Ammonium formation

Aldehydes and ketones may be converted into the corresponding primary amines by reduction of their oximes or hydrazones (p. 93). A method of more limited application, known as the Leuckart Reaction, consists of heating the carbonyl compound with ammonium formate, whereby the formyLamino derivative is formed, and can be readily hydrolysed by acids to the amine. Thus acetophenone gives the i-phenylethylformamide, which without isolation can be hydrolysed to i-phenylethylamine. 

Required Acetophenone, 30 g. ammonium formate, 50 g. benzene, 30 ml. hydrochloric acid, 30 ml. ether, 100 ml., sodium hydroxide. 

Formamide. Commercial formamide may contain excess of formic acid. It is purified by passing ammonia gas into the mixture until a slight alkaline reaction is obtained. The ammonium formate thus formed is precipitated by the addition of acetone the filtrate, after drying over anhydrous magnesium sulphate, is distilled under reduced pressure. Pure formamide has b.p. IO571I mm. 

The conversion of an aldehyde or ketone into the corresponding amine by heating with ammonium formate or with formamide and formic acid at about... 

The Leuckart reaction was originally conceived using a chemical called ammonium formate (HCOONH4) which is very similar to formamide (HCONH2) [30]. It is pretty much believed that this molecule donates its ammonium part to the P2P and then the formate part turns into formic acid (HCOOH) which then acts to reduce the intermediate into its stable formyl derivative (don t ask). 

Formate is an excellent hydride source for the hydrogenolysis of aryl halides[682]. Ammonium or triethylammonium formate[683] and sodium formate are mostly used[684,685]. Dechlorination of the chloroarene 806 is carried out with ammonium formate using Pd charcoal as a catalyst[686]. By the treatment of 2,4,6-trichloroamline with formate, the chlorine atom at the /iiara-position is preferentially removed[687]. The dehalogenation of 2,4-diha-loestrogene is achieved with formic acid, KI, and ascorbic acid[688]. 

The optically active 1,4-cyclohexenediol monoacetate 525, prepared by hydrolysis of the me.so-diacetate with lipase, was converted into the optically pure cyclohexenone 526 by an elimination reaction in the presence of ammonium formate. Optically active carvone (527) was prepared from 526[343],... 

Formic acid is a good reducing agent in the presence of Pd on carbon as a catalyst. Aromatic nitro compounds are reduced to aniline with formic acid[100]. Selective reduction of one nitro group in 2,4-dinitrotoluene (112) with triethylammonium formate is possible[101]. o-Nitroacetophenone (113) is first reduced to o-aminoacetophenone, then to o-ethylaniline when an excess of formate is used[102]. Ammonium and potassium formate are also used for the reduction of aliphatic and aromatic nitro compounds. Pd on carbon is a good catalyst[103,104]. NaBH4 is also used for the Pd-catalyzed reduction of nitro compounds 105]. However, the ,/)-unsaturated nitroalkene 114 is partially reduced to the oxime 115 with ammonium formate[106]... 

The alkyl azide 118 is reduced to a primary amine by the Pd on carbon-catalyzed reaction of ammonium formate in MeOH at room temperature. No racemization takes place with chiral azides[l 11,112]. 

Debenzylation of benzylamines and benzyl ethers is carried out with ammonium formate[l 13,l 14]. Hydrosilanes are also used for debenzylation[l I5. ... 

The o,p-dinitrostyrene (1 mmol) and ammonium formate (10 mmol) W ere dissolved in methanol and 10% Pd/ C (5% by wt) was added. The mixture was refluxed under nitrogen for 1 h. Formic acid (0.44 ml) w as added and reflux was continued for 0.5-1 h until the completion of the reaction (tic). The solution was filtered through Celite, evaporated in vacuo and eluted through silica gel with CH2CI2. 

The quahty of formamide suppHed by BASE is certified as having a minimum assay of 99.5%. The principal impurities in the material are ammonium formate, methanol, water, and traces of iron. The quaUty of formamide supphed by BASE is certified to meet the specifications given in Table 3. 

Methanol can be converted to a dye after oxidation to formaldehyde and subsequent reaction with chromatropic acid [148-25-4]. The dye formed can be deterruined photometrically. However, gc methods are more convenient. Ammonium formate [540-69-2] is converted thermally to formic acid and ammonia. The latter is trapped by formaldehyde, which makes it possible to titrate the residual acid by conventional methods. The water content can be determined by standard Kad Eischer titration. In order to determine iron, it has to be reduced to the iron(II) form and converted to its bipyridyl complex. This compound is red and can be determined photometrically. Contamination with iron and impurities with polymeric hydrocyanic acid are mainly responsible for the color number of the merchandized formamide (<20 APHA). Hydrocyanic acid is detected by converting it to a blue dye that is analyzed and deterruined photometrically. 

Preparation of Amines. Amines are prepared by heating aUphatic, aromatic, or cycHc ketones with ammonium formate, formamide, or an A/-substituted ammonium formate at 165—190°C (Leuckart reaction). For example, cx-methylbenzylamine is prepared by the reaction of acetophenone with ammonium formate. 

Oxazole synthesis from benzoin and nitriles or ammonium formate. 

Acids that are solids can be purified in this way, except that distillation is replaced by repeated crystallisation (preferable from at least two different solvents such as water, alcohol or aqueous alcohol, toluene, toluene/petroleum ether or acetic acid.) Water-insoluble acids can be partially purified by dissolution in N sodium hydroxide solution and precipitation with dilute mineral acid. If the acid is required to be free from sodium ions, then it is better to dissolve the acid in hot N ammonia, heat to ca 80°, adding slightly more than an equal volume of N formic acid and allowing to cool slowly for crystallisation. Any ammonia, formic acid or ammonium formate that adhere to the acid are removed when the acid is dried in a vacuum — they are volatile. The separation and purification of naturally occurring fatty acids, based on distillation, salt solubility and low temperature crystallisation, are described by K.S.Markley (Ed.), Fatty Acids, 2nd Edn, part 3, Chap. 20, Interscience, New York, 1964. 

Ammonium formate [540-69-2] M 63.1, m 116 , 117.3 , d 1.280. Heat solid in NH3 vapour and dry in vacuum till NH3 odour is faint. Recryst from abs EtOH and then keep in a desiccator over 99% H2SO4 in vacuo. It is very hygroscopic. Exists in two forms, stable needles and less stable plates. Also forms acid salts, i.e. HCO2NH4.3HCO2H and HCO2NH4.HCO2H. [J Am Chem Soc 43 1473 1921 63 3124 1941. ]... 

I. Ammonium formate may be made in quantity by treating solid ammonium carbonate with a slight excess of commercial... 

Pd-C using transfer hydrogenation. A number of methods have been developed in which hydrogen is generated in situ. These include the use of cyclohexene (1-8 h, 80-90% yield)," cyclohexadiene (25°, 2 h, good yields)," HC02H, ammonium formate (MeOH, reflux, 91% yield), ... 

Pd/C, cyclohexene, I M HCl, EtOH, 83% yield. Ammonium formate can also be used as a source of hydrogen. ... 

Other PK variations include microwave conditions, solid-phase synthesis, and the fixation of atmospheric nitrogen as the nitrogen source (27—>28). Hexamethyldisilazane (HMDS) is also an excellent ammonia equivalent in the PK synthesis. For example, 2,5-hexanedione and HMDS on alumina gives 2,5-dimethylpyrrole in 81% yield at room temperature. Ammonium formate can be used as a nitrogen source in the PK synthesis of pyrroles from l,4-diaryl-2-butene-l,4-diones under Pd-catalyzed transfer hydrogenation conditions. 

Diphenylisoinclole (29) can be prepared by a modified Leuckart reaction of o-dibenzoylbenzene (46), using an ammonium salt of formic acid the process is essentially a reductive alkylation of ammonia, accompanied by cyclization, and leads to 29 in 44% yield with ammonium formate, and 47 in 28% yield with methylammonium formate. 1,3-Diphenylisoindole. (29) can also be obtained in good yield by the reaction of 46 with 1,1-dimethylhydrazine. ... 

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