Synthesis from aromatic ketones

The production of optically active cyanohydrins, with nitrile and alcohol functional groups that can each be readily derivatized, is an increasingly significant organic synthesis method. Hydroxynitrile lyase (HNL) enzymes have been shown to be very effective biocatalysts for the formation of these compounds from a variety of aldehyde and aliphatic ketone starting materials.Recent work has also expanded the application of HNLs to the asymmetric production of cyanohydrins from aromatic ketones. In particular, commercially available preparations of these enzymes have been utilized for high ee (5)-cyanohydrin synthesis from phenylacetones with a variety of different aromatic substitutions (Figure 8.1). 

Roberge, C., Fleitz, F., Pollard, D. and Devine, P., Synthesis of optically active cyanohydrins from aromatic ketones evidence of an increased substrate range and inverted stereoselectivity for the hydroxynitrile lyase from Linum usitatissimum. Tetrahedron Asymm., 2007,18, 208. 

By this strategy, anilines 299 can be obtained from aromatics ketones 300 (equation 104). The Beckmann rearrangement/hydrolysis sequence is able to replace an acyl group by an amine and has been used in aromatic synthesis to attach directly nitrogen atoms to aromatic rings, providing an alternative strategy to the classical nitration/reduction sequence. 

Synthesis of aromatic ketones from carboxylic acid derivatives (Expts 6.126 and 6.127). 

SYNTHESIS OF AROMATIC KETONES FROM CARROXYLIC ACID DERIVATES... 

Arylacetic acids. A new synthesis of phenylacetic acids from aromatic ketones is illustrated for conversion of 6-methoxy-l-tetralone (1) into 6-methoxy-l,2,3,4-tetrahydronaphthalene-1-carboxylic acid (3). 

The Willgerodt reaction allows amide synthesis from aromatic aldehydes or ketones, using a secondary amine and a thiating agent. The mechanism of the more convenient Kindler modification, employing sulfur and morpholine, has been reviewed.281... 

Houben-Hoesch reaction Synthesis of aromatic ketones from activated aromatic compounds (e.g. phenols) and nitriles. 216... 

Thus these very simple reactions are easily handled on a large scale from current starting materials and constitute a good way for the synthesis of aromatic ketones, particularly of the 93 type. 

Harusawa, S., Yoneda, R., Kurihara, T., Hamada, Y, and Shioiri, T., A novel synthesis of a,P-unsaturated nitriles from aromatic ketones via cyanophosphates. Tetrahedron Lett., 25, 427, 1984. 

Synthesis of aromatic ketones, including those derived from mononitro-benzenes, can be achieved in good yields (60-90%) by using controlled-potential electro-oxidation of the corresponding o -complexes [25]. These o -complexes are formed (yields from 50 to 100%) with an excess of ketone and a strong base... 

A highly efficient Rh(I)-catalyzed one-pot synthesis of isoquinoline derivatives (55 and 56) was achieved from aromatic ketone, benzylamine, and alkyne (Scheme 7.39) [108]. The reaction works well when either electron-donating or electron-withdrawing groups are present in the benzene ring. 

Scheme 7.39 Rh(I)-catalyzed one-pot synthesis of isoquinoline derivatives from aromatic ketone, benzylamine, and alkyne...

Hydroxybenzaldehyde has an agreeable aromatic odor, but is not itself a fragrance. It is, however, a useful intermediate in the synthesis of fragrances. The methyl ether of -hydroxybenzaldehyde, ie, -anisaldehyde, is a commercially important fragrance. Anisaldehyde can be made in a simple one-step synthesis from hydroxybenzaldehyde and methyl chloride. Another important fragrance, 4-(p-hydroxyphenyl)butanone, commonly referred to as raspberry ketone, can be prepared from the reaction of -hydroxybenzaldehyde and acetone, followed by reduction (see Flavors and spices). 

BORSCHE - BEECH Aromatic Aldehyde Synthesis Synthesis of aromatic aldehydes and of akyl aryl ketones from aldoximes or semcaibazones and aromatic dlazonum salts... 

ROBINSON - ALLAN - KOSTANECKI Chromone Synthesis Synthesis of chromones or coumannes from o acyioxy aromatic ketones... 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

Nitroalkenes prepared from aromatic aldehydes are especially useful for natural product synthesis. For example, the products are directly converted into ketones via the Nef reaction (Section 6.1) or indoles (Section 10.2) via the reduction to phenylethylamines (Section 6.3.2). The application of these transformations are discussed later here, some examples are presented to emphasize their utility. Schemes 3.3 and 3.4 present a synthesis of 5,6-dihydroxyindole66 and asperidophytine indole alkaloid,67 respectively. 

In addition, iodine snccessfnlly catalyzed the electrophilic snbstitntion reaction of indoles with aldehydes and ketones to bis(indonyl)methanes [225], the deprotection of aromatic acetates [226], esterifications [227], transesterifications [227], the chemoselective thioacetalization of carbon functions [228], the addition of mercaptans to a,P-nnsatnrated carboxylic acids [229], the imino-Diels-Alder reaction [230], the synthesis of iV-Boc protected amines [231], the preparation of alkynyl sngars from D-glycals [232], the preparation of methyl bisnlfate [233], and the synthesis of P-acetamido ketones from aromatic aldehydes, enolizable ketones or ketoesters and acetonitrile [234],... 

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