Aromatic/heteroaromatic chloride

Keywords aromatic/heteroaromatic chloride, piperidine, morpholine, basic alumina, nucleophilic aromatic substitution, microwave irradiation... 

To a solution of aromatic/heteroaromatic chloride 1 (0.01 mol) in ethanol, was added piperidine/morpholine 2 (0.01 mol) followed by basic alumina (20 g) with constant stirring. The reaction mixture was thoroughly mixed and adsorbed material was dried in open vessel and placed in an alumina bath inside the microwave oven for 60-120 s. On completion of the reaction as followed by TLC observation, the mixture was cooled to room temperature and then product was extracted into ethanol (3 x 15 mL). Recovering the solvent under reduced pressure afforded the product 3, which was purified through recrystallization from ethanol-chloroform mixture. 

In a closely related publication, carboxylic acids were employed instead of acid chlorides in a microwave-assisted direct synthesis of 2-substituted benzoxazoles [79]. The reactions with 2-aminophenol were performed in a household microwave oven and worked well with aromatic, heteroaromatic, aj/i-unsalurated and arylalkyl carboxylic acids (35-82% yields). Phthalic acid formed only mono-benzoxazoles, while the use of succinic acid led to a mixture of mono- and bis-benzoxazoles. Phthalic and succinic anhydrides could... 

It is important to notice that certain A -heteroaromatic chlorides are much more readily carbonylated, due to the reduction of electron density in the aromatic ring and stronger polarization of the C-Cl bond. An overview of the alkoxycarbonyl-ation of A-heteroaryl chloride has been published recently [50b]. 

This concept was proven to be viable using the example of 4-nitrophenyl esters in the presence of a palladium(II) chloride/lithium chloride/isoquinoline catalyst system, the 4-nitrophenyl esters 3c of various aromatic, heteroaromatic and vinylic carboxylic acids were converted to the corresponding vinyl arenes 5k along with 4-nitrophenol (Figure 4.17). The latter was demonstrated to react with benzoic acid at the same temperature as required for the vinylation step (160 °C) to regenerate the corresponding ester [28], thus demonstrating that at least a two-step waste-minimized Mizoroki-Heck reaction is feasible. 

CuCN added in one portion to a soln. of Me3SiLi (from MejSiSiMej/MeLi/HMPA in hexane) in THF at —23°, stirred for 30 min, benzoyl chloride in THF added dropwise via syringe, stirred for 5 min at —23°, allowed to warm to room temp, over 1 h, and quenched with NH4CI - benzoyltrimethylsilane. Y 87%. The method is generally applicable to aliphatic, aromatic, heteroaromatic (furyl, thienyl), and bis-acylsilanes. F.e.s. A. Capperucci et al., J. Org. Chem. 53, 3612-4 (1988). 

Cook reported the iron/diphosphine-catalyzed alkylation of arene-, heteroarene-, and alkeneamides with primary alkyl halides (Eq. 19) [53] and, shortly after, the alkylation of aromatic amides with benzyl chlorides and secondary alkyl bromides (Eq. 20) [54]. The reaction with primary alkyl bromides proceeded well for aromatic, heteroaromatic, and alkenyl amides despite using phenylmagnesium bromide as a base, the reaction with benzyl chlorides proceeded well under air. As previously observed by Nakamura [28, 34], the slow addition of the Grignard reagent was crucial in order to achieve high yields, presumably because of the competing homocoupling [29]. Secondary alkyl bromides and iodides could be employed in the reaction with benzamides, but acyclic secondary alkyls underwent partial isomerization to the linear alkyl. 

In 2006, Griebenow and coworkers [31] described the palladium-catalyzed a-arylation of ketones on a solid support using modified Buchwald-Hairtwig reaction conditions. The coupling of immobilized 4-bromobenzamide (prepared from polystyrene Rink amide resin and 4-bromobenzoic acid chloride) with several aromatic, heteroaromatic, and aliphatic ketones was investigated. 

The low ionic character of the aluminium-silicon bond has been cleverly utilized to develop a very mild, general and effective synthesis of acyl silanes, successful for aliphatic, aromatic, heteroaromatic, a-aUcoxy, a-amino and even a-chiral and a-cyclopropyl acyl sUanes. Acyl chlorides are treated with lithium tetrakis(trimethylsilyl)aluminium or lithium methyl tris(trimethylsilyl) aluminium in the presence of copper(I) cyanide as catalyst to give the acyl silanes in excellent yields after work-up. Later improvements include the use of 2-pyridinethiolesters in place of acyl halides, allowing preparation of acyl silanes in just a few minutes in very high yields indeed (Scheme 9) °, and the use of bis(dimethylphenylsilyl) copper lithium and a dimethylphenylsilyl zinc cuprate species as nucleophiles. 

Silylation of Acid Chlorides. Reaction of hexamethyldisilane with MeLi and CuCN at —23 °C generates (Me3Si)2CuLi. It reacts in situ with aliphatic, aromatic, heteroaromatic, and steri-cally hindered acyl chlorides (68) to produce the corresponding acylsUanes (69) in fair to good yields (eq 32). ... 

Tetrabutylphosphonium and triphenylchlorophosphonium chlorides were reported to act as catalysts for the addition of diethylzinc to aldehydes (aromatic, heteroaromatic or aliphatic) and the dehydration of aromatic and aliphatic aldoximes to nitriles, respectively. Catalysis was so efficient that both types of reactions occurred at room temperature, even with phosphonium salts in pol)Tner-bonded form. 

The X-ray investigation of lH-3,5-dimethylpyrazole-4-diazonium chloride (4.7) demonstrates that heteroaromatic diazonium ions are very similar to those of the aromatic compounds (NN distance 111.3 pm, NC 136.9 pm, indicating a greater degree of NC double bond character (Brint et al., 1985). 

When aqueous solutions of aromatic and heteroaromatic diazonium salts are treated with cuprous chloride, -bromide, or -cyanide, the corresponding aromatic chlorides, bromides, or cyanides are formed, respectively. In many cases the anions mentioned must be present in excess. This reaction, the Sandmeyer reaction, was discovered by Sandmeyer in 1884. A variant carried out with copper powder and HBr or HC1 was for many years called the Gattermann reaction (Gattermann, 1890). As it is often confused with the Gattermann-Koch reaction (ArH + CO + HC1 ArCHO), and as it is mechanistically not significantly different from Sandmeyer s procedure, the name Gattermann reaction should be avoided. 

Finally, polymer 594 has been used as an arene-catalyst to activate nickel from nickel(II) chloride and lithium, in order to perform hydrogenation of different organic substrates such as afkenes, afkynes, carbonyl compounds and their imines, alkyl and aryl halides (chlorides, bromides and iodides), aromatic and heteroaromatic compounds as well as nitrogen-containing systems such as hydrazines, azoxy compounds or Af-amino oxides, giving comparable results to those obtained in the corresponding reaction in solution . 

Alkyl aryl ketones are convenient intermediates for preparing other substituted aromatic and heteroaromatic compounds. Challenger and co-workers " acetylated thieno[2,3-h]thiophene (1) with acetyl chloride and stannic chloride [Eq. (59)]. The 2-acetylthieno[2,3-A]-thiophene obtained by this method was reduced to the 2-ethyl derivative (20) identical with the product of an independent synthesis. ... 

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