Salt synthesis neutralized amines

The ability to reduce compounds under acidic conditions is ideal for the reduction of enamines. Protonation of nitrogen gives an iminium salt in acidic media that is then reduced with cyanoborohydride to an amine.Imines can be reduced in acidic media in the presence of many other functional groups, as shown by Cook s reduction of imine 165 to give 166 in 79% yield in a synthesis of substituted tetrahydro-P-carbolines. 2 This reagent is excellent for the reduction of iminium salts at neutral pH as well,l 3 and it is also useful for the reductive alkylation of amines. Dimethylamino derivatives such as 168 can be prepared from the amine (167 in this case) by treatment with formaldehyde and cyanoborohydride, even in the presence... 

The chlorohydrin process (24) has been used for the preparation of acetyl-P-alkylcholine chloride (25). The preparation of salts may be carried out mote economically by the neutralization of choline produced by the chlorohydrin synthesis. A modification produces choline carbonate as an intermediate that is converted to the desired salt (26). The most practical production procedure is that in which 300 parts of a 20% solution of trimethyl amine is neutralized with 100 parts of concentrated hydrochloric acid, and the solution is treated for 3 h with 50 parts of ethylene oxide under pressure at 60°C (27). 

FIGURE 8.3 Synthesis of amides by aminolysis of unisolated activated esters obtained using carbodiimide by (A) ammonium hydroxide,12 (B) diaminomethane dihydrochloride neutralized with Et3N,15 and (C) the amine of crystalline salts of additives, R = H, Me, Et.13 DCC = dicyclohexylcarbodiimide HOBt = 1-hydroxybenzotriazole HONSu = A-hydroxysuccin-imide HONp = p-nitrophcnol HODhbt = 3-hydroxy-4-oxo-3,4-dihydrobenzotriazine. 

All reagents used for the synthesis of cations should be purified according to literature procedures before use [19]. Amines such as 1-alkylimidazoles or pyridines are typically distilled from sodium hydroxide or calcium hydride if dry amines are required and stored under dry nitrogen or argon at 0°C. Haloalkanes are washed with sulfuric acid until no further color is extracted into the acid layer and then neutralized with NaHCC>3 and deionized water prior to distillation from CaC j. All solvents used in the syntheses should be dried and distilled prior to use. In order to obtain colorless halide salts it is recommended to perform all reactions under a protective atmosphere of a dry inert gas in order to exclude moisture and oxygen from the reaction. 

A more favorable synthesis of salts of the iron, cobalt and nickel carbonyl anions, which were initially prepared by disproportionation reactions of Fe(CO)5, Co2(CO)8, and Ni(CO)4 with pyridine and other amines, was found by treatment of the neutral carbonyls with alkali in aqueous or alcoholic solutions. Careful studies by Hieber revealed that Fe(CO)5 as well as Fe3(CO)12 reacted with exactly four equivalents of hydroxide ions to give the corresponding dianionic iron carbonylates (Scheme 4.4). These dianions are relatively strong bases and readily accept a proton from a water molecule to give the monoanionic hydrido carbonylates [I IFe(CO)4] and [HFe3(CO)n], respectively [36]. The related carbonylates of cobalt and manganese, [Co(CO)4] and [Mn(CO)5], were obtained by a similar way as [Fe(CO)4]2 [25]. With regard to the mechanism of Hieber s Basenreaktion , the most plausible explanation is based on an initial nucleophilic attack by the hydroxide ion at the carbon atom of a CO... 

Ketone synthesis. Lithium carboxylates react with (CaHjliPCI, to form an acyloxy-phosphonium salt (a), which reacts with Grignard reagents to provide ketones in generally high yield. If a free carboxylic acid is used, a tertiary amine is required to neutralize the... 

In the section on Sodium acetate we cite 10 procedures utilizing this reagent in ways other than for mere neutralization of a mineral acid amine salt most of them are taken from Organic Syntheses. In contrast, this publication records only two procedures utilizing KOAc. One, by Bedoukian, is for enolacetylation of an aldehyde, as part of a synthesis of an a-bromoaldehyde. Unfortunately no com-... 

The most common ionic liquids include alkylammonium, alkylphosphonium, A/-alkylpyridinium, and A/A/ -dialkylimidazolium cations. Two general methods for their preparation are acid-base neutralization reactions and metathesis of halide salts with a metal or ammonium salts. Alkylammonium, pyridinium, and imidazo-lium halides can be prepared by the reaction of the appropriate alkyl halide and amine. Preparation of l-ethyl-3-methylimidazolium chloride [emimjCl requires a sealed tube since it has a low boiling point. On the other hand, synthesis of [bmim] Cl can be achieved under conventional reflux conditions [33, 34]. 

Control of the pH is also of importance for the Mannich-based bispidine synthesis. Formation of an aldol product competes with the Mannich condensation in the basic pH region. It is for this reason that, in some cases, the reaction is sensitive to the order in which the reactants are added to the reaction mixture. It is possible to add the aldehyde and amine components one after another to a solution of the CH-acidic compound, but sometimes the aldol reaction can be disfavored by changing the order. This allows the imminium ion to be formed in advance. The precursors of 45 and 46 have been prepared by this method. In some cases, it has been useful to use a protonated amine component as the acetate salt (e.g., 49 or precursors for 44, 47, and 48), as the chloride salt (e.g., 11) or to carry out the reaction in acetic acid. Aromatic amines (e.g., aniline) give rise to para-substituted aromatic amines if the solution is not approximately neutral. In a very elegant procedure, a condensate of formaldehyde and aniline, which is the trimeric methyleneaniline, was prepared separately, and treated in the Mannich reaction with dimethyl acetonedicarboxylate and formaldehyde to yield the 3,7-diphenylbispidone... 

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