Michael addition reaction Amines

The Michael addition reaction of amines and thiols with bismaleimides or functionalized monomaleimides is a versatile tool ia the synthesis of chain-extended maleimide-terroinated prepolymers. These prepolymers generally are soluble ia organic solvents from which they can be processed to prepreg and molded to high quaUty, void-free laminates. 

Purines, N-alkyl-N-phenyl-synthesis, 5, 576 Purines, alkylthio-hydrolysis, 5, 560 Mannich reaction, 5, 536 Michael addition reactions, 5, 536 Purines, S-alkylthio-hydrolysis, 5, 560 Purines, amino-alkylation, 5, 530, 551 IR spectra, 5, 518 reactions, 5, 551-553 with diazonium ions, 5, 538 reduction, 5, 541 UV spectra, 5, 517 Purines, N-amino-synthesis, 5, 595 Purines, aminohydroxy-hydrogenation, 5, 555 reactions, 5, 555 Purines, aminooxo-reactions, 5, 557 thiation, 5, 557 Purines, bromo-synthesis, 5, 557 Purines, chloro-synthesis, 5, 573 Purines, cyano-reactions, 5, 550 Purines, dialkoxy-rearrangement, 5, 558 Purines, diazoreactions, 5, 96 Purines, dioxo-alkylation, 5, 532 Purines, N-glycosyl-, 5, 536 Purines, halo-N-alkylation, 5, 529 hydrogenolysis, 5, 562 reactions, 5, 561-562, 564 with alkoxides, 5, 563 synthesis, 5, 556 Purines, hydrazino-reactions, 5, 553 Purines, hydroxyamino-reactions, 5, 556 Purines, 8-lithiotrimethylsilyl-nucleosides alkylation, 5, 537 Purines, N-methyl-magnetic circular dichroism, 5, 523 Purines, methylthio-bromination, 5, 559 Purines, nitro-reactions, 5, 550, 551 Purines, oxo-alkylation, 5, 532 amination, 5, 557 dipole moments, 5, 522 H NMR, 5, 512 pJfa, 5, 524 reactions, 5, 556-557 with diazonium ions, 5, 538 reduction, 5, 541 thiation, 5, 557 Purines, oxohydro-IR spectra, 5, 518 Purines, selenoxo-synthesis, 5, 597 Purines, thio-acylation, 5, 559 alkylation, 5, 559 Purines, thioxo-acetylation, 5, 559... 

A typical second step after the insertion of CO into aryl or alkenyl-Pd(II) compounds is the addition to alkenes [148]. However, allenes can also be used (as shown in the following examples) where a it-allyl-r 3-Pd-complex is formed as an intermediate which undergoes a nucleophilic substitution. Thus, Alper and coworkers [148], as well as Grigg and coworkers [149], described a Pd-catalyzed transformation of o-iodophenols and o-iodoanilines with allenes in the presence of CO. Reaction of 6/1-310 or 6/1-311 with 6/1-312 in the presence of Pd° under a CO atmosphere (1 atm) led to the chromanones 6/1-314 and quinolones 6/1-315, respectively, via the Jt-allyl-r 3-Pd-complex 6/1-313 (Scheme 6/1.82). The enones obtained can be transformed by a Michael addition with amines, followed by reduction to give y-amino alcohols. Quinolones and chromanones are of interest due to their pronounced biological activity as antibacterials [150], antifungals [151] and neurotrophic factors [152]. 

Combinatorial solid-phase synthetic methodologies have been used extensively in drug development [8]. A new solid-phase synthesis of 2-imidazolidones has been discovered by Goff, based on a domino aminoacylation/Michael addition reaction [9]. Thus, when immobilized amine 10-26 (HMPB-BHA resin) was treated with phenylisocyanate in the presence of triethylamine, a smooth formation of 2-imida-zolidone took place. Acid-catalyzed removal from solid phase provided 10-27 in good yield (Scheme 10.6). 

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. ... 

Another approach for the synthesis of networks relies on the polycondensation of multifunctionalized polyesters with the appropriate multifunctionalized agent, provided that one of the partner is at least tri-functionalized. Toward this end, several reaction have been reported, such as the Michael addition of amines onto acrylates [184], the coupling of ketones and oxyamines [185], the click copper(II)-catalyzed azide-alkyne cycloaddition [186], and esterification reactions [25, 159, 187]. Interestingly, if esterification reactions are used, the crosslinks are then degradable. 

Xu et al reported using [bmim][OH] as a basic IL for the Aza-Michael addition reaction between various amines and a,(3-unsaturated carbonyl compounds and nitriles. The products were obtained in high yields and the IL could be recycled eight times without significant change in the product yields. 

Primary amines may interact with double bonds in a reaction analogous to a Michael addition reaction (e.g., fluvoxamine maleate, where the fluvoxa-mine primary amine group can interact with the double bond in the maleic acid counterion). Examples of excipients that contain double bonds include sodium stearyl fumarate and sorbitan monooleate. 

Scheme 5 Synthetic scheme of hyperbranched polyester amines from Michael addition reaction of poloxamer diacrylate and low molecular weight branched PEI, adapted with kind permission of Prof. Cho [23]. Copyright 2007 Wiley...

Ley SV, Mynett DM, Koot WJ, Solid phase synthesis of bicyclo[2,2,2]octane derivatives via tandem Michael addition reactions and subsequent reductive amination, Synlett., 1017-1020, 1995. 

As electron-rich olefins are more reactive, vinyl-sulfones are the most reactive species and are capable of reacting with thiols, amines, and even with small nucleophilic alcohol groups. Less reactive are acrylamides and acrylates, which are reactive towards amines and thiols. Maleimides are the least reactive of the mentioned species and allow selective addition of thiols in the presence of amines in the pH range 6.5-7.5. However, hydrolysis of the imide, especially at elevated pH values [35], may be a concern for certain applications. The mentioned Michael addition reactions do not require organic solvents and can be carried out at physiological temperature and pH [36], In acidic conditions, the reaction is either very slow or does not proceed because protonation removes the nucleophilic form in the case of amines, and the thiolate anion is usually the active species in Michael additions involving thiols [25],... 

One of the means used to modify monomers and polyester acrylates further is to amine modify them. This is normally done using a Michael addition reaction between the acrylate and an amine. The benefits of amine modification are normally seen with increased cure speed since this will tend to overcome the effects of oxygen inhibition in the cure process. Amine oligomers and synergists can also be low viscosity and give improved flexibility to a film. One disadvantage of these materials maybe that perhaps they do not possess the stability required of UV inkjet ink formulations. They are also very prone to yellowing and are unstable with some forms of adhesion promoters. 

Chan JW, Zhou H, Wei H, Hoyle C. (2008) Mechanism of the primary and secondary amine catalyzed thio-Michael addition reaction with (meth)acrylates. Abstracts of Papers, 235th ACS National Meeting, New Orleans, LA, United States, April 6-10,2008 168 pp. 

Several heteroatom nucleophiles, for example, amines, alcohols, thiols, carboxylates, and dialkylphosphines, undergo Michael addition reactions with alkene- and alkyne-substituted carbene complexes. Reaction of alkyne-substituted chromium carbenes with urea affords products derived from Michael... 

Figure 8.6 Example of a Michael addition reaction of an amine to a conjugated alkene.

Vinyl sulfone-modifled carbohydrates, such as 111, can be subjected to Michael addition reaction with primary or secondary amines to constmct 112 bearing amino groups at the C-2 carbon... 

Okumoto, S., Yamabe, S. A theoretical study of curing reactions of maleimide resins through Michael additions of amines. J. Org. Chem. 2000, 65, 1544-1548. 

Very efficient Michael addition reactions of amines, thiophenoi and acetylacetate to chalcone in a water suspension medium have been developed as completely organic solvent-free reactions. 

As a typical example of Michael addition of an amine to chalcone in a water suspension medium, a suspension of powdered chalcone (70a) in a small amount of water containing mBuNH2 (71e) and the surfactant hexadecyltrimethylammo-nium bromide (72) was stirred at room temperature for 4 h. The reaction product was filtered and air dried to give the Michael addition product 73e as a colorless powder in 98% yield. The filtrate containing 72 can be used again [34]. By the same procedure, Michael addition reactions of the various amines 71a-q to 70a were carried out and pure amineadducts were obtained in good yields (Table 15-19) [34], The solubility of the amines in water is not related to the efficiency of the reaction. Amines (71h-k) which are poorly soluble in water reacted with 70a in the water suspension as effectively as the water-soluble amines (Table 15-19). 

Chen and coworkers have reported a new domino Michael-Michael addition reaction between a,a-dicyanoalkene [26] derived from cyclohexanone and benzyli-deneacetone, resulting in a stepwise [4 + 2]-type cycloaddition to afford almost enantiopure bicyclic adduct 15. In contrast to the completely inert function of secondary ammonium salt, a primary amine, 9-amino-9-deoxyepiquinine lo [27], in combination with trifluoroacetic acid, was found to be highly efficient in the activation of the a, 3-unsaturated ketone by tandem iminium-enamine catalysis (Scheme 10.21) [28],... 

A mechanism for the formation exo-5-morpholinobicyclo[2.2.1]heptan-2-one via a ho-moenolate ion intermediate in a Michael-type addition reaction has been proposed. Michael addition reactions involving secondary amines and a,)S-unsaturated carbonyl compounds have been reported, but this was the first example of such a reaction involving the ho-moenolate ion. ... 

The aza-Michael addition is an important class of carbon-nitrogen bondforming reactions, and has been demonstrated to be a powerful tool in organic synthesis. EiScient aza-Michael addition reactions of alkyl amine (Scheme 8.34)... 

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