Ketones protonated, resonance forms

The salts of some enamines crystallize as hydrates. In such cases it is possible that they are derived from either the tautomeric carbinolamine or the amino ketone forms. Amino ketone salts (93) ( = 5, 11) can serve as examples. The proton resonance spectra of 93 show that these salts exist in the open-chain forms in trifluoroacetic acid solution, rather than in the ring-closed forms (94, n = 5, 11). The spectrum of the 6-methylamino-l-phenylhexanone cation shows a multiplet at about 2.15 ppm for phenyl, a triplet for the N-methyl centered at 7.0 ppm and overlapped by signals for the methylene protons at about 8.2 ppm. The spectrum of 93 ( = 11) was similar. These assignments were confirmed by determination of the spectrum in deuterium oxide. Here the N-methyl group of 93 showed a sharp singlet at about 7.4 ppm since the splitting in —NDjMe was much reduced from that of the undeuterated compound. 

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. 

By bond polarity and resonance, the carbonyl carbon and a carbon (i to the carbonyl carbon can be utilized as electrophilic centers—die carbonyl group by direct nucleophilic addition and die /3 carbon by Michael addition to an a,/3-unsaturated ketone. By resonance interaction, the a position in carbonyl compounds and y positions in o, /3-unsaturated carbonyl compounds can be converted to nucleophilic centers by proton removal. These normal polarities are used frequently in retrosynthetic planning as points of disconnection to establish potential bond-forming steps using carbonyl groups. 

Enamines are susceptible to acid-catalyzed hydrolysis (last step of the Stork enamine reaction) (96). Under acidic conditions, examines protonate to form the tautomeric iminium ion, which undergoes hydrolysis to the ketone as shown in Figure 57. The iminium ion undergoes hydrolysis quite readily since there is a contributing resonance form with a positive charge on the carbon (97). 

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. 

Balanced Yes. Medium Mildly acidic. A common acetate buffer is created from almost equal concentrations of acetic acid and sodium acetate. Sources The amine lone pair and the carbonyl lone pair. Sinks The ketone is a C=Y. Acidic Hs None within range of pH 5. Basic sites An oxygen and/or nitrogen lone pair could become protonated. Leaving groups None. Resonance forms The carbonyl charge separated form, —0 , shows the carbonyl carbon to be a good sink. 

Because LDA is a non-nudeophilic base, it should react with a ketone to give an enolate anion. In an actual experiment, 2-pentanone (32) reacts first with LDA to form the enolate anion (not shown) and then with benzaldehyde (25) to form the aldol alkoxide product (also not shown). Subsequent mild acid hydrolysis gives 33 in 80% yield. Virtually no self-condensation of 32 is observed in this experiment, which suggests that the reaction is largely irreversible. Assume that 2-pentanone reacts with LDA to give enolate anion 34 (the two resonance forms are 34A and 34B). As in all of these reactions, the carbanion form of the enolate 34A is the nucleophile. To account for the observed lack of self-condensation, the equilibrium for this acid-base reaction must be pushed toward 34 (the reasons for this will be discussed in Section 22.4.2). If this statement is correct, it means that 32 has been converted almost entirely to 34, so there is little or no 43 available to react. Therefore, a different carbonyl compound may be added in a second chemical step to give 35. This is an overstatement of the facts, but it is a useful assumption that explains the results. Note that benzaldehyde is used, which has no a-protons and cannot form an enolate anion. 

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... 

Oxygen-17 NMR provides a convenient means for monitoring perturbations of carbonyl groups which reduce carbon-oxygen TT bond order. Protonated ketones R2C0lT show the most dramatic effect. As is to be expected from the resonance forms and 5,... 

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. 

Enamino ketones can protonate not only on nitrogen or carbon but also on oxygen to give 12,13, and 14, respectively. Enamino ketones form stable perchlorates, chlorides, bromides, and iodides, and examination of their infrared (21,22), ultraviolet (23), and nuclear magnetic resonance (24,25) spectra show these salts to be O protonated. The salts of 4-dialkylamino-... 

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). 

This is an equilibrium reaction, and it raises a couple of points. First, there are two a-positions in the ketone, so what about the COCH3-derived enolate anion The answer is that it is formed, but since the CH3 group is not chiral, proton removal and reprotonation have no consequence. Racemization only occurs where we have a chiral a-carbon carrying a hydrogen substituent. Second, the enolate anion resonance structure with charge on carbon is not planar, but roughly tetrahedral. If we reprotonate this, it must occur from just one side. Yes, but both enantiomeric forms of the carbanion will be produced, so we shall still get the racemic mixture. 

Reduction is defined as acceptance of electrons. Electrons can be supplied by an electrode - cathode - or else by dissolving metals. If a metal goes into solution it forms a cation and gives away electrons. A compound to be reduced, e.g. a ketone, accepts one electron and changes to a radical anion A. Such a radical anion may exist when stabilized by resonance, as in sodium-naphthalene complexes with some ethers [122], In the absence of protons the radical anion may accept another electron and form a dianion B. Such a process is not easy since it requires an encounter of two negative species, an electron and a radical anion, and the two negative sites are close together. It takes place only with compounds which can stabilize the radical anion and the dianion by resonance. 

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. 

NA-Dimethylhydrazone 68, furnished from keto-acid 33 upon treatment with WV-dimethylhydrazine, was found to be extremely water sensitive. Attempts to form the hydrazone were thwarted by low yields under a number of conditions in which solvents were present. Azeotropic removal of water, with or without molecular sieves, was also unsatisfactory. Eventually, it was found most convenient to simply dissolve the keto-acid in neat dimethylhydrazine without desiccant. After heating for a number of hours, followed by cooling and removal of excess dimethylhydrazine, formation of the desired hydrazone was apparent by NMR due to loss of the methyl ketone resonance at 5 2.14. This initially formed hydrazone existed as a dimethylhydrazonium carboxylate, but it was found that reversion to free carboxylic acid 68 occurred in vacuo, as evidenced by the proton NMR run in dry CDClj. 

The resonance structure on the right is much more stable than the one on the left because the octet rule is satisfied for all of the atoms. The cation is actually the conjugate acid of a ketone. Because this cation is so much lower in energy than the usual carbocation, the transition state leading to it is also lower in energy (Hammond postulate). Thus, it is formed readily and the initial addition of the proton is very fast. 

The structures of the adducts were confirmed by H NMR. The regio-orientation of the pyrrole ring in compound (7) is apparent from the chemical shifts and splitting patterns of resonances due to the H-4a and H-7a protons. The doublet for H-7a is at a lower field than that for H-4a which appears as a multiplet due to spin-spin coupling with the H-5a, H-7a and H-4 (NH) protons. Proton NMR studies also reveal that there are two enolic forms of the ketone function in (7) but the major tautomer is the keto form (7a) (Scheme 1). 

Loss of water from the hydrate of the ester occurs by the same mechanism as loss of water from the hydrate of a ketone (Section 18-13). Protonation of either of the hydroxyl groups allows it to leave as water, forming a resonance-stabilized cation. Loss of a proton from the second hydroxyl group gives the ester. 

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. 

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