Trichloroacetate anion

When trichloroacetic acid is used to protonate an enamine (17,17a), the salt has only limited stability. The trichloroacetate anion undergoes decarboxylation and the trichloromethyl anion which is generated adds to the iminium salt, giving an a-amino trichloromethyl derivative (8). 

In step 1, carbon dioxide is lost from the trichloroacetate anion. In step 2, elimination of chloride anion produces dichlorocarbene. Step 2 is the same for both the above reaction and the base-induced elimination of HC1 from chloroform, and both reactions proceed through the trichloromethanide anion intermediate. 

The presence of counterions bearing hydrocarbon-miscible tails, such as the trichloroacetate anion just mentioned, or tetraalkylammonium cations, instead of the usual inorganic ions, may be an aid in solubilizing proteins in nonaqueous solvents. 

Table 59 presents activation parameters for the decarboxylation of trichloroacetic acid in various basic solvents. Presumably the acid is in the form of its anion in these solvents. The activation parameters fall into a fairly narrow range and the differences presumably represent specific solvation effects. In an acidic solvent, decanoic acid, the activation parameters for the decomposition of potassium trichloroacetate are increased considerably. The values are A/f = 41.4 kcal.mole" and A5 = 27.7 eu . The activation parameters presumably reflect a composite of a prior equilibrium between decanoic acid and the trichloroacetate anion along with decarboxylation of the latter anion. The rate of decarboxylation of sodium nitroacetate is about five times faster in methanol than in water . This effect was attributed to dispersion of the negative charge at the transition state , a process which is more favorable in the less polar methanol solvent. Similarly, the decar-... 

P. R. Khnk and J. L. Colaizzi. Effect of trichloroacetate anion on partition behavior of tetra-cycfines. /. Pharm. Sci., 62, 97-100 (1973)... 

Schweizer and O Neill, unsuccessful in an attempt to follow the Reutov-Eovtsova procedure using commercial potassium l-butoxide, developed a convenient synthesis of phenyl(trichloromethyl)mercury in which phenylmercuric bromide is treated with trichloroacetate anion generated in large excess from ethyl trichloro-acetate and commercial sodium methoxide. A mixture of 200 ml. of benzene, 0.18 mole of ethyl trichloroacetate, and 0.37 mole of pulverized phenylmercuric bromide is stirred for 1.5 mln< In an ice hath and 0.154 mole of sodium methoxide is added all... 

Molecular model of trichloroacetic acid, CI3CCOOH. The rather strong acidity of trichloroacetic acid is usually ascribed to the inductive effect of the three chlorine atoms attached to the end of the molecule opposite the acidic proton. Electron density is withdrawn away from the carboxylate group so that the trichloroacetate anion that is formed when the acid dissociates is stabilized. The acid is used in protein precipitation and in dermatological preparations for the removal of undesirable skin growths. 

It is always important to keep in mind the relative nature of substituent effects. Thus, the effect of the chlorine atoms in the case of trichloroacetic acid is primarily to stabilize the dissociated anion. The acid is more highly dissociated than in the unsubstituted case because there is a more favorable energy difference between the parent acid and the anion. It is the energy differences, not the absolute energies, that determine the equilibrium constant for ionization. As we will discuss more fully in Chapter 4, there are other mechanisms by which substituents affect the energy of reactants and products. The detailed understanding of substituent effects will require that we separate polar effects fiom these other factors. 

Trichloroacetic acid behaves somewhat similarly in that protonation of the enamine occurs l7J7d). Subsequent decarboxylation of the trichloro-acetate gives trichloromethyl anion, which adds to the iminium cation to give the trichloromethyl amine derivative. Thus the enamine (113) undergoes reaction with trichloroacetic acid to give N-[l-(trichloromethyl)cyclo-hexyl]-morpholine (8). The latter compound undergoes rearrangement on... 

Next, display electrostatic potential maps for acetUi chloroacetate, trichloroacetate, 2-chlorohutyrate a 4-chlorobutyrate anions. Compare potentials at the positi between the two oxygens. Classify the anions as havi large, intermediate or small charge in this region. 

Because the dissociation of a carboxylic acid is an equilibrium process, any factor that stabilizes the carboxylate anion relative to undissociated carboxylic acid will drive the equilibrium toward increased dissociation and result in increased acidity. An electron-withdrawing chlorine atom, for instance, makes chloroacetic acid (Ka = 1.4 x 10-3) approximately 80 times as strong as acetic acid introduction of two chlorines makes dichloroacetic acid 3000 times as strong as acetic acid, and introduction of three chlorines makes trichloroacetic acid more than 12,000 times as strong. 

A method that provides an alternative route to dichlorocarbene is the decarboxylation of trichloroacetic acid.161 The decarboxylation generates the trichloromethyl anion, which decomposes to the carbene. Treatment of alkyl trichloroacetates with an alkoxide also generates dichlorocarbene. 

This sort of delocalization stabilizes the ion in fact, the C13C00- anion is more stable than the parent molecule, CI3COOH. For this reason, the solvated anion resides in solution in preference to the acid. Ka is therefore large, making trichloroacetic acid one of the strongest of the common organic acids. 

Alternative procedures for the generation of dichlorocarbene and dibromocarbene under phase-transfer catalysed conditions are also available. Where the reactive substrate is labile under basic conditions, the thermal decomposition of solid sodium trichloroacetate or bromoacetate under neutral conditions in an organic solvent is a valuable procedure [10-12], The decarboxylation is aided by the addition of a quaternary ammonium salt, which not only promotes dissolution of the trihaloacetate anion in the organic solvent, but also stabilizes the trihalomethyl anion. Under optimum reaction conditions, only a catalytic amount of the quaternary ammonium salt is required, as a large amount of the catalyst causes the rapid generation of the dichlorocarbene with resultant side reactions. 

The facile elimination of the trichloromethyl anion favours the formation of (LXXXIX) and provides the driving force for triazine formation. The alternative possible initial formation of (XCI) seems less likely, since cyclohexylamine and ethyl trichloroacetate give cyclo-hexyltrichloroacetamide (CaHn-NH-CO-CCls) and not the cyclo-hexylurethan 600). 

Another strategy for the preparation of the core structure of palmarumycin or preussomerin commenced with acetate esters, such as trichloroacetate 221. Hydrolysis of the ester group of compound 221 with LiOH gave the anion 222, which cyclizes to bridged bis-l,3-dioxane 223 (Scheme 106) <19990L3>. It was calculated that bis-1,3-dioxane 223 and the protonated form of anion 222 are in thermodynamic equilibrium with a preference for 223 of almost 8 kcalmoP <2002JOC2735>. 

However, the reaction products were not, apparently, identified20f. Trifluoro-acetate and trichloroacetate were extracted and precipitated from the acidified solution as their silver and mercurous salts, respectively, and the carbon dioxide produced by pyrolysis of these was analyzed in the mass spectrometer. So the occurrence of side-reactions leading to other carboxylate salts cannot be completely ruled out. Just one possibility is the halodecarboxylation of the anion, followed by hydrolysis of the dihalocarbene or haloform produced, to formate, viz. 

However, reaction of acyclic dienamines with hydrazoic acid gives a mixture of products derived by 1,2-, 1,4- and 3,4 + 1,2-addition of HN3 to the diene system. In this case C-protonation is followed immediately by addition of the strongly nucleophilic azide anion, so that equilibrium of the C-protonated enamines cannot occur3c. Treatment of the morpholine dienamine of isophorone with trichloroacetic acid in boiling benzene resulted in decarboxylation and the 1,4-addition of a proton and the trichloromethyl anion. Basic hydrolysis of the adduct gave dienoic acid 54 (Scheme 4). 

It was found that most of the 2-deoxyribosylic compounds in a trichloroacetic acid extract of the bacteria are present chemically in such a combination that snake-venom treatment is required in order to make them microbiologically active. Furthermore, when the extract was tested without venom pretreatment but in the presence of thymidine, the growth-promoting effect of the 2-deoxyribosylic compounds was 10 times that displayed without thymidine and reached 60% of the activity obtained after venom treatment. The nature of the substances responsible for this effect has not yet been described. The acidic nature of the 2-deoxyri-bosylic compounds was shown by the fact that 98% of the mixture was adsorbed to a Dowex anion exchanger. In the eluted fractions, thymidine 5-phosphate, thymidine 5-pyrophosphate, and thsmiidine 5-triphosphoric acid were identified. From the major 2-deoxyribosylic fraction, thymidine rhamnosyl pyrophosphate (XIX) has been isolated. This substance was also identified in the thymidine-requiring mutant of Escherichia coli 15 T-. 

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