Protonation writing reaction mechanisms

Cyclic-AMP is formed from ATP in a reaction catalyzed by the enzyme adenylate cyclase. Assume that adenylate cyclase acts as a base to remove a proton from the 3 -hydroxyl group of ATP and write a mechanism for the formation of cAMP. 

The mechanism of the reaction could be either a base-induced enoiization reaction (Section 17-1) or ionization of the OH proton followed by a Cannizzaro-type reaction (Section 16-4E). Write each mechanism in detail and devise experiments that could be used to distinguish between them. 

You should be abife to write a mechanism for this reaction—ft is much the same es the formation of an acetal, but no acid catalyst is present so you will not need to protonate the carbonyl groups before the amines attack. 

Approach writing the mechanism in a logical fashion. For example, if the reagent is a strong base, look for acidic protons in the substrate, then look for a reasonable reaction for the anion produced. If the anion formed by deprotonation has a suitable leaving group, its loss would lead to overall elimination. If the anion formed is a good nucleophile, look for a suitable electrophilic center at which the nucleophile can react. (For further detail, see Chapter 3.)... 

In the paper cited (Jacobsen and Lahm, 1979), the mechanism proposed suggests that the starting material is dehydrated before cyclization occurs. This means that protonation of the less basic group leads to the product. Satisfy yourself that this is reasonable by writing possible reaction mechanisms that would result from protonation of the hydroxyl and carbonyl hydrogens. 

The aryne intermediate is usually written with a triple bond and a delocalized aromatic system, as shown in 3-44. The anion in the side chain reacts as a nucleophile with the electrophilic aryne. The resulting anion, 3-45, can remove a proton from ammonia to give 3-46. Because the product has been reached, we usually stop writing the reaction mechanism at this point. However, in the reaction mixture, amide will remove a proton from the carbon a to the cyano group of 3-46. Only during workup will the anion be protonated to give back 3-46. 

PROBLEM 7.8 Write a mechanism for the following reaction, a reduction-rearrangement in which zinc is a reducing agent. The first steps of a mechanism couid involve protonation of the nitrogen and reaction with zinc. 

Referring to the mechanism for the acid-catalyzed hydrolysis of methyl acetate, write the mechanism—showing all the curved arrows— for the acid-catalyzed reaction of acetic acid and methanol to form methyl acetate. Use HB and =B to represent proton-donating and proton-removing species, respectively. 

In any case, the oxygen electrode is a complex system and the overall reaction in either direction requires the transfer of four electrons and four protons. As a result, it is possible to write a very large number of reaction mechanisms but they are essentially of two types... 

The reduction of nitrobenzene to aniline is a typical oxidation-reduction reaction in which tin metal, Sn°, is oxidized to stannic ion, Sn, in the form of stannic chloride, SnCl4 hydrochloric acid serves as the source of protons. A plausible mechanism of this reaction is outlined in Scheme 21.3. Generally, the reduction occurs by a sequence of steps in which an electron is first transferred from a tin atom to the organic substrate to give an intermediate radical ion that is then protonated. The oxygen atoms on the nitro group are eventually removed as water molecules. It is left as an exercise to write a balanced equation for the overall reaction and to provide a mechanism for the reduction of N-phenylhydroxylamine (11) into aniline (see Exercises 13 and 14 at the end of this section). 

II. Avoid mixed media errors. In other words, when writing a mechanism for a reaction occurring in strongly basic media (contains hydroxide or alkoxides), do not create any intermediates that are strong acids (such as protonated and therefore positively charged carbonyls or alcohols). Similarly, when writing a... 

Write an equation for the proton transfer reaction that occurs when each of the following acids reacts with water. In each case, draw curved arrows that show the mechanism of the proton transfer ... 

The obvious question is. Why Will our mechanism for addition have to be severely changed to accommodate these new data In fact, we will be able to graft a small modification onto our general mechanism for addition reactions and avoid drastic changes. The way to attack a problem of this kind—explaining the formation of an unusual product—is to write the mechanism for the reaction as we have developed it so far and then see if we can find a way to rationalize the new product. In this case, protonation of 3-methyl-l-butene can give either a secondary... 

The reverse aldol reaction shown below gives a rate equation - Ar[starting material] [HO ]. Write a mechanism for this process that is consistent with the rate equation, remembering that proton transfers to or from oxygen and nitrogen atoms are rarely rate limiting. 

Write a detailed mechanism for this condensation using only the molecules whose models are provided. Treat all proton transfers, nucleophilic additions, and elimination reactions as separate steps, and use curved arrows to show electron movement. Which of these steps do you think will be favorable Unfavorable Why ... 

Acid-catalyzed hydrolysis of a nitrile to give a carboxylic acid occurs by initial protonation of the nitrogen atom, followed by nucleophilic addition of water. Review the mechanism of base-catalyzed nitrile hydrolysis in Section 20.7, and then write all the steps involved in the acicl-catalyzed reaction, using curved arrows to represent electron flow in each step. 

Thus we tend to favor the mechanism outlined in Reactions 12 and 13 (followed by Reactions 7 and 8). The mechanisms as presented do not indicate how the N-formyl product is formed although formation of a Ru-CO-N moiety at some stage seems essential metal-assisted hydride shifts are a possibility. An alternative role of the attacking piperidine in Reaction 12 or 17 could be that of a proton acceptor as discussed by others (1, 13). For example, a plausible scheme would be the following (writing R2 for C5H10)... 

Most of the Fischer esterification mechanism is identical with the mechanism of acetal formation. The difference is in the final step, where a carbocation loses a proton to give the ester. Write mechanisms for the following reactions, with the comparable steps directly above and below each other. Explain why the final step of the esterification (proton loss) cannot occur in acetal formation, and show what happens instead. 

Development of a carbocation center due to loss of chloride ion can account for the loss of stereochemistry at this carbon. It seems reasonable to write this step after removal of a proton to give the anion because, if chloride loss occurs before anion formation, the carbocation would be expected to react with solvent before the anion could be formed. In that case one might expect to isolate some of the compound in which chloride had been replaced by methoxyl. The effect of the solvent on the stereochemistry of the reaction is due to its ability to solvate the intermediate charged species involved in a stepwise mechanism. 

Problem 21.12 In acid-catalyzed aldol condensations acid is believed to perform two functions to catalyze conversion of carbonyl compound into the enol form, and to provide protonated carbonyl compound with which the enol can react. The reaction that then takes place can, depending upon one s point of view, be regarded either as acid-catalyzed nucleophilic addition to a carbonyl group, or as electrophilic addition to an alkene. On this basis, write all steps in the mechanism of acid-catalyzed aldol condensation of acetaldehyde. In the actual condensation step, identify the nucleophile and the electrophile. 

---