Reactions under reflux

Reactions under reflux with stirring. One assembly is depicted in Fig. II, 60, 6 a three-necked flask may be substituted for the flask and adapter. 

MW heated reactions in homogeneous media, using either neat reagents or in the presence of solvents, may also be performed at atmospheric pressure. This approach has been used particularly by Bose et al. [17]. (MORE Chemistry), who reported, for example, the rapid synthesis of heterocycles [18] in open vessels. Another approach, which avoids hazards due to the flammability of solvents, is to perform the reactions under reflux in a MW oven, which is modified to allow the reaction vessel to be attached to a reflux condenser outside the MW oven [7, 19]. It should be pointed out, however, that most of the available evidence shows that rate enhancements of MW heated reactions in homogeneous media at atmospheric pressure are small or nonexistent [19], This will be discussed in more detail later in this review (see also Chapt. 5 of this book). 

Although the reaction of alkali acetylides with oxirane proceeds slowly in liquid ammonia 15], it is an excellent method for preparing "homo-propargylic alcohols in quantities of 1 mol or more [2). Since oxirane is very volatile, considerable losses could occur if it is allowed to be swept along with the escaping ammonia vapour. One solution is to carry out the reaction under reflux, using a special condenser filled with dry ice and acetone. This would require regular addition of dry ice over a period of at least 12 h. It is much simpler to mix the acetylide... 

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. 

Similar results were obtained with chelation-controlled allylation mediated by radicals (Sch. 12) [28], In the presence of MgBr2 OEt2, the reaction of 2-iodoprop-ionate 29a with allyltributyltin 30 proceeded more readily even at a low temperature (-78 °C) than the reaction under reflux in hexane in the absence of the catalyst. The... 

Other ways to do this reaction would be to use what the dudes did in the old days ammonium formate [25]. This way uses 60g of ammonium formate, no formic acid, and a distillation setup. Another combination that works equally well is 1 1 formic acid and ammonia in place of formamide. It is also perfectly fine to remove the water under the distillation setup, then replace it with a reflux condenser and conduct the reaction under reflux for the 5 hours [10]. In fact, reflux is a good way to do any of these Leuckart reactions. 

A number of examples of dealkylations by chemical and catalytic methods are given in Table 4.7 (refs.89-93). A very general method for the cleavage of phenolic ethers consists in their reaction under reflux during 36 hours with an excess of 37% hydrobromic acid and a small amount of hexadecylammonium bromide. Phenyl n-pentyl ether gave phenol in 71% yield (ref.94). 

Safe Normal Operation of Reactions Under Reflux... 

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-... 

A further safety warning is necessary when running open-vessel reactions under reflux. The solvent being refluxed can in some cases function as an antenna for microwave radiation and so conduct microwaves out of the cavity into the external environment. This is likely to depend on the solvent and other parameters. When running microwave reactors in open-vessel reflux mode, a microwave leakage test should be performed to ensure that no microwaves are escaping from the cavity... 

Calorimeters can be adapted to run reactions under reflux and it is now possible to gain data just below, at and just above the boiling point of a reaction mixture. 

CALORIMETRY OF REACTIONS UNDER REFLUX In many chemical syntheses the reactants are allowed to self-heat until the reaction mixture boils. Energy is then extracted by refluxing the liquid until the reaction exotherm subsides. 

The components of the apparatus for heating a reaction under reflux on the microscale are the same as for a preparative scale reaction. A common set-up is shown in Figure 2.67. It is generally best to use a water-jacketed condenser to prevent any vapors from escaping a short-air condenser is frequently inadequate for the more volatile organic solvents such as diethyl ether and dichloromethane. 

Because volatile and flammable solvents are used in this experiment, flameless heating should be used for heating the reaction under reflux and for distilling the product. However, if it is necessary to use a small microburner to distill the product, be sure that no one is using flammable solvents in the laboratory. 

Miniscale apparatus for heating reaction under reflux, equipped with a gas trap and a separatory funnel for adding a solution. 

By a procedure identical to that described for the 2-(trimethylsilylethynyl)aniline S7a, 2-bromoaniIine S6d (2.09 g, 8.69 mmol) was converted into the known compound S7d (1.70 g, 76%) by the reaction under reflux for 16 h. 

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