Carboxylic adds formation from alcohols

Direct ester formation from alcohols (R1OH) and carboxylic adds (R2C02H) works in acid solution-but does not work at all in basic solution. Why not By contrast, ester formation from alcohols (R1OH) and carboxylic acid anhydrides, (R2C0)2O, or acid chlorides, RCOCl, is commonly carried out in the presence of amines such as pyridine or F.tjN. Why does this work ... 

Figure 5.21. Reaction schemes for the most common types of step-growth polymerization. Shown are (a/c) polyester formation, (b/d) polyamide formation, (e) polyamide formation through reaction of an acid chloride with a diamine, (f) transesterification involving a carboxylic acid ester and an alcohol, (g) polybenzimidazole formation through condensation of a dicarboxyhc add and aromatic tetramines, and (h) polyimide formation from the reaction of dianhydrides and diamines.

The addition of an alcohol to the carbonyl group of a carboxylic acid in the presence of an acid catalyst leads to ester formation (Scheme 2.15a). The acid catalyst increases the electron deficiency of the carbonyl carbon, thus overcoming the electron-donating effect of the hydroxyl group of the acid. This enhancement of the electron deficiency of the carbonyl group of the carboxylic add may be brought about by converting the acid to a derivative such as the anhydride or the acyl chloride. The reaction of these with alcohols leads to esters (Scheme 2.15b). Another method is to carry out the reaction of the alcohol with an acyl chloride or anhydride in the presence of a base such as pyridine, which may facilitate the removal of a proton from the alcohol. 

Keefer measured the solubility of cuprous chloride in solutions of various unsaturated alcohols S7> and unsaturated carboxylic acids 58), from which they were able to calculate the formation constants for the species H2MCuC1 and H2MCu2+, although HM-CuQ and HMCu were sometimes considered (H2M is a dibasic olefinic add). By comparison of the solubility of silver bromate in aqueous solutions of unsatured alcohols, it was shown that the cuprous complexes were considerably more stable than the corresponding silver(I) complexes. Whether this is generally true, as has been suggested S9) is open to speculation. 

Transition metals promote formation of w-allyl complexes from dienes by nucleophilic attack. Different nucleophiles and dienes participate in the reaction, which may take two routes where the nucleophile and the metal add either from the same (path a) or the opposite face of the diene (path b). Nucleophiles may be divided into two classes one, which includes alcohols, amines, carboxylates and malonates, reacts preferentially according to (a) ... 

It is believed that a strong base such as KOH or potassium alkoxide will deprotonate the active hydrogen from the reactants, such as alcohols, thiols, amines, carboxylic acids, and phenols, to generate the nucleophiles that add to acetylene, as illustrated by the formation of vinyl ether from alcohol and acetylene. This can qualitatively explain the reactivity order among primary, secondary, and tertiary alcohols, without considering the steric hindrance. It is known that tertiary alcohol is less acidic than secondary and primary alcohol, therefore, less potassium f-butoxide will be formed than primary potassium alkoxide from KOH. ... 

The process for the industrial production of permethric acid by Roussel-Uclaf starts from racemic trons-chrysanthemic acid, which is in turn accessed by the Martel synthesis (cf. 1,3-cycloelimination). After separation of the enantiomers with an amino-alcohol, the (IR)-enantiomer is subjected to ozonolysis. Basic epimerisation gives (IR)-cis-caronaldehyde hemiacetal. Water is added to the (IS)-enantiomer in the presence of a catalytic amount of sulfuric acid then the carboxylic add function is epimerised with the formation of a lactone. Magnesium bromide-catalysed ring-opening leads to (lR)-c s-chrysanthemic acid, which is converted into (IR)-ds-caronaldehyde hemiacetal by an analogous route. [105]... 

The reaction of olefins and their functional derivatives with carbon monoxide and alcohols to saturated carboxylic add esters generally proceeds at a lower velocity than the formation of the free acids as illustrated in the last chapter [504]. In the presence of nickel halogenide catalysts, reaction temperatures between 180-200 °C and pressures from 100 to 200 atm are required. Yields are in the range of 90 %. With cobalt catalysts reaction temperatures between 140 to 170 °C are recommended [505]. 

In the formation of microemulsions, both ionic and nonionic surfactants are used. Cosurfactants are alcohols or amines [1,5,6,13,14]. It has been shown [23] that straight chain amines are quite different from their corresponding alkanols as cosurfactant. For example, butylanfine is a more effective one on mass basis than triethylene glycol monobutyl ether. It is because the primary amine head group is more hydrophilic than alcohol, nitrile, carboxylic add, ketone, and aldehyde head groups. In the case of amine cosurfactants, the addition of acid makes the cosurfactant more hydrophilic whereas the addition of base makes it less hydrophilic. The relative degree of hydrophilidty at the oil/water interface determines the volume of microemulsion formation. Microanulsions represent complex phase behavior, and the chemical structure of the cosurfactant has a pivotal role to play on their phase behaviors. 

On the other hand, N2 isotherms of the samples D-S3 and D-S4 prepared in propanol, are similar. They exhibit a HI hysteresis loop type, which occnrs at high relative pressnre valnes, indicating the formation of large and uniform cylindrical pores. The pore size distribntion (not shown) reveals the formation of large mesopores which maximnm conld not be determined. Surface areas are lower than those of the samples prepared in water, 124 mVg for D-S3 and 252 mVg for D-S4. From these results, it can be seen that D-Sl, D-S2 and D-S5 have similar textural properties, probably due to the similar mechanism of formation, as proposed by Blinker [5], consequence of the use of water as solvent or a strong mineral acid in alcoholic solution. Samples D-S3 and D-S4 show similar textural properties, but markedly different from D-Sl, D-S2 and D-S5. The use of carboxylic acids in propanol might modify the mechanism of the sol-gel process. As reported before [4], carboxylic adds may modify the alkoxydes stmcture (TEOS and D), generating different types of precursors. The different hyi-olysis rate of each precursor under sol-gel conditions would modify the textural properties. 

The ketocarbene 4 that is generated by loss of Na from the a-diazo ketone, and that has an electron-sextet, rearranges to the more stable ketene 2 by a nucleophilic 1,2-shift of substituent R. The ketene thus formed corresponds to the isocyanate product of the related Curtius reaction. The ketene can further react with nucleophilic agents, that add to the C=0-double bond. For example by reaction with water a carboxylic acid 3 is formed, while from reaction with an alcohol R -OH an ester 5 is obtained directly. The reaction with ammonia or an amine R -NHa leads to formation of a carboxylic amide 6 or 7 ... 

The assiunption that functional group reactivity is independent of chain length can be verified kinetically by following a polyesterification. The simple esterification is an add-catalyzed process in which protonation of the acid is followed by interaction with the alcohol to produce an ester and water. If significant polymer formation is to be achieved, the water must be removed continuously from the reaction to displace the equilibriiun, and the water eUminated can be used to estimate the extent of the reaction. Alternatively, the rate of disappearance of carboxylic groups can be mea-smed by titrating aliquots of the mixture. 

CT-2103 is synthesized by converting Na-PG from its salt form to its protonated form followed by formation of an ester between the gamma carboxylate of the polymer and the 2 alcohol of pacMtaxel. A minor modification of combiiung the 2 steps via in situ formation of the PG add has been investigated with success. Carbodiimide coupling catalysed by DMAP was chosen as the appropriate reagent. Based on solubiMty, DMF was chosen as the reaction solvent. 

A synthesis of acylenamino carboxylic acids from acylamino acids has been described by Poisel and Schmidt 310,312,313). Acylamino acid esters are N-chlorinated with t-butylhypochlorite in the presence of catalytic quantities of base. A full equivalent of base can then be used to eliminate HCl, with the initial formation of acylimino esters as unstable primary products which then either add solvent (alcohol) to form a-acylamino-a-alkoxy acid derivatives (22), or (in the absence of protic solvents) rearrange to the acylenamino acid esters (21). The a-acylamino-a-methoxy carboxylic acid (22) esters can also be converted... 

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