Ammonia, as nucleophile

Inter- and Intramolecular Reactions with Aliphatic Amines and Ammonia as Nucleophiles... 

Scheme 9.19 Asymmetric allylic amination with ammonia as nucleophile.

In the described transformation the created acid chloride is attacked by aqueous ammonia as nucleophile to create the amide 5 in excellent yield. 

We have already mentioned that Dorfman and collaborators have developed a versatile technique to observe ort-lived carbenium ions in solution generated by dissociative pulse radiolysis. This novel approach to the characterisation of transient species has also allowed this schod to measure the rate constants of many electrophilic reactions between carbenium ions (the benzylium ion in particular) and various nucleophiles. In the first paper of the series Jones and Dorfman reported the rate constants of the benzylium ion reaction with methanol, ethanol, the bromide and the iodide ions in ethylene chloride at 24 C. Values of about 5 x 10 sec were obtained for the halide ions and of around 10 sec for the alcohols. Later studies confirmed that the reaction of halide ions vrith benzylium, diphenyl-methylium and triphenylmethylium ions is at the limit of diffusion control. Reaction rate constants of these three carbenium ions with amines and alcdiols were also reported in the same paper. More recently, these studies have been extended to include cyclopropylphenylmetiiylium ion as electrophile, ammonia as nucleophile and methylene chloride and trichloroethane as solvents These results are extremely... 

The formation of the above anions ("enolate type) depend on equilibria between the carbon compounds, the base, and the solvent. To ensure a substantial concentration of the anionic synthons in solution the pA" of both the conjugated acid of the base and of the solvent must be higher than the pAT -value of the carbon compound. Alkali hydroxides in water (p/T, 16), alkoxides in the corresponding alcohols (pAT, 20), sodium amide in liquid ammonia (pATj 35), dimsyl sodium in dimethyl sulfoxide (pAT, = 35), sodium hydride, lithium amides, or lithium alkyls in ether or hydrocarbon solvents (pAT, > 40) are common combinations used in synthesis. Sometimes the bases (e.g. methoxides, amides, lithium alkyls) react as nucleophiles, in other words they do not abstract a proton, but their anion undergoes addition and substitution reactions with the carbon compound. If such is the case, sterically hindered bases are employed. A few examples are given below (H.O. House, 1972 I. Kuwajima, 1976). 

A standard method for the preparation of an a ammo acid uses a bromo carboxylic acids as the substrate and aqueous ammonia as the nucleophile... 

Azide is widely useful as a surrogate for ammonia in nucleophilic substitution reactions, due to its high nucleophilicity, low basicity, and stability towards a variety of conditions for subsequent transformations. In particular, the azidolysis of... 

Addition of ammonia as a model nucleophile to nitrile oxides was studied by a semiempirical MNDO method, for fulminic acid and acetonitrile oxide (121). The reaction is exothermic and proceeds in two steps. The first (and rate-determining) step is the formation of a zwitterionic structure as intermediate. The second step, which involves transfer of a proton, is very fast and leads to the formation of Z-amidoximes in accordance with experimental data. Similar results were... 

Opening of the six-membered oxazine moiety of some [l,2,3]triazolo[5,l-c][l,4]oxazines was studied by Hoornaert et al. < 1994TL9767, 1996T8813>, and the result is shown in Scheme 9. Ring opening of 75 took place in alcohol or refluxing aqueous acetonitrile for 15 min to yield the [l,2,3]triazole derivative 76 in most cases in high yield. As nucleophiles, aliphatic alcohols, ammonia, or water were used. 

A diverse group of secondary and tertiary amines are readily synthesized from the reaction of primary and secondary amines with allylic carbonates in the presence of preformed iridium metalacycles, but the direct synthesis of primary amines via iridium-catalyzed allylic amination requires the use of ammonia as a nucleophile. The asymmetric allylation of ammonia had not been reported until very recently, and it is not a common reagent in other metal-catalyzed reactions. Nonetheless, Hartwig and coworkers developed the reactions of ammonia with allylic carbonates in the presence of la generated in situ [89]. Reactions conducted in the initial work led exclusively to the products from diallylation (Scheme 16). Further advances in... 

Catalyst activation became a necessity when reactions with bulky aliphatic amines and arylamines (cf Section 9.4.2) as nucleophiles were probed. It was also required for intramolecular aminations [8,18]. Thus, with Ph2CHNH2, an ammonia equivalent, conversion was only 11% upon application of procedure (a) (Table 9.2, entry 11), while the reaction promoted by the activated catalyst proceeded with high selectivity and yield. Catalyst activation is faster with ligand L2 than LI, and accordingly in situ activation occurs more readily for the former (cf entries 10 and 12). Examples presented in entries 16-20 further demonstrate the advantages of catalyst activation [53] (note that excellent results can be achieved with the simpH-fied ligand L5a). 

You have read (Unit 10, Class Xll) that the carbon - halogen bond In alkyl or benzyl haUdes can be easily cleaved by a nucleophile. Hence, an allqrl or ben l haUde on reaction with an ethanollc solution of ammonia undergoes nucleophilic substitution reaction m which the halogen atom Is replaced by an amino (-NHJ group. This process of cleavage of the C-X bond by ammonia molecule Is known as ammonolysis. The reaction Is carried out In a sealed tube at 373 K. The primary amine thus obtained behaves as a nucleophile and can further react with allqrl halide to form secondary and tertiary amines, and finally quaternary ammonium salt. 

These optimistic views received a first blow by the discovery of another category of nucleophilic aromatic photosubstitutions occurring in liquid ammonia as a solvent and nucleophile. In this medium the nitroanisoles still show the pattern that had become familiar, i.e., photosubstitution of OCH3 by NH2 with preference for reaction at the position meta with respect to the nitro-group. However, nitrobenzene, dinitrobenzenes, and nitrohalogenobenzenes... 

The amide derived from the carboxylic acid in Ugi adducts is in most cases tertiary, and therefore it cannot serve as nucleophilic partner in post-condensation transformations, unless a post-Ugi rearrangement converts it into a free amine [52, 54]. An exception is represented by Ugi adducts derived from ammonia, which give rise to two secondary amides, each of them potentially involved, as nucleophile, in nucleophilic substitution processes. Four competitive pathways are in principle possible (N- or 0-alkylations of the two amides), and the reaction is mainly driven by the stability of the formed rings. In the example shown in Fig. 12, 0-alkylation of the carboxylic-derived amide is favoured as it generates a 5-membered ring (oxazoline 62), while the alternative cyclization modes would have formed 3- or 4-membered rings [49]. When R C02H is phthalic acid, however, acylaziridines are formed instead via Walkylation [49]. In both cases, the intramolecular 8 2 reactions takes place directly under the Ugi conditions. 

Bis(organosilyl) peroxides are prepared by nucleophilic substitution reactions of hydrogen peroxide with chlorosilanes in the presence of base . Thus, bis(triorganosilyl) peroxide has been prepared from the reaction of 98% hydrogen peroxide and chlorosilane with ammonia as an HCl acceptor (equation 3). Bis(triphenylsilyl) peroxide 2 can also be prepared by the reaction of hydrogen peroxide and triphenyl silylamine (equation 4). 

Ammonia and amines can function as nucleophiles in SN2 displacement reactions of alkyl halides (Section 8-7E). Such processes provide syntheses of alkanamines only with those halides that are reactive in SN2 but not E2 reactions. For example,... 

A. C. Cope, H. L. Holmes, and H. O. House, Org. Reactions, 9, 107 (1957) House, p. 510. c Commonly catalyzed by ammonia or an amine, the Knovenagel reaction. Amine may in some cases act as proton acceptor, in other cases as nucleophilic catalyst. Dehydration usually occurs and shifts equilibrium in favor of product. 

For attack of F on acrylic acid, first a hydrogen bonded complex is formed which then proceeds to the transition state and then to a stable carbanion. The methyl in the methacrylic acid reduces stabilization of the carbanion as predicted. Subsequent studies using ammonia as the nucleophile indicated that attack proceeded by a rate-determining intramolecular proton transfer from the nucleophile to the ligand, assisted by a discrete water molecule that acts as a catalyst17. They predicted that acrolein underwent 1,4-addition, acrylic acid either 1,2- or 1,4-addition and acrylonitrile 1,2-addition. 

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