Proton donors ammonium chloride

There is nothing unusual about the acidic behavior of ammonium salts. In fact, any protonated amine can function as a proton donor. Because of this, many amine salts have been used as acids in synthetic reactions. If the chlorides are used, the amine salts are known as amine hydrochlorides. One of the earliest amine hydrochlorides studied with regard to its behavior as an acid is pyridine hydrochloride (pyridinium chloride), C5H5NH+C1. In the molten state, this compound undergoes many reactions of the type just shown. 

Many years ago, L. F. Audrieth studied numerous reactions of amine hydrochloride salts. These compounds contain a cation that is a protonated amine that can function as a proton donor. Consequently, the molten salts are acidic and they undergo many reactions in which they function as acids. This behavior is also characteristic of ammonium chloride as well as pyridine hydrochloride (or pyridinium... 

Direction a. Alkali metals transform saturated ketones into secondary alcohols. The reaction proceeds in the mixture of ethanol and liquid ammonia in the presence of ammonium chloride as a proton donor and follows Scheme 1.11 (Rautenstrauch et al. 1981). 

The solvent mixture (alcohol -l- liquid ammonia) is not a good medium for protonation. Ammonia has a pTfjj value of 34, and alcohols are characterized by pA" values of 16-19. Hence, a proton donor should be introduced from outside. Water is not effective as aprotonating agent its pA" value is 15.74 and close to that of alcohol. As for the ammonium cation, its pA value is 9.24. Therefore, ammonium chloride was proposed as a protonating additive. Besides, the addition of ammonium chloride assists buffer formation in the reaction solution. The authors used a small concentration of ammonium chloride because the metal can preferentially reduce the ketone, and not the ammonium ion (NH4+ e —> NH3 -I- V2H2). Despite low concentrations of ammonium chloride, the protonation... 

Notice the diversity in structure of lhe.se proton dunurs. They include the classical hydrochloric acid (reaction a). Ihc weakly acidic dihydrogen phosphate anion (reaction b). the ammonium cation as is found in ammonium chloride (reaction c), the carboxylic acetic acid (reaction d). Ihc cnolic form of phenobarbital (reaction e), Ihe carboxylic acid moiety of indomelhacin (reaction j), Ihc imidc of saccharin (reaction g). and the prolonaied amine of ephedrine (reaction h). Because all are proton donors, they mu.st be treated as acids when calculating the pH uf a solution or percent ionization of the drug. At the same lime, as nuted below, there are important differences in the pharmaceutical properties of ephedrine hydrochloride (an acid salt of an amine) and lho.se of indomelhacin. phenobarbital. or saccharin. 

Arylation reactions of aromatic ketimines were developed, and in many cases the products of the reaction were isolated after subsequent hydrolysis. Therefore, these arylations constitute an indirect method for the preparation of arylated aromatic ketones, the direct functionalizations of which are often more difficult. Thus, direct arylation of imine 42 with sodium tetraphenylborate catalyzed by [RhCl(cod)]2 afforded a mixture of mono- and diarylated benzophenone imines (44 and 45) (Scheme 9.16) [53]. The formation of the corresponding amine 46 clearly indicated that 42 also acted as a hydride acceptor in this transformation. Most likely, the reaction occurs via initial coordination by the benzophenone imine to a phenylrho-dium intermediate followed by orfho-rhodation to afford the five-membered rhoda-cyde intermediate 47 (Scheme 9.16). Subsequent reductive elimination generates the monophenylated product 44 and a rhodium hydride, which then reduces imine 42 in the presence of ammonium chloride as proton donor to regenerate the catalytically active speties. 

Alkali metals arc usually dissolved or suspended in liquid ammonia or low molecular weight aliphatic amines, hexamethylphosphoric triamide or alcohols. Often these reductions are carried out in the presence of a cosolvent, such as diethyl ether, tetrahydrofuran or 1,2-dimethoxyethane, in order to increase the solubility of the ketone in the reaction mixture. Ethanol (pKa 15.9), 2-propanol (pKa 16.5), 2-methyl-2-propanol (p a 18), water (pK 15.7) and ammonium chloride (pKa 9.2) arc the usual proton donors. Thus, ammonium chloride is the strongest acid that can be incorporated into liquid ammonia. Proton donors are present in the reaction medium from the beginning, added concurrently with the ketone, or are added during product isolation (" aprotic reduction ). 

Steroidal 4,6-dien-3-ones, such as 4, and related compounds (see Table 7) are reduced initially to the 3,5-dienolates 5. As expected, protonation occurs axially giving the thermodynamically more stable product61,62. Protonation of 5 with ammonium chloride leads to the formation of the 5-en-3-one 663. Addition of proton donors, such as an alcohol or water, leads primarily to the same product (6), but under these conditions the /Ly-unsaturated ketone undergoes isomerization to the more stable a,/i-unsaturated product 76 65. 

Conjugated addition of trialkylbutyltin hydride is promoted by the presence of water, the former acts as a hydride donor whereas water participates to the reaction as a protonating partner. In this context, the role of the proton carrying reagent is further demonstrated by the optimalization of the yield when ammonium chloride is added to the reaction medium as [75]. 

For this purpose the effect of the concentration of potassium chloride added to a borate buffer solution (total concentration of boric acid and potassium borate 0,10 mole/liter, pH 8,4) on polaro-gp ams for the Co (II) - cysteine system, with constant cobalt chloride (1,74 mmole/liter) and cysteine (0,08 mmole/liter) concentrations, was investigated. The borate buffer solution was used in place of the traditional ammoniacal buffer solution in order to avoid a number of complications and, primarily, decrease in the buffer capacity of the ammoniacal solution near the electrode when potassium chloride is added, since ammonium ions (being proton donors) also participate in the formation of the outer layer of the electric double layer. The pH value of the solution was selected so that the solution would contain approximately equal amounts of anions and cysteine zwitterions (pl am 8.33). 

Their common feature is that the transfer of charge characteristic of intermediate salt or complex formation between donor and acceptor molecules facilitates simultaneously the release of positive and negative groups from adjacent atoms. In ammonium hexachlorophosphate, for example, the formation of the salt reduces electrostatic interaction, making easier the removal of the hydrogen atoms as protons. A chloride ion would be easily detached from a hexachlorophosphate ion. 

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