Deprotonation-aromatization

Making organometallicsby deprotonating aromatic rings ortholithiation... 

Hindered phenolates have low nucleophilicity and in aprotic solvent may act usefully as EGBs. 2,6-Di-t-butyl-/ -cresol = 16.8) was reduced directly with concomitant hydrogen evolution to give, ex situ, the corresponding tetraethylammonium phenolate [59,60], which was clearly capable of deprotonating aromatic ketones and in the presence of aromatic aldehydes promoted aldol reaction to a, /3-unsaturated ketones which underwent Michael addition. The initial proton transfer from the aromatic ketone ] K = 24.7) is thermodynamically very unfavorable. Even so, aldol reaction took place within a matter of hours upon addition of an aromatic ketone together with an aromatic aldehyde leading to or, /3-unsaturated ketones which subsequently underwent Michael addition with a sec-... 

Making organometallics by deprotonating aromatic rings orthoiithiation... 

MeOCH=N Me2, which combines with the deprotonated aromatic. Both tris(piperidin-l-yl)methane and bis(dimethylamino)-r-butoxymethane are said to function even better than the commercially available DMFDMA. A variety of benzene substituents are tolerated and the approach has been utilised for syntheses of, amongst others, 4- and 7-indole-carboxylic esters. 

Another example of this type of study involved the H/D exchange reactions of deprotonated aromatic dicarboxylic acids [5]. In this case, the intent was to determine the difference in observed H/D exchange behavior as the relative position of the two carboxylic acid groups varied. Figure 2.5 sununarizes the H/D exchange behavior and illustrates that the spatial relationship of the deprotonated sites has a tremendous impact on the extent of the H/D exchange. 

SCHEME 26.21 Stmctures of a laterally deprotonated aromatic teitiary amide. 

As is broadly true for aromatic compounds, the a- or benzylic position of alkyl substituents exhibits special reactivity. This includes susceptibility to radical reactions, because of the. stabilization provided the radical intermediates. In indole derivatives, the reactivity of a-substituents towards nucleophilic substitution is greatly enhanced by participation of the indole nitrogen. This effect is strongest at C3, but is also present at C2 and to some extent in the carbocyclic ring. The effect is enhanced by N-deprotonation. 

Aromatization of indolines is important in completing synthetic sequences in which the directive effects of the indoline ring have been used to achieve selective carbocyclic substitution[l]. Several methods for aromatization have been developed and some of these are illustrated in Table 15.2. A range of reagents is represented. One type of procedure represents use of oxidants which are known to convert amines to imines. Aromatization then provides the indole. Such reagents must not subsequently oxidize the indole. Mereuric acetate (Entry 1) is known to oxidize other types of amines and presumably reacts by an oxidative deprotonation ot- to the complexed nitrogen. 

Like mthenium, amines coordinated to osmium in higher oxidation states such as Os(IV) ate readily deprotonated, as in [Os(en) (NHCH2CH2NH2)] [111614-75-6], This complex is subject to oxidative dehydrogenation to form an imine complex (105). An unusual Os(IV) hydride, [OsH2(en)2] [57345-94-5] has been isolated and characterized. The complexes of aromatic heterocycHc amines such as pyridine, bipytidine, phenanthroline, and terpyridine ate similar to those of mthenium. Examples include [Os(bipy )3 [23648-06-8], [Os(bipy)2acac] [47691-08-7],... 

Dioxins aromaticity, 3, 945 deprotonation, 3, 972 electronic energy levels, 3, 946 electrophilic reactions, 3, 965 half-wave potential, 3, 968... 

NMR and, 3, 951 aromaticity, 3, 945 delocalization energy, 3, 959 deprotonation, 3, 972 disulfones reactions, 3, 970 double bond character, 3, 945 electronic energy levels, 3, 946 electrophilic reactions, 3, 965 electrophilic substitution, 3, 960 half-wave potential, 3, 968 NMR, 3, 952 H NMR, 3, 951 nucleophilic reactions, 3, 969 oxidation, 3, 967 oxides... 

The Hiickel rule predicts aromaticity for the six-7c-electron cation derived from cycloheptatriene by hydride abstraction and antiaromaticity for the planar eight-rc-electron anion that would be formed by deprotonation. The cation is indeed very stable, with a P Cr+ of -1-4.7. ° Salts containing the cation can be isolated as a product of a variety of preparative procedures. On the other hand, the pK of cycloheptatriene has been estimated at 36. ° This value is similar to those of normal 1,4-dienes and does not indicate strong destabilization. Thus, the seven-membered eight-rc-electron anion is probably nonplanar. This would be similar to the situation in the nonplanar eight-rc-electron hydrocarbon, cyclooctatetraene. 

This type of addition process is particularly likely to be observed when the electrophile attacks a position that is already substituted, since facile rearomatization by deprotonation is then blocked. Reaction at a substituted position is called ipso attack. Addition products have also been isolated, however, when initial electrophilic attack has occurred at an unsubstituted position. The extent of addition in competition with substitution tends to increase on going to naphthalene and the larger polycyclic aromatic ring systems. ... 

Bromination has been shown not to exhibit a primary kinetic isotope effect in the case of benzene, bromobenzene, toluene, or methoxybenzene. There are several examples of substrates which do show significant isotope effects, including substituted anisoles, JV,iV-dimethylanilines, and 1,3,5-trialkylbenzenes. The observation of isotope effects in highly substituted systems seems to be the result of steric factors that can operate in two ways. There may be resistance to the bromine taking up a position coplanar with adjacent substituents in the aromatization step. This would favor return of the ff-complex to reactants. In addition, the steric bulk of several substituents may hinder solvent or other base from assisting in the proton removal. Either factor would allow deprotonation to become rate-controlling. 

All these kinetic results can be accommodated by a general mechanism that incorporates the following fundamental components (1) complexation of the alkylating agent and the Lewis acid (2) electrophilic attack on the aromatic substrate to form the a-complex and (3) deprotonation. In many systems, there m be an ionization of the complex to yield a discrete carbocation. This step accounts for the fact that rearrangement of the alkyl group is frequently observed during Friedel-Crafts alkylation. 

Many aromatic steroids submitted to the Birch reduction contain hydroxyl groups which are deprotonated to the corresponding alkoxides during the reduction, particularly if a tertiary alcohol is used as the proton donoi. The steroidal alkoxides and the one derived from the proton donor often precipitate and cause foaming of the reaction mixture, as was noted by Wilds and Nelson. These alkoxides can be kept in solution by adding an excess of the proton donor alcohol to the mixture the alcohol also assists in dissolving the starting hydroxylic steroid. A particularly useful reaction medium for hydroxylic steroids contains ammonia, tetrahydrofuran and -butyl alcohol in the volume ratio of 2 1 (Procedure 2, section V). This mixture... 

The mechanism of the indolization of aniline 5 with methylthio-2-propanone 6 is illustrated below. Aniline 5 reacts with f-BuOCl to provide A-chloroaniline 9. This chloroaniline 9 reacts with sulfide 6 to yield azasulfonium salt 10. Deprotonation of the carbon atom adjacent to the sulfur provides the ylide 11. Intramolecular attack of the nucleophilic portion of the ylide 11 in a Sommelet-Hauser type rearrangement produces 12. Proton transfer and re-aromatization leads to 13 after which intramolecular addition of the amine to the carbonyl function generates the carbinolamine 14. Dehydration of 14 by prototropic rearrangement eventually furnishes the indole 8. 

Good yields are usually obtained with aromatic aldehydes or ketones. Aliphatic aldehydes are poor substrates for the ordinary procedure, but react much better if the halo ester is first deprotonated with lithium diisopropylamide (LDA) in tetrahydrofuran at -78 °C, prior to addition of the aldehyde. 

In alkaline solution, the phenol 1 is deprotonated to the phenolate 4, which reacts at the ort/zo-position with dichlorocarbene 3. The initial addition reaction product 5 isomerizes to the aromatic o-dichloromethyl phenolate 6, which under the reaction conditions is hydrolyzed to the o-formyl phenolate." ... 

The process for initiating radical formation in aromatic amine-vinyl monomer systems have been studied by Feng et al. [80-86] who proposed the formation of an aminium radical as the active state of an exciplex as intimate ion-pair and then a cyclic transition state which then would undergo a proton transfer process of deprotonation leading to the formation of active radical species for initiation as follows ... 

The well-known photopolymerization of acrylic monomers usually involves a charge transfer system with carbonyl compound as an acceptor and aliphatic tertiary amine, triethylamine (TEA), as a donor. Instead of tertiary amine such as TEA or DMT, Li et al. [89] investigated the photopolymerization of AN in the presence of benzophenone (BP) and aniline (A) or N-methylaniline (NMA) and found that the BP-A or BP-NMA system will give a higher rate of polymerization than that of the well-known system BP-TEA. Still, we know that secondary aromatic amine would be deprotonated of the H-atom mostly on the N-atom so we proposed the mechanism as follows ... 

The end group of the polymers, photoinitiated with aromatic amine with or without the presence of carbonyl compound BP, has been detected with absorption spectrophotometry and fluororescence spectrophotometry [90]. The spectra showed the presence of tertiary amino end group in the polymers initiated with secondary amine such as NMA and the presence of secondary amino end group in the polymers initiated with primary amine such as aniline. These results show that the amino radicals, formed through the deprotonation of the aminium radical in the active state of the exciplex from the primary or secondary aromatic amine molecule, are responsible for the initiation of the polymerization. 

Some thermal rearrangement reactions of 1-benzoxepins show the participation of the solvent in the formation of stable products, e.g. 6172,247 and 7.177 The synthesis of methoxy-substituted 1-benzoxepins by O-methylation of the anions generated by the deprotonation of the respective oxo derivative with ferf-butoxide is often limited by the rapid aromatization to methoxy-substituted naphthalenes, e.g. 816 and 9,173 under the reaction conditions.16,173... 

However, on deprotonation even by weak bases the linearly conjugated system is transformed by tautomerization into the cyclically conjugated aromatic [22]pentaphyrin(1.1.1.0.0). 

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