The catalytic hydrogenolysis of 1-phenylbicyclo[4.1.0]heptane and the corresponding azidirine and epoxide

The hydrogenolysisof 1-phenylbicyclo[4.1.0]heptane (1a), cis-1-phenyl-2-methylbicyclo[4.1.0]heptane (1b), 1-phenyl-7-azabicyclo[4.1.0]heptane (2) and 1-phenyl-7-oxabicyclo[4.1.0]heptane (3) was studied using Ni, Pd, Rh and Pt as catalysts. The hydrogenolysis of the C₁C₇ bond of 1a and 1b led to the selective formation of trans-1-phenyl-2-methylcyclohexane (4a) with retention of configuration. Compound 1a gave not only 4a but also phenylcycloheptane (6a), which is the product of C₁C₆ bond fission, and the ratio of 6a to 4a increased in the sequence: Ni ? Pd, Rh < Pt. No C₁C₆ bond fission was observed in the hydrogenolysis of 1b. These results can be explained by a mechanism involving the formation of the π-benzyl complex.trans-2-Phenylcyclohexylamine (8) was obtained stereoselectively in the hydrogenolysis of 2 over Raney Ni. This selective formation can be ascribed to the competition of “SN i” and “radical” processes. The Pd catalysed hydrogenolysis gave cis-2-phenylcyclohexylamine (9) as the main product, while the presence of sodium hydroxide promoted the formation of 8.Raney Ni catalysed hydrogenolysis of 3 yielded a mixture of phenylcyclohexane (13) and 2-phenylcyclohexanols (10 and 11). trans-2-Phenylcyclohexanol (10) was the dominant isomer; the hydrogenolysis resulted in the predominant configurational retention. Compound 13 was confirmed to be produced via 1-phenylcyclohexene (12). This deoxygenation may be explained by a mechanism involving the radical cleavage reaction of 3. The presence of sodium hydroxide led to the formation of cis-2-phenylcyclohexanol (11). The Pd catalysed hydrogenolysis also gave mainly 11.The difference in behaviour of cyclopropane, azidirine and epoxide we ascribe to the differences in the affinity for the catalyst and differences in the electronegativity between C, N and O atoms.     

Tetrazolo-azido isomerization in heteroaromatics—IV : Reactions of tetrazolopolyazines with triphenylphosphine

Formation of iminophosphoranes from tetrazolopolyazines and triphenylphosphine has been studied kinetically in various solvents, and the mechanism explained as nucleophilic attack of the phosphine moiety on the trazolo ring. In the equilibrium system of tetrazolopolyazine (9) and azidopyrazine (9a) in chloroform, it is concluded that tetrazolo and azido moieties react competitively with triphenylphosphine. The mechanism of the reaction of tetrazolopolyazines with triphenylphosphine in chloroform is discussed on a phosphinium radical cation intermediate proposed.     

Preparations and reactions of 1,2,3-trialkyl-1,2-dihydroquinolines and its related compounds

Several 1,2,3-trialkyl-1,2-dihydroquinolines (4 and 5) were prepared from the reactions of N-alkylanilinomagnesium bromide (1 and 2) with aliphatic aldehydes (3). Solutions of these dihydroquinolines in carbon tetrachloride or chloroform gave the corresponding 1,2,3- trialkylquinolinium chlorides (10 and 11) in high yields. Alkali treatment of 1,3-dimethyl-2- ethylquinolinium chloride (10b) led to 1,3 - dimethyl - 2 - acetyl - 1,2 - dihydroquinoline (13), which was unstable and readily converted to 1,3-dimethyl-2-quinolone (6) in the air.     

Reaction of (1,3-dioxo-2,3-dihydro-1H-inden-2-ylidene)propanedinitrile with N-arylisoindolines

In a multistep reaction, 3,3′-(2-aryl-2H-isoindol-1,3-ylene)-di-(1,4-naphthoquinone-2-carbonitriles) 13a-f have been formed in 25-61% yield from a series of N-arylisoindolines 8a-f with (1,3-dioxo-2,3-dihydro-1H-inden-2-ylidene)propanedinitrile (1) in aerated pyridine. The structure of one of these products (13f) has been unambiguously confirmed by a single crystal X-ray structure analysis. Under otherwise the same conditions, 2-(3-methoxyphenyl)-isoindoline (8g) and 1 gave 38% of [4-(2,3-dihydro-1H-isoindol-2-yl)-2-methoxyphenyl]-1,3-dioxoindan-2-ylidene)acetonitrile (15). Rationales for these conversions involving the known rearrangement of the radical anion of 1 into the radical anion of 1,4-naphthoquinone-2,3-dicarbonitrile (3) are presented.     

Aporphines 10. Approaches to the synthesis of 7-hydroxyaporphines : Stereoselective synthesis of (±)-10,11-dimethoxy-7-oxoaporphine, (±)-7-hydroxyaporphine and (±)-7-hydroxynoraporphine

A new method for the stereoselective synthesis of 7-hydroxyaporphine (3a) and 7-hydroxynoraporphine (3b) via the 4-oxazolin-2-one 20 as a protecting group has been developed. Pschorr cyclization of 20 and hydrolysis of the oxazoloaporphine 21 with trifluoroacetic acid led exclusively to the dehydronoraporphine 22. Reduction of 21 with LAH gave 3a and treatment of 21 with methyllithium gave 3b. The synthesis of 10,11-dimethoxy-7-oxoaporphine (2) involving a Reissert alkylation-Pschorr cyclization sequence has been achieved.     

α-Acylamino radical cyclizations using allenes and vinylsilanes as addends: applications to the synthesis of (+)-heliotridine and (-)-dihydroxyheliotridine

Total syntheses of the pyrrolizidine bases (+)-heliotridine (4) and (-)-dihydroxyheliotridane (5) from (S)-3-acetoxysuccinimide are described. The syntheses of 4 and 5 revolve around free radical cyclizations involving the use of allenes and vinylsilanes, respectively, as addends.     

A new and short enantioselective synthesis of (R)-pantolactone

Dihydro-4,4-dimethyl-2(3H)-furanone 6, the key intermediate to (R)-pantolactone 2, has been synthesized in two steps via the radical cyclization of bromoether 5. Silyl enol ether 7, prepared from 6, on Sharpless asymmetric dihydroxylation gave (R)-pantolactone 2 in moderate yield and excellent enantioselectivity.     

An electron spin resonance study of radicals from chloramine-T—2 : Spin trapping of photolysis products of chloramine-t at alkaline pH

Irradiation of chloramine-T at alkaline pH in the presence of the spin trap 2-methyl-2-nitrosopropane gave evidence for the trapping of several sulfur-centred radicals and a carbon-centred radical. Trapping experiments with 5,5-dimethyl-pyrrolidine-1-oxide gave evidence for the production of a nitrogen- centred radical and a carbon-centred radical. The spin trap α-phenyl-t-butyl-nitrone gave evidence for a nitrogen-centred radical, a sulfur-centred radical and the H-atom adduct of the spin trap. The identity of the trapped species was confirmed by irradiation of the following chemical analogues of chloramine-T as “model [compounds” in alkaline solution; chloramine-B (sodium salt of N-chlorobenzene sulfonamide), p-toluenesulfonamide, p-toluenesulfonic acid, p-toluenesulfinic acid. To aid in the assignment of the radical adducts where mixtures of species occurred, computer simulation of the spectra was performed.     

Stereoselective synthesis of 2-methylenepyrrolizidines by tandem cyclization of N-propargylaminyl radicals

Tandem cyclization of N-propargylaminyl radicals, generated by N-chlorination of (E)-alk-4-enylamines 2a-d and 2f followed by treatment with tributyltin radical, afforded 2-methylenepyrrolizidines 3a-d and 3f in a highly stereoselective manner. A similar radical cyclization of (Z)-N-propargyl-1-methyl-5-phenylpent-4-enylamine (2e) gave pyrrolizidine 3b having the same stereochemistry as that obtained from the E isomer 2b.     

Thermal fragmentation and rearrangement of some N-phenylbenzamide oxime dervatives II. Synthesis of benzimidazoles

Thermolysis of N-phenylbenzamide oximes I, II and III (R = Cl, NO₂ and OCH₃) under nitrogen gives rise to benzimidazoles as the major products (45-52%), in addition to benzonitrile, arylamines, benzoic acid, phenols, benzanilides, 2-phenyl benzoxazoles and carbazoles. In the presence of naphthalene, I gave α- and β-naphthols beside the previous products. Also heating of I under reflux boiling tetralin lead to the formation of 1-hydroxytetralin, α-tetralone and 1,1′-bitetralyl as the major products. The isolated products have been interpreted in the terms of a free radical mechanism involving the homolysis of N-O and/or C-N bonds.     

Nucleophilic subsitution at silicon: Synthesis of sterically-hindered bis(2,6-di-t-butylaryloxy)silanes

The reaction of the monomethylsilane (8a) with two equivalents of the 4-(carboalkoxy)-2,6-di-t-butyl-substituted phenol (7b) in toulene using triethylamine as an acid acceptor gave the bis(aryloxy) adduct (9a). The analogus reaction of the dimethylsilane (8b) with sodium 2,6-di-t-butyl-4-(methoxycarboxyl)-phenolate (7a) gave only the monosubstitution product (10a). The reaction of the corresponding phenolate (7e) with 8b gave a mixture of 7a, 10a, and bis-adduct (9b), whereas, in the presence of 15-crown-5, the bis-adduct 9b was obtained. The bis-adducts 9c–e were prepared in an analogous manner. The reaction of n-hexyl 3,5-di-t-butyl-4-hydoxylbenzoate (7h) with the diphenylsilane (8c) gave only the monosubstitution product 12, while forcing conditions gave, unexpectedly, the methyl ether 13. The reaction of 4-(carboalkoxyethyl)-2,6-di-t-butylphenol (16a) with 8a gave the bis adduct. The reaction of 16a with 8b in THF, without a crown ether, gave a low yield of the monosubstitution product. The bis-adducts 17b–c were obtained by the reaction of 8b with the corresponding phenolates (16a–b) in tetraglyme. Compound 17b was also obtained by the reaction of 8b with 16a in THF with a crown ether. These results are discussed in terms of charge dispersal in the phenolate ion and the corresponding effect upon both ion-pairing and aggregation in solution.     

Photochemical ring closure of α,α-bisulfenylated carbonyl compounds: Stereoselective formation of cix-dihydrobenzothiophenes

Photochemistry of α,α-bisulfenylated ketone has been investigated. Irradiation of 2-phenylthiodihydrothiophen-3-one (1) in benzene gave the radical recombination products 9 (63%) and 10 (49%). In a polar solvent, the ionic chemistry became predominant. Brief irradiation of 1 in acetonitrile and methanol gave the cis-fused dihydrothiophene 11 as the major product in 43% and 20% yields, respectively. The stereoselective photocyclization was generally observed for other ketones (2–8) in acetonitrile solution (Table 1). The photo-products were easily dehydrated by treating with boron trifluoride etherate to give the corresponding benzothiophenes in high yields. Simple α-phenylthioketones are photoinert under the same conditions. The mechanism of this novel photocyclization of bisulfenylated ketones is also discussed.     

On the mechanism of the reductive cleavage of anti-9-phenyl-cis-bicyclo[6.1.0]nona-2,4,6-triene

Treatment of the title compound (1a) with potassium in liquid ammonia at ca ?33° immediately afforded the benzylcyclooctatetraene dianion (4a) which, upon quenching with iodine-pentane, gave benzylcyclooctatetraene (5) as the only isolable product. In contrast, treatment of1a with potassium amide in liquid ammonia at ?69° initially afforded the 9-phenylmethylenecyclooctatrienyl anion (6a) as a short-lived intermediate which was then converted to the α-aminobenzylcyclooctatetraene dianion (7a). These results, coupled with the observation that cis-bicyclo[6.1.0]nona-2,4-diene (12) in potassium amide-liquid ammonia affords the cis-bicyclo[6.1.0]nonadienyl anion (8b) which then slowly opens to the methylcyclooctatetraene dianion (4b) at ?12°, lead to the conclusion that4a is produced by a reductive cleavage of1avia a radical anion or dianion.     

Mechanisms of antioxidant action: The involvement of nitroxyl radicals in the antifatigue action of secondary amines

Isopropylaminodiphenylamine (IPPD, I) and a hindered bispiperidine (IIa) are effective antifatigue agents in vulcanized rubber. The former is also a powerful thermal antioxidant and antiozonant whereas the latter is not. An investigation of the mechanism of antifatigue action shows that both I and IIa are converted to the corresponding nitroxyl radical during dynamic flexing of the rubber and that the nitroxyl is continuously regenerated in a cyclical mechanism involving the corresponding hydroxylamines.     

Investigating cyclic sotolon,maple furanone and their dimers in solution using optical rotation,electronic circular dichroism and vibrational circular dichroism

The experimental optical rotation (OR), electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) spectra of (R)-3-hydroxy-4,5-dimethylfuran-2(5H)-one (sotolon, 1) and (R)-5-ethyl-3-hydroxy-4-methylfuran-2(5H)-one (maple furanone, 2) taken in chloroform were compared to their spectra calculated with time-dependent density functional theory (TDDFT). Sotolon was shown to exist as a dimer in chloroform while maple furanone remains a monomer. Transition state barriers for the enol/keto tautomerization of sotolon were calculated and found to be high. The VCD method offers promise to ultimately distinguish between the presence of monomers or dimers.     

Binary amorphous solids consisting of 2,4,6-triarylphenoxyl radicals and their dimers

Although molecular amorphous materials represent an important area of research in solid-state chemistry, studies pertaining to these systems have been restricted almost exclusively to amorphous solids based on a single molecule. In this study, we found that, while the 2,4,6-bis(4-tert-butylphenyl)phenoxyl radical (2_M) and its dimer (2_D) did not give single-component amorphous solids, they rapidly formed the corresponding binary amorphous solid IIa following their condensation from benzene, dichloromethane, chloroform, and ethyl acetate solutions. The formation of IIa could be attributed to the good solubilities of 2_M and 2_D in these solvents and the high packing efficiencies of these amorphous solids. IIa was also obtained when crystals of 2_D (IIb) were ground together. The solid-state formation of IIa would not only involve the locational exchange of 2_M and 2_D, but would also involve chemical exchanges.     

The synthesis of shihunine and related compounds from ortho-carboxyphenyl cyclopropyl ketone

Reaction of dicyclopropyl cadmium and phthalic acid monochloride monomethyl ester gives o-carboxyphenyl cyclopropyl ketone (2). Reaction of the methyl ester of 2 with methylamine gives 2 - methyl - 3 - hydroxy-3-cyclopropyl-1-isoindolinone (4b), which is converted by hydrogen halides in chloroform to the rearranged homoallylic halides 5a–c. Thionyl chloride in chloroform converts 2 to 3-(3-chloropropylidene) phthalide (7) which upon reaction with methylamine gives isoshihunine (8). Heating of keto acid 2 with aniline leads to N-phenyl-N-norshihunine (9), while upon heating of 2 with methylamine spiro [(1 - methylpyrrolidine) - 2 - 3′ - (2′ - methyl - 1′ - isoindolinone)] (10) is obtained. 10 is converted to shihunine (1) by 48% HBr solution. The mechanisms of the reactions are discussed.     

Synthesis of annulated dioxins as electron-rich donors for cation radical salts

The synthesis of a series of new alkoxylated linearly annulated dioxins is described together with their cyclic voltammetric behavior and some preliminary result on their ability to form cation radical salts. Of these dioxins, seven (8, 12, 19, 21, 27, 33, 34) are the first representatives of entirely new heterocyclic systems. Dioxins 8, 21, 22 and 27 gave good quality cation radical salts upon electrocrystallization.     

Beckmann and cyclization reactions of δ-oxo-α,β-unsaturated ketoximes obtained from pyrylium salts and hydroxylamine. formation of 2-aryl(or alkyl)amino-4,6-disubstituted pyrylium salts

The reaction of 2,4,6-trisubstituted pyrylium salts 1 with hydroxylamine gave regio- and stereo-selectively 1,3,5-trisubstituted 2-cis-pentene-1,5-dione 1-oximes 4. On cyclization, 3,5,5-trisubstituted 2-isoxazolines 6 and 2,4,6-trisubstituted pyridine 1-oxides 5 were obtained, originating in the antilsyn stereoisomers of oxime 4, respectively. Beckmann reaction of keto-ketoximes 4 with thionyl chloride unexpectedly gave 2-aryl (or alkyl) amino-4,6-di-substituted pyrylium salts 7, the first example of rearrangement/cyclization involving carbonylic oxygen as terminator. Crystallographic data are provided for (Z)-N-t-butyl-3,6,6-trimethyl-2-heptenecarboxamide 13b.     

Synthesis, photophysical and thermal studies of symmetrical and unsymmetrical zinc phthalocyanines

The novel zinc phthalocyanine (3) with malonylester and chloro groups on each benzo unit was synthesized from 4-diethoxymalonyl-5-chloro-phthalonitrile (1). The unsymmetrically substituted zinc phthalocyanine (5), carrying hexylthio, malonylester and chloro groups at the periphery, was obtained from 4-diethoxymalonyl-5-chloro-phthalonitrile (1) and 4,5-bis-hexylsulfanyl-phthalonitrile (2) by a statistical condensation method as an A₃B type unsymmetrical phthalocyanine compound. Transesterification of the malonyl esters of the new symmetrical and unsymmetrical phthalocyanines occurred during the cyclotetramerization of dinitriles with Zn(CH₃COO)₂ in 1-pentanol in the presence of DBU. Octa-hexylthio-substituted zinc phthalocyanine (4) was prepared according to the literature. The photophysical and thermal properties of all the phthalocyanine complexes are described for the first time. These novel symmetrical and unsymmetrical phthalocyanine macrocycles have been characterized by a series of spectroscopic methods including ¹H NMR, electronic absorption, IR and mass spectroscopy, in addition to elemental analysis. Their narrow long wavelength absorption band shows that the bulky substituents on the periphery prevent aggregation. The unsymmetrically substituted phthalocyanine (5) gave a greater fluorescence quantum yield in chloroform than the symmetrical analogues (3 and 4).