Aldehydes protonated, resonance forms

The proposed catalytic cycle is shown in Scheme 35 and begins with the imida-zolylidene carbene adding to the enal. Proton transfer provides acyl anion equivalent XLVII, which may be drawn as its homoenolate resonance form XLVIII. Addition of the homoenolate to aldehyde followed by tautomerization affords L the precursor for lactonization and regeneration of the carbene. 

Carbon dioxide is a symmetrical, linear triatomic molecule (0 = C=0) with a zero dipole moment. The carbon-to-hydrogen bond distances are about 1.16A, which is about 0.06A shorter than typical carbonyl double bonds. This shorter bond length was interpreted by Pauling to indicate that greater resonance stabilization occurs with CO2 than with aldehydes, ketones, or amides. When combined with water, carbonic acid (H2CO3) forms, and depending on the pH of the solution, carbonic acid loses one or two protons to form bicarbonate and carbonate, respectively. The various thermodynamic parameters of these reactions are shown in Table I. 

When esters are protonated at the carbonyl group, there are three resonance forms two corresponding to the ones that form with aldehydes and ketones and a third with positive charge on the alkylated oxygen. 

Generic process An addition and an elimination have occurred. Medium Definitely basic, predominant anion is hydroxide, plsTabH 15.7, whose pA"a would give a useful proton transfer A"eq up to about p Ta 26. Sources The carbonyl lone pair, water lone pair, and hydroxide anion. Best source Hydroxide anion, a lone pair source can behave as a nucleophile or as a base. Sinks Polarized multiple bond, the aldehyde carbonyl. Acidic Hs Water and the CH2 next to the aldehyde, pA a 16.7, are within range of hydroxide. Leaving groups None. Resonance forms ... 

After protons, C is the most widely detected nucleus in NMR. Proton cross-polarization and decoupling are usually applied to increase the S/N, and these types of experiment can result in substantial sample heating. Many forms of C-based NMR thermometers have been proposed. The first such system was based on the cis-trans conformational equilibrium of furfural, with the linewidths of carbon-3 and the aldehyde carbon being temperature-dependent. There are many disadvantages of linewidth-based measurements, and subsequent developments concentrated almost wholely on temperature-dependent C chemical shifts. The first such system utilized a temperature-dependent lanthanide-induced pseudocontact shift in a complex of acetone-de and ytterbium(III)1,1,1,2,2,3,3-heptafluoro-7,7-dimethyl-4,6-octadionate (Yb (fod)3). The 6co of the acetone-dg, measured with respect to a CS2 standard, was almost linearly dependent on 1 / T with a small quadratic term over a range 200-315 K. If a small amount of protonated acetone was added, then the proton resonance, measured with respect to the protons of TMS, was also found to be temperature dependent ... 

The carbene 163 exists in resonance with the species 163a. The nucleophilic reaction of 163a with an aldehyde, as shown, forms the 1,4-zwitterion 166. Now, proton transfer from carbon to oxygen generates the 1,3-zwitterion 167, which collapses to 164 after electron reorganization. 

The nuclear magnetic resonance spectra show no aldehydic protons, so that the aldehyde groups are fully hydrated or exist as hemiacetals. As shown, the ds isomer consists of two, anomeric, cyclic hemiacetals. The trans isomer, however, cannot form a cyclic hemiacetal in aqueous solution, it is hydrated (34, R = H) in alcoholic solvents (R OH), it forms a hemiacetal (34) and, in the anhydrous, solid form, it is probably a polymeric hemiacetal. The large changes in R/ values in changing from alcoholic to non-alcoholic solvents (see Section VI, p. 199) provide evidence for the easy formation of hemiacetals with alcohols. 

Triphenylmethide (19) is formed by the reaction of triphenylmethane (PhaCH) with sodium metal, as seen in Section 22.1. It is an unusual but effective base in this reaction because it is a relatively non-nucleophilic base (see Section 22.3). To explain the reaction with 60 and formation of product 61, a mechanism requires that the base first remove the acidic a-proton on C2 from the ester to form enolate anion 62. As with enolate anions derived from ketones and aldehydes, there are two resonance forms, and the carbanion form (62A) is the more nucleophilic. Therefore, resonance contribution 62A will lead to the... 

If the electrophile that reacts with an enolate is a proton, the products are called the keto and enol forms for both aldehydes and ketones. These species are isomers, not resonance forms. 

Whereas the pATa for the a-protons of aldehydes and ketones is in the region 17-19, for esters such as ethyl acetate it is about 25. This difference must relate to the presence of the second oxygen in the ester, since resonance stabilization in the enolate anion should be the same. To explain this difference, overlap of the non-carbonyl oxygen lone pair is invoked. Because this introduces charge separation, it is a form of resonance stabilization that can occur only in the neutral ester, not in the enolate anion. It thus stabilizes the neutral ester, reduces carbonyl character, and there is less tendency to lose a proton from the a-carbon to produce the enolate. Note that this is not a new concept we used the same reasoning to explain why amides were not basic like amines (see Section 4.5.4). 

In the first step of the conversion catalyzed by pyruvate decarboxylase, a carbon atom from thiamine pyrophosphate adds to the carbonyl carbon of pyruvate. Decarboxylation produces the key reactive intermediate, hydroxyethyl thiamine pyrophosphate (HETPP). As shown in figure 13.5, the ionized ylid form of HETPP is resonance-stabilized by the existence of a form without charge separation. The next enzyme, dihydrolipoyltransacetylase, catalyzes the transfer of the two-carbon moiety to lipoic acid. A nucleophilic attack by HETPP on the sulfur atom attached to carbon 8 of oxidized lipoic acid displaces the electrons of the disulfide bond to the sulfur atom attached to carbon 6. The sulfur then picks up a proton from the environment as shown in figure 13.5. This simple displacement reaction is also an oxidation-reduction reaction, in which the attacking carbon atom is oxidized from the aldehyde level in HETPP to the carboxyl level in the lipoic acid derivative. The oxidized (disulfide) form of lipoic acid is converted to the reduced (mer-capto) form. The fact that the two-carbon moiety has become an acyl group is shown more clearly after dissocia-... 

The hydroxymethyl cation forms of protonated ketones (264) and aldehydes (265) contribute to the resonance hybrid. Based on 13C NMR studies,94 548 551 the degree of contribution of the hydroxymethyl cation forms can be quite accurately estimated. Similar studies have been carried out using 170 NMR spectroscopy.552 Recent theoretical studies (MP2/6-31G level)553 for protonated acetone have supported the... 

The pinacol rearrangement is a dehydration of an alcohol that results in an unexpected product. When hot sulfuric acid is added to an alcohol, the expected product of dehydration is an alkene. However, if the alcohol is a vicinal diol, the product will be a ketone or aldehyde. The reaction follows the mechanism shown, below. The first hydroxyl group is protonated and removed by the acid to form a carboca-tion in an expected dehydration step. Now, a methyl group may move to fonn an even more stable carbocation. This new carbocation exhibits resonance as shown. Resonance Structure 2 is favored because all tire atoms have an octet of electrons. The water deprotonates Resonance Structure 2, forming pinacolone and regenerating the acid catalyst. 

Diprotonated, superelectrophilic intermediates were suggested to be involved in both conversions. Considering protonated aldehydes, benzal-dehyde gives a carboxonium ion that is significantly resonance stabilized and thus unreactive towards aromatic substrates such as o-dichlorobenzene or nitrobenzene. Pyridinecarboxaldehydes, however, show much higher electrophilic reactivities due to their ability to form via TV-protonation the superelectrophile (5, eq 8).10 A similar situation is seen in the hydroxyalkylation reactions of acetyl-substituted arenes. Acetophenone is fully protonated in excess triflic acid, but the resulting carboxonium ion (6) is... 

In the presence of strong bases, ketones and aldehydes act as weak proton acids. A proton on the a carbon atom is abstracted to form a resonance-stabilized enolate ion with the negative charge spread over a carbon atom and an oxygen atom. Reprotonation can occur either on the a carbon (returning to the keto form) or on the oxygen atom, giving a vinyl alcohol, the enol form. 

A carbonyl group dramatically increases the acidity of the protons on the a carbon atom because deprotonation gives a resonance-stabilized enolate ion. Most of the enolate ion s negative charge resides on the electronegative oxygen atom. The pKa for removal of an a proton from a typical ketone or aldehyde is about 20, showing that a typical ketone or aldehyde is much more acidic than an alkane or an alkene (pKa > 40), or even an alkyne (pKa = 25). Still, a ketone or aldehyde is less acidic than water (pKa = 15.7) or an alcohol (pA a = 16 to 18). When a simple ketone or aldehyde is treated with hydroxide ion or an alkoxide ion, the equilibrium mixture contains only a small fraction of the deprotonated, enolate form. 

In addition, its proton magnetic resonance spectrum unambiguously supported the 5-ketose structure (69). Rearrangements of epoxides to ketones when dicobalt octacarbonyl is used as the catalyst at temperatures above 100 , or when cobalt hydrocarbonyl is used at lower temperatures, are well known. By applying the technique of double irradiation to a sample of (68), the main component was shown to possess structure (68). Presumably, the free aldehyde group of the hydroformylation product immediately cyclized with the free hydroxyl group on C-3 to give the tricyclic structure (68). A third component (68a) (isolated in less than 5 % yield) was undoubtedly formed by subsequent reduction of the dialdose derivative (68). 

In acid, carbonyl compounds are in equilibrium with their protonated counterparts. Protonation is often the first step in nucleophilic addition or substitution of carbonyl groups. For aldehydes and ketones, the protonated carbonyl group is a resonance hybrid of two forms one with positive charge on the carbonyl oxygen and one with positive charge on the carbonyl carbon. 

The carbocation that is formed upon protonation of a carbonyl compound can lose H+ from the a-carbon to give an enol. Enols are good nucleophiles. Thus, under acidic conditions, carbonyl compounds are electrophilic at the carbonyl C and nucleophilic at the a-carbon and on oxygen, just like they are under basic conditions. Resonance-stabilized carbonyl compounds such as amides and esters are much less prone to enolize under acidic conditions than less stable carbonyl compounds such as ketones, aldehydes, and acyl chlorides in fact, esters and amides rarely undergo reactions at the a-carbon under acidic conditions. 

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