Halogen Substituted Acetic Acids

Psing a method of enthalpy dependent thermometric titrations , Jordan and Dumbaugh have measured the heats of ionization, at 26 C, of a number of acids. The heats and derived entropies of ionization of the halo-acetic acids are shown in Table 5. 

Free energies, heats and entropies of ionization, of the halo 04 etic acids 

The explanation of the increase in acid strength on substitution is often expressed as follows that chlorine, for example, is strongly electron-attracting and produces a displacement of the type Cl C(0) O II. From this, it is usually implied that the result is a weakening oi the 0—bond, leading to a more negative enthalpy of ionization. Such a simple explanation is not justified from the experimentally measured AH values. 

The entropies of ionization do show a monotonous increase with halogen substitution. It may be that the indjuctive effect of the 

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CF3CO2H. Colourless liquid, b.p. 72-5 C, fumes in air. Trifluoroacetic acid is the most important halogen-substituted acetic acid. It is a very strong acid (pK = o y) and used extensively for acid catalysed reactions, especially ester cleavage in peptide synthesis. 

IR K for H bond formation, ion pair formation between pyridine and halogen substituted acetic acids in GCli, CHCls. 

The Taft analysis has the working disadvantage that it requires two measurements to define a a value, and it also suffers from the problem that the parameters of some substituents cannot be obtained either because the ester decomposes too quickly for measurements to be made or because it would not decompose by ester hydrolysis. Such restrictions apply to the halogen substituents, nitrile or the nitro group, which would require study of such compounds as Hal-CO-OR, NC-CO-OR and O2N-CO-OR. This problem can be solved by use of Taft analysis of esters of the type X-CH2-CO-OR instead of X-CO-OR. In this analysis the similarity coefficient, p, for the substituted acetic acid derivatives is attenuated by 0.41 from the set value of p = 2.48 for the formic acid derivatives (Equations 8 and 9). The a constants based on formic acid derivatives are recorded in Table 1 in Appendix 3. ... 

Means to improve the material properties of plastics have been sought for decades. Improvement has sometimes come in the form of compounds such as mineral fillers, antioxidants, and flame-retardants. One of the first searches for an improved material was centered on cellulose nitrate. Cellulose nitrate is colorless and transparent, which enabled it to be used as photographic film. However, it is extremely flammable, and its early use in motion picture film and concomitant exposure to hot lights led to numerous fires. In 1900, Henri Dreyfus substituted acetic acid for nitric acid in the synthesis of cellulose nitrate, and created instead a less flammable material, cellulose acetate. Today, polymers are often halogenated in order to achieve flame-retardation. 

Halogen exchange with KF is not successful ia acetic acid (10). Hydrogen bonding of the acid hydrogen with the fluoride ion was postulated to cause acetate substitution for the haUde however, the products of dissolved KF ia acetic acid are potassium acetate and potassium bifluoride (11). Thus KF acts as a base rather than as a fluorinating agent ia acetic acid. 

Halogens react with benzo[6]furan by an addition-elimination mechanism to give 2- and 3-substituted products (76JCS(P2)266). Treatment of benzo[6]thiophene with chlorine or bromine in acetic acid gives predominantly 3-substituted products (71JCS(B)79). 2,2,3,3,4,5,6,7-Octachloro-2,3-dihydrobenzothiophene is obtained when benzo[6]thio-phene is treated with chlorine in the presence of 1 mole of iodine (80JOC2l5l). 

An electronegative substituent, particularly if it is attached to the a carbon, increases the acidity of a carboxylic acid. As the data in Table 19.2 show, all the rnono-haloacetic acids are about 100 times more acidic than acetic acid. Multiple halogen substitution increases the acidity even more trichloroacetic acid is 7000 times more acidic than acetic acid ... 

A particularly common cr-substitution reaction in the laboratory is the halogenation of aldehydes and ketones at their a- positions by reaction with Cl2, Br2, or I2 in acidic solution. Bromine in acetic acid solvent is often used. 

An aqueous solution containing 0.10 mole/liter of chloroacetic acid, ClH2CCOOH, is tested with indicators and the concentration of H (aq) is found to be 1.2 X 10 2 M. Calculate the value of Ka (if necessary, refer back to Section 11-3.2). Compare this value with KA for acetic acid—the change is caused by the substitution of a halogen atom near a carboxylic acid group. 

Bromine in acetic acid converted 3-formylindole into low yields of the 5- (6%) and 6-bromo (3%) derivatives along with smaller amounts of 5,6-dibromo and 2,3,5,6-tetrabromo species (67G1304). 3-Acyl-2-aminoindoles (22) displayed high selectivity for 6-halogenation (Scheme 16), but at the same time w/ico-substitution of the acyl group can occur,... 

Benzofurazan (benz-1,2,5-oxadiazole) reacted with bromine by addition to give a4,5,6,7-tetrabromo adduct. Bromine in hydrobromic acid solution 4-brominated both 5-methyl- and 5-bromo-benzofurazans (74JHC8I3). When 4,7-dinitrobenzofurazan was treated with ammonium chloride in refluxing acetic acid, nucleophilic displacement gave rise to the 4-chloro-7-nitro derivative (83URP1004375). Naphtho[l, 2-c]furazans (42) are mainly 4-halogenated, but there is minor substitution in the 8-position (73CHE1331). 

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