Carboxyhc acid reactions

Diphenic acid. Phenanthrene upon oxidation in acetic acid solution at 85° with 30 per cent, hydrogen peroxide gives diphenic acid (diphenyl-2 2 -di-carboxyHc acid) no phenanthraquinone is formed under these experimental conditions. The reaction is essentially an oxidation of phenanthrene with peracetic acid. (For another method of preparation, see Section I V,74.)... 

Benzanilide and similar compounds are very slowly hydrolysed by concentrated hydrochloric acid hydrolysis is quite rapid with 60-70 per cent, sulphuric acid (for experimental details, see Section IV,52). In the preliminary experiment boil 0 5-1 Og. of the compound with 10-20 ml. of dilute sulphuric acid (1 1 by volume) imder reflux for 20-30 minutes. Dilute with 10ml.of water and filteroflfanyacid which may be precipitated if the carboxyhc acid is hquid and volatile, distil it directly from the reaction mixture. Render the residue alkaline and isolate the base as above. 

Positive-Tone Photoresists based on Dissolution Inhibition by Diazonaphthoquinones. The intrinsic limitations of bis-azide—cycHzed mbber resist systems led the semiconductor industry to shift to a class of imaging materials based on diazonaphthoquinone (DNQ) photosensitizers. Both the chemistry and the imaging mechanism of these resists (Fig. 10) differ in fundamental ways from those described thus far (23). The DNQ acts as a dissolution inhibitor for the matrix resin, a low molecular weight condensation product of formaldehyde and cresol isomers known as novolac (24). The phenoHc stmcture renders the novolac polymer weakly acidic, and readily soluble in aqueous alkaline solutions. In admixture with an appropriate DNQ the polymer s dissolution rate is sharply decreased. Photolysis causes the DNQ to undergo a multistep reaction sequence, ultimately forming a base-soluble carboxyHc acid which does not inhibit film dissolution. Immersion of a pattemwise-exposed film of the resist in an aqueous solution of hydroxide ion leads to rapid dissolution of the exposed areas and only very slow dissolution of unexposed regions. In contrast with crosslinking resists, the film solubiHty is controUed by chemical and polarity differences rather than molecular size. 

Acid-C t lyzed Chemistry. Acid-catalyzed reactions form the basis for essentially all chemically amplified resist systems for microlithography appHcations (61). These reactions can be generally classified as either cross-linking (photopolymerization) or deprotection reactions. The latter are used to unmask acidic functionality such as phenohc or pendent carboxyhc acid groups, and thus lend themselves to positive tone resist apphcations. Acid-catalyzed polymer cross-linking and photopolymerization reactions, on the other hand, find appHcation in negative tone resist systems. Representative examples of each type of chemistry are Hsted below. 

Difluoroethanol is prepared by the mercuric oxide cataly2ed hydrolysis of 2-bromo-l,l-difluoroethane with carboxyHc acid esters and alkaH metal hydroxides ia water (27). Its chemical reactions are similar to those of most alcohols. It can be oxidi2ed to difluoroacetic acid [381-73-7] (28) it forms alkoxides with alkaH and alkaline-earth metals (29) with alkoxides of other alcohols it forms mixed ethers such as 2,2-difluoroethyl methyl ether [461-57-4], bp 47°C, or 2,2-difluoroethyl ethyl ether [82907-09-3], bp 66°C (29). 2,2-Difluoroethyl difluoromethyl ether [32778-16-8], made from the alcohol and chlorodifluoromethane ia aqueous base, has been iavestigated as an inhalation anesthetic (30,31) as have several ethers made by addition of the alcohol to various fluoroalkenes (32,33). Methacrylate esters of the alcohol are useful as a sheathing material for polymers ia optical appHcations (34). The alcohol has also been reported to be useful as a working fluid ia heat pumps (35). The alcohol is available ia research quantities for ca 6/g (1992). 

The formyl cation, HCO, is also likely to be an intermediate in the modification of the Koch reaction whereby formic acid reacts with olefins to give carboxyhc acids (20) ... 

AH corrosion inhibitors in use as of this writing are oil-soluble surfactants (qv) which consist of a hydrophobic hydrocarbon backbone and a hydrophilic functional group. Oil-soluble surfactant-type additives were first used in 1946 by the Sinclair Oil Co. (38). Most corrosion inhibitors are carboxyhc acids (qv), amines, or amine salts (39), depending on the types of water bottoms encountered in the whole distribution system. The wrong choice of inhibitors can lead to unwanted reactions. Eor instance, use of an acidic corrosion inhibitor when the water bottoms are caustic can result in the formation of insoluble salts that can plug filters in the distribution system or in customers vehicles. Because these additives form a strongly adsorbed impervious film at the metal Hquid interface, low Hquid concentrations are usually adequate. Concentrations typically range up to 5 ppm. In many situations, pipeline companies add their own corrosion inhibitors on top of that added by refiners. 

Esters. The monoisobutyrate ester of 2,2,4-trimethyl-1,3-pentanediol is prepared from isobutyraldehyde ia a Tishchenko reaction (58,59). Diesters, such as trimethylpentane dipelargonate (2,2,4-trimethylpentane 1,3-dinonanoate), are prepared by the reaction of 2 mol of the monocarboxyhc acid with 1 mol of the glycol at 150—200°C (60,61). The lower aUphatic carboxyHc acid diesters of trimethylpentanediol undergo pyrolysis to the corresponding ester of 2,2,4-trimethyl-3-penten-l-ol (62). These unsaturated esters reportedly can be epoxidized by peroxyacetic acid (63). 

The reaction of a hydroperoxide with 2-methylaziridine [75-55-8] has been described (94). The reaction of ethyleneknine with phenols (95) and carboxyHc acids (96,97) produces ethylamine ethers and esters, respectively. However, these reactions frequentiy yield product mixtures which contain polyaminoalkylated oxygen nucleophiles and polymers, in addition to the desked products (1). The selectivity of the reaction can often be improved by using less than the stoichiometric amount of the aziridine component (98,99). 

Carboxyhc acids react with aryl isocyanates, at elevated temperatures to yield anhydrides. The anhydrides subsequently evolve carbon dioxide to yield amines at elevated temperatures (70—72). The aromatic amines are further converted into amides by reaction with excess anhydride. Ortho diacids, such as phthahc acid [88-99-3J, react with aryl isocyanates to yield the corresponding A/-aryl phthalimides (73). Reactions with carboxyhc acids are irreversible and commercially used to prepare polyamides and polyimides, two classes of high performance polymers for high temperature appHcations where chemical resistance is important. Base catalysis is recommended to reduce the formation of substituted urea by-products (74). 

Acetoiicetyliition Reactions. The best known and commercially most important reaction of diketene is the aceto acetylation of nucleophiles to give derivatives of acetoacetic acid (Fig. 2) (1,5,6). A wide variety of substances with acidic hydrogens can be acetoacetylated. This includes alcohols, amines, phenols, thiols, carboxyHc acids, amides, ureas, thioureas, urethanes, and sulfonamides. Where more than one functional group is present, ring closure often follows aceto acetylation, giving access to a variety of heterocycHc compounds. These reactions often require catalysts in the form of tertiary amines, acids, and mercury salts. Acetoacetate esters and acetoacetamides are the most important industrial intermediates prepared from diketene. 

This reaction is commercially important because it serves as a basis for the manufacture of polycarbonate. Carboxyhc acids react with phosgene to give acid chlorides (26) (see Carboxylic acids). 

Because almost any diacid can be leaddy converted to the acid chloride, this reaction is quite versatile and several variations have been developed. In the interfacial polymerization method the reaction occurs at the boundary of two phases one contains a solution of the acid chloride in a water-immiscible solvent and the other is a solution of the diamine in water with an inorganic base and a surfactant (48). In the solution method, only one phase is present, which contains a solution of the diamine and diacid chloride. An organic base is added as an acceptor for the hydrogen chloride produced in the reaction (49). Following any of these methods of preparation, the polymer is exposed to water and the acid chloride end is converted to a carboxyhc acid end. However, it is very difficult to remove all traces of chloride from the polymer, even with repeated washings with a strong base. 

The reverse reaction is an intramolecular acidolysis of amide group by the o-carboxyhc acid to reform anhydride and amine. This unique feature is the result of an ortho neighboring effect. In contrast, the acylation of an amine with ben2oic anhydride is an irreversible reaction under the same reaction conditions. The poly(amic acid) stmcture (8) can be considered as a class of polyamides. Aromatic polyamides that lack ortho carboxylic groups are very... 

In addition to the nitrile and alcohol routes for fatty amine preparation, processes have been described by Unocal and Pennwalt Corporation, using an olefin and secondary amine (14—16) by Texaco Inc., hydrogenation of nitroparaffins (17—20) by Onyx Corporation, reaction of an alkyl haUde with secondary amines (21,22) by Henkel Cie, GmbH, reduction of an ester in the presence of a secondary amine (23) by catalytic hydroammonolysis of carboxyhc acids (24) and by the Hofmann rearrangement (25). 

Nitriles. Nitriles can be prepared by a number of methods, including ( /) the reaction of alkyl haHdes with alkaH metal cyanides, (2) addition of hydrogen cyanide to a carbon—carbon, carbon—oxygen, or carbon—nitrogen multiple bond, (2) reaction of hydrogen cyanide with a carboxyHc acid over a dehydration catalyst, and (4) ammoxidation of hydrocarbons containing an activated methyl group. For reviews on the preparation of nitriles see references 14 and 15. 

The Guerbet reaction can be used to obtain higher alcohols 2-propyl-1-heptanol [10042-59-8] from 1-pentanol condensation and 6-methyl-4-nonanol from 2-pentanol (80—83). Condensations with alkah phenolates as the base, instead of copper catalyst, produce lower amounts of carboxyhc acids and requke lower reaction temperatures (82,83). The crossed Guerbet reaction of 1-pentanol with methanol in the presence of sodium methoxide catalyst afforded 2-heptanol in selectivities of about 75% (84). 

The pyrazolone-3-carboxyhc acid (71) has been isolated by reaction of oxazolone (70) with hydrazonyl chloride (eq. 18) (46). 

Pyrans and related compounds react with ammonia to give pyridines. A commercially useful example is the reaction of dehydroacetic acid (derived from diketene) with ammonia to give 2,6-dimethyl-4-pyridinone [7516-31 -6] via 2,6-dimethyl-4-pyridinone-3-carboxyhc acid [52403-25-5]. Chlorination of the pyridone gives clopidol [2971-90-6] (56), a coccidiostat (72,73). 

PUtzing erReaction. Quinoline-4-carboxyhc acids are easily prepared by the condensation of isatin [91-56-5] (16) with carbonyl compounds (50). The products may be decarboxylated to the corresponding quinolines. The reaction of isatin with cycHc ketones has been reported, eg, the addition of cyclohexanone gives the tricycHc intermediate (17) [38186-54-8] which upon oxidation produces quinoline-2,3,4-tricarboxyhc acid [16880-83-4] (51). 

Esterification is frequendy carried out by direct reaction of the carboxyhc acid with an alcohol in the presence of a small amount of mineral acid, usually concentrated sulfuric or hydrochloric acid. The esters of commercial importance in both 0- and -hydroxyben2oic acid are the methyl esters. Direct esterification has the advantage of being a single-step synthesis, but being an equihbrium it is easily reversed. The reaction to the ester is driven by either of... 

Sahcyhc acid, upon reaction with amyl alcohol and sodium, reduces to a ring-opened ahphatic dicarboxyhc acid, ie, pimelic acid (eq. 5). The reaction proceeds through the intermediate cyclohexanone-2-carboxyhc acid. This novel reaction involves the fission of the aromatic ring to i j -hexahydrosahcyhc acid when sahcyhc acid is heated to 310°C in an autoclave with strong alkah. Pimelic acid is formed in 35—38% yield and is isolated as the diethyl ester. 

Condensation catalysts include both acids and bases, as well as organic compounds of metals. Both tin(II) and tin(IV) complexes with carboxyhc acids ate extremely useful. It has been suggested that the tin catalyst is converted to its active form by partial hydrolysis followed by reaction with the hydrolyzable silane to yield a tin—sdanolate species (eqs. 22 and 23) (193,194). 

Carboxyhc acid ester, carbamate, organophosphate, and urea hydrolysis are important acid/base-catalyzed reactions. Typically, pesticides that are susceptible to chemical hydrolysis are also susceptible to biological hydrolysis the products of chemical vs biological hydrolysis are generally identical (see eqs. 8, 11, 13, and 14). Consequentiy, the two types of reactions can only be distinguished based on sterile controls or kinetic studies. As a general rule, carboxyhc acid esters, carbamates, and organophosphates are more susceptible to alkaline hydrolysis (24), whereas sulfonylureas are more susceptible to acid hydrolysis (25). 

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