Solvent-free reactions ultrasound

Niralwad et al. (2010) reported an efficient synthesis of octahydroquinazolinone derivatives (112) under ultrasound irradiation via the reaction of dimedone (60), aromatic aldehyde (111), and ureas (98 or 99) using [tbmim]Cl2/AlCl3 as an acidic ionic liquid catalyst (Scheme 8.37). This protocol has advantages in terms of (i) a short reaction time, (ii) a solvent-free reaction, (iii) high yield, (iv) easy workup, (v) being environmentally friendly, and (vi) recyclability of ionic liquid. 

Ionic liquids have been a popular topic of interest in 2002 and a review of the applications of these solvents in organic synthesis has been published (02ACA75>. New, densely functionalized fluoroalkyl-substituted imidazolium ionic liquids have been reported <02TL9497>. An ultrasound-assisted preparation of a series of ambient-temperature ionic liquids, l-alkyl-3-methylimidazolium halides, which proceeds via efficient reactions of 1-methyl imidazole with alkyl halides/terminal dihalides under solvent-free conditions, has been described <02OL3161>. New hydrophilic poly(ethyleneglycol)-ionic liquids have been synthesized from... 

In presence of a base, a-bromo acetals can be converted into ketene acetals, products difficult to obtain by the classical processes. The reaction was studied in the presence of KOH in solvent-free conditions. The effects of a phase transfer agent as well as that of ultrasound, a non-classical method of activation especially efficient in heterogeneous solid-liquid systems due to cavitation phenomenon, were studied (Table 6) [87]. 

The KF/A1203 was used for the condensation of cyanoacetic ester, aromatic aldehydes, and dimedone at room temperature under ultrasound irradiation to give 281 (X = COOR) (04SC4565). In contrast, 281 (X = CN, R1 = Ph) was obtained on MW irradiation of dimedone with 443 without catalyst under solvent-free conditions (02SC2137). The reaction was also achieved in DMF under MW (07SL480) or ultrasound irradiation (04MI562). 

Aldol reactions. Aldol products are obtained in good yields from reaction of ketones with glyoxylic acid monohydrate with assistance of ultrasound irradiation. Substrate-control (by 1,3- + 1,5-asynmietric induction) of the aldol reaction involving y-amino-a-ketoesters under solvent-free conditions is very effective.- With lithium dicyclohexylamide and InCl, the reaction of esters with aldehydes furnishes P-hydroxy esters, and that of a-bromo esters affords a,p-epoxy esters." These are typical Reformatsky and Darzens reaction products, respectively. 

Anionic -elimination Ketene acetal synthesis by j8-elimination of haloacids from halogenated acetals under solvent-free PTC conditions under well controlled conditions using thermal activation (A), ultrasound (US), or microwave irradiation [152] (MW) has been described. Mechanistically, as the TS is more charge delocalized than the GS and the polarity is enhanced during the course of the reaction, a favorable microwave effect is expected, and is actually observed (Eqs. (65) and (66), Scheme 4.16). 

Carbonyl compounds are also rapidly regenerated from the corresponding semi-carbazone and phenylhydrazone derivatives by use of montmorillonite KIO clay impregnated with ammonium persulfate (Scheme 8.16) [59]. Interestingly, the microwave or ultrasound irradiation techniques can be used in these solvent-free procedures. Microwave exposure achieves deprotection in minutes whereas ultrasound-promoted reactions require 1-3 h for regeneration of carbonyl compounds [59]. 

In attempts to prepare homoallyl alcohol in an environmental friendly process, Andrews and co-workers reported its synthesis using a solvent-free method mediated by tin under ultrasound. Experiments showed that the alcohols were produced in excellent yields with aldehydes but that no products were produced using ketones. However, the existence of toxic allyltin compounds in the final products prevented the method from being applied downstream in fine chemical applications. On the other hand, according to Wang et carbonyl allylation reactions mediated by SnCl2 in aqueous solution without a Lewis acid under ultrasonic irradiation were successfully carried out. 

A multi-component one-potreaction of ethyl acetoacetate (57), aromatic aldehydes (58), hydrazine (31), and malononitrile (50) in water afforded dihydropyrano[2,3-c] pyrazoles (59) in good yields (79%-95%) under ultrasonic irradiation in relatively short reaction times (15-40 min). In the absence of nltrasound, the products were obtained in comparatively lower yields (70%-86%) and longer reaction times (60-300 min) (Zou et al. 2011). Darandale et al. (2012) reported a simple and practical ultrasound-promoted synthetic protocol for the synthesis of dihydropyrano[2,3-c] pyrazoles (59) nsing sodium bisulfite (NaHSOj) as a green catalyst in solvent-free conditions. The latter method provides the advantage of a shorter reaction time (30 s) and excellent yields (97%-99%) (Scheme 8.19). 

Cyclic ketene acetals can be generated from cyclic p-bromo acetals and potassium hydroxide (Eq. 35).The best results were obtained by using a combination of ultrasound irradiation and solvent-free PTC. jhis reaction occurs in the "dry" state in the presence of TBAB at room temperature. 

For some examples (a) C. Cui, C. Zhu, X.-J. Du, Z.-P. Wang, Z.-M. Li, W.-G. Zhao, Green Chem. 2012, 14, 3157-3163. Ultrasound-promoted sterically congested Passerini reactions under solvent-free conditions, (b) K. Sato, T. Ozu, N. Takenaga, Tetrahedron Lett. 2013, 54, 661-664. Solvent-free synthesis of azulene derivatives via Passerini reaction by grinding. 

In addition to varying the substrates, other authors have worked on the conditions in order to extend the scope of the reaction. In particular, MW [127] and ultrasound [128] irradiations have been applied successfully, decreasing considerably the reactions times. On the other hand, different catalysts have been used substituting the classical secondary or tertiary amines [129], for example, L-proline [130], imidazole [131], cesium carbonate (Cs COj) [132], amine-functional polysiloxanes (AFPs) [133], MgAa mixed oxide as a heterogeneous solid base catalyst [134], ZnO (under solvent-free conditions) [135], bovine serum albumin (BSA) [136], and guanidine-based IL [137]. 

A few Lewis acids have been shown to catalyze the Yonemitsu-type reactions of indoles, aldehydes, and several CH acids (Scheme 13.79). Dimethyhnalonate 358 was successfully reacted with indole 327 and several aldehydes 357 under solvent-free ultrasound irradiation conditions to provide the desired products 359 in moderate yields [135]. Ytterbium triflate was used as the Lewis-acidic catalyst in this case. A copper-salen complex was utilized in water at elevated temperature to facilitate the Yonemitsu-type reaction of indoles 360, aldehydes 361, and malonodinitrile 21 [136]. In close similarity copper(II) acetate was used in polyethylene glycol at elevated temperatures to provide Yonemitsu-type products 366 in moderate to high yields (48-98%) [137]. 

Safari et al. [45] successfully demonstrated for the first time that Cu powder and ultrasound 300 W/H2O could be used as an excellent and efficient catalyst for convenient synthesis of 2,3-dihydroquinazohn-4(l//)-one derivatives under solvent-free conditions and microwave irradiation (Scheme 13.8). The protocol proves to be efficient and environmentally benign in terms of easy workup, high yields, and ease of recovery of catalyst. In addition, the present method is superior in terms of green media, the amorrrrt of catalyst, and reaction time. 

C. Gutierrez-Sanchez et al. synthesized an important insecticide intermediate, namely, hymecromone from the condensation of resorcinol and EAA at moderate temperatures in low yield. However, in solvent-free conditions under ultrasound irradiation and in the presence of zeolites the desired product has been obtained in higher yield, required shorter reaction time, and naturally more environmental friendly conditions with nearly 100% selectivity (09MI318). 

Bandyopadhyay et al. [50] synthesized a series of novel N-substituted pyrrole derivatives. The autiiors sought a simple and solvent-free ultrasound-assisted reaction for tiie synthesis of N-substituted pyrroles (12) by reacting 2,5-dime-thoxytetrahydrofuran (10) with aromatic, aliphatic, polyaromatic, and heteropolyaromatic amines (11) using bismuth nitrate pentahydrate as catalyst (Scheme 4). It should be mentioned that the addition of the bismuth salt, which is environmentally benign and nontoxic, increased tiie reaction yield from 55% to 99% and reduced the reaction time from 5h to 5 min. 5-(lH-Pyrrol-l-yl)-l,10-phenantiiroline and l-(phenanthren-2-yl)-lH-pyrrole have demonstrated cytotoxic specificity against liver cancer cell lines in vitro when compared with normal cultured primary hepatocytes. 

Mojtahedi and coworkers [76] performed a mild condensation of hydrazine derivatives with various p-keto esters under solvent-free conditions using ultrasound irradiation to S5mthesize pyrazolone derivatives within short reaction times and good yields. Pyrazolones are conventionally S5mthesized by the treatment of p-keto esters (76) with hydrazine substrates (77) under acidic conditions at elevated temperature [77,78] however, these authors reported a novel and environmentally safe procedure for rapid preparation of various pyrazolone derivatives (78) using ultrasound irradiation (Scheme 19). 

Li et al. [106] synthesized 1,5-benzodiazepine derivatives (141), in good yields, by the condensation reaction of o-phenylenediamine (138) and ketones (139), catalyzed by [l-methyl-3-(3-sulfopropyl)imidazolium methyl sulfate] under ultrasound irradiation using n-hexane as solvent. Shinde et al. [105] describe the implementation of ultrasound irradiation for the rapid synthesis of (141) under solvent-free conditions. They reported, for the first time, the use of camphorsulfonic acid (140) as a novel catalyst, in combination with ultrasound technique. Conventional method was also discussed (Scheme 36). 

Shingare and co-workers have presented for the first time a successful implementation of ultrasound irradiation for the rapid synthesis of a-hydroxy phosphonates (521) and a-amino phosphonates (525) under solvent-free conditions from triethyl phosphite (524), aromatic aldehydes (523) and amines (522) using camphor sulfonic acid (CSA) (Scheme 130). One-pot, three-component Kabachnik-Fields synthesis of a-aminophos-phonates (529) from carbonyl compounds (526), primary amines (527), and dibenzyl/dimethyl/diethyl substituted phosphites (528) has been carried out in high yields, using H-beta zeolite as a reusable catalyst (Scheme 131). Zhang and co-workers have developed the nickel-catalysed Arbuzov type phosphonylation to afford phenyl substituted phosphonates (532) in the reaction of aryl triflates (530) with triethyl phosphite (531), in which KBr, as an additive, promoted the Sn2 catalytic step (Scheme 132). ... 

The generation of these free radicals and excited molecules of solvents and dissolved solutes set in a series of reactions which are either faster than those reactions that are carried out in the absence of ultrasound or sometimes result in end products, which are entirely different and unexpected. 

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