Weak amine base

The mechanism of catalysis of ester aminolysis by weak amine bases of substituted phenylquinoline-6- and -8-carboxylates were evaluated, and the solvent effects were examined by semiempirical SM2.1/AM1, ab initio SCIPCM [124] and PS-Solv [125]. All these models predicted that a zwitterionic tetrahedral intermediate should be formed in this reaction. The results did not support the proposed earlier proton slide mechanism and allowed to propose a mechanism which was fully consistent with the experimental observations [126]. 

But what about this cyclisation In stronger protic bases like KOH in water, all the cyclisations are reversible and the more stable ketone 27 is formed by thermodynamic control. In buffered conditions (weak amine base and weak acid) only the more reactive aldehyde enolises and 30 is formed by kinetic control. 

The mild reaction conditions (relatively weak amine bases, short reaction times) of the CIR of (hetero)aryl halides and l-(hetero)aryl propargyl alcohols opens a modular entry to chalcones, which are as Michael acceptors suitable starting points for consecutive multicomponent syntheses of heterocycles in a one-pot fashion [28, 86]. Both catalytic generations of ynones and enones have set stages for diversity-oriented multicomponent syntheses of heterocycles in a consecutive one-pot fashion. 

The drug happens to be a weak amine base having pKa value of 7.8 at the normal body temperature (98.4°F). Hence, it is almost very elose to plasma pH (7.4) and, therefore, well-acceptable for the preparation of a buffer mixture for eontrolling the extraeellular pH. 

The Bode group have documented an NHC-catalyzed enantioselective synthesis of ester enolate equivalents with a,p-unsaturated aldehydes as starting materials and their application in inverse electron demand Diels-Alder reactions with enones. Remarkably, the use of weak amine bases was crucial DMAP (conjugate acid = 9.2) andN-methyl morpholine (NMM, conjugate acid pAa = 7.4) gave the best results. A change in the co-catalytic amine base employed in these reactions could completely shift the reaction pathway to the hetero-Diels-Alder reaction, which proceeded via a catalytically generated enolate. An alternative pathway that occurred via a formal homoenolate equivalent was therefore excluded. It is demonstrated that electron-rich imidazolium-derived catalysts favor the homoenolate pathways, whereas tri-azolium-derived structures enhance protonation and lead to the enolate and activated carboxylates (Scheme 7.71). 

The thermodynamic and analytical aspects of acid-base reactions in aprotic solvents are surveyed in reviews by Davis [1, 2]. The correlation of acid-base strength in water and aprotic solvents is of major importance. Early kinetic work by Bell and co-workers on the acid catalysis of (i) the ethyldiazoacetate-phenol interaction [3] (ii) the rearrangement of N-bromoacetanilide [4] and (iii) the inversion of /-menthone [5] established an order of acid strengths in aprotic media and the importance of intra-molecular hydrogen bonds e.g in picric acid). A thermodynamic method using reference acids and bases is more direct, and Bell and Bayles [6] employed the indicator acid Bromophenol Blue to obtain a basicity order for weak amine bases. Kinetic measurements on these systems have recently been made, and are considered in detail in Section 7. 

Diborane [19287-45-7] the first hydroborating agent studied, reacts sluggishly with olefins in the gas phase (14,15). In the presence of weak Lewis bases, eg, ethers and sulfides, it undergoes rapid reaction at room temperature or even below 0°C (16—18). The catalytic effect of these compounds on the hydroboration reaction is attributed to the formation of monomeric borane complexes from the borane dimer, eg, borane-tetrahydrofuran [14044-65-6] (1) or borane—dimethyl sulfide [13292-87-0] (2) (19—21). Stronger complexes formed by amines react with olefins at elevated temperatures (22—24). 

The behavior of 3 toward ether or amines on the one hand and toward phosphines, carbon monoxide, and COD on the other (Scheme 2), can be qualitatively explained on the basis of the HSAB concept4 (58). The decomposition of 3 by ethers or amines is then seen as the displacement of the halide anion as a weak hard base from its acid-base complex (3). On the other hand, CO, PR3, and olefins are soft bases and do not decompose (3) instead, complexation to the nickel atom occurs. The behavior of complexes 3 and 4 toward different kinds of electron donors explains in part why they are highly active as catalysts for the oligomerization of olefins in contrast to the dimeric ir-allylnickel halides (1) which show low catalytic activity. One of the functions of the Lewis acid is to remove charge from the nickel, thereby increasing the affinity of the nickel atom for soft donors such as CO, PR3, etc., and for substrate olefin molecules. A second possibility, an increase in reactivity of the nickel-carbon and nickel-hydrogen bonds toward complexed olefins, has as yet found no direct experimental support. 

Wright illustrated the effectiveness of chloride-catalyzed nitration for a number of amines of different basicity. Wright showed that weakly basic amines like iminodiacetonitrile and its dimethyl and tetramethyl derivatives are all nitrated in high yield with nitric acid-acetic anhydride mixtures in the absence of chloride ion. In contrast, the slightly more basic 3,3 -iminodipropionitrile is not appreciably nitrated with acetic anhydride-nitric acid, but the inclusion of a catalytic amount of the hydrochloride salt of the amine base generates the corresponding nitramine in 71 % yield. ... 

Amine-based drugs, such as oral antihistamines, are weak bases that are absorbed well by the mucosal cells lining the small intestine, where the pH is alkaline and the drugs tend to lose their protons and become nonionized. 

Several reports describe additives for example, tertiary amine bases, weak acids, and strong acids have been examined, with limited effect, except for the strong acids, which stop the reaction completely.101 C2-symmetric chiral diols substantially improve proline-catalysed ee, conversion efficiency, and yield in the reaction of acetone with benzaldehyde, with addition of (S )-BINOL giving further improvement.102... 

B is correct. Amines (—NH2) behave as weak Lewis bases and are most similar to ammonia (NH3). A Lewis base is any species that can donate a pair of electrons and form a coordinate covalent bond. Amides contain a carbonyl carbon and therefore are not similar to ammonia. Ether and ethanol are not nitrogen-containing compounds. 

Triflate, tosylate and mesylate are the anions of strong acids. The weak conjugate bases are poor nucleophiles. Nucleophilicity increases in parallel with the base strength. Thus, amines, alcohols and alkoxides are very good nucleophiles. Base strength is a rough measure of how reactive the nonbonding electron pair is thus, it is not necessary for a nucleophile to be anionic. 

Schering-Plough uses (S)-4-phenyl-2-oxazolidinone in the large-scale production of their cholesterol absorption inhibitor Zetia (ezetimibe) (11) (Scheme 23.l).40 2 Condensation of the alcohol 12 with imine 13 in the presence of a Lewis acid such as TiCl4 and tertiary amine base yields compound 14. Silylation followed by intramolecular cyclization with tetrabutylammonium fluoride (TBAF) yields the protected ezetimibe 15. Removal of the protecting groups is carried out with weak acid to afford Ezetimibe (11). 

Weak Amine salt Strong and moderately strong acids, weak bases 4-8... 

LSD has three nitrogen atoms. One is part of an amide, which makes it a very weak base. One is a 3° alkylamine, and these are usually the strongest amine bases (see Table 25.3). The third is part of a nitrogen heterocycle. The lone pair on the N atom of the nitrogen heterocycle is part of an aromatic n system containing 10 it electrons. (Recall from Section 17.7 that 10 7t electrons are aromatic by Huckel s rule.) As a result, the lone pair on the nitrogen atom in the heterocycle is delocalized so the nitrogen atom is a very weak base. 

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