A-Chlorination of carboxylic acids

A number of other methods exist for the a halogenation of carboxylic acids or their derivatives. Acyl halides can be a brominated or chlorinated by use of NBS or NCS and HBr or HCl. The latter is an ionic, not a free-radical halogenation (see 14-2). Direct iodination of carboxylic acids has been achieved with I2—Cu acetate in HOAc. " ° Acyl chlorides can be a iodinated with I2 and a trace of HI. Carboxylic esters can be a halogenated by conversion to their enolate ions with lithium A-isopropylcyclohexylamide in THF and treatment of this solution at -78°C with... 

OL-Chlorination of carboxylic acids.2 A Hell-Volhard-Zelinsky type of a-chlori-nation of carboxylic acids with chlorosulfonic acid is possible if a competing free radical chlorination is suppressed. For this purpose, 1 is superior to oxygen 3 in addition, the reaction is applicable to both short- and long-chain acids (equation I). 

The quantity of organic peroxide required is generally about 0.1 per cent b ed on the SOaCIs used. The employment of a solvent or diluent such as carbon tetrachloride is advantageous in the chlorination of carboxylic acids that react vigorously and also in the case of solid materials. The data in Table 6-7 indicate the scope and nature of the results obtained by this procedure. 

Derivatives of both two- and four-valent tin have found use as catalysts in urethane foams. In addition to the more commonly used dibutyltin (IV) dilaurate, dibutyltin (IV) diacetate, dialkyltin (IV) oxide or salts of two-valent tin with a variety of carboxylic acids such as stannous octoate, hexoate and naphthenate, there are also available chlorine-containing compounds (dibutyltin dichloride, SnCl2, SnClJ, sulphur-containing compounds (e.g. tributyltin laurylmercaptate), and complexes such as stannous quinolinolate or dibutyltin bis(acetylacetonate). Other catalysts... 

Gas-liquid reactions are used in several industrial processes. In the synthesis of chemical compounds, gas-liquid reactions are used in, for example, the oxidation of hydrocarbons. For a synthesis reaction, it is typical that one organic compound is transformed into another organic compoimd in the presence of a homogeneous catalyst. Typical reactions are, for example, chlorination of aromatic compounds in the production of chlorinated hydrocarbons, chlorination of carboxylic acids (mainly acetic acid), and oxidation of toluene and xylene in the production of benzoic acid and phthalic acid. In the production of hydrogen peroxide (H2O2), an oxidation process can also be used, namely oxidation of anthraquinole to anthraquinone. 

The procedure can be extended to achieve selective a-bromination and iodination of carboxylic acids and the general mechanism of the a-halogenation is outlined in Chapter 5, p 170. The autocatalytic effects in the selective a-chlorination of propionic acid to the 2-chloro and 2,2-dichloro acids have been studied in a semibatch reaction at 90-130 °C. The reaction was performed in the presence of chlorosulfonic acid and dichloroacetic acid as catalysts and oxygen as the radical scavenger. Kinetic experiments indicated autocatalytic formation of both products and that the selectivity was independent of the chlorine concentration in the liquid phase. The results confirmed the validity of the proposed reaction scheme which involved formation of the reaction intermediate, propanoyl chloride from propionic acid and chlorosulfonic acid, the acid-catalysed enolization of the acid, and a hydroxyl-chlorine exchange reaction. The acid-catalysed enolization was the rate-determining step in the reaction sequence. ... 

Section 19 16 Halogenation at the a carbon atom of carboxylic acids can be accom plished by the Hell-Volhard-Zehnsky reaction An acid is treated with chlorine or bromine m the presence of a catalytic quantity of phospho rus or a phosphorus trihalide... 

Thioesters Like chlorine sulfur is a third row element with limited ability to donate a pair of 3p electrons into the carbonyl tt system With an electronegativ ity that IS much less than Cl or O however its destabilizing effect on the carbonyl group IS slight and thioesters he m the middle of the group of carboxylic acid derivatives m respect to reactivity... 

So do anhydrides and many compounds that enolize easily (e.g., malonic ester and aliphatic nitro compounds). The mechanism is usually regarded as proceeding through the enol as in 12-4. If chlorosulfuric acid (CISO2OH) is used as a catalyst, carboxylic acids can be ot-iodinated, as well as chlorinated or brominated. N-Bromosuccinimide in a mixture of sulfuric acid-trifluoroacetic acid can mono-brominate simple carboxylic acids. ... 

A 4 1 0.04 molar ratio of carboxylic acid, chlorosulfonic acid, and chloranil was used. A 2 1 mixture of chlorine and oxygen was passed into the reaction for 3 hours. 

I he present procedure, a modification of one reported earlier by ilie submitters," has been applied to the a-chlorination of a scries of aliphatic carboxylic acids (Table I). In these reactions... 

You see in Chapter 10 that aldehydes and ketones contain a carbonyl group attached to carbon or hydrogen atoms. In the case of carboxylic acids and their derivatives, a carbonyl group is attached to an electronegative element such as oxygen, chlorine, or nitrogen. The presence of these elements tends to increase the 5+ charge on the carbonyl carbon, which makes the carbon atom more susceptible to nucleophilic attack. 

The reactions catalyzed by Lewis acids are conducted for 10-20 hours at — 20 C to give hypochlorites in almost quantitative yield.82 Chlorine monofluoride activated by hydrogen fluoride to enhance its electrophilicity transforms the carbonyl function in esters of carboxylic acids to a difluoromethyl group. The reactions are carried out by passing 2molar equivalents of chlorine monofluoride gas through a solution of the ester in an equal volume of hydrogen fluoride at - 70 to - 30°C.83... 

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