Aldehydes, aromatic, alkylation

Keywords o-alkyl aromatic aldehyde, photocyclization, benzocyclobutanol... 

The term "aromatic aldehyde" is usually used in perfumery, as it is here, to include both the true aromatic aldehydes and the alkyl aromatic aldehydes, in which the aldehydic group is attached to a side chain rather than onto the benzene ring. 

Since 1972, updates on Friedel-Crafts alkylation, aromatic aldehyde synthesis, nitration, etc., were regularly published in books and extensive reviews. However, improvements in Friedel-Crafts acylations were scantly considered, despite the great practical application of the aromatic ketones in different fields of the fine and pharmaceutical chemistry. 

The cycloadduct 2 is formed by a Diels-Alder reaction of the dienophile methyl 2-ethylacrylate and the diene generated by photochemical activation of the aromatic aldehyde. Irradiation of an ortho alkyl aromatic aldehyde (or ketone) gives an intermediate orf/io-quinodimethane (see Section 3.1.2). Cycloaddition with an activated alkene dienophile then gives the tetrahydronaphthalene product 2. See K. C. Nicolaou and D. Gray, Angew. Chem. Int. Ed., 40 (2001), 761. 

Carbonylation of satarated hydrocarbons to oxygenated hydrocarbons is difficult due to the high stability of C—H or C—C bonds. Superadds, which are generally corrosive and volatile, are often used. Imidazohum or pyridinium chloroaluminates have proven to be suitable catalysts [47]. Alkylaromatic compounds (e.g., toluene or xylene) can also react with carbon monoxide in the presence of an acidic chloroaluminate IL to form an alkyl aromatic aldehyde [48]. 

Claisen-Schmidt reaction. Aromatic aldehydes condense with aliphatic or mixed alkyl-aryl ketones in the presence of aqueous alkali to form ap-unsaturated ketones ... 

Hydrazinopyridazines are easily formylated with formic acid or ethyl formate and acety-lated with acetic anhydride. A-Pyridazinylthiosemicarbazides are obtained from thiocyanates or alkyl- and aryl-isothiocyanates. Hydrazinopyridazines condense with aliphatic and aromatic aldehydes and ketones to give hydrazones. 

Sodium (metal). Used as a fine wire or as chips, for more completely drying ethers, saturated hydrocarbons and aromatic hydrocarbons which have been partially dried (for example with calcium chloride or magnesium sulfate). Unsuitable for acids, alcohols, alkyl halides, aldehydes, ketones, amines and esters. Reacts violently if water is present and can cause a fire with highly flammable liquids. 

Here a typical property of three-membered rings wdth two hetero atoms is shown and this property is also found in the diaziridines. Only with the oxaziranes which are substituted by aryl groups in the 3-position does the hydrolysis by acids occur according to Eq. (14) with formation of an aromatic aldehyde and alkyl hydroxylamine. 

Most oxaziranes withstand temperatures of 100 C for a short time, e.g., on distillation. At higher temperatures isomerization and decomposition occur. Oxaziranes derived from aromatic aldehydes are here again differentiated from the alkyl-substituted oxaziranes. 

Sometimes ihe intermediate imine is isolated, but generally it is nol and may even be inferior to direct alkylation (5following sequence for it was desired to acetylate ihe alkylated product as formed, A solution of 50 mmol of an aromatic aldehyde (I) and 50 mmol of aminoaceialdehyde dimethylacetal (2), refluxed 1.5 h in toluene under nitrogen, gave after distillation nearly quantitative yields of the SchifTs base 3 (5d). 

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-... 

Arai and co-workers have used chiral ammonium salts 89 and 90 (Scheme 1.25) derived from cinchona alkaloids as phase-transfer catalysts for asymmetric Dar-zens reactions (Table 1.12). They obtained moderate enantioselectivities for the addition of cyclic 92 (Entries 4—6) [43] and acyclic 91 (Entries 1-3) chloroketones [44] to a range of alkyl and aromatic aldehydes [45] and also obtained moderate selectivities on treatment of chlorosulfone 93 with aromatic aldehydes (Entries 7-9) [46, 47]. Treatment of chlorosulfone 93 with ketones resulted in low enantioselectivities. 

The oxazaborolidines are easily prepared by heating ephedrine with borane dimethyl sulfide or the appropriate boronate ester. The aluminum reagent C is obtained by mixing ephedrine and trimethylaluminum. Borolidinc A is superior to its methyl derivative B and to the aluminum analog C. The diastereomeric borolidine obtained from borane and (S,S)-pseu-doephedrine failed to show any cnantioselectivity25. A variety of aromatic aldehydes can be enantioselectively alkylated in the presence of A, however, with heptanal the enantioselectivity is poor25. 

Aromatic aldehydes and ketones can be alkylated and reduced in one reaction vessel by treatment with an alkyl- or aryllithium, followed by lithium and ammonia and then by ammonium chloride." ... 

The dimerization of ketones to 1,2-diols can also be accomplished photochemi-cally indeed, this is one of the most common photochemical reactions. The substrate, which is usually a diaryl or aryl alkyl ketone (though a few aromatic aldehydes and dialkyl ketones have been dimerized), is irradiated with UV light in the presence of a hydrogen donor such as isopropyl alcohol, toluene, or an amine. In the case of benzophenone, irradiated in the presence of 2-propanol, the ketone molecule initially undergoes n — k excitation, and the singlet species thus formed crosses to the T, state with a very high efficiency. 

Novel chiral thiolated amino alcohols have been recently synthesised and then evaluated by Vilaivan el al. as a potential new class of ligands for Cu-catalysed nitroaldol reactions. Amino alcohol ligands bearing Ai-(2-alkyl-thio)benzyl substituents provided only modest enantioselectivities (22-46% ee) while those carrying Al-2-thienylmethyl substituents provided better enantioselectivities of up to 75% ee for the nitroaldol reaction between p-nitro-benzaldehyde and nitromethane. A range of aromatic aldehydes were acceptable substrates giving moderate to high enantioselectivities of up to 88% ee, as shown in Scheme 10.32. 

On the other hand, the oxidation of the alkyl substituent in alkyl aromatic compounds can be carried out by various methods efficiently. For example, CAN has been used to oxidize substituted toluene to aryl aldehydes. Selective oxidation at one methyl group can be achieved (Eq. 7.19).44 The reaction is usually carried out in aqueous acetic acid. 

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