A New Solution—phase Parallel Synthesis of 2—Alkyamino—3—aryl—5—phenylmethylene—3,5—dihydro—4H—imidazol—4—ones

Thirteen new 2-alkylaminoimidazolones(4) wre rapidly synthesized by a new solution-phase parallel synthetic method,which includes aza-Wittig reaction of iminophosphorane(1) with aromatic isocyanate to give carbodi-imide(2) and subsequent reaction of 2 with various aliphatic primary amine in a parallel fashion.The products were confirmed by ^1H NMR,MS,IR and X-ray crystallographic analysis.The unusual selectivity of the cyclization was probably due to the deometry of the guanidine intermediate.     

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).     

A Simple One‐Pot Synthesis of N‐Alkyl‐2,5‐diaryl‐1,3‐dioxol‐4‐amines

An efficient procedure for the synthesis of N‐alkyl‐2,5‐diaryl‐1,3‐dioxol‐4‐amines 3 via a one‐pot reaction of aromatic aldehydes 2 and alkyl isocyanides 1 at room temperature in good yields is described (Scheme 1, Table).     

Report on an Unusual Cascade Reaction between Azulenes and 2,3‐Dichloro‐5,6‐dicyano‐1,4‐benzoquinone (=4,5‐Dichloro‐3,6‐dioxocyclohexa‐1,4‐diene‐1,2‐dicarbonitrile; DDQ)

The oxidation of 1‐(3,8‐dimethylazulen‐1‐yl)alkan‐1‐ones 1 with 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (=4,5‐dichloro‐3,6‐dioxocyclohexa‐1,4‐diene‐1,2‐dicarbonitrile; DDQ) in acetone/H₂O mixtures at room temperature does not only lead to the corresponding azulene‐1‐carboxaldehydes 2 but also, in small amounts, to three further products (Tables 1 and 2). The structures of the additional products 3 – 5 were solved spectroscopically, and that of 3a also by an X‐ray crystal‐structure analysis (Fig. 1). It is demonstrated that the bis(azulenylmethyl)‐substituted DDQ derivatives 5 yield on methanolysis or hydrolysis precursors, which in a cascade of reactions rearrange under loss of HCl into the pentacyclic compounds 3 (Schemes 4 and 7). The found 1,1′‐[carbonylbis(8‐methylazulene‐3,1‐diyl)]bis[ethanones] 4 are the result of further oxidation of the azulene‐1‐carboxaldehydes 2 to the corresponding azulene‐1‐carboxylic acids (Schemes 9 and 10).     

Photocycloaddition Reactions of 5,5‐Dimethyl‐3‐(3‐methylbut‐3‐en‐1‐ynyl)cyclohex‐2‐en‐1‐one

The title cyclohexenone 1d undergoes photodimerization selectively at the exocyclic C?C bond to give a 1 : 1 mixture of 1,2‐dialkynyl‐1,2‐dimethylcyclobutanes 6 and 7 . On irradiation in the presence of 2,3‐dimethylbuta‐1,3‐diene, 1d affords bicyclo[8.4.0]tetradeca‐1,2,3,7‐tetraen‐11‐one 9 . This – formal – (6+4)‐cycloadduct undergoes quantitative isomerization to 3‐cycloheptadienyl‐2,5,5‐trimethylcyclohex‐2‐enone 11 on treatment with basic silica gel.     

Two‐Step Synthesis of 1,3‐Disubstituted 3,4‐Dihydro‐4‐thioxoquinazolin‐2(1H)‐ones from 1‐Bromo‐2‐fluorobenzenes

An efficient synthesis of 3‐alkyl‐3,4‐dihydro‐4‐thioxobenzoquinazolin‐2(1H)‐ones 3 has been accomplished in two steps and in satisfactory yields from 1‐bromo‐2‐fluorobenzenes 1 . Thus, the reaction of 1‐fluoro‐2‐lithiobenzenes, generated by the Br/Li exchange between 1 and BuLi, with alkyl isothiocyanates, gives N‐alkyl‐2‐fluorobenzothioamides 2 , which, in turn, react with a series of isocyanates in the presence of NaH to give the desired products 3 .     

Synthesis of Bis‐Heterocyclic 1H‐Imidazole 3‐Oxides from 3‐Oxido‐1H‐imidazole‐4‐carbohydrazides

The reaction of 1H‐imidazole‐4‐carbohydrazides 1 , which are conveniently accessible by treatment of the corresponding esters with NH₂NH₂?H₂O, with isothiocyanates in refluxing EtOH led to thiosemicarbazides (=hydrazinecarbothioamides) 4 in high yields (Scheme 2). Whereas 4 in boiling aqueous NaOH yielded 2,4‐dihydro‐3H‐1,2,4‐triazole‐3‐thiones 5 , the reaction in concentrated H₂SO₄ at room temperature gave 1,3,4‐thiadiazol‐2‐amines 6 . Similarly, the reaction of 1 with butyl isocyanate led to semicarbazides 7 , which, under basic conditions, undergo cyclization to give 2,4‐dihydro‐3H‐1,2,4‐triazol‐3‐ones 8 (Scheme 3). Treatment of 1 with Ac₂O yielded the diacylhydrazine derivatives 9 exclusively, and the alternative isomerization of 1 to imidazol‐2‐ones was not observed (Scheme 4). It is important to note that, in all these transformations, the imidazole N‐oxide residue is retained. Furthermore, it was shown that imidazole N‐oxides bearing a 1,2,4‐triazole‐3‐thione or 1,3,4‐thiadiazol‐2‐amine moiety undergo the S‐transfer reaction to give bis‐heterocyclic 1H‐imidazole‐2‐thiones 11 by treatment with 2,2,4,4‐tetramethylcyclobutane‐1,3‐dithione (Scheme 5).     

The Synthesis of 2‐(Chromon‐2/3‐yl)‐3‐(5‐thione‐4‐hydro‐1,3,4‐thiadiazol‐2‐yl)‐4‐oxo‐thiazolidine

2‐Formylchromones and 3‐formylchromones as the first materials singly reacted with 2‐amino‐5‐mercapto‐1,3,4‐thiadiazole to give the corresponding Schiff bases, which on cyclocondensation with mercapto‐acetic acid in 1,4‐dioxane yielded target compounds named 4‐oxo‐thiazolidines. The structures of all the synthetic compounds were confirmed by elemental analysis and IR, ¹H NMR, LC‐MS (ESI) spectral data.     

Synthesis of 3‐Aryl‐2‐methoxyinden‐1‐one (Z)‐Phenylhydrazones via Hydrobromic Acid‐Mediated Cyclization of 2‐(1‐Aryl‐2‐methoxyethenyl)benzaldehyde Phenylhydrazones

2‐(1‐Aryl‐2‐methoxyethenyl)benzaldehydes 2 , obtained by successive treatment of 1‐(1‐aryl‐2‐methoxyethenyl)‐2‐bromobenzenes 1 with BuLi and 1‐formylpiperidine, were transformed to the corresponding phenylhydrazones 3 on treatment with PhNHNH₂. When these hydrazones were allowed to react with conc. HBr, cyclization, followed by dehydrogenation with air occurred, furnished 3‐aryl‐2‐methoxyinden‐1‐one (Z)‐phenylhydrazones 4 .     

Transition‐metal‐catalyzed reactions of 5‐methylene‐2‐oxazolidinone and 5‐methylene‐1,3‐thiazolidine‐2‐thione with isocyanates

5‐Methylene‐2‐oxazolidinone (1) and 5‐methylene‐1,3‐thiazolidine‐2‐thione (4) react with various isocyanates to give the corresponding urethanes 3 and 5 in high yields in the presence of palladium(0) or palladium(II) catalyst under mild reaction conditions. A mechanism is proposed. Copyright © 2003 John Wiley & Sons, Ltd.