Carboxylic acids with sodium hydroxide

The reaction of a carboxylic acid with sodium hydroxide (NaOH) produces the sodium salt of the carboxylic acid. The sodium salt then reacts with an acid chloride to form the anhydride. Figure 12-16 illustrates the final step in this process. In this reaction, the carboxylate ion behaves as a nucleophile and attacks the carbonyl Ccirbon atom of the acid chloride. The reaction of a carboxylic acid with sodium hydroxide also generates water, which, if not removed, reacts with the acid chloride and lowers the yield of the reaction. 

Pyridine is a tertiary amine its aqueous solution shows an alkaline reaction and precipitates the hydroxides of metals, some of which are soluble in an excess of the amine. Salts of pyridine like those of other amines form characteristic double salts with metallic halides. The ferrocyanide of pyridine and the addition-product of pyridine and mercuric chloride are difficultly soluble in water these compounds are used in the purification of the base. Pyridine is a very stable compound it can be heated with nitric acid or chromic acid without undergoing change but at 330° it is converted by a mixture of nitric acid and fuming sulphuric acid into nitropyridine, a colorless compound that melts at 41° and boils at 216°. At a high temperature pyridine is converted into a sulphonic acid by sulphuric acid. Chlorine and bromine form addition-products, e.g., C5H5N.CI2, at the ordinary temperature when these are heated to above 200°, substitution-products are formed. The hydroxyl derivative of pyridine is made by fusing the sulphonic acid with sodium hydroxide it resembles phenol in chemical properties. The three possible carboxyl derivatives of pyridine are known. The a-acid is called picolinic acid, the jS-acid nicotinic acid (664), and the 7-acid isonicotinic acid. 

Carboxylic acids display the typical reactions of all acids due to the presence of excess H+(aq) ions in their aqueous solutions (see page 307). For example, they react with bases to form a salt plus water. Their salts are called carboxylates. The carboxylate salt formed by the reaction of ethanoic acid with sodium hydroxide is called sodium ethanoate, CHjCOO Nah... 

Since the silver salts of the carboxylic acids are usually soluble in dilute nitric acid, they must be prepared by treating an aqueous solution of a neutral salt of the acid (and not the free acid itself) with silver nitrate solution. It is not practicable to attempt to neutralise the acid with sodium or potassium hydroxide solution, because the least excess of alkali would subsequently cause the white silver salt to be contaminated with brown silver oxide. The general method used therefore to obtain a neutral solution j to dissolve the acid in a small excess of ammonia solution, and then to boil the solution until all free... 

Reaction of 2-aminoquinoline derivatives with BrCH2C0C02Et gave imidazoquinoline-2-carboxylate 473 which upon hydrolysis with sodium hydroxide gave the corresponding acid which had been tested against the passive cutaneous anaphylaxis (78GEP2802493, 78BEP858605) (Scheme 79). 

Discussion. Many of the common carboxylic acids are readily soluble in water and can be titrated with sodium hydroxide or potassium hydroxide solutions. For sparingly soluble organic acids the necessary solution can be achieved by using a mixture of ethanol and water as solvent. 

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. 

Preparation and Reactions of S-b-MM. As mentioned in the introduction, we were interested in block copolymers of styrene and alkali metal methacrylates with overall molecular weights of about 20,000 and methacrylate contents on the order of 10 mol%. The preparation of such copolymers by the usual anionic techniques is not feasible. An alternative is to prepare block copolymers of styrene and methacrylic esters by sequential anionic polymerization, followed by a post-polymerization reaction to produce the desired block copolymers. The obvious first choice of methacrylic esters is methyl methacrylate. It is inexpensive, readily available, and its block copolymers with styrene are well-known. In fact, Brown and White have reported the preparation and hydrolyses of a series of S-b-MM copolymers of varying MM content using p-toluenesulfonic acid (TsOH) (6). The resulting methacrylic acid copolymers were easily converted to their sodium carboxylates by neutralization with sodium hydroxide. 

A pH gradient is produced by incorporating a mixture of Ampholines with appropriate p/ values in either a polyacrylamide slab or column. An acid is used at the anode and an alkali at the cathode, the pH of these being approximately the same as the pi values of the two extremes of the Ampholine range. Phosphoric acid and sodium hydroxide are suitable for wide range separations while various amino or carboxylic electrolytes are used for intermediate pH ranges. 

Refluxing of 9-fluorenone-l-carboxylic acid with zinc dust and copper sulfate in aqueous potassium hydroxide for 2.5 hours afforded 9-fluorenol-1-carboxylic acid in 94% yield [1004]. Reduction with sodium borohydride in aqueous methanol at 0-25° converted 5-ketopiperidine-2-carboxylic acid to /ra j-5-hydroxypiperidine-2-carboxylic acid in 54-61% yield [1005], On the other hand, reduction of V-benzyloxycarbonyl-5-ketopiperidine-2-carboxylic acid gave 89% yield of V-benzyloxycarbonyl-cis-5-hydroxypiperidine-2-car-boxylic acid under the same conditions [1005],... 

Carboxylic acids with six or fewer carbon atoms are soluble in water because of the polarity of the acid functional group and the ability of the acidic hydrogen atom to hydrogen bond. Carboxylic acids with more than six carbon atoms react with and dissolve in either aqueous sodium bicarbonate or aqueous sodium hydroxide solution. 

Treatment of pulegone dibromide with sodium hydroxide leads to a cyclopentane-carboxylic acid [216], Unidirectional opening of the cyclopropanone intermediate is caused by the bromine atom at the p-position which acts as a donor. 

Hydroxypyridine undergoes the Kolbe reaction (with carbon dioxide to give the carboxylic acid) the Na salt reacts mainly at the 2-, and the K salt at the 6-position. Uracil undergoes the Reimer-Tiemann reaction with sodium hydroxide/chloroform to give 5-formyluracil. 

The methoxy group in 7-methoxy,2 7-methoxy-6-methyl,41 and 7-methoxy-4-methylisatin41 has been cleaved to the corresponding hydroxy group with pyridine hydrochloride, while treatment with sodium hydroxide cleaves the 6-methoxy group of 5-chloro-6,7-dimethoxy-l-methylisatin.48 5-Acetamidoisatins have been hydrolyzed to 5-aminoisatins.30 Isatin carboxylic acids have been converted to amides and esters by means of standard procedures.52,53... 

Extraction of the original solution with sodium hydroxide will have removed phenols, enols and carboxylic acids. Separation of these may be readily accomplished by redissolving the acidic components in diethyl ether (or other suitable solvent). Extraction with saturated aqueous sodium hydrogen carbonate will remove the carboxylic acids, enabling the phenolic (or enolic) components to be recovered by evaporating the dried organic phase. Acidification of the aqueous extract will liberate the carboxylic acid components which may then be isolated by extraction in the usual way. 

We also found that ester functionality was compatible with this reduction sequence. Thus, treatment of the ester-lactone 81 with sodium borohydride and boron trifluoride etherate provided the tetrahydropyran 123 in 55% purified yield. Upon reaction with sodium hydroxide, 81 underwent simple ester hydrolysis to furnish the carboxylic acid 127 (see Table 3). 

The 2,2-dimethyl-5-chloro-2,3-dihydrobenzofuran-7-carboxylic acid, methyl ester were heated at reflux with sodium hydroxide and water for 2-3 h. After cooling, the mixture was extracted with diethyl ether and ethyl acetate. The aqueous layer was acidified with hydrochloric acid and again extracted with ethyl acetate and diethyl ether. These latter organic extracts were combined and washed with water, dried over sodium sulfate, and concentrated in vacuum. Crystallization of the resulting solid from ethyl acetate/hexane provided the desired 2,2-dimethyl-5-chloro-2,3-dihydrobenzofuran-7-carboxylic acid, 71% yield, melting point 158.5°-160°C. 

Although carboxylic acids are weak, they are capable of reacting with bases stronger than water. Thus while benzoic acid shows limited water solubility, it reacts with sodium hydroxide to form the soluble salt sodium benzoate. (Sodium benzoate is a preservative in soft drinks.)... 

In a similar manner, reaction of the derivatives (41 R1 = H, Me) with sodium hydroxide gives the corresponding 7-hydroxy-[l,2,5]oxadiazolo[3,4-c][l,2,5]thiadiazine 5,5-dioxides, as sodium salts, and the 3-aminofurazan-4-carboxylic acids <83H(20)235l>. 

Phenols are less acidic than carboxylic acids, with values of pKa around 10. Phenols are depro-tonated by (and therefore soluble in) solutions of sodium hydroxide but not by solutions of sodium bicarbonate. Explain how you would use extractions to isolate the three pure compounds from a mixture of p-cresol (p-methylphenol), cyclohexanone, and benzoic acid. 

The alkaline hydrolysis of esters to give carboxylate salts is known as saponification, because it is the process used to make soap. Traditionally, beef tallow (the tristearate ester of glycerol—stearic acid is octadecanoic acid, C17H35CO2H) was hydrolysed with sodium hydroxide to give sodium stearate, Cj HssCC Na, the principal component of soap. Finer soaps are made from palm oil... 

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