Intermolecular addition reactions ammonia

Computational studies of the intermolecular addition of ammonia to ethylene have shown that the reaction is enthalpicaUy favored. The intermolecular reactions are entropi-cally disfavored. The thermodynamics for additions of arylamines to vinylarenes have been measured recently in solution. These studies are summarized in Equation 16.56, and have shown that additions to vinylarenes occur with free energies near zero. Additions of arylamines to vinylarenes are favored thermodynamically, but additions to -substituted vinylarenes are unfavorable, and high concentrations are needed to obtain the addition products in acceptable )deld. 

Addition of ammonia and amines to alkenes (hydroamination) is thermodynamically feasible, but kinetically hindered, hence it requires activation of either of the reactants1,2,51. The intramolecular reaction is generally more easily accomplished than the intermolecular reaction and allows the stereochemistry to be controlled to a certain degree. 

In addition to these findings, the most remarkable example of the improvement of the stability of a gold catalyst was reported by Bertrand and coworkers. In their studies of intermolecular hydroamination reactions of allenes and alkynes, which were either conducted with ammonia or hydrazine, they showed that their gold catalysts based on abnormal NHC ligands have amazing thermal stability [38]. Due to the fact that the amines used are capable of coordinating to the open side of the catalytic species and therefore can block the catalyst, these reactions require high reaction temperatures. Therefore, the reactions are carried out at temperatures of 160-200 °C (see Scheme 9.19) [38]. 

The scope aromatic C-N bond formation extends beyond simple amine substrates. For example, selected imines, sulfoximines, hydrazines, lactams, azoles, and carbamates give useful products from intermolecular aromatic C-N bond formation. Intramolecular formation of aryl amides has been reported. In addition, allylamine undergoes arylation, providing a readily cleaved amine alternative to the ammonia surrogates benzylamine, t-butylcarbamate, or benzophenone imine. Although it is an amine substrate, the reaction of this reagent is included here because of its special purpose. 

An intermolecular version of the arylation of carbamates has been recently published by Hartwig et al. (Eq. (21)) [132]. His group showed that reactions catalyzed by a combination of Pd(OAc)2 and P( -Bu)3 formed /V-aryl carbamates from aryl bromides or chlorides and f-butylcarbamate as substrate. Again, the reaction conditions were not as mild as those for amination, but were similar to those of the intramolecular reactions. For the intermolecular reactions, the use of sodium phenox-ide as base was crucial. Reactions using Cs2C03 showed low conversions. Those involving NaO-r-Bu as base rapidly formed a gel, presumably from the deproto-nated carbamate, and also showed little or no conversion. The products of these reactions serve as conveniently protected anilines, and r-butylcarbamate can be considered one type of ammonia surrogate. In addition, the products of these reactions are suitable for subsequent directed metalation procedures [100]. 

The amount of oxidant used should be in 20% excess over theory, and the pH of the reaction solution should be kept constant at 6.8-7.0 by controlled addition of 10% aqueous ammonia. Addition times vary between 6 and 24 h, with purer products noted upon slower addition. For the formation of intermolecular homodimers, the peptide thiol solution must be more concentrated (> 1 mg/ml = 1 mM)), and addition is carried out inversely, i.e. oxidizing solution added to peptide solution. 

The enzyme-mediated transformation of a hydroxylamino arene into an ortho-2Vcm-nophenol corresponds to a chemical rearrangement known as the Bamberger reaction (25), which generates the 4-aminophenol from hydroxylaminobenzene under acidic conditions. It is likely that this intermolecular rearrangement proceeds via an arylnitrene, which by the additional function of a hydroxylamino lyase can generate protocatechuate plus ammonia rather than 4-amino-3-hydroxybenzoate from 4-hydroxylaminobenzoate. 

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