Solvent-free conditions application examples

Other methodologies feature solvent-free conditions with neat starting material, tandem or cascade, catalyzed or uncatalyzed reactions, the use of aqueous media at high temperature and nonextractive techniques for product isolation. Examples appear among the following microwave-assisted applications. 

Under these solvent-free conditions, the oxidation of primary alcohols (e. g. benzyl alcohol) and secondary alcohols (e.g. 1-phenyl-l-propanol) is rather sluggish and poor and is of little practical utility. Consequently, the process is applicable only to a-hydroxyketones as exemplified by various examples including a mixed benzylic/ali-phatic a-hydroxyketone, 2-hydroxypropiophenone that delivers the corresponding vicinal diketone [106,107]. 

Recent examples, for instance, of the catalytic application of the commercially available macroporous Amberlyst-15 include the Michael addition of pyrroles to a,P-unsaturated ketones (Scheme 10.4) [48]. In this process, the acid ion exchange resin (dry, 10% w/w) allows on to obtain mono and dialkylated pyrroles 5 and 6 in reasonable yields. Similarly, this catalyst (dry, 30% w/w) can catalyze the aza-Michael reaction of amines with a,P-unsaturated ketones, esters and nitriles to afford 7 in 75-95% yields under solvent-free conditions. Interestingly, yields were significantly lower using typical solvents such as DCM (dichloromethane), CH3CN, THF, DMF or EtOH [49], Recycling the catalyst is possible in both cases, but a smooth decrease in the yield is observed for each new run. 

There are many examples of the successful application of MW-assisted chemistry to organic synthesis these include the use of benign reaction media, solvent-free conditions, and application of solid supported and reusable catalysts. Over the past few years, it was demonstrated that many transition-metal-catalyzed bond transformations can be significantly enhanced by employing MW heating under sealed-vessel conditions, in most cases without requiring an inert atmosphere. 

Several papers investigated the use of SPME for VFA analysis in wastewater and in air. Briefly, a fiber is exposed to the sample headspace or inserted directly into the sample. Analytes adsorb onto the fiber and are subsequently desorbed at high temperatures in the GC injection port. SPME is a solvent-free technique which introduces less potential contaminants into the GC compared to direct injections. SPME is also rapid since no further sample preparation steps are required. It may be used for routine analysis provided that the specific autosampler required for this method is available and that the optimized method conditions are suitable for autosampler application. Further information on principles and other applications of this technique can be found elsewhere. " " Parameters which have been optimized for VFA analysis are fiber coating, fiber exposure time, sample temperature, sample pH, sample agitation, potential salt addition, and desorption parameters. Surrogate standards employed for VFA analysis were 2-ethylbutyric acids for GC/FID or GC/MS and C-labeled organic acids for GC/MS. The method was optimized using standards in deionized water and only a few wastewater samples were analyzed as examples. 

In some exploratory experiments test conditions were selected for the phenol/ formaldehyde condensation. It was found that catalytic test experiments could best be carried out at a relatively high temperature, 180 C, to increase conversions generally a reaction time of 4Vi h was found suitable to compare materials with higher and lower deactivation rates. Application of 1,4-dioxane as a solvent did not improve the selectivity much, and therefore the experiments were carried out solvent free. Selectivities could be improved considerably when a higher phenol/formaldehyde-ratio was applied (see for example Figure 3) but, again to compare different catalysts, a molar ratio of 2/1 was considered most suitable in the catalytic test experiments. 

Two other interesting reports on IMFIDA reactions describe the application of solvent-free, solid-support catalyzed microwave technology. Indeed, as mentioned previously in Scheme 11.2, the IMHDA reaction for synthesis of octahydroacridine 6 was efficiently catalyzed by Si02/ZnCl2 under microwave irradiation conditions [36]. In another example (Scheme 11.10), sesamol 31 and 3-methyl-2-butenal 32 reacted to provide 35, under basic KIO-K clay-catalyzed solvent-free microwave conditions. The IMHDA reaction of o-quinone methine 34 produced the expected chromene 35 in 84% yield within 8 min. Conventional heating conditions at 110 °C (K10-K+, 60 min) were longer and provided the desired product 35 in an equivalent 91% yield but with 9% of another, unidentified product (Scheme 11.10) [34b]. 

Microwave-induced 1,3-dipolar cydoaddition reactions involving azomethine ylides have been widely reported in the literature. In 2002 many examples were described in a book chapter by de la Hoz [3j], which provides extensive coverage of the subject. The objective of this section is to highlight some of the most recent applications and trends in microwave synthesis, and to discuss the impact of this technology. Highly stereoselective intramolecular cycloadditions of azomethine ylides have been performed under solvent-free microwave conditions. 

Reactive ylides, in apolar solvents under salt-free conditions, preferentially form olefins with the (Z)-configuration (see Section C.l). To optimize this effect, various techniques have been developed for preparing salt-free ylide solutions [21-25]. The phosphonium salt is deprotonated, for example with sodium amide in THF or liquid ammonia [23], with sodium hexamethyldisilazane in an ether solvent such as THF [21], or with potassium r-butoxide in THF or toluene [22], with the addition of crown ether if appropriate [24]. A particularly elegant application of the salt-free Wittig reaction is the instant-ylide technique [25]. 

There is only a single example of application of this method to the synthesis of biologically interesting compounds. Stockland et al. carried out rhodium-catalyzed hydrophosphinylation of ethynyl steroids of type 185, as shown in Scheme 47.46, to obtain terminal phosphinates or phosphine oxide derivatives 186.As mentioned earlier, the reaction afforded -products exclusively. The authors examined different reaction conditions, with a focus on the green approach hence, solvent-free and aqueous conditions were used in combination with microwave heating. 

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