Esterification, microwave-assisted

Wu and Sun have presented a versatile procedure for the liquid-phase synthesis of 1,2, ,4-tctrahydro-/i-carbolines [77]. After successful esterification of the MeO-PEG-OH utilized with Fmoc-protected tryptophan, one-pot cyclocondensations with various ketones and aldehydes were performed under microwave irradiation (Scheme 7.68). The desired products were released from the soluble support in good yields and high purity. The interest in this particular scaffold is due to the fact that the l,2,3,4-tetrahydro-/f-carboline pharmacophore is known to be an important structural element in several natural alkaloids, and that the template possesses multiple sites for combinatorial modifications. The microwave-assisted liquid-phase protocol furnished purer products than homogeneous protocols and product isolation/ purification was certainly simplified. 

Scheme 4.1 Microwave-assisted esterification of benzoic acid.

Carbonyl)chlorohydridotris(triphenylphosphine)ruthenium(II) was used as a catalyst in the transfer hydrogenation of benzaldehyde with formic acid as a hydrogen source. Under these conditions, the reduction ofbenzaldehyde to benzyl alcohol is accompanied by esterification of the alcohol with the excess of formic acid to provide benzyl formate (Scheme 4.16). In this microwave-assisted reaction, the catalyst displayed improved turnover rates compared to the thermal reaction (280 vs. 6700 turnovers/h), thus leading to shorter reaction times36. 

A differently anchored Mukaiyama reagent is the N-methylpyridinium iodide salt 57 [71], which has been obtained by reaction of the Merrifield resin with N-Boc-aminocaproic acid in the presence of cesium carbonate to give the supported ester 55 (Scheme 7.19). Further Boc-deprotection and reaction with 6-chloronicoti-noyl chloride in the presence of Hxinig s base furnished the anchored 2-chloro-pyridine 56, which was transformed into the final N-methylpyridinium salt 57 after N-methylation in neat methyl iodide. This supported reagent has been used in the rapid microwave-assisted esterification of carboxylic acids and alcohols in the presence of triethylamine as base, with dichloromethane as solvent at 80 °C, the products being obtained in high purity after simple resin filtration [72],... 

Microwave-assisted esterification by a heterogeneous acid catalyst has been studied in a low dielectric constant medium (see Scheme 35) [64]. A continuous-flow setup has been devised in the system and the heterogeneous acid catalyst (Amberlyst A15 sulphonic acid cation-exchange resin) 61 localized in a polyethylene active flow cell. Use of a low dielectric constant medium (hexane) ensured absorption of microwave radiation only to the reacting species. In this case, the findings suggest a comparable esterification reaction under both microwave and thermal conditions. Furthermore, the presence of water in the catalytic resin resulted in a reduction of the reaction rate irrespective of the type... 

N.Z. Kiss, K. Ludanyi, L. Drahos, G. Keglevich, Novel synthesis of phosphinates by the microwave-assisted esterification of phosphinic acids, Synth. Commtm. 39 (2009) 2392-2404. 

G. Keglevich, E. Balint, N.Z. Kiss, E. Jablonkai, L. Hegedus, A. Griin, 1. Greiner, Microwave-assisted esterification of phosphinic acids, Curr. Org. Chem. 15 (2011) 1802-1810. 

G. Keglevich, N.Z. Kiss, Z. Mucsi, T. Kortvelyesi, Insights into a surprising reaction the microwave-assisted direct esterification of phosphinic acids, Org. Biomol. Chem. 10 (2012) 2011-2018. 

In the recent past, Keglevich and coworkers demonstrated the synthesis of several phosphole derivatives (74) based on the McCormack reaction,followed by microwave-assisted esterification of the phosphinic acid using different alcohols in yields up to 94% (Scheme 34). ... 

When a similar transformation was attempted using a dialkylether in place of an aryl alkyl ether, yields obtained were much lower. An alternative microwave-assisted method for promoting esterification uses phase transfer catalysis. Irradiation of potassium acetate with alkyl halides for 1-2 min (Aliquat 336, 5-10%) gives the product in good to excellent yields (> 92%) (Bram et al., 1990). 

Microwave-assisted organic synthesis has been found equally important to cany out some other chemical reactions like protection, deprotection, hydrolysis, esterification, cyclization, etc. 

It is well known that in esterifications of phosphinic acids, it does not normally react with alcohols under thermal conditions, but in the presence of microwave exposure, the esterifications took place, which shows the importance of microwaves. It was observed that maximum 12-15% conversions were attained on traditional heating. It was found that due to the consequence of the hydrophobic medium established by the long chain alcohol/phosphinic ester, microwave-assisted esterifica-hons were not reversible. The potential of the microwave technique in the synthesis of phosphinates can be understood on the basis of the energetics of the esterification of phosphinic acids under microwave conditions. A series of new cychc phosphinates with lipophilic alkyl groups was synthesized by Keglevich et al. (2012). 

Li et al. (2009) have studied the synthesis of alkyl ferulates under microwave inadiatioa They observed the reactions time ranged from 3-5 min, which was much shorter than the traditional synthetic methods, as well as the alkyl ferulates were obtained in higher yields. It was the first time, when they have reported an efficient microwave-assisted esterification of ferulic acid with alcohols. 

The kinetics of the acid-catalyzed esterification reaction of 2,4,6-trimethylbenzoic acid in i-PrOH under microwave irradiation have been investigated [84], A simple and practical technique for MW-assisted synthesis of esters has been reported wherein the reactions are conducted either on solid mineral supports or by using a phase transfer catalyst (PTC) in the absence of organic solvents [85], The esterification of enols with acetic anhydride and iodine has also been recorded [86],... 

Thus, microwave irradiation can assist us in carrying out various reactions like cyclization, esterification, hydrolysis, protection, deprotection, etc. in preparing organic molecules of interest in limited time and with good yields. 

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