Carboxyhc acid reactivity

As a class of compounds, nitriles have broad commercial utility that includes their use as solvents, feedstocks, pharmaceuticals, catalysts, and pesticides. The versatile reactivity of organonitnles arises both from the reactivity of the C=N bond, and from the abiHty of the cyano substituent to activate adjacent bonds, especially C—H bonds. Nitriles can be used to prepare amines, amides, amidines, carboxyHc acids and esters, aldehydes, ketones, large-ring cycHc ketones, imines, heterocycles, orthoesters, and other compounds. Some of the more common transformations involve hydrolysis or alcoholysis to produce amides, acids and esters, and hydrogenation to produce amines, which are intermediates for the production of polyurethanes and polyamides. An extensive review on hydrogenation of nitriles has been recendy pubHshed (10). 

Chemical Properties and Industrial Uses. Chloroacetic acid has wide appHcations as an industrial chemical intermediate. Both the carboxyhc acid group and the cx-chlorine are very reactive. It readily forms esters and amides, and can undergo a variety of cx-chlorine substitutions. 

The polyaddition reaction is influenced by the stmcture and functionaHty of the monomers, including the location of substituents in proximity to the reactive isocyanate group (steric hindrance) and the nature of the hydroxyl group (primary or secondary). Impurities also influence the reactivity of the system for example, acid impurities in PMDI require partial neutralization or larger amounts of the basic catalysts. The acidity in PMDI can be reduced by heat or epoxy treatment, which is best conducted in the plant. Addition of small amounts of carboxyHc acid chlorides lowers the reactivity of PMDI or stabilizes isocyanate terrninated prepolymers. 

As with the carboxyhc acid group, the reactivity of these sulfonic acid derivatives may be predicted from the properties of the leaving group, and sulfonyl chlorides are the most reactive (see... 

In order to develop the liquid membrane techniques, i.e., emulsion Hquid membrane (ELM), supported liquid membrane (SLM), non-dispersive extraction in hollow fiber membrane (HFM), etc., for practical processes, it is necessary to generate data on equilibrium and kinetics of reactive extraction. Furthermore, a prior demonstration of the phenomena of facilitated transport in a simple liquid membrane system, the so-called bulk liquid membrane (BLM), is thought to be effective. Since discovery by Li [28], the liquid membrane technique has been extensively studied for the separation of metal ion, amino acid, and carboxyHc acid, etc., from dilute aqueous solutions [29]. 

The reactivity of carboxyhc acid derivatives depends on the basicity of the substituent attached to the acyl group. Therefore, the less basic the substituent, the more reactive is the derivative. In other words, strong bases make poor leaving groups. Carboxylic acid derivatives undergo a variety of reactions under both acidic and basic conditions, and almost aU involve the nucleophilic acyl substitution mechanism (see Section 5.5.5). 

Sterically unsaturated hypervalent hahdes are quite reactive. Typical reactions involve the transfer of halogen and a reduction in coordination number. For example, hydrolysis is usually facile and sometimes violent (equations 21 and 22). Many of the fluorides are excellent fluorinating reagents. SF4 is usefiil for the conversion of ketones and carboxyhc acids... 

Construction of the thiomorpholine moiety starts by protection of the carboxylic acid in penicillamine (102) by reaction with hexyl dimethylsUane (Dmhs). Condensation of 103 with 1,2-dichloroethane leads to formation of the heterocychc ring by sequential displacement of halogen by nitrogen and sulfur to yield 104. Reaction of intermediate 104 with the benzophe-none (101), leads to formation of the sulfonamide (105). Mild acid then serves to reveal the free carboxyhc acid (106). This function is then converted to the acid chloride with oxalyl chloride. Treatment of this reactive intermediate with hydroxylamine leads to acylation on nitrogen to afford the proteinase inhibitor 107. ... 

There are several different routes to carboxamides. Usually a carboxyhc acid is converted to a more reactive intermediate, e.g. an acid chloride, which is then reacted with an amine. For practical reasons it is preferable to form the reactive intermediate in situ. We have found that arylboronic acids bearing electron-withdrawing aromatic groups, e.g. 3,4,5-trifluorophenylboronic acid, 3,4,5-F3C( H2B(OH)2, and 3,5-bis(tri-fluoromethyl)phenylboronic acid, 3,5-(CF3)2C6H3B(OH)2, act as highly efficient catalysts in the amidation of carboxylic acids with amines [167]. The catalysts are useful in the reaction of primary and secondary amines with a variety of carboxylic acids (Eq. 114). 

A carboxyhc acid derivative will undergo a nucleophilic acyl substitution reaction provided that the newly added group in the tetrahedral intermediate is not a much weaker base than the group that was attached to the acyl group in the reactant. The weaker the base attached to the acyl group, the easier it is for both steps of the nucleophilic acyl substitution reaction to take place. The relative reactivities toward nucleo-phihc acyl substitution acyl halides > acid anhydrides > carboxylic acids and esters > amides > carboxylate ions. 

Neutral Lewis bases such as water, alcohols, and carboxyhc acids are much weaker nucleophiles than their conjugate bases. When comparing species that have the same nucleophilic atom, a negatively charged nucleophile is more reactive than a neutral one. 

Nucleophiles, 142-143, 162, 302-305 relative reactivity, 312—315 solvation and reactivity, 322—323 Nucleophilic acyl substitution, 774—830 of acyl chlorides, 780-783, 820 of amides, 804—807, 808, 821 of carboxyhc acid anhydrides, 783—787, 820 of esters, 790—800, 820 of thioesters, 800 Nucleophilic addition... 

Boron-mediated asymmetric aldol condensation methodology developed by Evans [90] served as an inspiration for preparation of daunosamine starting from chiral oxazoUdinones. It appeared that the choice of chiral auxiUary is quite important for the stereochemical outcome of planned reactions [91]. A successful series of reactions started from N -succinoylation of (R)-3-(l-oxo-3-carbomethoxypropyl)-4-diphenylmethyl)oxazolidin-2-one as a novel chiral auxihary. The chain extension was achieved in aldol condensation with protected lactaldehyde and the key intermediate 132 was converted into the target aminosugar 135, via Curtius rearrangement of carboxyhc acid azide, and reduction of lactone to lactol, as depicted in Scheme 24 [58]. Unexpectedly, boron catalysts were rather ineffective in the aldol condensation step and had to be replaced with more reactive lithiiun enolates (which proved to be non-Evans syn selective). 

Bp3-OEt2 followed hy DiisobutyUduminum Hydride is used for the 1,2-reduction of y-aimno-Q, -unsaturated esters to give unsaturated amino alcohols, which are chiral building blocks for a -amino acids. Q , -Unsaturated nitroalkenes can be reduced to hydroxylamines by Sodium Borohydride and BF3-OEt2 in THF extended reaction times result in the reduction of the hydroxylamines to alkylamines. Diphenylamine-borane is prepared from sodium borohydride, BF3-OEt2, and diphenylamine in THF at 0 °C. This solid is more stable in air than BF3-THF and is almost as reactive in the reduction of aldehydes, ketones, carboxyhc acids, esters, and anhydrides, as well as in the hydrob-oration of alkenes. 

In addition, carboxylic esters, ethers, amides, urethanes, and sulfones are implicitly permitted because polyesters, polyethers, polyamides, polyurethanes, and polysulfones are among the types of polymers allowed under the exemption, as long as these functional groups have not been modified to enhance their reactivity. One such group that would not be allowed is the dinitrophenyl ester of a carboxyhc acid, which is far more reactive due to the activating functionality ... 

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