Continuous microwave irradiation

Scheme 2.6 Pulsed versus continuous microwave irradiation (bmimPF6 = l-butyl-3-methylimidazolium hexafluorophosphate).

A perhaps more exotic substrate for the Heck reaction is 1,2-cyclohexanedione [25], The reactivity of this molecule under Heck coupling conditions can probably be attributed to its resonance enol form. This reaction is attractive, because the literature contains relatively few examples of the preparation of 3-aryl-l,2-cyclohexane-diones. Yields varied from good to modest when classic heating and electron-rich aryl bromides were used, and reaction times typically ranged from 16 to 48 h. Similar yields were obtained under continuous microwave irradiation with a single-mode microwave reactor for 10 min at 40-50 W (Eq. 11.10) [25],... 

Two samples, one prepared under continuous microwave irradiation for 5 min and one prepared during five 6-s pulses, were analyzed by XRD, EDS, and TEM. The precursor chromium powder was also analyzed by XRD (Figure 7.3) to provide a benchmark. The XRD pattern of the sample prepared under pulsed irradiation, presented in Figure 7.4, contained CtjN peaks in addition to the Cr peaks that are present in Figure 7.3. The processed material was also analyzed by EDS. Although the pattern from analysis at 30 kV in Figure 7.5 did not detect nitridation, the EDS pattern at 5 kV revealed that a nitride compound was present on the surface. 

Chen et al. [137] employed microwave irradiation for the preparation of amine-or anhydride-terminated hb-PIs. A BB 2-type triamine monomer, namely 2,4,6-tris (4-aminophenyl)pyridine (TAPP) (1-16, Scheme 9a), was synthesized under microwave irradiation to prepare a series of amine- and anhydride-terminated triphenylpyridine-containing hb-PIs by A2 + BB 2 polymerization. Several commercially available aromatic dianhydrides, namely pyromellitic dianhydride (PMDA, 1-23, Scheme 9b), BTDA, and ODPA, were used as A2 type monomers to react with the BB 2 type aromatic triamine (TAPP). The addition of dianhydride to triamine with a monomer molar ratio of 1 1 yielded the amine-terminated polymer, whereas the reverse monomer addition order with a molar ratio of 2 1 gave the anhydride-terminated polymer. Slow monomer addition was used to avoid any high local concentration. The authors kept the total solid content below 0.08 mol/L for the amine-terminated polymer and 0.06 mol/L for the anhydride-terminated polymer to prevent insoluble gels. During the whole polymerization, continuous microwave irradiation was employed to enhance the reactivity and... 

The scope and efficiency of [4+2] cycloaddition reactions used for the synthesis of pyridines continue to improve. Recently, the collection of dienes participating in aza-Diels Alder reactions has expanded to include 3-phosphinyl-l-aza-l,3-butadienes, 3-azatrienes, and l,3-bis(trimethylsiloxy)buta-l, 3-dienes (1,3-bis silyl enol ethers), which form phosphorylated, vinyl-substituted, and 2-(arylsulfonyl)-4-hydroxypyridines, respectively <06T1095 06T7661 06S2551>. In addition, efforts to improve the synthetic efficiency have been notable, as illustrated with the use of microwave technology. As shown below, a synthesis of highly functionalized pyridine 14 from 3-siloxy-l-aza-1,3-butadiene 15 (conveniently prepared from p-keto oxime 16) and electron-deficient acetylenes utilizes microwave irradiation to reduce reaction times and improve yields <06T5454>. 

Current single-mode continuous-flow microwave reactors allow the processing of comparatively small volumes. Much larger volumes can be processed in continuous-flow reactors that are housed inside a multimode microwave system. In a 2001 publication, Shieh and coworkers described the methylation of phenols, indoles, and benzimidazoles with dimethyl carbonate under continuous-flow microwave conditions using a Milestone ETHOS-CFR reactor (see Fig. 3.11) [104]. In a typical procedure, a solution containing the substrate, dimethyl carbonate, 1,8-diazabicy-clo[5.4.0]undec-7-ene (DBU) base, tetrabutylammonium iodide (TBAI), and a solvent was circulated by a pump through the microwave reactor, which was preheated to 160 °C and 20 bar by microwave irradiation (Scheme 4.31). Under these condi-... 

Microwave heating has also been employed for performing retro-Diels-Alder cycloaddition reactions, as exemplified in Scheme 6.94. In the context of preparing optically pure cross-conjugated cydopentadienones as precursors to arachidonic acid derivatives, Evans, Eddolls, and coworkers performed microwave-mediated Lewis acid-catalyzed retro-Diels-Alder reactions of suitable exo-cyclic enone building blocks [193, 194], The microwave-mediated transformations were performed in dichloromethane at 60-100 °C with 0.5 equivalents of methylaluminum dichloride as catalyst and 5 equivalents of maleic anhydride as cyclopentadiene trap. In most cases, the reaction was stopped after 30 min since continued irradiation eroded the product yields. The use of short bursts of microwave irradiation minimized doublebond isomerization. 

The first application of microwave irradiation in conjunction with dry media in the generation of nitrile oxide intermediates was reported by Hamelin [29]. In this example, methyl nitroacetate (170) was mixed with a dipolarophile in the presence of catalytic amounts of toluene-p-sulfonic acid (PTSA) (10% weight). Subsequent microwave irradiation led to the formation of the corresponding heterocyclic adducts (Scheme 9.52). Reactions were performed in an open vessel from which water was continuously removed [103], Likewise, irradiation in a domestic oven of a mixture of ethyl chloro(hydroxyimino)acetate (173) and a dipolarophile over alumina led to the same results in only a few minutes (Scheme 9.52) [103]. 

Because the reaction is driven by protonation of the carbonyl functionality, reacting species were expected to be localized on the bed of the acid catalyst subjected to microwave irradiation. Hexane was used as a nonpolar solvent to minimize solvent absorption and superheating. Elimination of catalyst superheating in a continuous-flow reactor was most probably the reason why no significant differences were observed between the reaction rates under the action of microwave and conventional heating. 

No rate enhancement was observed when the reaction was performed under microwave irradiation at the same temperature as in conventional heating [47]. Similar reaction kinetics were found in both experiments, presumably because mass and heat effects were eliminated by intense stirring [47]. The model developed enabled accurate description of microwave heating in the continuous-flow reactor equipped with specific regulation of microwave power [47, 48]. Calculated conversions and yields of sucrose based on predicted temperature profiles agreed with experimental data. 

Wan et al. [61] also reported the highly effective conversion of methane to aromatic hydrocarbons over Cu, Ni, Fe, and Al catalysts. The effects of the type of catalyst, its configuration, and the microwave irradiation conditions on reaction path and product selectivity were examined under both batch and continuous-flow conditions. 

Traditional Heck arylation of the corresponding ethyl vinyl ether afforded high yields with most of the aryl bromides investigated (Eq. 11.11). Under continuous singlemode microwave treatment the transformations were complete within 10-12 min [25], Heck reactions without solvent in a domestic microwave oven have been examined by Diaz-Ortiz [26]. The reactions were conducted in closed vessels with reported temperatures of 150 °C. A study was performed in which reactions performed with microwave irradiation were compared with oil-bath-heated reactions with identical reaction times and temperatures. The isolated yields tended to substantially favor the microwave-heated reactions (Eq. 11.12). 

Gelens E, De Kanter FJJ, Schmitz RF et al (2006) Efficient library synthesis of imidazoles using a multicomponent reaction and microwave irradiation. Mol Divers 10(1) 17-22 Acke DRJ, Orru RVA, Stevens CV (2006) Continuous synthesis of tri- and tetrasubstituted imidazoles via a multicomponent reaction under microreactor conditions. QSAR Comb Sci 25(5-6) 474-483... 

JOU2236). In the case of TCE 33 the cyclization proceeds without a catalyst on short heating (73CB914). However, continuous heating leads to bis(6-hydroxy-2,4-dioxo-l,2,3,4-tetrahydropyrimidin-5-yl)malononi-trile. Modern modification involves a three-component reaction of aromatic aldehyde, malononitrile, and barbituric acid with solvent-free conditions under microwave irradiation (4-8 min, 70-95%) (03TL8307). 

Using this reaction block in a domestic microwave oven, the optimum conditions for the reaction were found to be four cycles of 2 min irradiation at 180 W followed by 2 min of rest. The cyclic approach was forced by the expandable vessels reaching their full capacity (20 times the reaction volume) after 2 min of irradiation, thereby requiring a rest period to allow the gas to contract before continuing the irradiation. These issues could obviously have been avoided by utilising reaction temperature control. In the above approach, there is no way of assessing the time spent at reflux thereby making reaction optimisation a difficult task due to reproducibility issues. 

Phenylacetylene lg (102 mg, 1.0 mmol) was added to a mixture of KF/A1203 (600 mg, 40% by weight) and cupric chloride (500 mg, 3.7 mmol) contained in a clean, dry 10-mL round-bottomed flask. The mixture was stirred at room temperature to ensure efficient mixing. The flask was then fitted with a septum (punctured by an 18 gauge needle), placed in the microwave and irradiated at 30% power for 2 min and then allowed to cool. The microwave irradiation was then continued for 6 min. After cooling, hexane (3 mL) was added and the slurry stined at room temperature to ensure product removal from the surface. The mixture was filtered and the product was purified by flash chromatography to yield 76 mg of diphenylbutadiyne 2g (75%). 

As was mentioned above, every efficient application of microwave energy to perform chemical syntheses requires reliable temperature measurement as well as continuous power feedback control, which enable heating of reaction mixtures to a desired temperature without thermal runaways. Moreover, power feedback control systems that are operated in the most microwave reactors enable a synthesis to be carried out without knowing the dielectric properties or/and conductive properties of all the components of the reaction mixture in detail. On the other hand, temperature control during microwave irradiation is a major problem that one faces during microwave-assisted chemical reactions. In general, temperature in microwave field can be measured by means of ... 

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