1H-1,3-Benzazaphospholes: The Organometallic Route and a New Three-Step Synthesis with Reductive Ring Closure

Abstract

Primary and N -secondary 2-phosphanylanilines were synthesized via metallation of 2-bromoanilines, coupling with ClP(NMe 2 ) 2 , alcoholysis and reduction with LiAlH 4 , and subsequently reacted with formimidoester hydrochloride to give 1,3-benzazaphospholes. For 1 H -1,3-benzazaphospholes, a shorter alternative three-step synthesis was developed, based on N -acylation of 2-bromoaniline, NiCl 2 -catalyzed arylation of triethyl phosphite and a new reductive cyclization of amidophosphonic acid ester with excess LiAlH 4 .The complex chemistry of phospholes and phosphole anions has found considerable interest in recent years. 1,2 Little is known, however, about metal derivatives or complexes of related 1,3-azaphospholes 3 or annulated azaphospholes. 4Ð7 The early papers presented an interesting ambident reactivity of the Ò N Ó-lithiated and the first stable RP=C(Li)-X species, but since then no further work on these compounds has been reported. 8 One of the reasons may be the cumbersome synthetic access of azaphospholes 8 and benzazaphospholes 4,5 by multi-step procedures. We describe here in more detail the organometallic route 5 and a new and shorter way to prepare 1 H -1,3-benzazaphospholes. The original synthesis of 1 H -1,3-benzazaphospholes was based on cyclocondensations of various carbonic acid derivatives with 2-phosphanylanilines. The latter were prepared by photoinitiated MichaelisÐBecker reaction of sodium diethyl phosphite with 2-iodoaniline in liquid ammonia and subsequent reduction with LiAlH 4 . 9 For further studies of benzazaphospholes, we explored a preliminary reported organometallic route 5 with respect to a more general use in the synthesis of 2-phosphanylanilines. 2-Bromoaniline (1) was reacted successively with three equivalents of butyllithium, phosphorous acid bis(dimethylamide) chloride and ethyl alcohol in a one-pot reaction. After removal of volatile components (bath temperatutre 100¡C/0.01 Torr), the resulting mixture was reduced with excess LiAlH 4 to give 2-phosphanylaniline 2 in a total yield of 30% (Scheme 1). Small impurities of secondary phosphanes could not be removed by distillation but did not interfere with the further reaction of 2 with formimidoester hydrochloride affording the non-basic 1 H -1,3-benzazaphosphole 3 , which can easily be purified. Scheme 1For N -substituted derivatives, the following reaction sequence was established. 2-Bromo-N -acylanilides 4 , obtained from 1 ,were reduced with LiAlH 4 to give N -alkyl-2-bromoanilines 5 . The latter were dilithiated and reacted with ClP(NMe 2 ) 2 to give 6 which were converted to 7 with ethanol. Then 7 was reduced to 8 with LiAlH 4 and the latter underwent cyclocondensation with formimidoester hydrochloride affording the N -alkyl-1,3-benzazaphospholes 9 (Scheme 2). Shortcomings of these procedures were low yields in the substitution of the tri-or dilithium compounds if the reactions were carried out on a larger scale. Scheme 2A further disadvantage is the easy replacement of bromine by hydrogen during the reduction of 4 with...

Diels–Alder Reactions with the >C=P– Functionality of Annelated Azaphospholes

“…It is necessary that both ends of the four-atoms chain, YH 2 and ZH 2 , are sufficiently activated by the presence of an EWG, because otherwise the reaction may stop at the intermediate stage 16. …”

Electron‐Rich Aromatic 1,3‐Heterophospholes – Recent Syntheses and Impact of High Electron Density at σ2P on the Reactivity

“…Whereas many phosphaalkenes tend to undergo self‐addition or addition of polar reagents,4,5 the aromatically stabilized 1 H ‐1,3‐azaphospholes and their benzo‐ or pyrido[ b ]‐anellated representatives are usually stable to water, aqueous acids, and bases and also to ROH, R 2 NH, ethereal HCl, or PhSH9 and resemble the phosphinines in this respect 7. The only exceptions so far are two NH‐functional 2‐ tert ‐butyl‐1,3‐benzazaphospholes, which slowly add water at the P=C bond on treatment with dilute aqueous sulfuric acid, yielding the corresponding benzazaphospholine P ‐oxides 33c,37. 1,2,4‐Diazaphospholes are similarly stable whereas N ‐bridging heteroaromatic anellated 1,3‐azaphospholes of the 2‐phosphindolizine type are susceptible to hydrolysis with ring opening.…”

π-Excess σ2 P,O Hybrid Ligands: Synthesis of the First 4-Methoxy-1H-1,3-benzazaphospholes

“…When treated with dilute aqueous sulfuric acid to separate basic nitrogenous impurities, compound 6 underwent slow addition of water, as previously observed for 2-tert-butyl-1H-1,3-benzazaphosphole. 21 Slow concentration of a sample containing the water adduct 9 along with unconverted benzazaphosphole 6 in benzene-d 6 resulted in cocrystallization to give single crystals of an adduct 10, consisting of the two molecules 9 and 6 in a 1:3 molar ratio together with two molecules of benzene-d 6 . In contrast to 6, benzazaphosphole 8 was stable to dilute aqueous sulfuric acid.…”

“…22 Elucidation of the structures of the new compounds 3-8 is based on conclusive multinuclear solution NMR spectra, supplemented by analytical or high-resolution mass spectrometry data. The characteristic shift ranges, the coupling patterns, and the position-dependent J PH and J PC coupling constants 3,7,8,[20][21][22][23] were used to assign the 1 H and 13 C NMR signals and thereby confirm the structures. The phosphorus chemical shifts characterize the compound type through the specific shift ranges for diethyl arylphosphonates, primary arylphosphanes, and benzazaphospholes.…”

“…The phosphorus chemical shifts characterize the compound type through the specific shift ranges for diethyl arylphosphonates, primary arylphosphanes, and benzazaphospholes. The increased shielding at phosphorus in the 4-methoxysubstituted benzazaphospholes 6 and 8 (δ = 56.8 and 61.5 ppm) compared with 2-tert-butyl-and 1-neopentyl-1,3benzazaphospholes lacking a methoxy group (δ = 65.1 21 and 70.8 ppm 8b ), corresponding to upfield shifts Δδ = −8.3 and −9.3 ppm, is attributable to the +M effect of the methoxy group in the position ortho to phosphorus and to the increased π-density at σ 2 P, rather than to steric screening by the methoxy group. This corresponds to the more significant electronic effects of N-substituents compared to the steric screening by substituents at the carbon atom of the P=C bond.…”