Reaction under reflux conditions

Figure 3.8. Modification of a microwave cavity for performing chemical reactions under reflux conditions.

Wiss, J., Stoessel, F. and Kalle, G. (1990) Determination of heats of reaction under refluxing conditions. Chimia, 44 (12), 401-5. 

Independent of the mode chosen for the investigation of a reaction under reflux conditions, as mentioned, other facts may add to the difficulties which are caused either by changing physicochemical properties of the reaction mixture or by the device used. 

It is known from thermodynamics that the boiling point at constant pressure depends on the purity of the more volatile component. The majority of chemical reactions under reflux conditions are performed in a solvent for the reactants. Due to the change in composition of the reaction mixture, changes in the boiling temperature may be observed. In the case of irreversible reactions, this change in composition will occur until the limiting component has been consumed or until the equilibrium conversion has been reached. This fact usually results in differing calibration factors determined be-... 

In this way, the operational range of the Kolbe-Schmitt synthesis using resorcinol with water as solvent to give 2,4-dihydroxy benzoic acid was extended by about 120°C to 220°C, as compared to a standard batch protocol under reflux conditions (100°C) [18], The yields were at best close to 40% (160°C 40 bar 500 ml h 56 s) at full conversion, which approaches good practice in a laboratory-scale flask. Compared to the latter, the 120°C-higher microreactor operation results in a 130-fold decrease in reaction time and a 440-fold increase in space-time yield. The use of still higher temperatures, however, is limited by the increasing decarboxylation of the product, which was monitored at various residence times (t). 

Methyl esterification When prohexadione was treated with methanolic HCl (3%, w/v) or sulfuric acid-methanol (1 %, v/v) under reflux at 75 °C for 60 min, or with BFs-methanol (14%, w/v) under reflux at 75 °C for 30 min, the yield of the methyl ester of prohexadione was 95,93 and 82%, respectively (prohexadione, 10 qg, volume 2 mL of methanolic HCl, 2 mL of sulfuric acid-methanol and 1 mL of BFs-methanol). A solution of 1% (v/v) sulfuric acid in methanol was chosen for ease of preparation. Even if prohexadione was treated with 1% sulfuric acid in methanol at room temperature for 12h, the yield of prohexadione methyl ester was not different from that under reflux conditions as described in Section 6.3. The conditions for methyl esteriflcation in Section 6.3 were chosen because of shortening of the analysis time and the reproducibility of the reaction yield in residue analysis samples which could contain large quantities of contaminants. 

Oda et al. reported that under reflux conditions, the zinc-promoted reaction of 2,3-dichloro-l-propene with aldehydes and ketones in a two-phase system of water and toluene containing a small amount of acetic acid gave 2-chloroallylation products (Eq. 8.31).64 No conversion occurred when tin was used as the promoter. The absence of water completely shuts down the reaction. Interestingly, the action of 2,3-dichloropropene plus zinc powder in aqueous ethanol gives the dechlorination product, allene.65... 

LaClair (44) and Soloway et al. (SO) have modified the dehydrohalogenation reaction to permit the determination of p,p -DDT in dusts and oil solutions containing technical DDT. The reaction between the base and the halide is carried out at 20° to 30° C., as Cristol (16) has found that under proper conditions at this temperature the p,p -DDT reacts completely, whereas the o,p -DDT and most of the impurities react only slightly. The Association of Official Agricultural Chemists (3) tentative method for the determination of the purity of p,p -DDT, which employs the dehydrohalogenation procedure, has been modified by Fleck (30) so that the reaction is carried out at 25° C. instead of under reflux conditions. 

Compound 139 was synthesized by the reaction between macrocyclic triamine 138 and dimethoxy-Ar,Ar-di m e t hy 1 -methanamine in ethanol under reflux conditions (Equation 17) <1996JOC2020, 1997TL1911, 2001TL2735, 2004BCC174>. 

The yields for the optimized microwave-assisted Biginelli condensations are in general comparable to or higher than those obtained using the standard reflux conditions. More importantly, however, reaction times have been brought down from several hours (4—12 h) under reflux conditions to 10-20 min employing microwave... 

Inter- and intramolecular hetero-Diels-Alder cycloaddition reactions in a series of functionalized 2-(lH)-pyrazinones have been studied in detail by the groups of Van der Eycken and Kappe (Scheme 6.95) [195-197]. In the intramolecular series, cycloaddition of alkenyl-tethered 2-(lH)-pyrazinones required 1-2 days under conventional thermal conditions involving chlorobenzene as solvent under reflux conditions (132 °C). Switching to 1,2-dichloroethane doped with the ionic liquid l-butyl-3-methylimidazolium hexafluorophosphate (bmimPF6) and sealed-vessel microwave technology, the same transformations were completed within 8-18 min at a reaction temperature of 190 °C (Scheme 6.95 a) [195]. Without isolating the primary imidoyl chloride cycloadducts, rapid hydrolysis was achieved by the addition of small amounts of water and subjecting the reaction mixture to further microwave irradia-... 

Finally, another related study from the Sun laboratory concerned the synthesis of hydantoins utilizing acryloyl chloride to prepare a suitable polymer support [87]. All steps were carried out under reflux conditions in a dedicated microwave instrument utilizing 50-mL round-bottomed flasks. Identical reactions under classical thermal heating did not proceed in the same time period. 

Reaction of dibromoacetyl derivatives with thioamides or thioureas affords the corresponding 1,3-thiazoles under reflux conditions (Scheme 17).39... 

Chloro-2-ethynyladamantane (33) was the major product when 31 was reacted with concentrated hydrochloric acid. If 1,4-dioxane was used as the solvent, 82% of 2-(formylmethylene)adamantane (32) was obtained together with only 3% of the chloro product 33 (equation 11). It is remarkable that no reaction takes place even under reflux conditions with ethereal hydrogen chloride29. 

Under reflux conditions on a small scale in acetonitrile, the reaction was complete only after 24 h (entry 1). In a microwave reactor at 150°C, 86% isolated yield was achieved after 20 min reaction time (entry 2). Running the same reaction in DMSO or DMF at 150°C gave complete conversion of starting material, but because of losses during work-up, isolated yield was lower (entries 3 and 4). For scale-up trials, the Voyager SF was used, and the reaction was performed at 180°C for 20 min... 

An efficient pathway to 3,8-dihydro derivatives of the same ring system 496 was published by Lee et al. < 1994S1057, 1997S1461 > the ureido ethylidenehydrazones of type 494 were treated with triphenylphosphine in the presence of triethylamine in a carbon tetrachloride solution under refluxing conditions to yield the product 496 in acceptable yields. The transformation was rationalized to proceed via the zwitterionic intermediate 495. It is important to note that, in the cases of R = aryl group, the reaction proceeded in a totally different direction to furnish... 

Some N-glycosides have been synthesized as nucleoside analogues by Vilarrasa and co-workers <1996TL901>, the result is shown in Scheme 8. The starting compound, [l,2,4]triazolo[5,l-c][l,2,4]triazine-4(l//)-one 54, was reacted with tri-0-benzoyl-/3-diribofuranosyl bromide under two different reaction conditions. In the presence of silver triflate at low temperature, the zwitterionic 2-substituted compound 55 was obtained, whereas under reflux conditions in acetonitrile the neutral 1-substituted compound 56 was formed. 

One procedure for the synthesis of these title ring systems appeared recently <2003S1079>. Yadav and Kapoor described that the transformation of some oxadiazole and thiadiazole derivatives bearing specially substituted methylsulfinyl side chain 131, when reacted with thionyl chloride, give ring-closed compounds 134. The reaction was carried out in pyridine under reflux conditions in 74-79% yield. As shown in Scheme 25, the authors assume that the first step is the formation of the sulfonium salt 132 which undergoes cyclization with hydrogen chloride and sulfur dioxide elimination to 133 and, finally, demethylation of this intermediate leads to the final product 134. 

Indian authors reported the ring closure of the imidazolylamidine 240 to the tricyclic fused triazine 241 <1998IJB1283>. The reaction with aliphatic orthoesters was carried out under reflux conditions to yield the products in excellent yields. 

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