Formate, ammonium, with ketones

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

Condensation of hydroxyamino-ketones (166) with ketones and ammonium acetate leads to the formation of 2H -imidazole-1 -oxides (167) (Scheme 2.59) (324). 

Dicarbonyl compounds can be prepared by the reactitxi of ketones with 3-butenyl halide as a CU component, following oxidation of the terminal double bond. A modified method for 3-butenylation of ketones by the palladium-catalyzed reaction of 4-acetoxy-2-butenylmethyl carbonate with ketones, followed by the palladium-catalyzed reaction of ammonium formate was reported (Scheme 15)." ... 

Many water-insoluble ketones, aliphatic, aryl aliphatic, and heterocyclic, respond favorably to treatment with ammonium formate or formamide to form with subsequent hydrolysis the primary amines. A typical procedure for the synthesis of a-phenylethylamine (66%) from acetophenone and ammonium formate has been applied to many other ketones (65-84%). Nuclear alkoxyl, halo, and nitro groups are not disturbed. The reaction with formamide as the reducing agent is catalyzed by ammonium formate, ammonium sulfate, or magnesium chloride. ... 

In 1885, R. Leuckart reported that the reaction of ammonia and primary or secondary amines with ketones (and aldehydes) was possible with ammonium formate, to produce the corresponding primary, secondary, or tertiary amine.1 This reaction became known as the Leuckart reaction. In 1891, Wallach reported that the use of excess formic acid led to an improvement in yield, and that the reaction could be carried out at lower temperatures.2 The Leuckart-Wallach reaction was bom. Wallach went on to apply this reaction to a wide variety of carbonyl compounds, including alicyclic and terpenoid ketones.5... 

In an acetonitrile suspension, the intermediate a-cyanoalkoxide can be trapped by acyl chlorides to give cyanohydrin esters. In a preparation of synthetic pyrethroids, the comparison between the sonicated reaction and its PTC equivalent gave an advantage to the latter in terms of reaction time and yield. i A modest change in stereoselectivity is observed in some cases. The same reaction in the presence of ammonium chloride leads to a-amino nitriles, the first step of the Strecker amino acid synthesis.4 72 xhe procedure is more efficient in the presence of alumina. The formation of by-products, cyanohydrins or benzoins, is avoided. From an experimental viewpoint, the work-up is considerably easier than with conventional procedures, and consists mostly of a simple filtration. With ketones, and in the presence of ammonium carbonate, a hydantoin is formed (Eq. 21)7 ... 

An attractive method for the generation of ester enolates involves treatment of a-trimethylsilyl esters with quaternary ammonium fluorides. Enolates thus formed couple with ketones to form j3-hydroxy esters in 70—90% yield, although strangely no reaction was observed with j8-ionone or benzylacetone. The same group has reported the preparation of the silylated base (115), which can be used to effect specific ester enolate formation in the presence of an aldehyde leading... 

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. 

The formation of ethyl isopropylidene cyanoacetate is an example of the Knoevenagel reaction (see Discussion before Section IV,123). With higher ketones a mixture of ammonium acetate and acetic acid is an effective catalyst the water formed is removed by azeotropic distillation with benzene. The essential step in the reaction with aqueous potassium cyanide is the addition of the cyanide ion to the p-end of the ap-double bond ... 

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. 

These association reactions can be controlled. Acetone or acetonylacetone added to the solution of the polymeric electron acceptor prevents insolubilization, which takes place immediately upon the removal of the ketone. A second method of insolubiUzation control consists of blocking the carboxyl groups with inorganic cations, ie, the formation of the sodium or ammonium salt of poly(acryhc acid). Mixtures of poly(ethylene oxide) solutions with solutions of such salts can be precipitated by acidification. 

Treatment of a-hydroxy-ketones or -aldehydes with ammonium acetate (65BSF3476, 68BSF4970) results in the formation of dihydropyrazines, presumably by direct amination of the hydroxyketone followed by self-condensation (79AJC1281). Low yields of pyrazines have been noted in the electrolysis of ketones in admixture with KI and ammonia, and again it appears probable that the a-aminoketone derived by way of the a-iodoketone is the intermediate (69CI(L)237>. 

Ketonic carbonyl groups are commonly encountered in steroids and their reduction is facile, even in the absence of an alcohol. The lithium-ammonia reduction of androsta-l,4-diene-3,17-dione affords androst-4-ene-3,17-dione in 20% yield but concurrent reduction of the C-17 ketone results in formation of testosterone in 40% yield, even though the reduction is performed rapidly at —40 to —60° and excess lithium is destroyed with solid ammonium chloride. Similar reduction of the C-17 carbonyl group has been observed in other compounds. In the presence of an alcohol, a ketone is complete-... 

The reduction of y-nitroketone acetals as in Eq. 6.50 with ammonium formate in the presence of Pd/C gives the corresponding amines in good yields. However, the reduction of y-nitro ketones are reduced to cyclic nitrones (Eq. 6.51).97 This reduction is far superior to the classical method using Zn/NH4C1 due to improved yield and simple workup. 

Reaction of phenyl vinyl ketone with cyclopentanone under thermal conditions resulted in a diastereomeric mixture of 1,5,9-triketones 374 via a double Michael reaction. Treatment of this mixture with ammonium formate in polyethyleneglycol-200 under microwave irradiation conditions led to the very fast and efficient formation of a 2 1 diastereomeric mixture of cyclopental flquinolizidines 375 and 376 <2002T2189>. When this reductive amination-cyclization procedure was carried out starting from the purified /ra r-isomer of 374, the result was identical to that obtained from the cis-trans mixture, showing the operation of thermodynamic control (Scheme 86). 

Lucifer Yellow CH is soluble in aqueous solution, and it should be stable for awhile if protected from light. The reagent is available as three different salts of the sulfonate groups. The ammonium salt of the fluorophore is soluble to a level of 9 percent in water, while the lithium and potassium salts have a solubility of 5 and 1 percent, respectively. A concentrated stock solution of the fluorophore may be prepared in water and an aliquot added to a buffered reaction medium to facilitate the transfer of small quantities. For aqueous reactions, a pH range of 5-9 will result in efficient hydrazone formation with aldehyde or ketone residues. 

The best way to take advantage of the organic solvent effect without simultaneously diluting the sample is by employing solvent extraction. By this method the element to be analyzed can actually be concentrated and a solution of the element is obtained in essentially pure organic solvent. One of the most commonly used systems involves formation of the metal chelate with ammonium 1-pyrro-lidinecarbodithioate (APDC) and then extracting this into methylisobutyl ketone (MIBK). APDC chelates of many elements form and extract into MIBK from acid solution. 

The enantioselective addition of a nucleophile to a carbonyl group is one of the most versatile methods for C C bond formation, and this reaction is discussed in Chapter 2. Trifluoromethylation of aldehyde or achiral ketone via addition of fluorinated reagents is another means of access to fluorinated compounds. Trifluoromethyl trimethylsilane [(CF SiCFs] has been used by Pra-kash et al.87 as an efficient reagent for the trifluoromethylation of carbonyl compounds. Reaction of aldehydes or ketones with trifluoromethyltrime-thylsilane can be facilitated by tetrabutyl ammonium fluoride (TBAF). In 1994, Iseki et al.88 found that chiral quaternary ammonium fluoride 117a or 117b facilitated the above reaction in an asymmetric manner (Scheme 8-42). 

Terminal allenes.1 A synthesis of 1,2-dienes (3) from an aldehyde or a ketone involves addition of ethynylmagnesium bromide followed by reaction of the adduct with methyl chloroformate. The product, a 3-methoxycarbonyloxy-l-alkyne (2), can be reduced to an allene by transfer hydrogenolysis with ammonium formate catalyzed by a zero-valent palladium complex of 1 and a trialkylphosphine. The choice of solvent is also important. Best results are obtained with THF at 20-30° or with DMF at 70°. 

The ammonium catalyst can also influence the reaction path and higher yields of the desired product may result, as the side reactions are eliminated. In some cases, the structure of the quaternary ammonium cation may control the product ratio with potentially tautomeric systems as, for example, with the alkylation of 2-naph-thol under basic conditions. The use of tetramethylammonium bromide leads to predominant C-alkylation at the 1-position, as a result of the strong ion-pair binding of the hard quaternary ammonium cation with the hard oxy anion, whereas with the more bulky tetra-n-butylammonium bromide O-alkylation occurs, as the binding between the cation and the oxygen centre is weaker [11], Similar effects have been observed in the alkylation of methylene ketones [e.g. 12, 13]. The stereochemistry of the Darzen s reaction and of the base-initiated formation of cyclopropanes under two-phase conditions is influenced by the presence or absence of quaternary ammonium salts [e.g. 14], whereas chiral quaternary ammonium salts are capable of influencing the enantioselectivity of several nucleophilic reactions (Chapter 12). 

Carbanions, generated by the reaction of benzylsilanes with tetra-n-butylammo-nium fluoride react with non-enolizable aldehydes to produce the alcohol [67], When a stoichiometric amount of the ammonium fluoride is used, the methylarene corresponding to the benzylsilane is frequently a by-product and arises from formation of the hydrogen difluoride salt during the reaction. When only catalytic amounts of the ammonium fluoride initiate the reaction, the formation of the methylarene is suppressed. In a similar type of reaction (although the mechanism is not known) between aldehydes and ketones, allyl bromide, and tin in the presence of trimethylsilyl chloride the yield of the but-l-en-4-ol is raised significantly by the addition of tetra-n-butylammonium bromide, particularly in the reactions with... 

The formation of cyclopropanes from 7C-deficient alkenes via an initial Michael-type reaction followed by nucleophilic ring closure of the intermediate anion (Scheme 6.26, see also Section 7.3), is catalysed by the addition of quaternary ammonium phase-transfer catalysts [46,47] which affect the stereochemistry of the ring closure (see Chapter 12). For example, equal amounts of (4) and (5) (X1, X2 = CN) are produced in the presence of benzyltriethylammonium chloride, whereas compound (4) predominates in the absence of the catalyst. In contrast, a,p-unsatu-rated ketones or esters and a-chloroacetic esters [e.g. 48] produce the cyclopropanes (6) (Scheme 6.27) stereoselectively under phase-transfer catalysed conditions and in the absence of the catalyst. Phenyl vinyl sulphone reacts with a-chloroacetonitriles to give the non-cyclized Michael adducts (80%) to the almost complete exclusion of the cyclopropanes. 

Palladium-catalysed C-C bond formation under Heck reaction conditions, which normally requires anhydrous conditions and the presence of copper(I) salts, is aided by the addition of quaternary ammonium salts. It has been shown that it is frequently possible to dispense with the copper catalyst and use standard two-phase reactions conditions [e.g. 18, 19]. Tetra-/i-butylammonium salts catalyse the palladium-catalysed reaction of iodoarenes with alkynes to yield the arylethynes in high yield [20, 21], whereas the reaction with 3-methylbut-1 -yn-3-ol (Scheme 6.30) provides a route to diarylethynes [22]. Diarylethynes are also formed from the reaction of an iodoarene with trimethylsilylethyne [23], Iodoalkynes react with a,p-unsaturated ketones and esters to produce the conjugated yne-eneones [19],... 

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