For normal carboxylic acids

It is apparent that the Lewis-acid solvents (alcohols, carboxylic acids, and chlorinated hydrocarbons) provide much better selectivity for a given capacity than do the Lewis-base solvents (ketones, esters, amines, phosphoryls). Furthermore, branching of the solvent molecule is important, as shown In Fig. 15.2-7. The dashed lines relate selectivity so KD for normal carboxylic acids (solid points) and normal alcohols (open points). Branched carboxylic acids give substantially higher selectivities than do straight-chain acids for a given value of K0. The same is liue for alcohols. 

As mentioned above (page 1018), thermal decarbonylation of non-enolizable a>oxo carboxylic acids is preferably carried out with their anils, but it can also be effected by concentrated sulfuric acid. For example, phenylglyoxylic acid is cleaved to benzoic acid and carbon monoxide when gently warmed in concentrated sulfuric acid. Such decarbonylations catalysed by protonic acids are known also for normal carboxylic acids such as triphenylacetic59 and... 

The three p/C.,s for citric acid are 3.1,4.7, and 5.4. Explain why the first pK is lower than for normal carboxylic acids, and why the third pK, is higher than normal. 

GC Retention time indices (Ig) The Ig values were calculated by linear interpolation of the unknown between retention times of a series of methyl esters of normal carboxylic acids under the GC conditions cited for OV-17 column and nitrogen as carrier gas. The method was similar to the one suggested by Van den Dool and Kratz (4j. The I value of each standard was arbitrarily given the carbon number of the acid of the ester thus hexanoate was given a value of 6.0. The IF values of the various peaks in the total extracts (SDE method) of all the three samples and of various authentic compounds were determined under corresponding GC conditions using the same column. 

Fig. 7.5. Application of the reaction principle underlying Figure 7.4 for the conversion of tertiary carboxylic acid amides into acylating agents for alcohols. Very mild workup conditions lead to the orthoesters D, while the normal carboxylic acid esters B are obtained with aqueous standard workup.

For a carboxylic acid and an amine to form an amide, the carboxylic acid usually must be activated that is, it must be converted to a more reactive functional group. Conversion to an acyl chloride is a common way to accomplish this for normal organic reactions (see Chapter 19). However, acyl chlorides are quite reactive and do not give high enough yields in peptide synthesis because of side reactions. Therefore, milder procedures for forming the amide bond are usually employed. In one method the carboxylic acid is reacted with ethyl chloroformate (a half acyl chloride, half ester of carbonic acid) to produce an anhydride. Treatment of this anhydride with an amine results in the formation of an amide ... 

Many carboxy derivatives are available by primary syntheses. Otherwise the best route to simple pyrimidinecarboxylic acid derivatives is oxidative. This statement is even more applicable to our present situation with readily available acyl-, alkenyl-, or alkynylpyrimidine substrates from the coupling procedures, which serve as excellent substrates for oxidative reactions. The normal carboxylic acid reactions are observed ester formation, ester hydrolysis, aminolysis, acid chloride formation and reactions. A carboxy group in an electrophilic position may readily be lost when the pyrimidine ring is further depleted of 7t-electrons by its substitution pattern selective decarboxylation can be effected in pyrimidinedicarboxylic acids. 

These observations suggested a cyclic intermediate (I) in which parts of the two reacting molecules supply the bulk of the stabilisation for the charged intermediates. The normal carboxylic acid formed in the oxidation was not... 

In one of the components of the mixture, the acidity is brought by a carboxylic rest, while in the other, it is one of the protonated amines that is acidic. This mixture is globally represented by the symbol H2Y . The composition of this mixture is constant regardless of the pH value (see the problem with the microconstants— Chap. 5). Moreover, pKa = 1.99 and even pKai =2.67 are values that are too low to belong to normal carboxylic acids, but this point cannot be explained by the occurrence of several protonation sites. They probably should be ascribed to structural factors, such as, for example, the withdrawing inductive effect of the protonated amino group located at the proximity of the carboxylic groups of interest. pK 4 = 10.26 seems to be a normal value for a protonated amine. The structure of the HY form should probably be written as... 

Although the term ester used without a modifier is normally taken to mean an ester of a carboxylic acid alcohols can react with inorganic acids m a process similar to the Fis cher esterification The products are esters of inorganic acids For example alkyl nitrates are esters formed by the reaction of alcohols with nitric acid... 

Mass Spectrometry Aside from a peak for the molecular ion which is normally easy to pick out aliphatic carboxylic acids undergo a variety of fragmentation processes The dominant fragmentation m aromatic acids corresponds to loss of OH then loss of CO... 

Acyl chlorides react with carboxylic acids to yield acid anhydrides When this reaction is used for preparative purposes a weak organic base such as pyridine is normally added Pyridine is a catalyst for the reaction and also acts as a base to neutralize the hydrogen chloride that is formed... 

If the starting material contains M-H or M-C bonds a further complication can arise due to the possibility of a CO2 insertion reaction. Thus, both [Ru(H)2(N2)(PPh3)3] and [Ru(H)2(PPh3)4] react to give the formate [Ru(H)(OOCH)(PPh3)3], and similar CO2 insertions into M-H are known for M = Co, Fe, Os, Ir, Pt. These normal insertion reactions are consistent with the expected bond polarities M +-H and 0 =C +=0, but occasionally abnormal insertion occurs to give metal carboxylic acids... 

When compounded to form ebonites they show improved chemical resistance especially to carboxylic acids and may be used for some oxidative chemicals depending on type and operating temperatures. Ebonites can be compounded to be suitable for working temperatures up to at least 100°C, but, due to brittleness, are not normally suitable for sub-zero temperatures. 

Notice in the list of Lewis bases just given that some compounds, such as carboxylic acids, esters, and amides, have more than one atom ivith a lone pair of electrons and can therefore react at more than one site. Acetic acid, for example, can be protonated either on the doubly bonded oxygen atom or on the singly bonded oxygen atom. Reaction normally occurs only once in such instances, and the more stable of the two possible protonation products is formed. For acetic add, protonation by reaction with sulfuric acid occurs on... 

Perhaps the most important reaction of alcohols is their oxidation to carbonyl compounds. Primary alcohols yield either aldehydes or carboxylic acids, secondary alcohols yield ketones, but tertiary alcohols are not normally oxidized. Pyridinium chlorochromate (PCC) in dichloromethane is often used for oxidizing primary alcohols to aldehydes and secondary alcohols to ketones. A solution of Cr03 in aqueous acid is frequently used for oxidizing primary alcohols to carboxylic acids and secondary alcohols to ketones. 

A third method of aldehyde synthesis is one that we ll mention here just briefly and then return to in Section 21.6. Certain carboxylic acid derivatives can be partially reduced to yield aldehydes. The partial reduction of an ester by dhsobutylaluminum hydride (DIBAH), for instance, is an important laboratory-scale method of aldehyde synthesis, and mechanistically related processes also occur in biological pathways. The reaction is normally carried out at —78 °C (dry-ice temperature) in toluene solution. 

The theory of titrations between weak acids and strong bases is dealt with in Section 10.13, and is usually applicable to both monoprotic and polyprotic acids (Section 10.16). But for determinations carried out in aqueous solutions it is not normally possible to differentiate easily between the end points for the individual carboxylic acid groups in diprotic acids, such as succinic acid, as the dissociation constants are too close together. In these cases the end points for titrations with sodium hydroxide correspond to neutralisation of all the acidic groups. As some organic acids can be obtained in very high states of purity, sufficiently sharp end points can be obtained to justify their use as standards, e.g. benzoic acid and succinic acid (Section 10.28). The titration procedure described in this section can be used to determine the relative molecular mass (R.M.M.) of a pure carboxylic acid (if the number of acidic groups is known) or the purity of an acid of known R.M.M. 

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