Nucleophilic substitution process hydrogenation reaction

In Volume 13 reactions of aromatic compounds, excluding homolytic processes due to attack of atoms and radicals (treated in a later volume), are covered. The first chapter on electrophilic substitution (nitration, sulphonation, halogenation, hydrogen exchange, etc.) constitutes the bulk of the text, and in the other two chapters nucleophilic substitution and rearrangement reactions are considered. 

Aromatic nitro compounds undergo nucleophilic aromatic substitutions with various nucleophiles. In 1991 Terrier s book covered (1) SNAr reactions, mechanistic aspects (2) structure and reactivity of anionic o-complexes (3) synthetic aspects of intermolecular SNAr substitutions (4) intramolecular SNAr reactions (5) vicarious nucleophilic substitutions of hydrogen (VNS) (6) nucleophilic aromatic photo-substitutions and (7) radical nucleophilic aromatic substitutions. This chapter describes the recent development in synthetic application of SNAr and especially VNS. The environmentally friendly chemical processes are highly required in modem chemical industry. VNS reaction is an ideal process to introduce functional groups into aromatic rings because hydrogen can be substituted by nucleophiles without the need of metal catalysts. 

Nitrobenzene and many of its 2-, 3-, and 4-substituted derivatives are converted into nitroaniline derivatives by treatment with sulfenamides in the presence of t-BuOK (eq 90). In this conversion, termed vicarious nucleophilic substitution (VNS), the base presumably promotes both the formation of the nucleophilic sulfenamide anion and the -elimination of the thiocar-bamoyl group from the other examples of t-BuOK-promoted VNS reactions of nitrobenzenes have appeared in recent years. An interesting example of this process involves the synthesis of dithianylated nitrobenzenes which are hydrolyzable to aldehydes (eq 91). The treatment of mixtures of m-nitroaniUne and enoUzable ketones with t-BuOK in DMSO leads to nitroindoles by oxidative nucleophilic substitution of hydrogen (eq 92). The proposed mechanism for this transformation involves attack of the potassium enolate of the ketone on the ring, spontaneous oxidation of the a-adduct, and imine formation and tautomerization. 

Two examples of nucleophilic aromatic substitution for hydrogen reactions were described from which we have proposed two new atomically efficient processes for the manufacturing of commercially relevant aromatic amines. Our mechanistic studies have revealed that the direct oxidation of a-complex intermediates by either nitro groups or O2 can eliminate the need for chlorination of benzene as a starting point for the manufacturing of aromatic amines. Accordingly, these reactions demonstrate the key objective of alternate chemical design which is not to make the waste in the first place. 

The initially formed adducts can be converted into products of nucleophilic substitution of hydrogen in a variety of ways oxidation with external oxidants, conversion into nitrosoarenes according to intramolecular redox stoichiometry, vicarious substitution, cine- and fe/e-elimination, ANRORC, etc. These processes have been discussed in a concise way in our preceding reviews [4,6-10]. The major message of those reviews is that nucleophilic substitution of hydrogen, in its many variants, is the main, primary process, whereas the conventional nucleophilic substitution of halogens X, the SnAt process, is just a secondary ipso reaction [9, 10]. 

Another important type of the Sn processes is oxidative nucleophilic substitution of hydrogen (ONS). It suggests that aromatization of the intermediate o -adduct (Scheme 26) proceeds by action of an oxidative agent either an external one (e.g., KMnOa, CAN), or air oxygen, or one of components being present in the reaction mixture, for example, the starting nitro compoimd [5]. 

It has been reported that 3,6-diaryl-l,2,4-trizine-4-oxides undergo nucleophilic substitution of hydrogen with the a-halomethyl aryl sulfones by two alternative pathways, namely, by means of VNS or through intramolecular deoxygenative process. The first pathway has been found to be dominative one in the reaction of... 

It should be stressed that although outcome of these reactions is identical to that of classical Sj Ar of halogens, the substitution proceeds at the carbon atom of the ring connected with hydrogen thus, it is fully justified to consider cZwe-, tele-, and ANRORC substitutions as processes of nucleophilic substitution of hydrogen Sj H. 

The alkylation of aromatic nitro compounds by carbanions having a leaving group at the nueleophilic center is called Vicarious Nucleophilic Substitution of Hydrogen (VNS) (Seheme 36.1). This reaction is one of the scarce general processes that result in the formal nucleophilic aromatic substitution of hydrogen. 

Section 4 9 The potential energy diagrams for separate elementary steps can be merged into a diagram for the overall process The diagram for the reac tion of a secondary or tertiary alcohol with a hydrogen halide is charac terized by two intermediates and three transition states The reaction is classified as a ummolecular nucleophilic substitution, abbreviated as SnI... 

The reactions of alcohols with hydrogen halides to give alkyl halides (Chapter 4) are nucleophilic substitution reactions of alkyloxonium ions m which water is the leaving group Primary alcohols react by an 8 2 like displacement of water from the alkyloxonium ion by halide Sec ondary and tertiary alcohols give alkyloxonium ions which form carbo cations m an S l like process Rearrangements are possible with secondary alcohols and substitution takes place with predominant but not complete inversion of configuration... 

Two kinds of starting materials have been examined in nucleophilic substitution reactions to this point. In Chapter 4 we saw that alcohols can be converted to alkyl halides by reaction with hydrogen halides and pointed out that this process is a nucleophilic substitution taking place on the protonated fonm of the alcohol, with water serving as the... 

Oxidation of unfunctionalized alkanes is notoriously difficult to perform selectively, because breaking of a C-H bond is required. Although oxidation is thermodynamically favourable, there are limited kinetic pathways for reaction to occur. For most alkanes, the hydrogens are not labile, and, as the carbon atom cannot expand its valence electron shell beyond eight electrons, there is no mechanism for electrophilic or nucleophilic substitution short of using extreme (superacid or superbase) conditions. Alkane oxidations are therefore normally radical processes, and thus difficult to control in terms of selectivity. Nonetheless, some oxidations of alkanes have been performed under supercritical conditions, although it is probable that these actually proceed via radical mechanisms. 

According to eqn. (56) a nucleophilic substitution takes place, i.e. the component Y is attached to the a-carbon atom. Similarly in reaction (57) Ye attaches itself to the central atom of the X-group (such as the nitrogen atom in the nitro group). The last equation illustrates a typical oxidation process, producing an aldehyde or ketone with the removal of a hydrogen atom attached to the a-carbon atom. 

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