Carboxylic acids shifts 228

NMR The H NMR signals for the hydroxyl protons of phenols are often broad and their chemical shift like their acidity lies between alcohols and carboxylic acids The range is 8 4-12 with the exact chemical shift depending on the concentration the solvent and the temperature The phenolic proton m the H NMR spectrum shown for p cresol for example appears at 8 5 1 (Figure 24 4)... 

If a molecule contains several asymmetric C atoms, then the diastereomers show diastereotopic shifts. Clionasterol (28a) and sitosterol (28b) for example, are two steroids that differ only in the absolute configuration at one carbon atom, C-24 Differing shifts of C nuclei close to this asymmetric C atom in 28a and b identify the two diastereomers including the absolute configuration of C-24 in both. The absolute configurations of carboxylic acids in pyrrolizidine ester alkaloids are also reflected in diastereotopic H and C shifts which is used in solving problem 54. 

CARBON DISULPHIDE 2-Thiothiazolidine-4-carboxylic acid (TTCA) in End of shift 5 mg/g ... 

The methyl ester (100, R = CH3), derived from this A-nor acid by treatment with diazomethane, is different from the ester (102) obtained either by Favorskii rearrangement of 2a-bromo-5a-cholestan-3-one (101) or by the action of cyanogen azide on 3-methoxy-5a-cholest-2-ene (103) followed by hydrolysis on alumina. The ketene intermediate involved in photolysis of (99) is expected to be hydrated from the less hindered a-side of the molecule to give the 2j -carboxylic acid. The reactions which afford (102) would be expected to afford the 2a-epimer. These configurational assignments are confirmed by deuteriochloroform-benzene solvent shifts in the NMR spectra of esters (100) and (102). ... 

The ketocarbene 4 that is generated by loss of Na from the a-diazo ketone, and that has an electron-sextet, rearranges to the more stable ketene 2 by a nucleophilic 1,2-shift of substituent R. The ketene thus formed corresponds to the isocyanate product of the related Curtius reaction. The ketene can further react with nucleophilic agents, that add to the C=0-double bond. For example by reaction with water a carboxylic acid 3 is formed, while from reaction with an alcohol R -OH an ester 5 is obtained directly. The reaction with ammonia or an amine R -NHa leads to formation of a carboxylic amide 6 or 7 ... 

Conversion of Amides into Carboxylic Acids Hydrolysis Amides undergo hydrolysis to yield carboxylic acids plus ammonia or an amine on heating in either aqueous acid or aqueous base. The conditions required for amide hydrolysis are more severe than those required for the hydrolysis of add chlorides or esters but the mechanisms are similar. Acidic hydrolysis reaction occurs by nucleophilic addition of water to the protonated amide, followed by transfer of a proton from oxygen to nitrogen to make the nitrogen a better leaving group and subsequent elimination. The steps are reversible, with the equilibrium shifted toward product by protonation of NH3 in the final step. 

Basic hydrolysis occurs by nucleophilic addition of OH- to the amide carbonyl group, followed by elimination of amide ion (-NH2) and subsequent deprotonation of the initially formed carboxylic acid by amide ion. The steps are reversible, with the equilibrium shifted toward product by the final deprotonation of the carboxylic acid. Basic hydrolysis is substantially more difficult than the analogous acid-catalyzed reaction because amide ion is a very poor leaving group, making the elimination step difficult. 

As has been outlined for the Strecker synthesis, the Ugi reaction also proceeds via initial formation of a Schiff base from an aldehyde and an amine. The imine intermediate is attacked by the isocyanidc, a process which is supported by protonation of the imine by the carboxylic acid component. The resulting a-amino nitrilium intermediate is immediately trapped by the carboxylate to give an 6>-acyl imidiate. All steps up to this stage are reversible. Only the final oxygen to nitrogen acyl shift is irreversible and delivers the A-acyl-a-amino amide as the thermodynamically favored product which contains two amide groups. 

From the preceding discussion, it is easily understood that direct polyesterifications between dicarboxylic acids and aliphatic diols (Scheme 2.8, R3 = H) and polymerizations involving aliphatic or aromatic esters, acids, and alcohols (Scheme 2.8, R3 = alkyl group, and Scheme 2.9, R3 = H) are rather slow at room temperature. These reactions must be carried out in the melt at high temperature in the presence of catalysts, usually metal salts, metal oxides, or metal alkoxides. Vacuum is generally applied during the last steps of the reaction in order to eliminate the last traces of reaction by-product (water or low-molar-mass alcohol, diol, or carboxylic acid such as acetic acid) and to shift the reaction toward the... 

Carboxylic acids exchange with amides and esters these methods are sometimes used to prepare anhydrides if the equilibrium can be shifted, for example. 

In the sixth chapter the activation of O-H bonds of water, alcohols and carboxylic acids, and their addition to multiple bonds is reported. Since the formally oxidative addition of ROH gives rise to hydrido(hydroxo) complexes, [MH(OR)Ln] which are postulated as intermediates in many important reactions (water gas shift reaction, Wacker-chemistry, catalytic transfer hydrogenations etc.) the authors of this chapter,... 

The equilibrium in this first step favors tlie shift to anhydride formation if the second mole of carboxylic acid in the second step with forms imidazole to form a salt that is insoluble in the solvent used (ether, tetrahydrofuran, benzene). 

The drum compounds are thermally quite stable. For example, the cyclopentane carboxylic acid drum, 3, was heated at 300°C for 3 h in vacuum. The material obtained was soluble in CDCI3, and Sn NMR showed a single line at -A91.A ppm, compared to the starting material -A85.8. The shift is presumably due to loss of solvent molecules present in the crystal in the starting material. 

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