Addition reactions reversibility

As with other reversible nucleophilic addition reactions the equilibria for aldol additions are less favorable for ketones than for aldehydes For example only 2% of the aldol addition product of acetone is present at equilibrium... 

Michael condensations are catalyzed by alkaU alkoxides, tertiary amines, and quaternary bases and salts. Active methylene compounds and aUphatic nitro compounds add to form P-substituted propionates. These addition reactions are frequendy reversible at high temperatures. Exceptions are the tertiary nitro adducts which are converted to olefins at elevated temperatures (24). 

Iodine adds to carbon—carbon double bonds to form polyiodine derivatives. These addition reactions are reversible, however, and do not go to completion. 

The stmcture of individual block polymers is deterrnined by the nature of the initiator (1,2-propanediol above), the sequence of addition of propylene and ethylene oxides, and the percentage of propylene and ethylene oxides in the surfactant. Thus, when the order of addition is reversed, a different stmcture is obtained in which the hydrophobic moieties are on the outside of the molecule. With ethylene glycol as the initiator, the reactions are as foUows ... 

When the addition and elimination reactions are mechanically reversible, they proceed by identical mechanistic paths but in opposite directions. In these circumstances, mechanistic conclusions about the addition reaction are applicable to the elimination reaction and vice versa. The principle of microscopic reversibility states that the mechanism (pathway) traversed in a reversible reaction is the same in the reverse as in the forward direction. Thus, if an addition-elimination system proceeds by a reversible mechanism, the intermediates and transition states involved in the addition process are the same as... 

Aldehydes and ketones undergo reversible addition reactions with alcohols. The product of addition of one mole of alcohol to an aldehyde or ketone is referred to as a hemiacetal or hemiketal, respectively. Dehydration followed by addition of a second molecule of alcohol gives an acetal or ketal. This second phase of the process can be catalyzed only by acids, since a necessary step is elimination of hydroxide (as water) from the tetrahedral intermediate. There is no low-energy mechanism for base assistance of this... 

Ring-chain tautomerism via intramolecular reversible addition reactions to the C=0 group 95AHC(64)251. 

The hydration reaction just described is typical of what happens when an aldehyde ot ketone is treated with a nucleophile of the type H-Y, where the Y atom is electronegative and can stabilize a negative charge (oxygen, halogen, or sulfur, for instance). In such reactions, the nucleophilic addition is reversible, with the equilibrium generally favoring the carbonyl reactant rather than the tetrahedral addition product. In other words, treatment of an aldehyde or... 

Aldehydes and unhindered ketones undergo a nucleophilic addition reaction with HCN to yield cyanohydrins, RCH(OH)C=N. Studies carried out in the early 1900s by Arthur Eapworth showed that cyanohydrin formation is reversible and base-catalyzed. Reaction occurs slowly when pure HCN is used but rapidly when a small amount of base is added to generate the nucleophilic cyanide ion, CN. Alternatively, a small amount of KCN can be added to HCN to catalyze the reaction. Addition of CN- takes place by a typical nucleophilic addition pathway, yielding a tetrahedral intermediate that is protonated by HCN to give cyanohydrin product plus regenerated CN-. 

Glycolysis is a ten-step process that begins with isomerization of glucose from its cyclic hemiacetal form to its open-chain aldehyde form—a reverse nucleophilic addition reaction. The aldehyde then undergoes tautomerixa-tion to yield an enol, which undergoes yet another tautomerization to give the ketone fructose. 

We said in Section 19.10 that aldehydes and ketones undergo a rapid and reversible nucleophilic addition reaction with alcohols to form hemiacetals. 

Just as the Kiliani-Fischer synthesis lengthens an aldose chain by one carbon, the Wohl degradation shortens an aldose chain by one carbon. The Wohl degradation is almost the exact opposite of the Kiliani-Fischer sequence. That is, the aldose aldehyde carbonyl group is first converted into a nitrile, and the resulting cyanohydrin loses HCN under basic conditions—the reverse of a nucleophilic addition reaction. 

An elimination reaction is, in a sense, the reverse of an addition reaction. It involves the elimination of two groups from adjacent carbon atoms, converting a saturated molecule into one that is unsaturated. An example is the dehydration of ethanol, which occurs when it is heated with sulfuric acid ... 

This is, of course, the reverse of the addition reaction by which ethanol is farmed. 

The intramolecular Michael addition11 of a nucleophilic oxygen to an a,/ -unsaturated ester constitutes an attractive alternative strategy for the synthesis of the pyran nucleus, a strategy that could conceivably be applied to the brevetoxin problem (see Scheme 2). For example, treatment of hydroxy a,/ -unsaturated ester 9 with sodium hydride furnishes an alkoxide ion that induces ring formation by attacking the electrophilic //-carbon of the unsaturated ester moiety. This base-induced intramolecular Michael addition reaction is a reversible process, and it ultimately affords the thermodynamically most stable product 10 (92% yield). 

As observed with cyclohexanones, the diastereoselectivity of the addition reaction of trimeth-ylaluminum to 2-methylcyclopentanone depends on the stoichiometry of the reactants. Thus, addition of one equivalent of trimcthylaluminum proceeds via preferential tram attack whereas, due to the "compression effect , addition of an excess of the reagent leads to the formation of the equatorial alcohol via predominant attack from the cis side (Table 3)6. In contrast to the addition reactions with trimethylaluniinum, no reversal of the diastereoselectivity upon change of reagent stoichiometry was observed in the addition of triphenylaluminum to 2-methylcyclopentanone6. Even with an excess of the aluminum reagent trans attack predominates. However, the diastereoselectivity is lower than with the use of an equimolar amount of the reactants. 

On the other hand, in the presence of Lewis acids such as titanium(lV) chloride or eerium(TIT) chloride, the (S)-e s-conformer predominates via chelation of the two carbonyl groups and a reversed stereochemistry of the addition reaction is observed1 °. 

Addition of (R,S)-9 to the aromatic benzaldehyde proceeded with higher enantiosclcctivity than the addition of the diastereomeric reagent (S,S)-9. The reverse is true for additions to aliphatic aldehydes. Thus, the highest enantioselectivity of 92% ee was observed in the addition of (R,R)- 9 to cyclohexanccarboxaldehyde. The low chemical yields of most addition reactions can be improved by addition of the Lewis acid diethylaluminum ethoxide. The presence of the Lewis acid solely enhanced the chemical yield without changing the enantioselectivity of the addition reactions. 

The addition reaction requires the presence of 4 equivalents of HMPA, thus partial racemization of optically active aldehydes under these basic conditions is anticipated. Unfortunately, the addition of magnesium bromide, zinc chloride or cadmium iodide reverses the regioselectivity11 ... 

Lithiated areneacetonitriles react with a,/i-unsaturated ketones at low temperatures using short reaction times to give both 1,2- and 1,4-adducts. The 1,2-addition is reversible and under thermodynamic control (higher temperatures and longer reaction times) only the 1,4-adducts, i.e., <5-oxonitriles, arc obtained. When lithiated arylacetonitrile is added to 2-substituted 2-cy-cloalkenones in THF or in THF/HMPA mixtures at — 70-0°C, followed by protonation or alkylation under kinetically controlled conditions, predominantly cis- or fnms-2,3-disubstitut-ed cycloalkanones respectively, are obtained. 

The 1961 report that Vaska s compound (IrCl(CO)(PPh3)2) reversibly binds dioxygen sparked off an intense study of addition reactions of this and related compounds that has continued unabated up to the present day [125], Vaska s compound may be prepared as yellow air-stable crystals by various reactions, such as conventional substitution... 

Scheme 5-14 may be called a two-dimensional system of reactions, in contrast to Scheme 5-1 which consists of a one-dimensional sequence of two acid-base equilibria. In Scheme 5-14 the (Z/E) configurational isomerism is added to the acid-base reactions as a second dimension . The real situation, however, is yet more complex, as the TV-nitrosoamines may be involved as constitutional isomers of the diazohydroxide. In order not to make Scheme 5-14 too complex the nitrosoamines are not included, but are shown instead in Scheme 5-15. The latter also includes the addition reactions of the (Z)- and ( )-diazoates (5.4 and 5.5) to the diazonium ion to form the (Z,Z)-, (Z,E)- and (2 2i)-diazoanhydrides (5.6, 5.7 and 5.8) as well as proto-de-nitrosation reactions (steps 10, 11 and 12). This pathway corresponds to the reverse reaction of diazotization, as amine and nitrosating reagent (nitrosyl ion) are formed in this reaction sequence.

When the substituent groups in the polyphosphazenes were azobenzene [719] or spiropyran [720] derivatives, photochromic polymers were obtained, showing reversible light-induced trans-cis isomerization or merocyanine formation, respectively. Only photocrosslinking processes by [2+2] photo-addition reactions to cyclobutane rings could be observed when the substituent groups on the phosphazene backbone were 4-hydroxycinnamates [721-723] or 4-hydroxychalcones [722-724]. 

---