Water Michael reactions

Acrolein reacts slowly in water to form 3-hydroxypropionaldehyde and then other condensation products from aldol and Michael reactions. Water dissolved in acrolein does not present a hazard. The reaction of acrolein with water is exothermic and the reaction proceeds slowly in dilute aqueous solution. This will be hazardous in a two-phase adiabatic system in which acrolein is suppHed from the upper layer to replenish that consumed in the lower, aqueous, layer. The rate at which these reactions occur will depend on the nature of the impurities in the water, the volume of the water layer, and the rate... 

Once formed, 7 and 8 undergo a Michael reaction that gives rise to ketoenamine 9. Ring closure, to form 10, and loss of water then afforded 1,4-dihydropyridine 11. The presence of 9 and 10 could not be detected thus ring closure and dehydration were deduced to proceed faster than the Michael addition. This has the result of making the Michael addition the rate-determining step in this sequence. Conversely, if the reaction is run in the presence of a small amount of diethylamine, compounds related to 10 could be isolated. Diol 20 has been isolated in an unique case (R = CFb). Attempts to dehydrate this compound under a variety of conditions were unsuccessful. Stereoelectronic effects related to the dehydration may be the cause. In related heterocyclic ring formations, it has been determined that dehydration (20 —> 10) is about 10 times slower than diol formation (19 —> 20). Therefore, one would expect 20 to... 

The Michael reaction with enamines is exemplified in this procedure. In a second (spontaneous) step of the reaction, an aldol-type condensation occurs resulting in cyclization. Finally, the morpholine enamine of the product forms and is hydrolized by the addition of water to yield a mixture of octalones, which is separated by fractional crystallization. J -Octalone-2 can be reduced by lithium in anhydrous ammonia to the saturated tra/i5-2-decalone (Chapter 3, Section III). 

Coniine, molecular model of. 28 structure of, 294 Conjugate acid, 49 Conjugate base, 49 Conjugate carbonyl addition reaction, 725-729 amines and, 727 enamines and, 897-898 Gilman reagents and, 728-729 mechanism of, 725-726 Michael reactions and, 894-895 water and. 727 Conjugated diene, 482... 

Jenner investigated the kinetic pressure effect on some specific Michael and Henry reactions and found that the observed activation volumes of the Michael reaction between nitromethane and methyl vinyl ketone are largely dependent on the magnitude of the electrostriction effect, which is highest in the lanthanide-catalyzed reaction and lowest in the base-catalyzed version. In the latter case, the reverse reaction is insensitive to pressure.52 Recently, Kobayashi and co-workers reported a highly efficient Lewis-acid-catalyzed asymmetric Michael addition in water.53 A variety of unsaturated carbonyl derivatives gave selective Michael additions with a-nitrocycloalkanones in water, at room temperature without any added catalyst or in a very dilute aqueous solution of potassium carbonate (Eq. 10.24).54... 

There are only few examples of organic reactions catalysed effectively by Lewis acids which can be carried out in pure water without any organic co-solvent. While water can be used successfully for the uncatalysed Michael addition of 1,3-diketones (Table 4, entry D)22, the corresponding reaction of /i-kctocsters does not give satisfactory results. On the other hand, the Yb(OTf)3 catalysed Michael reaction of various /i-ketoesters (Table 21, entry A)257 and a-nitroesters (Table 21, entry B)258 takes place. 

The reaction is considered as a combination of a Michael reaction, the conjugate addition of an enolate anion on to an unsaturated carbonyl compound, plus an aldol reaction followed by elimination of water. 

The imidazolium-based ionic liquid [bmim][BF ] has been used as a catalyst in the aza-Michael reaction of various aliphatic amines to unsaturated compounds with different electron withdrawing groups in good yields as shown in Scheme 76. Water was used as the solvent in order to obtain up to 98% yield in 7 h. In the presented example, 95% yield in 7 h was achieved [198], The ionic liquid could be recovered and reused five times without loss of activity. 

Andreana and Santra have investigated the influence of the solvent on the generation of molecular diversity arising from a set of MCR substrates under microwave irradiation [36]. They have found that by using water as solvent, both 2,5-DKPs and 2-azaspiro[4.5]deca-6,9-diene-3,8-diones were obtained through aza-Michael reaction and 5-exo Michael cyclization, respectively. Nevertheless,... 

The Michael reactions [149-152] between cyclohexanone and trons-nitroalkenes were also explored by Xiao and co-workers utilizing bifunctional pyrrolidine-thiourea 213 and the pyrrolidine-thioureas 214-217 (Figure 6.61) [344]. The model Michael reaction between cyclohexanone and trons-nitrostyrene identified water as the best solvent and 217 to be the most efficient catalysts concerning the activity and asymmetric induction (90% yield 96% ee dr 98 2 in 12 h at 35 °C) in the presence of benzoic acid (10mol%) as additive. The optimized catalytic system allowed the formation of a broad spectrum of Michael adducts such as 1-6 resulting from... 

Similarly, the 2-cyano-6-oxazolopiperidine 75 (Scheme 16) can be used to provide a variety of substituted piperidines <99TL3731, 99H(51)2065>. Conversion to the enamide 76 provides a means to introduce C-3 alkyl groups by Michael reaction <99TL3699>. Electrochemical bis-bromination and dehydrohalogenation affords the vinyl bromide 77, which can imdergo substitution at the 4-position by the addition of nucleophiles as simple as water <99T8931>. 

Quantitative studies of Michael-type additions in aqueous solutions are relatively scarce. Recently the rate-determining steps of the Michael reaction were investigated with substituted pyridines as nucleophiles (Heo and Bunting, 1992). The uncatalyzed Michael reaction proceeds nicely under neutral conditions when water is used as solvent, without any catalyst. 

A direct organocatalytic Michael reaction of ketones or aldehydes with /3-nitrostyrene has been reported in brine solution, using a bifunctional catalyst system proline-derived diamine (70) and TFA.203 In some cases the conversion, yield, de, and ee all exceeded 95%. Results in water were poor, mainly due to polymerization, which is catalysed by amines. It is proposed that sodium cations stabilize the anionic intermediate formed from (70) and /3-nitrostyrene, thus minimizing polymer formation. While organic co-solvent is not required, an organic-rich phase is proposed to concentrate the Michael reactants and catalysts, thus accelerating the reaction. 

The chiral imidazolidinone 45 also catalyzes the Mukaiyama-Michael reaction between 2-silyloxy furans and a,/ -unsaturated aldehydes, affording enantiomeri-cally highly enriched y-butenolides (Scheme 4.18) [33]. For optimum catalytic performance, hydroxyl additives are necessary, and addition of 2 equiv. water proved best. 

Michael reactions are one of the most useful carbon-carbon bond-forming reactions in organic synthesis, and Lewis acid-catalysed versions have been developed to solve problems which are often observed in traditional, base-catalysed Michael reactions. Sc(DS)3 can be also applied to Michael reactions in water as shown in Equation (3) [26]. Compared with Yb(OTf)3-catalysed Michael reactions in water [27],... 

All Michael reactions are performed in water at a concentration of up to 50 wt% of amine, to which 2.5-4 moles of acrylonitrile per mole of primary amine are added. In the double cyanoethylation, the first acrylonitrile molecule reacts at room temperature, while the reaction temperature has to be raised to 80°C to accomplish the double Michael adduct. The reaction time required to achieve complete conversion increases with generation from 1 h for DAB-JenAfter completion of the reaction the excess acrylonitrile is removed by distillation, making use of the water-acrylonitrile azeotrope. 

Whereas a stoichiometric amount of TiCU was used in the original liquid-phase reactions [87], it was found that a catalytic amount of Sc(OTf)3 was effective in solid-phase Michael reactions of PSSEEs with a,/3-unsaturated ketones [88], Whereas the 1,5-dicarbonyl compound was obtained in 38 % yield in the model reaction of PSSEE 5 with chalcone and a stoichiometric amount of TiCU, the yield was improved to 93 % by use of 20 mol % Sc(OTf)3 as a catalyst in the same reaction. In addition to improvement of the yield, it should be noted that after the reaction Sc(OTf)3 was readily removed from the product resins by filtration because it is soluble in water the insoluble titanium residue which appeared after quenching the reaction by addition of water in the TiCU-mediated reaction was often difficult to remove and would contaminate the product resins. 

Michael reactions. Many commonly known conjugate additions can be carried out in water" in the presence of Yb(OTf)j, sometimes also at high pressure and sometimes on silica gel supports. ... 

Table 1.3 Ionic-tagged pyrrolidines for the asymmetric Michael reaction under neat conditions or in water...

A quinone methide is a relatively unstable species the unsubstituted case has been reported to have a lifetime of 15 seconds in methanol at room temperature [47], However, more substituted, more hindered quinone methides can be prepared in the presence of water and can have long lifetimes (years) in chloroform solutions [48], The instability of quinone methides can be attributed to facile reactions that regenerate an aromatic system. An anion (nucleophile) can add to the a-carbon to rearomatize the system via a familiar Michael reaction [49], The added anion can also be a leaving group (Figure 10.6, step 1) in other words, quinone methide formation is a reversible reaction... 

Tris(pentafluorophenyl)boron is an air-stable, water-tolerant Lewis acid for aldol, Diels-Alder, and Michael reactions.68 It is effective at 2 mole% in some reactions. Its recycle has not been demonstrated. 

A huge acceleration of the Michael reaction of nitroalkanes with methyl vinyl ketone was mentioned when going from non-polar organic solvents to water. The hydrophobic effect could be at least to some extent involved, since additives, such as glucose or saccharose, accelerate the reaction even more [72]. Cetyltrimethylam-monium chloride as an amphiphilic species which can influence the hydrophobic interactions was found to promote the Michael reaction of various nitroalkanes with conjugated enones in dilute aqueous solutions of sodium hydroxide [73],... 

Methyl-l-nitro-2-propanol, the product expected from the base-catalyzed addition of nitromethane to acetone, spontaneously loses water to give 2-methyl-1-nitro-l-propene as an intermediate which, with excess nitromethane, undergoes a Michael reaction to yield 2,2-dimethyl-l,3-dinitropropane see Ref. 6(a). 

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