Itshak Granoth

SYNTHESIS, REACTIVITY AND CONFORMATION OF 10,11-DIHYDRODIBENZO-[b,f]PHOSPHEPIN AND DIBENZO[b,f]PHOSPHEPIN DERIVATIVES. PHOSPHORUS ANALOGUES OF IMINOBIBENZYL ANTIDEPRESSANTS

Abstract Derivatives of the novel dibenzo[b,f]phosphepin system are prepared from 10,11-dihydro-5-phenyl-5H-bibenzo[b,f]phosphepin 5-oxide (2). New members in the 10,11-dihydro-5H-dibenzo[b,f]phosphepin series, including phosphorus analogues (7, 10) of the andidepressant drug imipramine (30), are also reported. Products of nucleophilic substitution at tetrahedral phosphorus in 2 appear to be determined by the relative apicophilicity of the nucleophile. Conformational analysis based on 1H NMR data suggests folded (“butterfly”) conformation for the tricyclic compounds. The twisted boat conformation of the central ring in the 10,11-dihydro compounds bears a pseudo-equatorial P[dbnd]O oxygen or a P[dbnd]S sulfur, in solution. Symmetric AA‘BB’ spin systems are found in 4,5 and 7, and their solution conformations appear to be similar to those of analogous 10,11-dihydrodibenzo[b,f]azepine derivatives. The interaction of some compounds with NMR shift reagents and their mass spectral fragmentations are discussed.

Friedel–Crafts acylation–cyclisation reactions of 3-bromophenyl ethers with phosphorus trichloride and oxalyl chloride to give the corresponding phenoxaphosphine and xanthen-9-one derivatives

Condensations of 4-chloro- and 4-fluoro-phenyl 3-bromophenyl ether (3) with phosphorus trichloride and with oxalyl chloride in the presence of aluminium chloride gave, essentially in a one-step reaction, 7-bromo-2-chloro-phenoxaphosphine 10-oxide (4) and 6-bromo-2-fluoroxanthen-9-one (7), respectively. Best yields were obtained in dilute solutions.

Preparation of a dibenzo[b,e]phosphorin. Selective phosphine oxide reduction by trichlorosilane

5,10-Dihydro-5-phenyldibenzo[b,e]phosphorin-10-one 5-oxide (3) has been prepared by the action of polyphosphoric acid on o-diphenylphosphinylbenzoic acid, and has been selectively reduced by trichlorosilane to the ketophosphine (4).

Lithium aluminium hydride-mediated methylation of diphenylmethane and allied compounds by bis-2-(methoxyethyl) ether

Diphenylmethane (1) yields mainly 1,1-diphenylethane or 2,2-diphenylpropane (10) upon heating with lithium aluminium hydride in bis-(2-methoxyethyl) ether, depending on the reaction conditions. Cyclic analogues of diphenylmethane are αα-dimethylated much faster than diphenylmethane itself under the same conditions. 1,1-Diphenylcyclopropane (11) is reduced to 2,2-diphenylpropane by lithium aluminium hydride on prolonged heating in bis-(2-methoxyethyl) ether. Evidence for the formation of the cyclopropane (11) as a by-product from diphenylmethane, bis-(2-methoxyethyl) ether, and lithium aluminium hydride is presented.

Novel specific carbon–carbon bond formation; substituent and solvent effects associated with hydride addition to aromatic olefins

2,2-Diarylpropanes are conveniently prepared from 1,1-diarylethylenes, lithium aluminium hydride, and anisole in tetrahydrofuran while 1,1-diarylethanes are obtained at 140 °C in bis(methoxyethyl) ether; hydride addition to 1,1-diarylethylenes is decelerated by 2-methyl substituents, and o- and p-methoxy, but not m-methoxy.

Deoxygenation of aromatic sulphoxides by thionyl chloride in the presence of cyclohexene. Synthesis of substituted phenoxathiins

2,3,7,8-Tetrachlorophenoxathiin (1b) and bis-3,4-dichlorophenyl ether (2), structural analogues of the highly toxic pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (1a), have been synthesized. The preparation of (1b) by the aluminium chloride-catalysed condensation of (2) with thionyl chloride involves deoxygenation, and some aromatic chlorination also occurs. The scope of the latter reactions for the preparation of substituted phenoxathiins has been studied. Aromatic sulphoxides undergo deoxygenative chlorination upon treatment with thionyl chloride, but only deoxygenation occurs in the presence of cyclohexene, which traps the by-product chlorine.

A stable bromoalkoxyphosphorane, a model for the postulated five-co-ordinate intermediate in the Arbuzov and related reactions

A stable model for the postulated intermediate in Arbuzov and related reactions, bromoalkoxyphosphorane (6), is obtained from the reaction of bromine and the phosphine ether (8). The analogous phosphine (13), however, gives benzyl bromide and the ionic alkoxyphosphonium bromide (17). The latter when heated produces a further equivalent of benzyl bromide and a new dioxyphosphorane (18). The phosphorane (18) is also formed upon spontaneous cyclodehydration of the product obtained in the reaction of methylmagnesium bromide and the diester (19). The methiodide (21) shows chemical shift nonequivalence of every benzylic methyl and benzylic proton. Rotation around the appropriate C–P bonds is presumed to be strictly hindered and proceeds with ΔG‡ of ca.18 kcal/mol at 80 °C. Surprisingly, bromoalkoxyphosphorane (6) is not very sensitive to water and is also prepared from the phosphine oxide (10) and 48% HBr.

Stable acyloxy-chlorophosphorane obtained from 2-(diphenylphosphinyl)-benzoic acid and thionyl chloride

The title reaction gives the novel acyloxy-chlorophosphorane (1) and the analogous fluoride (9) is similarly obtained.

A monocyclic phosphorane oxide anion and the extraordinary reactivity of its tautomeric phosphine oxide alkoxide

Deprotonation of the alcohol (2) gives the phosphorane oxide anion (3) which equilibrates with its exceptionally reactive tautomeric phosphine oxide alkoxide (4).

Stereoselective reductions and alcohol deoxygenation by a phosphine in the 5,10-dihydrodibenzo[b,e]phosphorin series

The stereospecific reductions of the 5-methyldibenzo[b,e]phosphorin-10(5H)-one (4) by NaH2Al(OC2H4OMe)2 and LiHAl(OBut)3 give the pseudoaxial and pseudoequatorial alcohols (14) and (13), respectively. Alcohol (13), but not (14), undergoes ready oxygen transfer from carbon to phosphorus. LiAlH4 deoxygenates the pseudo-equatorial alcohol 5-methyl-5,10-dihydrodibenzo[b,e]phosphorin-10-ol 5-oxide (6), but not the corresponding pseudoaxial alcohol (7), to the phosphine oxide (8). Neither the isomeric alcohols (6) and (7) nor their acetate esters (17) and (18) equilibrate or isomerize under electron impact at 200 °C.