Inorganic chemistry,vinylogy is the transmission ofelectronic effects through aconjugated organic bonding system.[1] The concept was introduced in 1926 byLudwig Claisen to explain theacidic properties offormylacetone and relatedketoaldehydes. Formylacetone, technicallyCH3(C=O)CH2CH=O, only exists in the ionized formCH3(C−O−)=CH−CH=O orCH3(C=O)−CH=CH−O−.[2] Its adjectival form,vinylogous, is used to describefunctional groups in which the standard moieties of the group are separated by a carbon–carbondouble bond.
For example, acarboxylic acid is defined as acarbonyl group (C=O) directly attached to ahydroxyl group (OH): O=C–OH. A vinylogous carboxylic acid has avinyl unit (−HC=CH−, vinylene) between the two groups that define the acid: O=C–C=C–OH. The usualresonance of a carboxylate can propagate through the alkene of a vinylogous carboxylate. Likewise,3-dimethylaminoacrolein is the vinylogous-amide analog ofdimethylformamide.
Due to the transmission of electronic information through conjugation,vinylogous functional groups often possess "analogous"reactivity orchemical properties compared to theparent functional group. Hence, vinylogy is a usefulheuristic for the prediction of the behavior of systems that are structurally similar but contain intervening C=C bonds that are conjugated to the attached functional groups. For example, a key property of carboxylic acids is theirBrønsted acidity. The simplest carboxylic acid,formic acid (HC(=O)−OH), is a moderately strong organic acid with a pKa of 3.7. We would expect vinylogous carboxylic acids to have similar acidity. Indeed, the vinylog of formic acid, 2-formyl-1-ethen-1-ol,HC(=O)−CH=CH−OH has a substantial Brønsted acidity, with an estimated pKa ~ 5–6. In particular, vinylogous carboxylic acids are substantially stronger acids than typicalenols (pKa ~ 12). Vitamin C (ascorbic acid,see below) is a biologically important example of a vinylogous carboxylic acid.
The insertion of ao- orp-phenylene (i.e., a benzene ring in the 1,2- or 1,4-orientation) also results in some similarities in reactivity (calledphenylogy), although the phenylogous effect is generally weaker, as conjugation through the aryl ring requires consideration of resonance forms or intermediates in whicharomaticity is disrupted.[3][4]
Vinylogous reactions are believed to occur whenorbitals of the double bonds of the vinyl group and of an attached electron-withdrawing group (EWG; the π orbitals) are aligned and so can overlap and mix (i.e., areconjugated). Electrondelocalization enables the EWG to receive electron density through participation of the conjugated system.
A classic example of vinylogy is the relatively high acidity of the γ-hydrogen inCH3CH=CHC(O)R. The acidity of the terminal methyl group is similar to that for the methyl ketoneCH3C(O)R.[5]
Vinylogous reactions also includeconjugate additions, where anucleophile reacts at the vinyl terminus, akin to the addition of the nucleophile to the carbonyl of the methyl ketone. In a vinylogous variation of thealdol reaction, anelectrophile is attacked by a nucleophilic vinylogousenolate (see first and following image). The vinylogous enolate reacts at the terminal position of the double bond system (the γ-carbon), rather than the α-carbon immediately adjacent to the carbonyl, as would a simple enolate.Allylic electrophiles often react by vinylogous attack of a nucleophile rather than direct addition.
A further example of vinylogous reactivity:ascorbic acid (Vitamin C) behaves as a vinylogous carboxylic acid by involvement of its carbonyl moiety, a vinyl group within the ring, and the lone pair on the hydroxyl group acting as theconjugated system. Acidity of the hydroxyl proton at the terminus of the vinyl group in ascorbic acid is more comparable to a typical carboxylic acid than analcohol because two majorresonance structures stabilize the negative charge on theconjugate base of ascorbic acid (center and right structures in last image), analogous to the two resonance structures that stabilize the negative charge on the anion that results from removal of a proton from a simple carboxylic acid (cf. first image).
