Nucleophilic aliphatic Subject

A sulfonyl chloride group rapidly reacts with amines in the pH range of 9-10 to form stable sulfonamide bonds. Under these conditions, it also may react with tyrosine —OH groups, aliphatic alcohols, thiols, and histidine side chains. Conjugates of sulfonyl chlorides with sulf-hydryls and imidazole rings are unstable, while esters formed with alcohols are subject to nucleophilic displacement (Nillson and Mosbach, 1984 Scouten and Van der Tweel, 1984). The only stable derivative with proteins therefore is the sulfonamide, formed by reaction with e-lysine... 

An obvious difficulty arises with this rather elaborate rationale when phosphoramidate and aryl phosphoramidate monoanions are compared for example, the dissimilarity of the dioxan effect yet the identity of product distribution observed in methanol-water competition experiments. Preliminary studies in the author s laboratory have revealed striking differences in the hydrolytic behavior between a series of phosphoramidafes derived from primary aliphatic amines and the above aryl systems. No linear structure-reactivity relationship between the logarithmic rate of hydrolysis of the monoanion species and the pKa of the amine is observed19. Moreover, the rate of hydrolysis of phosphoramidate monoanions derived from aliphatic amines is at least 104 times slower than those formed from aryl amines. In contrast, only a thirtyfold decrease in rate is observed for the corresponding ApKa in the O-phos-phate monoester series. The suspicion that mechanism (1), even with the above proposed modification, is not an accurate description of phosphoramidate monoanion hydrolysis derives some further support from the observation that the monoanion is subject to nucleophilic attack by substituted pyridines al-... 

Kinetic studies of the nucleophilic reactions of azolides have demonstrated that the aminolyses and alcoholyses proceed via a bimolecular addition-elimination reaction mechanism, as does the neutral hydrolysis of azolides of aromatic carboxylic acids. Aliphatic carboxylic acid azolides which are subject to steric hindrance can be hydrolyzed in aqueous medium by an 5n1 process. There have been many studies of these reactions, and evidence supporting both 5n1 and 5n2 processes leaves the impression that there are features of individual olysis reactions which favour either an initial ionization or a bimolecular process involving a tetrahedral intermediate (80AHC(27)241, B-76MI40701). 

Aliphatic and aromatic nucleophilic substitution reactions are also subject to micellar effects, with results consistent with those in other reactions. In the reaction of alkyl halides with CN and S Oj in aqueous media, sodium dodecyl sulfate micelles decreased the second-order rate constants and dodecyltrimethylammonium bromide increased them (Winters, 1965 Bunton, 1968). The reactivity of methyl bromide in the cationic micellar phase was 30 to 50 times that in the bulk phase and was negligible in the anionic micellar phase a nonionic surfactant did not significantly affect the rate constant for n-pentyl bromide with S2O3-. Micellar effects on nucleophilic aromatic substitution reactions follow similar patterns. The reaction of 2, 4-dinitrochlorobenzene or 2, 4-dinitrofluorobenzene with hydroxide ion in aqueous media is catalyzed by cationic surfactants and retarded by sodium dodecyl sulfate (Bunton, 1968, 1969). Cetyltrimethylammonium bromide micelles increased the reactivity of dinitrofluorobenzene 59 times, whereas sodium dodecyl sulfate decreased it by a factor of 2.5 for dinitrochlorobenzene, the figures are 82 and 13 times, respectively. A POE nonionic surfactant had no effect. 

Successful mixed condensations of esters are subject to the same general restrictions as outlined in the consideration of mixed aldol condensations. One carbonyl compound must act preferentially as the acceptor and the other as the nucleophile. To compete with self-condensation of aliphatic esters, the carbonyl acceptor must be relatively electrophilic. The systems that have been commonly employed are esters of aromatic acids, formate esters, and oxalate esters. In each instance, these esters contain groups that are electron-withdrawing relative to alkyl and do not possess enolizable hydrogens. They are therefore good electrophiles, but cannot function as the nucleophile. Some examples are shown in Section C of Scheme 2.6. 

This general scheme is valid for both aliphatic and aromatic polyimides. Since this is the route preferably used for aromatic, aliphatic and cycloaliphatic polyimides of technical importance, it has been the subject of numerous studies, and the main aspects of the meehanisms and kinetics are fairly well known [16]. It is a two-step reaction. In the first step the nucleophilic attack of the amine groups to the carbonyl groups of the dianhydride gives rise to the opening of the rings yielding an intermediate poly(amic acid) (Scheme 2). 

The formation of carbon-carbon bonds in aromatic systems often takes place by an electrophilic attack on the ring by a carbonium ion or a species with carbonium ion character. The large family of reactions related to Friedel-Crafts reaction are of this type. In aliphatic chemistry carbon electrophiles are more likely to be encountered as carbonyl groups or as such compounds as halides and tosylates, which are subject to nucleophilic displacement. Many examples of these types of reactions have been discussed, particularly in Chapters 1, 2, and 6. There are also some valuable synthetic procedures in which carbon-carbon bond formation results from electrophilic attack by a carbonium ion on an alkene. It is this group of reactions that we will now consider. 

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