Alpha carbon atom

Aldol Addition and Related Reactions. Procedures that involve the formation and subsequent reaction of anions derived from active methylene compounds constitute a very important and synthetically useful class of organic reactions. Perhaps the most common are those reactions in which the anion, usually called an enolate, is formed by removal of a proton from the carbon atom alpha to the carbonyl group. Addition of this enolate to another carbonyl of an aldehyde or ketone, followed by protonation, constitutes aldol addition, for example... 

AEyl chloride reacts with sodamide in Hquid ammonia to produce benzene when sodamide is in excess, hexadiene dimer is the principal product, with some trimer and tetramer (C24, six double bonds). AEylation at carbon atoms alpha to polar groups is used in the preparation of a-aEyl-substituted ketones and nittiles. Preparation of P-diketone derivatives, methionic acid derivatives, and malonic ester, cyanoacetic ester, and P-keto-ester derivatives, etc, involving substitution on an alpha carbon between two polar carbonyl groups, is particularly facEe. 

TV-Substituted amides and lactams possess potentially reactive C—H bonds on carbon atoms alpha to the nitrogen and carbonyl group. These hydrogen atoms are easily abstracted by excited carbonyl compounds (e.g., acetone or benzophenone) to produce radicals which undergo olefin addition <9a,98 97) ... 

Twenty different amino acids are commonly found in proteins, as shown in Figure 24.2. Each amino acid is referred to by a three-letter shorthand code, such as Ala (alanine), Gly (glycine), Pro (proline), and so on. All 20 are called alpha-la-) amino acids because the amino group in each is connected to the carbon atom alpha to (next to) the carboxylic acid group. Nineteen of the 20 have an -NH2 amino group, and one (proline) has an -NH- amino group as part of a ring. 

The protons on the a carbon atom absorb between 6 2.0 and 6 2.5, in about the same position as the protons on a carbon atom alpha to a ketone or an aldehyde. The proton NMR spectrum of butanoic acid is shown in Figure 20-6. 

Molecules that contain a central carbon atom (alpha-carbon) attached to a carboxyl group (COOH), an amine group (NH2), hydrogen atom (H), and a side chain (R group). (Figure 1.6)... 

These reactions appear to proceed through the formation of a common carbanion obtained by the attack of the base on a hydrogen atom attached to a carbon atom alpha to one of the unsaturated groups. For the a,0-/3,7 equilibria of unsaturatcd carbonyl compounds, the isomerization may be outlined as follows ... 

The carcinogenicity of dimethylnitrosamine and 4-nitrosomorpholine was reduced by deuterium substitution for hydrogen on carbon atoms alpha to the amino nitrogen.81 82 Consistent with the hypothesis that alpha-carbon oxidation is required for reactive metabolite formation from nitrosamines, there is a substantial primary deuterium isotope effect (ku/kg = 3.8) on the rate of dimethylnitrosamine N-demethylation. 3 Specific deuteration of 3-methylcholanthrene, a potent polycyclic hydrocarbon carcinogen, showed that oxidation of the 1-carbon atom is critical in the tumor-initiating process in mouse skin. ... 

Competition of a different kind occurs in reactions of esters and lactones since these compounds contain hydrogen atoms alpha to a carbonyl group and alpha to an ether function. A priori, abstraction of either type of hydrogen might be expected. In fact, reaction of phenanthrenequinone at 4358 A led in quantitative yield to products of reaction at the carbon atom alpha to the ether function (52,53) in ethyl acetate 132>, ethyl propionate 132>, and y-butyrolactonee) 110>. 

The reactions of ethyl acetate, ethyl propionate, and y-butyrolacetone with phenanthrenequinone to give exclusively products of reaction (52, 53) at the carbon atom alpha to the ether oxygen have been discussed. Methyl acetate reacted 110> similarly. Preliminary results 127> suggest that suitable substitution on the carbon atom alpha to the carbonyl group can affect the orientation of addition. 

The aldehydic proton normally displays coupling to protons bonded to the carbon atom alpha to the carbonyl group. The coupling constants for such vinyl protons tend to be significantly larger than the corresponding coupling constant observed for aliphatic protons. 

One of the steps of an aldol type of condensation forms a bond in which one carbon is alpha to a carbonyl group and the other is attached to a basic atom (oxygen). Both the alpha rule and the rule of reactivity of a bond from an atom attached to a basic atom indicate that this bond is active towards a fission in which the electron pair is retained by the carbon atom alpha to the carbonyl... 

The abstraction takes place mostly on the carbon atom alpha to the double bond, although in alcohols and esters other radicals may also be formed. If produced by chain transfer, they terminate the propagation of a chain if produced by a catalyst radical, they destroy a potential polymerization initiator and reduce the effective catalyst concentration. These reactions compete with the normal addition polymerization [reaction (2)], and the over-all result is a slow rate of polymerization and the formation of low-molecular-weight polymer. 

Thus, all of these amine acrylates have a carbon atom alpha to nitrogen which has two methylene protons. This type of site may be the site of oxidation which is common to all of these amine acrylates producing the same photoyellowing chromophore in each to a lesser or greater extent depending on the nature of the alkyl groups. 

All ketones and aldehydes with a carbon atom alpha to 3. the carbonyl group can be converted to an enolate anion by treatment with a catalytic amount of base. (15.1)... 

A carbon atom alpha to a carbonyl function may become nucleophilic either by forming an etiolate (Eq. 18.3) or an enol (Eq. 18.4). In the crossed-aldol reaction described in the previous section (Scheme 18.4), the nucleophilic character of the carbon atom alpha to a ketone function was provided by enolate formation. However, in the experiment that follows, nucleophilicity at the a-carbon atom is promoted by enol formation. The overall reaction is the acid-catalyzed conversion of 2-methylpropanal (26) and 3-buten-2-one (27) into 4,4-dimethyl-2-cyclohexen-1-one (29), as shown in Equation 18.12. For the first stage of the reaction, the enol form of 26 serves as the nucleophile in the 1,4- or conjugate addition to the a,3-unsaturated ketone 27 to give 28. In the second stage, an enol is the nucleophile in the cyclization of 28 by an intramolecular aldol condensation that is acid-catalyzed. The conjugate addition to give 28 is an example of a... 

The substituted aniline 36 is next converted into the amide 37 by reaction with the difunctional reagent a-chloroacetyl chloride, CICH2COCI (Eq. 21.21). Selective substitution at the acyl carbon atom in this step reflects the substantially greater reactivity of nucleophiles with acid chlorides as compared to alkyl chlorides. This results from the difference in electrophilicities and steric environments of the two possible sites for nucleophilic attack. Therefore, reaction at the carbon atom alpha to the carbonyl carbon atom to give 39 or the disubstitution product 40 is a minor competing reaction at best. 

Log P (log of the octanol/water partition coefficient) values were obtained from Basak et al. (1984), Hunter et al. (1985), and Veith et al. (1983). Taft substituent constants a ) were obtained from Dean (1985). The substituent constants were obtained from Charton (1981). For the analysis, the values of the substituent constants for the carbon atom alpha to the cyano, alcohol, or carbonyl carbon were summed. If there was more than one alpha carbon, the highest surh was used. When a sigma constant was not listed in the references, a value was estimated from values for similar structures. This was done only for alkyl groups or substituents on alkyl chains where a trend in sigma constant values versus alkyl chain length could be determined. 

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