Adventures with heterocycles

Elucidation of mechanisms and discovery of novel reactions are interconnected, as four research chapters from the Munich laboratory demonstrate. 1) In a new opening of the furan ring, 2-methoxyfuran and tetra-acceptor-substituted ethylenes furnish methyl acrylates, which are cis-3-substituted by a cyclopropyl ring that bears the four acceptor groups. Experiments with trans- and cis-1,2-bis(trifluoromethyl)-1,2-dicyanoethylenes (BTE) clarify the role of zwitterionic intermediates. 2) The concerted nature of 1,3-dipolar cycloaddition is well established. On reacting thiocarbonyl S-ylides as electron-rich 1,3-dipoles with tetra-acceptor-substituted ethylenes, the switching to a two-step pathway via zwitterion was diagnosed from a loss of stereospecificity and the formation of strained 7-membered cyclic ketene imines. 3) Stable as crystals, these ketene imines rearrange to 5-membered thiolanes in solution. In contrast to open-chain ketene imines, the cyclic representatives add vinyl ether at the C=N bond and show a novel pathway of dimerization. 4) Cycloadducts of isoquinolinium N-phenylimide with ethylenic dipolarophiles undergo an acid-catalyzed [3.3] sigmatropic hydrazo rearrangement. An exception is the conversion of the dimethyl maleate adduct (C21H20N2O4) by acid into a yellow compound C24H22N2O6; the structure and the astounding mechanism were clarified.     

Organic azides: an exploding diversity of a unique class of compounds

Since the discovery of organic azides by Peter Griess more than 140 years ago, numerous syntheses of these energy-rich molecules have been developed. In more recent times in particular, completely new perspectives have been developed for their use in peptide chemistry, combinatorial chemistry, and heterocyclic synthesis. Organic azides have assumed an important position at the interface between chemistry, biology, medicine, and materials science. In this Review, the fundamental characteristics of azide chemistry and current developments are presented. The focus will be placed on cycloadditions (Huisgen reaction), aza ylide chemistry, and the synthesis of heterocycles. Further reactions such as the aza-Wittig reaction, the Sundberg rearrangement, the Staudinger ligation, the Boyer and Boyer-Aubé rearrangements, the Curtius rearrangement, the Schmidt rearrangement, and the Hemetsberger rearrangement bear witness to the versatility of modern azide chemistry.     

Polysoaps with fluorocarbon hydrophobic chains

A series of amphiphilic copolymers is prepared by copolymerization of choline methacrylate with 1,1,2,2-tetrahydroperfluorooctyl methacrylate in varying amounts. The copolymers bearing fluorocarbon chains are studied concerning their effects on viscosity, solubilization and surface activity in aqueous solution, exhibiting a general behavior characteristic for polysoaps. The results are compared with the ones obtained for an analogous series of amphiphilic copolymers bearing hydrocarbon chains.     

Rotaxanes with fluorocarbon blocking groups

A novel [2]-rotaxane has been prepared in which perfluoropropyl stoppers have been utilized as electronic blocking groups. To further investigate this capability, a linear compound that was precapped with perfluoropropyl groups was also prepared. This compound did not demonstrate rotaxane formation when mixed with dibenzo-24-crown-8, providing further evidence that the perfluoropropyl groups were effective electronic stoppers for the macrocycle. [structure: see text]     

Reaction of tetraphenylmethylenediphosphine with aromatic azides

Conclusions Some tetraphenylmethylenediphosphinemono- and tetraphenylmethylenediphosphinedi-(arylimines) were obtained.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp. 1159–1161, May, 1967.     

Reactions of carbethoxyalkylidenetriphenylphosphoranes with aryl azides

The title reaction has been shown to give a complex mixture of products from which triazoles (12 and 17), maleates (13), fumarates (14), triphenylphosphine oxide (15), iminophosphoranes (16) and triazenes (18) have been isolated. Their formation is rationalized by two reaction paths, involving addition of the azide onto the CC and CP bonds of the ylide. Diazoesters 5 and 19, which should result from CP addition, were not isolated, but are believed to give rise to compounds 13,14 and 18.     

Reactions of α-difluoro azides with olefins

Reactions of α-difluoro azides with olefins result in oxidative fluoroamination or amination of the C=C bond.     

Reactions of trichloroacetyl isothiocyanate with organic azides

Benzyl azide reacts with trichloroacetyl isothiocyanate to give 7a in chloroform solution, and 11 in acetone solution. These 1,2,4-oxathiazolidines were characterized by ¹³C nmr spectroscopy (Scheme 2), but could not be isolated since they deteriorated via the carbodiimide 8a into the 1,2,4-thiadiazolidine 9a . The oxathiazoline 6a is assumed as an intermediate and was trapped by isocyanates and dicyclohexylcarbodiimide to give the 1,2,4-thiadiazolidines 10a,b and 12 respectively. Isopropyl azide also reacts with trichloroacetyl isothiocyanate to give the labile oxathiazolidine 7b , which decomposes to the carbodiimide 8b and the 1,2,4-thiadiazolidine 9b . In the case of diphenylmethyl azide, however, no evidence was obtained for the presence of the oxathiazolidine 7c in the ¹H nmr spectra; only the carbodiimide 8c was observed. A mechanistic rationalization is presented in Scheme 1.     

Study on the reactions of fluoroalkanesulfonyl azides with indole derivatives

The reactions of fluoroalkanesulfonyl azides 1 with different indole derivatives have been studied in detail. Treatment of 1 with equimolar amount of 1,3-dimethylindole 3 in 1,4-dioxane at room temperature afforded 2-(1,3-dimethyl-1,3-dihydro-indolinylidene) fluoroalkanesulfonylimines 5 in moderate to good yields. However, under the same reaction conditions, in the case of 1 with 1,2-dimethylindole 4, the corresponding 2-fluoroalkanesulfonyl (1,2-dimethyl-1H-indol-3-yl)-amide 6 was obtained in moderate yields. In addition, the reactions of 1 and indole 7 gave different products under different conditions. Possible mechanisms of these reactions were proposed.     

Study the reactions of fluoroalkanesulfonyl azides with N-alkylindoles

The reactions of fluoroalkanesulfonyl azides R_fSO₂N₃1 with N-alkylindoles 2 have been studied in detail. It was found that both solvent and the amount of the azides seriously affected the product distribution. 1 reacted with equimolar of 2 in ether or 1,4-dioxane affording 2-(N-substituted-indolinylidene)fluoroalkane sulfonylimines 3 as major product; While, treatment of 2 with 2 equiv. of 1 in ethanol, an unexpected product N-substituted-2-fluoroalkanesulfonimino-3-diazo-indolines 4 were obtained in good yield. The reaction mechanism was discussed.     

Cobalt-catalyzed intramolecular C-H amination with arylsulfonyl azides

Cobalt complexes of porphyrins are effective catalysts for intramolecular C-H amination with arylsulfonyl azides. The cobalt-catalyzed process can proceed efficiently under mild and neutral conditions in low catalyst loading without the need of other reagents or additives, generating nitrogen gas as the only byproduct. The catalytic system can be applied to primary, secondary, and tertiary C-H bonds and is suitable for a broad range of arylsulfonyl azides, leading to high-yielding syntheses of various benzosultams.     

Reactions of fluoroalkanesulfonyl azides with cyclic vinyl ethers

The addition reactions of fluoroalkanesulfonyl azides to dihydropyran or dihydrofuran were studied. These reactions do not give the corresponding N-fluoroalkanesulfonyl azilidines but N-fluoroalkanesulfonyl-tetrahydropyranon-2-imines or N-fluoroalkanesulfonyl-tetrahydro-furano-2-imines. The reaction mechanism is discussed.     

Asymmetric Schmidt reaction of hydroxyalkyl azides with ketones

An asymmetric equivalent of the Schmidt reaction permits stereocontrol in ring expansions of symmetrical cyclohexanones. The procedure involves the reaction of chiral 1,2- and 1,3-hydroxyalkyl azides with ketones under acid catalysis; the initial reaction affords an iminium ether that can be subsequently opened with base. A systematic study of this reaction is reported, in which ketone substrates, chiral hydroxyalkyl azides, and reaction conditions are varied. Selectivities as high as ca. 98:2 are possible for the synthesis of substituted caprolactams, with up to 1,7-stereoselection involved in the overall process. The fact that either possible migrating carbon is electronically identical provides an unusual opportunity to study a ring-expansion reaction controlled entirely by stereoelectronic factors. The mechanism of the reaction and the source of its stereoselectivity are also discussed.     

Photochemical modification of polyethylene surface with aryl azides

It has been shown that the formation of a covalently grafted modifying layer takes place during the photolysis of polycrystalline layers of 2-azidoanthraquinone and 4-azidobenzoyl azide on the surface of polyethylene. Its thickness is determined by the amount of the azide applied, and phenyl isocyanate groups formed by the photolysis of 4-azidobenzoyl azide are prone to further functionalization of the modified surface with primary amines.     

Emulsions and microemulsions with a fluorocarbon phase

A phase III clinical study of a perfluorooctyl bromide emulsion demonstrated reduction and avoidance of donor blood transfusion in surgery. Novel fluorocarbon-in-water emulsions are being investigated, including emulsions highly stabilized by fluorocarbon–hydrocarbon diblocks and targeted emulsions for molecular imaging, diagnosis and drug delivery. Reverse water-in-fluorocarbon emulsions and microemulsions that have potential for pulmonary drug delivery are also being studied. Microemulsions with highly fluorinated components are being actively investigated, with applications in polymerization technology and as research tools.