Leaving groups amines

O R Substitution of lactam N-atom Basicity of leaving group amine, electron-with-drawing substituents in amino moiety Increases with basicity Monobactams are ca. 100 times less reactive than penicillins with leaving groups of similar basicity [76] [90]... 

Allyl bromides are excellent electrophiles, since bromine Is electronegative and bromide Is a good leaving group. Amines are weak bases and good nucleophiles. Sodamide Is an excellent base. 

Alkyl iodides are electrophiles, since iodine is electronegative and iodide is a good leaving group. Amines are good nucleophiles, since the nitrogen possesses a lone pair. Sodium ethoxide is an excellent base. 

Fig. 7 Bronsted plot of the second-order rate constants for the hydroxide-ion catalysed hydrolysis of acyclic amides (- -), monocyclic P-lactams (O), and bicyclic P-lactams (A) against for the leaving group amine. Data refer to 30°C and are taken from Proctor et ai, 1982...

A consequence of the different dependence upon leaving group basicity is that the rate enhancement of p-lactams compared with acyclic amides depends upon the basicity of the leaving group amine. P-Lactams of weakly basic amines are ca 500-fold more reactive than an acyclic amide of the same... 

The mechanism of the alkaline hydrolysis was reviewed in the previous section and it has already been mentioned that decreasing the basicity of the leaving group amine increases the rate of alkaline hydrolysis of penicillins. The Bronsted p,g of —0.55 (Proctor et al., 1982) is indicative of rate-limiting formation of a tetrahedral intermediate [32]. 

Allylic acetoxy groups can be substituted by amines in the presence of Pd(0) catalysts. At substituted cyclohexene derivatives the diastereoselectivity depends largely on the structure of the palladium catalyst. Polymer-bound palladium often leads to amination at the same face as the aoetoxy leaving group with regioselective attack at the sterically less hindered site of the intermediate ri -allyl complex (B.M. Trost, 1978). 

Allylic amine is a less reactive leaving group[7], but the allylic ammonium salts 214 (quaternary ammonium salts) can be used for allylalion(l30,131]. Allylic sulfonium salts are also used for the allylation[130]. The allylic nitrile in the cyclic aminonitrile 215 can be displaced probably via x-allylic complex formation. The possibility of the formation of the dihydropyridinium salts 216 and subsequent conjugate addition are less likelyfl 32],... 

Imidazole can be A -allylated. The A -glycosylimidazole 299 is prepared by regiospecific amination at the anomeric center with retention of configuration. Phenoxy is a good leaving group in this reaction[181]. Heterocyclic amines such as the purine base 300 are easily allylatedfl 82]. 

The product of this series of steps is an alkyl diazonium ion, and the amine is said to have been diazotized Alkyl diazonium ions are not very stable decomposing rapidly under the conditions of their formation Molecular nitrogen is a leaving group par excel lence and the reaction products arise by solvolysis of the diazonium ion Usually a car bocation intermediate is involved... 

The perhydrolysis reaction could theoretically continue to give four moles of peracid per mole of TAED but stops at this stoichiometry because of the substantial increase in the conjugate acid pify of the leaving group going from an amide (p-R = 17) to an amine (pif = 35) (94,95). Nonanoyloxybenzene sulfonate (NOBS) [101482-85-3] is used in detergent products in the United States and Japan. The NOBS perhydrolysis reaction is shown in equation 20 (96). 

Methyl bromide slowly hydrolyzes in water, forming methanol and hydrobromic acid. The bromine atom of methyl bromide is an excellent leaving group in nucleophilic substitution reactions and is displaced by a variety of nucleophiles. Thus methyl bromide is useful in a variety of methylation reactions, such as the syntheses of ethers, sulfides, esters, and amines. Tertiary amines are methylated by methyl bromide to form quaternary ammonium bromides, some of which are active as microbicides. 

In the anthraquinone series, apart from the special case of the amination of leucoquinizarin, sulfonic acid and nitro are the preferred leaving groups. 1-Aminoanthraquinone is manufactured from anthraquinone-l-sulfonic acid or 1-nitroanthraquinone, and 2-amino anthraquinone (betamine) from anthraquinone-2-sulfonic acid. 

One of the best leaving groups is molecular nitrogen in alkyl diazonium ions. Diazonium ions are generated by nitrosation of primaiy amines. The diazonium ions generated from alkyl amines are veiy unstable and immediately decompose with loss of nitrogen. 

Aziridines can best be obtained by ring closure of amine derivatives which contain a tm 5-oriented leaving group at the -position, see (89). The variable conformational and steric influences in the steroid skeleton limit the generality of a particular synthetic method and necessitate a selection of reagents based on the position of fusion of the aziridine ring. 

In the second major method of peptide synthesis the carboxyl group is activated by converting it to an active ester, usually a p-nitrophenyl ester. Recall from Section 20.12 that esters react with ammonia and amines to give fflnides. p-Nitrophenyl esters are much more reactive than methyl and ethyl esters in these reactions because p-nitrophenoxide is a better (less basic) leaving group than methoxide and ethoxide. Simply allowing the active ester and a C-protected amino acid to stand in a suitable solvent is sufficient to bring about peptide bond formation by nucleophilic acyl substitution. 

NaOH, MeOH, rt, 80% yield. Cleavage occurs under such mild conditions because the N-O nitrogen in this case is a much better leaving group than the typical aliphatic amine. 

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