Studies on the rearrangement of ortho-nitrobenzylidenemalonates and their Analogues to 2-aminobenzoate derivatives

Abstract

Reaction of the diethyl 2-nitro-4-(trifluoromethyl)benzylidenemalonate with diethylamine in alcohols resulted in the reduction of the nitro group and the oxidation of the vinylic carbon attached to the phenyl ring. Simultaneous migration of the malonic fragment gave the appropriate 2-amino-4-(trifluoromethyl)benzoate esters. The presence of at least two nitro groups, or one nitro group and trifluoromethyl group on the phenyl ring, attached to the α-carbon and strongly electron withdrawing substituents at the β-carbon (CO2Et, CN) in ortho-nitrobenzylidene systems is necessary for this reductive–oxidative rearrangement to proceed. Reaction of nitrocinnamates with thiols in the presence of triethylamine in tetrahydrofuran gave Michael addition products with different regioselectivity of addition. Ethyl 2-nitrocinnamate undergoes standard β-addition of thiols to a carbon–carbon double bond. However, 2,4-dinitro- and 2,4,6-trinitrocinnamates undergo α-addition of thiols, indicating that the presence of two nitro groups on the phenyl ring can reverse polarity of the carbon–carbon double bond in cinnamate acceptors.Key words: abnormal Michael reactions, aromatic nitro compounds, benzylidene compounds, rearrangements.

Theoretical and Experimental Study of the Regioselectivity of Michael Additions

“…(Table 1); reactants correspond to the central well; solid curves are used where energies of stationary points have been calculated [B3LYP//HF/6Ϫ31ϩG(d)]; dashed curves are schematic; energies are relative to E P β , which is set to zero; R, TS, I, and P represent reactants, transition state, intermediate, and product, respectively; subscripts denote α-or β-addition; for consistency, energies include a cyanide anion and a THF molecule with the reactants, a protonated THF molecule with the transition states and intermediates, and a THF molecule with the products Synthetic Experiments: A few reactions yielding α-addition have been reported previously. [13,14] In addition, we performed reactions of cinnamic aldehyde 22 and ester 25 with propanethiol. These reactions gave the α-addition products 26 and 27, respectively (see Scheme 2 and Exp.…”

“…; our theoretical calculations confirm that 22 favors α-addition; the α-addition of PrSH to 24 and the β-addition to 23 are described in ref. [14] …”

“…[6] The trends just described for 1Ϫ10 are also exhibited by the pentadienals and pentadienoate 11Ϫ16. A trifluoromethyl (14) or nitro (16) (15) is again intermediate between the trifluoromethyl and nitro groups in promoting α-addition. The influence of the EWGs is smaller when they are separated from C β by the extra double bond.…”

“…[2] Recently, reverse addition of nucleophiles (at C α ) to α,β-unsaturated carbonyl compounds possessing strongly electron-withdrawing groups (EWGs) at C β has been reported. [13,14] This process can be understood as a competition between EWGs on either side of the activated double bond. For example, reactions of dimethylamine or methanol with methyl 3,3-bis(trifluoromethyl)propenoate (8) give the corresponding α-adducts, [13] as do additions of thiols to 2,4-dinitro-(e.g., 24) and 2,4,6-trinitrocinnamates.…”

“…For example, reactions of dimethylamine or methanol with methyl 3,3-bis(trifluoromethyl)propenoate (8) give the corresponding α-adducts, [13] as do additions of thiols to 2,4-dinitro-(e.g., 24) and 2,4,6-trinitrocinnamates. [14] Phosphane-catalyzed reaction of nitrogen nucleophiles with 2-alkynoates redirects the regioselectivity of ad-respect to properties of the substituents. The difference between the reaction barriers for α-vs. β-addition decreases as the strength of electron-withdrawing groups increases until, for sufficiently strong electron-withdrawing groups, α-addition becomes favored.…”