P-Hydroxy carbonyls

Synthesis The synthesis uses rather more vigorous conditions than those which gave the p-hydroxy carbonyl compoimds. In fact tBull. Chem. Japan. 1952, 25, 54, Chem. Abs..l954. 48. 5143) you can either treat the p-hydroxy compoimd with HCl in acetic acid or do the condensation in base ... 

The study of acid-base interaction is an important branch of interfacial science. These interactions are widely exploited in several practical applications such as adhesion and adsorption processes. Most of the current studies in this area are based on calorimetric studies or wetting measurements or peel test measurements. While these studies have been instrumental in the understanding of these interfacial interactions, to a certain extent the interpretation of the results of these studies has been largely empirical. The recent advances in the theory and experiments of contact mechanics could be potentially employed to better understand and measure the molecular level acid-base interactions. One of the following two experimental procedures could be utilized (1) Polymers with different levels of acidic and basic chemical constitution can be coated on to elastomeric caps, as described in Section 4.2.1, and the adhesion between these layers can be measured using the JKR technique and Eqs. 11 or 30 as appropriate. For example, poly(p-amino styrene) and poly(p-hydroxy carbonyl styrene) can be coated on to PDMS-ox, and be used as acidic and basic surfaces, respectively, to study the acid-base interactions. (2) Another approach is to graft acidic or basic macromers onto a weakly crosslinked polyisoprene or polybutadiene elastomeric networks, and use these elastomeric networks in the JKR studies as described in Section 4.2.1. 

The rhodium-catalyzed conversion of a-diazo-p-hydroxy carbonyl into P-dicarbonyl compounds (Table 23, Entries 6-8) in general seems to be preferable to the acid-catalyzed reaction because of higher yields and absence of side-reactions 37S,377). From a screening of 20 metal salts and complexes, Rh2(OAc)4, RhCl(PPh3)3, PdCl2 and CoCl2 emerged as the most efficient catalysts for the transformation of a-diazo-P-hydroxy esters into P-ketoesters 376). This reaction has become part of... 

Rearrangement of epoxy silyl ethers. When treated with 1 equiv. of TiCl4, a-silyloxy epoxides rearrange to p-hydroxy carbonyl compounds. 

Aldol Reaction The formation of an aldol (P-hydroxy carbonyl compound) through the catalyzed condensation of an enol/enolate with a carbonyl compound. 

A great deal of the interest in isoxazolines stems from their use in the synthesis of acyclic compounds (19). The approach to p-hydroxy carbonyl compounds via... 

Cleavage reactions of carbohydrates also occur on treatment with aqueous base for prolonged periods as a consequence of base-catalyzed retro-aldol reactions. As pointed out in Section 18.9, aldol addition is a reversible process, and p-hydroxy carbonyl compounds can be cleaved to an enolate and either an aldehyde or a ketone. 

The aldol reaction is an addition of metal enolates to aldehydes or ketones to form P-hydroxy carbonyl compounds.1 The simplest aldol reaction would be the reaction of acetaldehyde lithium enolate with formaldehyde (Scheme 2.1). As the transition state of this reaction involves six atoms, the aldol reaction is another example where a six-membered transition state is presumed to be operating. The transition state of the aldol reaction is very similar to those of Claisen and Cope rearrangements, and therefore the remarkable facility of the lithium enolate reaction is attributed to the stability of an aromatic transition state.2... 

The P-hydroxy carbonyl products of aldol reactions are often very easily dehydrated to give a,P-unsaturated carbonyl compounds and, if you spot an a,P-unsaturated carbonyl group in the molecule, you should aim to make it by an aldol reaction. You will first need to do an FGI to the P-hydroxy carbonyl compound, then disconnect as before. 

One of the most important methods of C-C bond formation involves the aldol condensation in which the carbanion derived from an aldehyde or ketone reacts with a second carbonyl component to give a p-hydroxy-carbonyl derivative (Scheme 3.79). 

The P-hydroxy carbonyl compounds formed in the aldol reaction dehydrate more readily than other alcohols. In fact, under the basic reaction conditions, the initial aldol product is often not isolated. Instead, it loses the elements of H2O from the a and P carbons to form an a,P-unsaturated carbonyl compound. 

All alcohols—Including P-hydroxy carbonyl compounds—dehydrate in the presence of acid. Only p-hydroxy carbonyl compounds dehydrate in the presence of base. 

An aldol reaction is often called an aldol condensation, because the p-hydroxy carbonyl com x>und that is initially formed loses H2O by dehydration. A condensation reaction is one in which a small molecxile, in this case H2O, is eliminated during a reaction. 

It may or may not be possible to isolate the P-hydroxy carbonyl compound under the conditions of the aldol reaction. When the a,P-unsaturated carbonyl compound is further conjugated with a carbon-carbon double bond or a benzene ring, as in the case of Reaction [2], elimination of H2O is spontaneous and the P-hydroxy carbonyl compound carmot be isolated. 

Dehydration of the initial P-hydroxy carbonyl compound drives the equilibrium of an aldol reaction to the right, thus favoring product formation. Once the conjugated a,p-unsaturated carbonyl compound forms, it is not re-converted to the P-hydroxy carbonyl compound. 

Problem 24.2 What unsaturated carbonyl compound is formed by dehydration of each p-hydroxy carbonyl compound ... 

Acid-catalyzed dehydration of p-hydroxy carbonyl compounds occurs by the mechanism discussed in Section 9.8. With this in mind, draw a stepwise mechanism for the following reaction. 

To utilize the aldol reaction in synthesis, you must be able to determine which aldehyde or ketone is needed to prepare a particular P-hydroxy carbonyl compound or a,P-unsaturated carbonyl compound—that is, you must be able to work backwards, in tbe retrosynthetic direction. 

When a carbonyl group has two different a carbons, choose the side that contains the OH group (in a p-hydroxy carbonyl compound) or is part of the C=C (in an a,p-unsaturated carbonyl compound). 

When two different aldehydes, both having a H atoms, are combined in an aldol reaction, four different P-hydroxy carbonyl compounds are formed. Four products form, not one, because both aldehydes can lose an acidic a hydrogen atom and form an enolate in the presence of base. Both enolates can then react with both carbonyl compounds, as shown for acetaldehyde and propanal in the following reaction scheme. 

As we learned in Section 23.3, the a hydrogens between two carbonyl groups are especially acidic, and so they are more readily removed than other a H atoms. As a result, the p-dicarbonyl compound always becomes the enolate component of the aldol reaction. Figure 24.2 shows the steps for the crossed aldol reaction between diethyl malonate and benzaidehyde. In this type of crossed aldol reaction, the initial P-hydroxy carbonyl compound always loses water to form the highly conjugated product. 

The aldol reaction is synthetically useful because it forms new carbon-carbon bonds, generating products with two functional groups. Moreover, the P-hydroxy carbonyl compounds formed in aldol reactions are readily transformed into a variety of other compounds. Figure 24.3 illustrates how the crossed aldol product obtained from cyclohexanone and formaldehyde (CH2=0) can be converted to other compounds by reactions learned in earlier chapters. 

Conversion of a p-hydroxy carbonyl compound into other compounds... 

The p-hydroxy carbonyl compound formed from the crossed aldol reaction can be reduced with NaBH4, CH3OH (Section 20.4A) to form a 1,3-diol (Reaction [1]) or dehydrated to form an a,p-unsaturated carbonyl compound (Reaction [2]). Reduction of the c(,p-unsaturated carbonyl compound forms an allylic alcohol with NaBHi (Reaction [3]), or a ketone with H2 and Pd-C (Reaction [4]) see Section 20.4C. Reaction of the a,p-unsaturated carbonyl compound with an organometalllc reagent forms two different products depending on the choice of RM (Reaction [5]) see Section 20.15. 

Aldol reaction to form a p-hydroxy carbonyl compound or an a,p-unsaturated carbonyl compound... 

Aldol condensation (Section 24. IB) An aldol reaction in which the initially formed P-hydroxy carbonyl compound loses water by dehydration. 

Aldol reaction (Section 24.1 A) A reaction in which two molecules of an aldehyde or ketone react with each other in the presence of base to form a p-hydroxy carbonyl compound. 

P-Hydroxy carbonyl compound (Section 24.1 A) An organic compound having a hydroxy group on the carbon p to the carbonyl group. 

Dehydration of P-Hydroxy Carbonyl Compounds with Base 920... 

Aldol and related Carbonyl compounds p-Hydroxy carbonyl compounds 173... 

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