Reactivation nucleophilic agents

Hydrides are reactive nucleophilic agents able to initiate growth slowly. The whole process will have the character of degradative transfer the polymerization of a-methylstyrene will be stopped at a certain conversion. The double bond at the chain end will increase the acidity of the penultimate styrene unit and the corresponding C—H bond will be weakened by resonance stabilization of the anion... 

To set the stage for the crucial aza-Robinson annulation, a reaction in which the nucleophilic character of the newly introduced thiolactam function is expected to play an important role, it is necessary to manipulate the methyl propionate side chain in 19. To this end, alkaline hydrolysis of the methyl ester in 19, followed by treatment of the resulting carboxylic acid with isobutyl chlorofor-mate, provides a mixed anhydride. The latter substance is a reactive acylating agent that combines smoothly with diazomethane to give diazo ketone 12 (77 % overall yield from 19). 

A form of vitamin B12 can produce methyl carbanion, a reactive species that is responsible for methylation of Hg (see Figure 8.2, Craig 1986, and IAEA Technical Report 137). Methyl carbanion acts as a nucleophilic agent toward Hg ions. 

In the first step, a resin-bound secondary amine is acylated with bromoacetic acid, in the presence of N,N-diisopropylcarbodiimide. Acylation of secondary amines is difficult, especially when coupHng an amino acid with a bulky side chain. The sub-monomer method, on the other hand, is facilitated by the use of bromoacetic acid, which is a very reactive acylating agent Activated bromoacetic acid is bis-reactive, in that it acylates by reacting with a nucleophile at the carbonyl carbon, or it can alkylate by reacting with a nucleophile at the neighboring ah-phatic carbon. Because acylation is approximately 1000 times faster than alkylation, acylation is exclusively observed. 

Acylation of carbon nucleophiles can also be carried out with more reactive acylating agents such as acid anhydrides and acyl chlorides. These reactions must... 

Acyl chlorides are highly reactive acylating agents and react very rapidly with alcohols and other nucleophiles. Preparative procedures often call for use of pyridine as a catalyst. Pyridine catalysis involves initial formation of an acyl pyridinium ion, which then reacts with the alcohol. Pyridine is a better nucleophile than the neutral alcohol, but the acyl pyridinium ion reacts more rapidly with the alcohol than the acyl chloride.103... 

The introduction of powerful electron-withdrawing substituents (NO2, CN, a polynitrogen heterocycle) at the a-C atom of AN stabilize anions of AN, thus facilitating their generation. At the same time, stabilization of anions of AN leads to a decrease in their reactivity and such anions act as milder nucleophilic agents. It will be seen from the following that this leads to an increase in the contribution of C-alkylation. 

When electron-withdrawing substituents are present in position 3, their behaviour is somewhat different their reactivity towards nucleophilic agents is lower. 

The different reactivity of the halogens at C-7 and C-5 allows them to be reacted in two steps with two different nucleophilic agents under mild conditions at C-7, and then under harsher conditions at C-5 (71PHA534 81KFZ31 91PHA184). 

In general, the chlorinated and the mixed analogs are more toxic than those containing only fluorine as a halogen.6,204 Further, there exists a direct relationship between toxicity and reactivity towards nucleophilic agents. -Isomers are, in general, more toxic than Z-isomers. 

The only drawback of strategies for the synthesis of tertiary amines that are based on the quaternization of polystyrene-bound /V-nucleophiles is that quaternizations on polystyrene only proceed sluggishly and generally require the use of highly reactive alkylating agents (methyl, allyl, or benzyl halides or sulfonates see Section 10.2). 

Support-bound indoles can be modified in several ways. N-Alkylation of polystyrene-bound indoles has been achieved by treatment with reactive alkylating agents (Mel, BnBr, BrCH2C02R) in conjunction with NaH or KOrBu as a base in DMF at room temperature (Entries 1 and 2, Table 15.7). The aminomethylation of indole at C-3 proceeds smoothly on cross-linked polystyrene. The resulting (aminomethyl)in-doles are thermally unstable and undergo substitution reactions with various carbon nucleophiles (e.g. cyanide or nitroacetates) at higher temperatures (Entry 4, Table... 

A number of nucleophilic agents, which are very reactive in SN2 reactions, are of the type X-Y, where both atoms have unshared electron pairs. Examples include HOO , H2NO , CIO , and H2NNH2, all of which are more reactive than the closely related nucleophiles HO and NH3. 

Exercise 16-4 Which compound in each of the following pairs would you expect to be more reactive toward addition of a common nucleophilic agent such as hydroxide ion to the carbonyl bond Indicate your reasoning. 

Exercise 29-14 The terminal carbon of the epoxide ring of epichlorohydrin generally is quite a bit more reactive toward nucleophilic agents than is the carbon bonded to chlorine. Work out a mechanism for the following reaction that takes account of this fact (review Section 15-11D) ... 

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