Michael addition, acidic mechanism

The mechanism is presumed to involve a pathway related to those proposed for other base-catalyzed reactions of isocyanoacetates with Michael acceptors. Thus base-induced formation of enolate 9 is followed by Michael addition to the nitroalkene and cyclization of nitronate 10 to furnish 11 after protonation. Loss of nitrous acid and aromatization affords pyrrole ester 12. 

The powerful nucleophilicity of enaimnes illows the dclthcion of rutro ilkenes to take place without the presence of Lewis acids The isolanon of secondary products, which can be explained by an initial Michael addition, suggests the participation of zwitlerionic intermediates m the mechanism of the reaction fEq 8 97i... 

Adiponitrile is produced at over 1 million tpa and, being used in the manufacture of hexamethylene diamine and (to a small extent) adipic acid, it is by far the highest-volume organic material that is produced electro-chemically. The mechanism (Scheme 7.13) involves electrolytic reduction of acrylonitrile followed by protonation, further reduction, Michael addition and a final protonation step. 

The reaction mechanism is shown in Figure 4 and is adapted from work by Fiego et al. [9] on the acid catalysed condensation of acetone by basic molecular sieves. The scheme has been modified to include the hydrogenation of mesityl oxide to MIBK. The scheme begins with the self-condensation of acetone to form diacetone alcohol as the primary product. The dehydration of DAA forms mesityl oxide, which undergoes addition of an addition acetone to form phorone that then can cyclise, via a 1,6-Michael addition to produce isophorone. Alternatively, the mesityl oxide can hydrogenate to form MIBK. 

Further details of this pathway have been given by Gieg [317] to explain the formation of 6-(2-aminophenyl)-2-hydroxy-6-oxohexa-2,4-dienoic acid. In the original pathway (Fig. 17) it is formed by a meta cleavage of 2 -aminobiphenyl-2,3-diol, but the mechanism reported subsequently suggests that it is formed from an unidentified X unstable compound via intramolecular Michael addition forming a six-membered ring (Fig. 18). 

The mechanism by which the hydroperoxide intermediate, (42) (Scheme 29) is converted into the products of Scheme 28 is not clear. The follow-up reaction of (42) may be diverted by reaction with an enone that undergoes epoxidation in 85 to 90% yield. Scheme 29, [121]. The epoxidation reaction does not take place directly from O2 and 02 but requires the formation of an intermediate of type (42) derived either from the enone or from an external carbon acid as in Scheme 29. Yields are considerably improved using an external carbon acid since the Michael addition between the enone and its anion otherwise competes with the epoxidation. For... 

During the coverage period of this chapter, reviews have appeared on the following topics reactions of electrophiles with polyfluorinated alkenes, the mechanisms of intramolecular hydroacylation and hydrosilylation, Prins reaction (reviewed and redefined), synthesis of esters of /3-amino acids by Michael addition of amines and metal amides to esters of a,/3-unsaturated carboxylic acids," the 1,4-addition of benzotriazole-stabilized carbanions to Michael acceptors, control of asymmetry in Michael additions via the use of nucleophiles bearing chiral centres, a-unsaturated systems with the chirality at the y-position, and the presence of chiral ligands or other chiral mediators, syntheses of carbo- and hetero-cyclic compounds via Michael addition of enolates and activated phenols, respectively, to o ,jS-unsaturated nitriles, and transition metal catalysis of the Michael addition of 1,3-dicarbonyl compounds. ... 

The mechanism of these MCRs involving Meldrum s acid should include Knoevenagel condensation and Michael addition cascade process [100, 113] (Scheme 37). To form positional isomeric reaction product, arylliden derivatives of Meldrum s acid are attacked by exocyclic NH2-group instead of endocyclic nucleophilic center. 

The Michael addition is an enolate ion addition to an a,(3 unsaturated Ccirbonyl. This reaction takes advantage of the increased acidity of a hydrogen atom that s a to two carbonyl groups. This enolate ion is very stable, so it s less reactive than normal enolates. The more-stable enolate leads to a greater control of the reaction so that only one or two products form instead of multiple products from a less stable (and therefore more reactive) enolate. An example of this type of reaction is in Figure 11-24 with the mechanism in Figure 11-25. 

The base-catalyzed Michael addition of oxazolin-5-ones to alkynic ketones produces 4-(3-oxopropenyl) derivatives (405) (79CB3221). The latter compounds are cleaved on warming with oxalic acid dihydrate in acetic acid to y-diketones (406). The mechanism of this transformation corresponds to a vinylogous Dakin-West reaction (Scheme 90). 

Exercise 24-13 Propanedinitrile [malononitrile, CH2(CN)2] reacts with tetracyano-ethene in the presence of base to yield a compound of formula HC3(CN)5, which is a monobasic acid of strength similar to sulfuric acid. What is the structure of this compound and why is it such a strong acid Write a mechanism for the formation of the compound that is based in part on the Michael addition (Section 17-5B). 

In the case of 1,3-thiazine-2-ylidene compounds, hydrolysis of N-methylimino-5-ethoxycarbonyl-l,3-thiazine 188 (R = Me) is carried out in an acid medium. Formic acid does not react. Incorporation of water was found in the course of subsequent research (formic acid/aqueous triethyla-mine either formic acid or acetic acid/water 50-50 formic acid/aqueous formaldehyde) and resulted in the isolation of three compounds 5-ethoxy-carbonyl-2-oxo-2,3-dihydro-6//-l, 3-thiazine (189), 5-ethoxycarbonyl-l-methyl-2-thioxo-l,2,3,4-tetrahydropyrimidine (190) and 5-ethoxy-car-bonyl-3-methyl-2-thioxo-l, 2,3,4-tetrahydropyrimidine (191). The authors have proposed a mechanism involving cleavage of the C-6-S bond and reclosure of the six-membered ring by a Michael addition (Scheme 75). 

This is an important mechanism, and we have seen the consequences of attack by an intramolecular nucleophile (ligand) in earlier chapters. A particularly interesting example is seen in the intramolecular Michael addition of a co-ordinated amide at a cobalt(m) centre to yield an amino acid derivative (Fig. 5-44). 

The Michael addition mechanism, whereby sulfur nucleophiles react with organic molecules containing activated unsaturated bonds, is probably a major pathway for organosulfur formation in marine sediments. In reducing sediments, where environmental factors can result in incomplete oxidation of sulfide (e.g. intertidal sediments), bisulfide (HS ) as well as polysulfide ions (S 2 ) are probably the major sulnir nucleophiles. Kinetic studies of reactions of these nucleophiles with simple molecules containing activated unsaturated bonds (acrylic acid, acrylonitrile) indicate that polysulfide ions are more reactive than bisulfide. These results are in agreement with some previous studies (30) as well as frontier molecular orbital considerations. Studies on pH variation indicate that the speciation of reactants influences reaction rates. In seawater medium, which resembles pore water constitution, acrylic acid reacts with HS at a lower rate relative to acrylonitrile because of the reduced electrophilicity of the acrylate ion at seawater pH. 

Further evidence for the addition of H2S to carbon-carbon double bonds very early in sediments, and further insights into reaction mechanisms, have been reported by Vairavamurthy and Mopper in 1987 and 1989 (109.110). They identified 3-mercaptopropionic acid (3-MPA) as a major thiol in anoxic intertidal marine sediment and demonstrated that the thiol formation could occur by the reaction of HS with acrylic acid in sediment water and seawater at ambient temperature The formation of 3-MPA was hypothesized to occur by a Michael addition mechanism whereby the nucleophile HS adds to the activated double bond in the a,/3-unsaturated carbonyl system ... 

Normally, the nucleophile or the Michael acceptor needs to be activated in the Michael additions. To achieve this activation, either the nucleophile is deprotonated with strong bases or the acceptor is activated in the presence of Lewis acid catalysts under much milder conditions. Recently, important advances have been made with Lewis acid catalysts and these developments continue. Four possible mechanisms are suggested for the catalyst action in conjugate additions to enones under nonbasic conditions [38]. First is the... 

Do you remember Figure 12.13 2-Methyl-l,3-cyclopentanedione and 2-methyl-1,3-cyclohexanedione in acetic acid undergo Michael additions to methyl vinyl ketone to form 1,5-diketones. Their structure reappears in Figure 12.19 as the substrate A. In the discussion of the formation mechanism of these 1,5-diketones you were probably not at all surprised to... 

Fig. 13.68. Michael addition to an tt,/kunsaturated ketone. A sequence of reactions is shown that effects the 1,4-addition of acetic acid to the unsaturated ketone. See Figure 17.51 regarding step 2 and Figure 13.37 for the mechanism of step 3. The stereochemistry of reaction steps 1 and 2 has not been discussed in the literature. The third step consists of a decarboxylation as well as an acid-catalyzed epimerization of the carbon in the position a to the carbonyl group. This epimerization allows for an equilibration between the cis,trans-isomeric cyclohexanones and causes the trans-configuration of the major product.

Part [1] illustrates the three-step mechanism for the Michael addition that forms the first carbon-carbon o bond, generating the 1,5-dicarbonyl compound. The first step always involves removal of the most acidic proton to form an enolate. 

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