Carbonyls amine addition

The most typical situation can be depicted for amine additions to a carbonyl group (Eq. 9)... 

The objective was to engineer a catalytic carbonylation-amination-Michael addition cascade employing carbon monoxide (1 atm). This cascade, if viable, could, conceptually, proceed via either of two pathways (Scheme 9). 

The successful synthesis of 2-thienyl and substituted 2- and 3-thienyl-acetylenes in yields as high as 60-80% opened a wide variety of synthetic applications. Various addition reactions with carbonyl compounds or epoxides could be carried out with ease. Aliphatic as well as aromatic amine addition reactions, or condensation reactions with hydrazine or hydroxylamine could be easily performed. 

Carbon-nitrogen bond formation, by reductive amination, 59, 1 Carbon-phosphorus bond formation, 36, 2 Carbonyl compounds, addition of... 

According to the available experimental data, it is impossible to distinguish between these mechanisms, but the second mechanism seems to be preferred [Scheme (7)] for, according to this Scheme, the reaction of amine addition proceeding through a cyclic transition state is completed in one step, whereas for the reaction to occur according to Scheme (2) or (6) it is additionally necessary to transfer the proton. Then, it is probable that the different mechanisms [Schemes (3) and (5)] may precede formation of one and the same transition state [Scheme (7)]. Note finally that the mechanism of bifunctional catalysis [Scheme (7)] is extremely popular in different reactions of nucleophilic substitution at the saturated carbon atom and reactions with participation of a carbonyl group32>. 

As alternatives to 4-nitrophenyl chloroformate, carbonyl diimidazole [100-102] or di-A-succinimidyl carbonate [103,104] can be used to convert polymeric alcohols into alkoxycarbonylating reagents suitable for the preparation of support-bound carbamates. Polystyrene-bound alkoxycarbonyl imidazole is less reactive than the corresponding 4-nitrophenyl carbonate, and sometimes requires heating to undergo reaction with amines. Additional activation of these imidazolides can be achieved by N-methylation (Entry 9, Table 14.7). 

Nucleophilic catalysis is a process of particular significance in reactions of carboxylic acid derivatives. As an example we may cite hydrolysis catalyzed by a tertiary amine (Scheme 20). The catalysis is effective because initial attack of the amine will be faster than attack by the less nucleophilic water the amine addition yields the intermediate 27 which, because of the positive charge, has an extremely reactive carbonyl group and is attacked by water much faster than the original compound. The fact that a given base is acting by nucleophilic catalysis... 

Carbonyl substitution on the allyl ligand leads to amine addition to the allyl terminus remote from the carbonyl moiety (equation 266).202... 

Dissolve or buffer-exchange the antibody at 4 mg protein/mL in PBS devoid of amine-, thiol-, and carbonyl-containing additives, since these components will also react with the labeling reagent. Do not cover or cap the container. 

Studies of the same system in ethanol [22] showed that this solvent favoured the formation of the CIP (A, = 690 nm), evolving already 25 ps after photolysis. For this to occur, the amine and the ketone must be cosolvated in the ground state. Indeed, decreasing stretching frequencies of the benzophenone carbonyl by addition of amine indicates ground state complex formation prior to photoinduced electron transfer (cf. Scheme 2). However, 50 to 300 ps after the laser flash, a new... 

We can now look at specific examples, and see how the principles above can lead to the aromatic heterocycles. In the first of the two broad categories, where only C-heteroatom bonds need to be formed, and for the synthesis of five-membered heterocycles, precmsors with two carbonyl groups related 1,4 are required, thus 1,4-diketones react with ammonia or primary amines to give 2,5-disubstituted pyrroles two successive heteroatom-to-carbonyl carbon additions and loss of two molecules of water produce the aromatic ring, though the exact order of these several steps is never certain. 

The Michael addition of secondary amines to a,)S-unsaturated carbonyl compounds under MWI essentially required the presence of water to drive the amine addition to completion and the presence of at least 10 mole equivalents of the amine. Besides increasing the polarity and possibly some micellar effect, water facilitates protonation of the resulted enolate from amine addition. In a typical procedure, benzalacetophenone was mixed with morpholine (469) and water in a teflon flask and subjected to MWI for 2 min to yield 93% of the 1,4-adduct 471 (Scheme 92). The method was also extended to other morpholine derivatives 472 and 473 in 30% and 100% yields, respectively (00SC643). 

The change in rate-determining step from carbinolamine dehydration to carbinol amine formation occurs as the pH decreases [5,8,9]. As shown in Fig. 1 for the hydrolysis of substituted benzylidene-l,l-dimethylethyl amines, the pH rate profiles vary dramatically at lower pH values. The high pH rates are due to attack of hydroxide ion on protonated imine, which is the reverse of the dehydration of carbinolamine. At lower pH values the term due to water addition to protonated imine becomes substantial for those imines with electron withdrawing substituents. At even lower pH values the rate drops because of the change in rate determining step to the decomposition of the carbinolamine intermediate, which is the reverse of carbinolamine formation. In those cases where the zwitterionic intermediate formed by amine addition to a carbonyl compound ( j in Scheme 1) is very unstable, the required proton-transfer steps (kh Scheme 1) may become rate-determining. This... 

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