOH/AcOH mixture is reported. This new protocol has the advantages of high yields, short reaction times, ease of operation, and simple purification. All structures were confirmed by IR, ¹H‐ and ¹³C‐NMR, and MS analyses. A plausible mechanism for this type of reaction is proposed (Scheme 2).     

Synthesis of 5‐Aryl‐3‐(methylsulfanyl)‐1H‐pyrazoles via Three‐Component Reaction of 1,1‐Bis(methylsulfanyl)‐2‐nitroethene,Aromatic Aldehydes,and Hydrazine

An efficient approach for the preparation of functionalized 5‐aryl‐3‐(methylsulfanyl)‐1H‐pyrazoles 2 is described. This three‐component reaction between benzaldehydes 1 , NH₂NH₂?H₂O, and 1,1‐bis(methylsulfanyl)‐2‐nitroethene proceeds in EtOH under reflux conditions in good‐to‐excellent yields. The structures of 2 were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS). A plausible mechanism for this type of reaction is proposed (Scheme 2).     

Über Umlagerungen bei der Cyclialkylierung von Arylpentanolen zu 2,3‐Dihydro‐1H‐inden‐Derivaten, 2. Mitteilung

On Rearrangements by Cyclialkylations of Arylpentanols to 2,3‐Dihydro‐1 H ‐indene Derivatives. Part 2. An Unexpected Rearrangement by the Acid‐Catalyzed Cyclialkylation of 2,4‐Dimethyl‐2‐phenylpentan‐3‐ol under Formation of trans ‐2,3‐Dihydro‐1,1,2,3‐tetramethyl‐1 H ‐indene The acid catalyzed‐cyclialkylation of 4‐(2‐chloro‐phenyl)‐2,4‐dimethylpentan‐2‐ol ( 1 ) gave two products: 4‐chloro‐2,3‐dihydro‐1,1,3,3‐tetramethyl‐1H‐indene ( 2 ) and also trans‐4‐chloro‐2,3‐dihydro‐1,1,2,3‐tetramethyl‐1H‐indene ( 3 ). A mechanism was proposed in Part 1 (cf. Scheme 1) for this unexpected rearrangement. This mechanism would mainly be supported by the result of the cyclialkylation of 2,4‐dimethyl‐2‐phenylpentan‐3‐ol ( 4 ), which, with respect to the similarity of ion II in Scheme 1 and ion V in Scheme 2, should give only product 5 . This was indeed the experimental result of this cyclialkylation. But the result of the cyclialkylation of 1,1,1,2′,2′,2′‐hexadeuterated isomer [²H₆]‐ 4 of 4 (cf. Scheme 3) requires a different mechanism as for the cyclialkylation of 1 . Such a mechanism is proposed in Schemes 5 and 6. It gives a satisfactory explanation of the experimental results and is supported by the result of the cyclialkylation of 2,4‐dimethyl‐3‐phenylpentan‐3‐ol ( 9 ; Scheme 7). The alternative migration of a Ph or of an i‐Pr group (cf. Scheme 6) is under further investigation.     

Chiral Heterospirocyclic 2H‐Azirin‐3‐amines as Synthons for 3‐Amino‐2,3,4,5‐tetrahydrofuran‐3‐carboxylic Acid and Their Use in Peptide Synthesis

The heterospirocyclic N‐methyl‐N‐phenyl‐5‐oxa‐1‐azaspiro[2.4]hept‐1‐e n‐2‐amine (6 ) and N‐(5‐oxa‐1‐azaspiro[2.4]hept‐1‐en‐2‐yl)‐(S)‐proline methyl ester ( 7 ) were synthesized from the corresponding heterocyclic thiocarboxamides 12 and 10 , respectively, by consecutive treatment with COCl₂, 1,4‐diazabicyclo[2.2.2]octane, and NaN₃ (Schemes 1 and 2). The reaction of these 2H‐azirin‐3‐amines with thiobenzoic and benzoic acid gave the racemic benzamides 13 and 14 , and the diastereoisomeric mixtures of the N‐benzoyl dipeptides 15 and 16 , respectively (Scheme 3). The latter were separated chromatographically. The configurations and solid‐state conformations of all six benzamides were determined by X‐ray crystallography. With the aim of examining the use of the new synthons in peptide synthesis, the reactions of 7 with Z‐Leu‐Aib‐OH to yield a tetrapeptide 17 (Scheme 4), and of 6 with Z‐Ala‐OH to give a dipeptide 18 (Scheme 5) were performed. The resulting diastereoisomers were separated by means of MPLC or HPLC. NMR Studies of the solvent dependence of the chemical shifts of the NH resonances indicate the presence of an intramolecular H‐bond in 17 . The dipeptides (S,R)‐ 18 and (S,S)‐ 18 were deprotected at the N‐terminus and were converted to the crystalline derivatives (S,R)‐ 19 and (S,S)‐ 19 , respectively, by reaction with 4‐bromobenzoyl chloride (Scheme 5). Selective hydrolysis of (S,R)‐ 18 and (S,S)‐ 18 gave the dipeptide acids (R,S)‐ 20 and (S,S)‐ 20 , respectively. Coupling of a diastereoisomeric mixture of 20 with H‐Phe‐O^tBu led to the tripeptides 21 (Scheme 5). X‐Ray crystal‐structure determinations of (S,R)‐ 19 and (S,S)‐ 19 allowed the determination of the absolute configurations of all diastereoisomers isolated in this series.     

On the Preparation of 2‐Substituted Cephalosporins,Part 2

Cephalosporin sulfoxides 1 and 2 containing an enone‐ or dienone‐type moiety at position 2 were treated with 2,3‐dimethylbuta‐1,3‐diene or diethyl azodicarboxylate to synthesize, in Diels? Alder reactions, the new cephalosporin derivatives 4 and 5 with a cyclic substituent (Scheme 1). Under the same conditions, ethyl diazoacetate and diazomethane reacted differently: while reactions of 1 and 3 with the former lead to compounds 7 – 10 corresponding to the 1,3‐dipolar cycloaddition route (Scheme 2), diazomethane produced only enol ethers 12 and 13 , respectively (Scheme 3). This difference could be rationalized by assuming two different reaction pathways: an orbital‐symmetry‐controlled concerted cycloaddition and an ionic one.     

Über Umlagerungen bei der Cyclialkylierung von Arylpentanolen zu 2,3‐Dihydro‐1H‐inden‐Derivaten, 3. Mitteilung

On Rearrangements by Cyclialkylations of Arylpentanols to 2,3‐Dihydro‐1 H ‐indene Derivatives. Part 3. The Acid‐Catalyzed Cyclialkylation of 3,4‐Dimethyl‐ and 3‐([ ² H ₃ ]Methyl)‐4‐methyl‐3‐phenylpentan‐2‐ol The cyclialkylation of 2‐([²H₃]methyl)‐4‐methyl‐4‐phenyl[1,1,1‐²H₃]pentan‐3‐ol ( 4 ) yielded a 1 : 1 mixture of 1,1‐di([²H₃]methyl)‐2,3‐dimethyl‐1H‐indene ( 5 ) and of 2,3‐dihydro‐2,3‐di([²H₃]methyl)‐1,1‐dimethyl‐1H‐indene ( 6 ) (Scheme 1) [1]. However, it was not clear whether the transposition takes place through the successive migration of a Ph, a Me and again the Ph group (Scheme 2, Path A: shift IV → VII → VIIa ) or through Ph‐, Me‐, and then i‐Pr‐group (Scheme 2, Path B: IV → VII → VIIb ). The cyclialkylation of 3‐([²H₃]methyl)‐4‐methyl‐3‐phenylpentan‐2‐ol ( 7 ) yielded only one product, the 2,3‐dihydro‐2‐([²H₃]methyl)‐1,1,3‐trimethyl‐1H‐indene ( 8 ), in accordance with the migrations according to Path A. This result is also a support for the total mechanism proposed for the cyclialkylation of 4 (Scheme 2). The transition of a tertiary to a secondary carbenium ion is not definitely ensured (see [1]).     

An Approach to the Synthesis of 7‐Amino‐6‐imino‐9‐phenyl‐6H‐benzo[c]chromene‐8‐carbonitrile Derivatives via a Three‐Component Reaction under Ultrasonic Irradiation

An efficient synthesis of 7‐amino‐6‐imino‐9‐phenyl‐6H‐benzo[c]chromene‐8‐carbonitrile derivatives 3 by a three‐component reaction of salicylaldehydes (=2‐hydroxybenzaldehydes) 1 , malononitrile (=propanedinitrile), and 2‐(1‐arylethylidene)malononitrile 2 under ultrasonic irradiation in EtOH is reported. Good yields, short reaction times, and easy purification are the main advantages of the present method. The structures were confirmed spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses. A plausible mechanism for this reaction is proposed (Scheme 2).     

One‐Step Synthesis of Dialkyl 2‐[(4‐Methylphenyl)sulfonyl]‐1H‐pyrrole‐3,4‐dicarboxylates by Reaction of Acetylenedicarboxylates with ‘Tosylmethyl Isocyanide’ (TsMIC) and Triphenylphosphine

The reactive 1 : 1 adducts in the reaction between Ph₃P and dialkyl acetylenedicarboxylates have been trapped with ‘tosylmethyl isocyanide’ (TsMIC ; 1 ) to yield dialkyl 2‐[(4‐methylphenyl)sulfonyl]‐1H‐pyrrole‐3,4‐dicarboxylates 3 (Scheme 1). The structures of the highly functionalized compounds 3 were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses. A plausible mechanism for this type of cyclization is proposed (Scheme 2).     

Synthesis of Optically Active 1‐(1‐Phenylethyl)‐1H‐imidazoles Derived from 1‐Phenylethylamine

The three‐component reaction of (R)‐ or (S)‐1‐phenylethylamine ( 6 ), formaldehyde, and an α‐(hydroxyimino) ketone 5 , i.e., 3‐(hydroxyimino)butan‐2‐one ( 5a ) or 2‐(hydroxyimino)‐1,2‐diphenylethanone ( 5b ), yields the corresponding enantiomerically pure 1‐(1‐phenylethyl)‐1H‐imidazole 3‐oxide 7 in high yield (Schemes 2 and 3). The reactions are carried out either in MeOH or in AcOH. Smooth transformations of the N‐oxides into optically active 1‐(1‐phenylethyl)‐1H‐imidazoles 10 and 2,3‐dihydro‐1‐(1‐phenylethyl)‐1H‐imidazole‐2‐thiones 11 are achieved by treatment of 7 with Raney‐Ni and 2,2,4,4‐tetramethyl‐3‐thioxocyclobutanone ( 12 ), respectively (Scheme 4).     

A Facile and Efficient Synthesis of Arylsulfonamido‐Substituted 1,5‐Benzodiazepines and N‐[2‐(3‐Benzoylthioureido)aryl]‐3‐oxobutanamide Derivatives

A facile and efficient synthesis of 1,5‐benzodiazepines with an arylsulfonamido substituent at C(3) is described. 1,5‐Benzodiazepine, derived from the condensation of benzene‐1,2‐diamine and diketene, reacts with an arylsulfonyl isocyanate via an enamine intermediate to produce the title compounds of potential synthetic and pharmacological interest in good yields (Scheme 1). In addition, reaction of benzene‐1,2‐diamine and diketene in the presence of benzoyl isothiocyanate leads to N‐[2‐(3‐benzoylthioureido)aryl]‐3‐oxobutanamide derivatives (Scheme 2). This reaction proceeds via an imine intermediate and ring opening of diazepine. The structures were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses. A plausible mechanism for this type of cyclization is proposed (Scheme 3).