Hydrogens enolizable

Enolizable hydrogens can be replaced by deuterium (and 0 by 0) by passage of a sample through a deuterated (or 0 containing) gas chromatography column. There are many enol-keto intereonversions and acidifications of enolate ions to the keto forms listed in Organic Syntheses. No attempt is made to list them here. 

The title compound has been deuterium labelled1 with 2H at C(3) (1), and in the vinyl group (2) by deuterium exchange of the enolizable hydrogen atoms in 3 followed by... 

An example of anomalous behavior in closely related systems was reported some time ago during an investigation of the cychzation products derived from coumarin semicarbazones (Scheme 6.21). Thus, 78a reacted cleanly with chloro-acetic acid to yield 79a, which cyclized to the expected product 80a upon treatment with sodium acetate. On the other hand, 79b did not cyclize under the same reaction conditions. This was attributed to the absence of the enolizable hydrogen (Ph vs. H). The authors did not comment on the possibility of cyclization of 79b to 80b. The closely related urea analogue 81 did not react with chloroacetic acid thereby... 

With vinylketene adducts (2-vinylcyclobutanones) possessing an enolizable hydrogen, the presence of triethylamine used for generating the ketene will occasionally cause double-bond isomerization resulting in alkylidenecyclobutanones 22.138,139 These derivatives are not readily prepared by alkylideneketene to alkene cycloadditions because of the extreme reactivity towards dimerization of these ketenes. 

Conditions 90 mg of sugar in 0.6 ml of lAf K2C03 at 30° C. c The value of kH based on the equivalent weight of the sugar with respect to two enolizable hydrogens is 0.146 for comparison with the aldoses, this constant is doubled. 

Variants on this theme have provided many useful preparative procedures and a few representative examples are provided in Scheme 73.212-214 Acetic acid is a relatively unreactive substrate and is often used as a solvent. However, more enolizable substrates, especially those possessing two activating groups, are readily oxidized on a stoichiometric basis at 25-50 C in acetic acid. If the products contain enolizable hydrogens, over oxidation is a potential problem (see the first example). The reactions can often be monitored by the disappearance of the characteristic brown color of the oxidant. While it is clear... 

If the products contain an enolizable hydrogen, overoxidation is a concern. When cyclopentanones are involved, the cyclic products are often more rapidly oxidized than the starting materials. However, further oxidation of the cyclic products is not necessarily undesirable. For example, Snider has developed a simple synthesis of phenols in which a manganese(III)-mediated 6-endo radical cyclization is followed by oxidative aromatization.154 An example of this process is provided in Scheme 34. Snider has also shown that the overoxidation can be blocked with a chlorine atom, as shown by the second example in Scheme 34.153... 

Similar enamine cyclization processes occur in several other successful heterocycle syntheses, e.g. in the Fischer indole synthesis. In this case, however, a labile N—N bond of a l-aryl-2-vinylhydrazine is cleaved in a [3,3]-sigmatropic rearrangement, followed by cyclization and elimination of ammonia to yield the indole (B. Robinson, 1963, 1969 R. J. Sundberg, 1970). Regioselectivity is only observed if R2 contains no enolizable hydrogen, otherwise two structurally isomeric indoles are obtained. Other related cyclization reactions are found in the Pechmann synthesis of triazoles (T.L. Gilchrist, 1974) and in G. Bredereck s (1939) imidazole synthesis (M.R. Grimmett, 1970). 

With certain types of compounds this method of reduction fails. In general, /3-keto esters (XX) and /3-diketones which are capable of enoliza-tion form the aluminum salt of the enolic form and aje not reduced. However, if there are no enolizable hydrogens (XXI), reduction proceeds smoothly. If a phenolic ketone or a keto acid forms a salt which is... 

Azoles can be produced from products of palladium-catalyzed hydrazone arylation and can serve as substrates for arylation reactions to produce N-aryl azoles. The Fischer indole synthesis uses N-ary I hydrazones, and these hydrazones can be generated by palladium-catalyzed chemistry. Benzophenone hydrazone was found by both the Yale and MIT groups to be a particularly effective substrate for palladium-catalyzed reactions, as summarized in Eq. (24) [140,141]. Reactions of benzophenone hydrazone with either aryl bromides or iodides occur in high yields using either DPPF- or BINAP-ligated palladium. These reactions are general and occur with electron-rich, electron-poor, hindered or unhindered aryl halides. The products of these reactions can be converted to hydrazones that bear enolizable hydrogens and are suitable for indole synthesis in the presence of acid and ketone [140]. 

A significant drawback of the standard conditions for palladium-catalyzed animation of aryl halides is the use of strong base. This procedure precludes the use of substrates with aromatic nitro groups, many substrates with enolizable hydrogens, substrates with esters other than /-butylesters, and substrates with base-sensitive stereochemistry, such as some protected amino acids. Thus, conditions that employ milder bases are required. A solution that involves reaction temperatures as low as those for reactions employing sodium f-butoxide has not been developed. However, carbonate and phosphate bases can be used with certain catalysts at reaction temperatures comparable to those of reactions involving the first- and second-generation catalysts. 

If an asymmetric carbon atom has an enolizable hydrogen atom, a trace of acid or base allows that carbon to invert its configuration, with the enol serving as the intermediate. A racemic mixture (or an equilibrium mixture of diastereomers) is the result. 

If you want a more controlled reaction with addition of formaldehyde to an aldehyde or ketone without the reduction step, you can sometimes succeed with a weaker base such as potassium carbonate. Typically in these reactions all the enolizable hydrogen atoms (green) are replaced by molecules of formaldehyde (black). 

Alkynes from aldehydes or ketones. The reaction of the anion ef 1 with diaryl ketones, ArCOAr, to form alkynes, ArC=CAr, was reported first by Colvin and Hamill, but the method was said to fail or give low yield with substrates with enolizable hydrogens. Since then experimental details have been perfected, and the method has proved to be useful." The anion of 1 is prepared with potassium f-butoxide, and the reaction with the carbonyl compound is conducted for 12-16 hours at —78° before it is allowed to warm to the ambient temperature. Linder these conditions, alkynes can be obtained in 50-80% yield from aldehydes, diaryl ketones, and alkyl aryl ketones, but not from dialkyl ketones. The proposed mechanism is shown in equation (I). 

Coupling of ketones with two different enolizable hydrogen atoms gives a mixture of 1,4-diketones in which the less crowded product predominates ... 

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