2,4-Dinitrofluorobenzene , reaction with amines

Fluorobenzene-type compounds have been used as functional groups in homobifunctional crosslinking agents (Chapter 4, Section 4). Their reaction with amines involves nucleophilic displacement of the fluorine atom with the amine derivative, creating a substituted aryl amine bond (Reaction 9). Detection reagents incorporating reactive aryl chemistry include 2,4-dinitrofluorobenzene and trinitrobenzenesulfonate (Eisen et al., 1953). These compounds form... 

PROBLEM 14.75 2,4-Dinitrofluorobenzene is a better electrophile for SNAr reactions than the corresponding chloride (see Fig. 14.95). 2,4-Dinitrofluorobenzene reacts with amines at room temperature to give orange-colored adducts. Show the mechanism of the reaction between 2,4-dinitrofluorobenzene and dimefhylamine. Predict the product. Why is the fluoride more reactive than the chloride Why is the product highly colored ... 

Amine 212 was also coupled with peptides [233], acetic anhydride [215, 234], dinitrobenzoyl chloride [235] or a ferrocene carboxylic add chloride [215, 236] in good yields. Reaction with dinitrochlorobenzene [237] or dinitrofluorobenzene... 

On the other hand, Nudehnan and Palleros104a reported a quadratic dependence of the observed second-order rate constant on the concentration of 2-methoxyaniline in its reaction with 2,4-dinitrofluorobenzene (DNF) in benzene. This behavior is similar to that previously reported in the reaction with 4-methoxyaniline in benzene104b. These kinetic results are interpreted in terms of reaction by the dimer of the amine which forms a cyclic intermediate with the substrate (Scheme 11). 

One of the most historically significant examples of aromatic nucleophilic substitution is the reaction of amines with 2,4-dinitrofluorobenzene. This reaction was used by Sanger " to develop a method for identification of the N-terminal amino acid in proteins, and the process opened the way for structural characterization of proteins and other biopolymers. 

Mechanistic features of SNAr displacement reactions involving amino nucleophiles have been the object of many investigations, a major point of interest being the occurrence of base-catalyzed paths. Strongly activated aryl halides react readily with ammonia and with primary and secondary amines to give the corresponding arylamines. Thus, for example, 2,4-dinitrofluorobenzene is used to tag the amino end of a peptide or protein chain. 

An HPLC technique has been developed [59] for volatile carcinogenic N-nitrosamines which shortens the chromatographic analysis time by a factor of five compared with GLC methods. The nitrosamines are converted into their amine reduction products which are then treated with 2,4-dinitrofluorobenzene (DNFB) in order to form the amines. The amines are then separated and detected at 340-360 nm. The reactions involved are shown in Fig.4.31. 

The steric bulk of the amine also influences the slow step. Thus no base catalysis is found in the reaction between 2,4-dinitrofluorobenzene (DNFB) and aniline However, with A-methylaniline general base... 

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