Aromatic amines with acetophenone

Oximes of aliphatic and aromatic ketones are catalytically reduced in the presence of hydrogen to ketimines. Acetophenone oxime gives the imine in 30% yield [28]. This reaction is not of practical value and gives much poorer yields than the direct reaction of ammonia or amines with the carbonyl compounds. 

The excellent enantioselectivity and wide scope of the CBS reduction have motivated researchers to make new chiral auxiliaries [3]. Figure 1 depicts examples of in situ prepared and preformed catalyst systems reported since 1997. Most of these amino-alcohol-derived catalysts were used for the reduction of a-halogenated ketones and/or for the double reduction of diketones [16-28]. Sulfonamides [29,30], phosphinamides [31], phosphoramides [32], and amine oxides [33] derived from chiral amino alcohols were also applied. The reduction of aromatic ketones with a chiral 1,2-diamine [34] and an a-hydroxythiol [35] gave good optical yields. Acetophenone was reduced with borane-THF in the presence of a chiral phosphoramidite with an optical yield of 96% [36]. 

The formation of Schiff bases by the reaction of ketones with amines is more difficult. Acetophenone and other aryl alkyl ketones which are slow to react under the usual conditions will combine with aromatic amines at 160-180° in the presence of a zinc chloride-aniline salt. In another procedure, 2-acetylthiophene and aniline are condensed in boiling toluene with the aid of a water separator. ... 

Features of the free-radical initiation processes are similar for both the homopolymerization of functionalized monomers and copolymerization of the latter with conventional monomers. Common chemical initiators were applied. Azo-bis(isobutyro nitrile) was mostly used in bulk polymerization. No interference with phenolic hydroxy groups was observed in polymerization of 2-hydroxybenzo-phenoiKs, acetophenones, salicylates and of their derivatives [47]. The most rigorous eliinination of oxygen from the reaction mixture was necessary to achieve polymerization of monomeric hindered phenolic antioxidants or derivatives of 2-(2-hydroxyphenyl)benzotriazole [48]. An oxygen-free atmosphere is also an advantage for aromatic amines. A higher initiator level and/or increased temperature appear to be necessary to achieve normal polymerization rates with (D-functionalized monomers [46]. 

A tandem Kornblum ox/daf/on/imidazole formation reaction was used during the preparation of new fluorescent nucleotides by B. Fischer and co-workers.The adenosine monophosphate free acid was mixed with 10 equivalents of 2-bromo-(p-nitro)-acetophenone and dissolved in DMSO. The required pH value was maintained with the addition of DBU which also served as a base. The Kornblum oxidation of the alkyl halide yielded the glyoxal, which reacted in situ with the aromatic amine to form the desired imidazole derivative. 

Tiimethylsilyl)ethanesulphonyl chloride, Me3SiCH2CH2S02Cl, is useful for the protection of primary and secondary amines as sulphonamides, which are smoothly cleaved by fluoride ion. Use of the triazene moiety as a protecting group for aromatic amines is illustrated in eqnation 110. The protected compounds react with s-butyllithium, followed by an electrophile E (carbon dioxide, acetophenone or trimethylsilyl chloride), to give, respectively, the corresponding carboxyhc acid, alcohol or trimethylsilyl daivative, which are converted into the free amines by the action of nickel -aluminium alloy in aqueous-methanolic potassium hydroxide-... 

An important use of H CHO has been found in amino[ " C]methylations of nucleophiles in the presence of primary and secondary amines (Mannich reaction). Nucleophilic substrates include C—H acidic aliphatic compounds (e.g. aldehydes, ketones, esters, nitroalkanes and nitriles), and reactive aromatic and heteroaromatic substrates such as indoles, furans and phenols. The amino[ C]methylations of some C—H acidic methyl, methylene and methine substrates are exemplified in Figure 5.44. The immediate products, alkyl- or dialkylamino[ C]methylene derivatives ( Mannich bases ), can undergo a number of useful synthetic transformations. Condensation of H CHO with acetophenone and dimethylamine provided the carbon- 14-labeled /3-aminoketone 147 in 51 % yield. /3-Aminocarbonyl compounds such as 147. whQe stable at room temperature, can eliminate... 

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. 

Preparative scale reduction of oximes at a mercury or lead cathode in acid solution has been used in the conversion of the carbonyl function to amine. Originally, 30-50% sulphuric acid was used as solvent [195] but ethanol with dilute hydrochloric acid is usually satisfactory. Aliphatic and aromatic oximes give amines in 64-86% yields [196]. Aromatic ketoximes are also reducible in alkaline solution and acetophenone oxime has been converted to 1-phenylethylamine in a tri-potassium orthophosphate solution [197], The reduction of oximes in acid solution is tolerant of many other substituents as indicated by a number of examples [198, 199, 200. Phenylglyoxa monoxime in acid solution is however reduced at both the carbonyl and the oxime centres by sodium amalgam to yield 2-amino-1-phenylethanol [201]... 

Aromatic Ketones The DIOP-Rh [116] and DBPP-Rh [117] complexes, in conjunction with a tertiary amine, have been employed in the asymmetric hydrogenation of acetophenone, albeit with moderate enantioselectivity (80 and 82% respectively Tab. 1.10). The asymmetric hydrogenation of aromatic ketones was significantly improved by using the Me-PennPhos-Rh complex, with which enantioselectivities of up to 96% ee were achieved [36]. Interestingly, the additives 2,6-lutidine and potassium bromide were again found to be crucial for optimum selectivity, although their specific role has not been determined. 

An imine moiety can, interestingly, be interposed in the ether linkage used to connect the two halogenated aromatic rings. The requisite oxime (55-1) is obtained in a straightforward fashion by reaction of imidazo acetophenone (54-2) with hydroxyl-amine alkylation with a,2,3-trichlorotoluene leads to oxiconazole (55-2) [60]. 

Asymmetric hydrogen transfer from 2-propanol to aromatic ketones such as acetophenone (99) has been achieved by using the same chiral Ru complex in 2-propanol containing KOH at room temperature, and (S)-1 -phenylethanol (100) with 98% ee was obtained [68,69]. Similarly, efficient Ru-catalysed transfer hydrogenation of aromatic ketones using the cyclic amino alcohol [(I. S, 3R,4i )-2-azanorbomylmetha-nol] (110) [70] and bis(oxazolinylmethyl) amine (111) [71] was reported. 

Reeve and Christian compared Raney Ni and Raney Co (W-7 type) for the hydrogenation of six aliphatic and aromatic aldoximes and ketoximes in the presence or absence of ammonia.26 From the results summarized in Table 8.1, it is notable that Raney Co gives high yields of primary amine in ethanol or dioxane without addition of ammonia as seen in the results with butyraldoxime, 2-butanone oxime, and acetophenone oxime. On the other hand, Raney Ni usually requires an ammoniacal solvent for best results, with the exception of acetophenone oxime, which gave high yields of primary amine in the absence of ammonia. 

Many types of aromatic substrate are known to undergo a cyclometallation reaction when exposed to alkylpentacar-bonylmanganese complexes under thermal conditions. It is well established that the treatment of ligand appended arenes with alkylmanganesepentacarbonyl complexes can lead to the formation of [C,Y] heterochelates of Mn(CO)4 (Y being a two-electron donor ligand) (Equation 6). For instance, aromatic compounds such as W,W-dimethylbenzyl-amine, alkyl benzyl thioethers, 2-phenylpyridine, acetophenone, benzaldehyde, and diazobenzene can be readily... 

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