Monomode MW reactor

However, the possibility of the participation of nonthermal effects in MW-assisted reactions in nonpolar solvents is still an open question. Loupy et al. [55] observed an increase in yield and purity of the diazepine 36, in the reaction of ethyl acetoacetate with o-phenylenediamine using monomode MW reactor with focused MW heating, when compared with conventional heating with the same temperature profile. 

MW-assisted MCRs can also be conducted in standard organic solvents under both open and sealed vessel conditions. If solvents are heated in an open vessel, the boiling point of the solvent typically limits the reaction temperature that can be reached. The recent availability of modern monomode MW reactors [23] with on-line monitoring of both temperature and pressure has meant that MAOS in sealed vessels are increasingly commonly employed and this will be the method of choice for performing MW-assisted MCRs in the future, essentially if coupled with solvent-free procedures (cf Chapters 4 and 8). 

The reaction vas performed using i-PrOH as solvent in the presence of a catalytic amount of piperidine. The mixture vas irradiated in a monomode MW reactor for 5 min at 100 °C to furnish pyridones of type 17 in 27-96% yield. 

The reaction was conducted in a monomode MW reactor with an irradiation time of 2 min at 75 °C. The reaction was also performed under conventional thermal conditions, which resulted in reduced yields (60-70%) and prolonged reaction times (1 h). 

More advanced MW exploitation involves use of a monomode MW reactor equipped with a robotics interface that can be used for automated sequential library synthesis. The Biginelli reaction performed using this procedure employs a diverse set of starting compounds to prepare a 48-compound library of 26 [65], AcOH-EtOH was used as solvent and a catalytic amount of Yb(OTf)3 was added. When the unattended automation capabilities of the MW synthesizer are used a library of this size can be synthesized in 12 h. 

In their variation of Radziszewski s four-component reaction, an aldehyde, NH4OAC, a diketone, and an amine were combined to produce imidazoles 33. The reaction was performed in an automated monomode MW reactor at 160 °C using a mixture of chloroform and acetic acid as solvent. Product yields were up to 90%, depending on the nature of the different R groups. 

By use of a monomode MW reactor and MeOH as solvent reaction times could be reduced to 10 min (at 160 °C) compared to the original procedures by Blackburn et al. [72]. The more reactive, electron rich, amidines in combination with benzyl-isocyanide gave high yields (65-93%). Less reactive amidines gave reduced conversions to product and some side products were observed. 

Yet another procedure used to prepare fused pyrroles is three-component condensation of an acyl bromide, pyridine, and an acetylenic compound, catalyzed by basic alumina, to give the corresponding indolizines 42 in 87-94% yield (Scheme 17.31) [84]. The mixture was irradiated for 8 min in a monomode MW reactor vdth a temperature limit of 250 °C. 

Another MW-assisted application of the Ugi-de-Boc cyclization sequence (vide supra) is the construction of the interesting N-containing heterocyclic core of a qui-noxalinone 48. When the reaction was performed at room temperature good yields were obtained but it took 36-48 h to complete [89]. Tempest et al. modified the procedure to reduce reaction times and to simplify the purification of the Ugi condensation products [75]. They did this by irradiating a mixture of F-Boc protected diamine with a slight excess of phenylglyoxylic acid 46, aldehyde, and isonitrile in MeOH in a monomode MW reactor for 10-20 min at 100 °C, initially obtaining intermediate 47 (Scheme 17.35). 

Intermediate 50 was subsequently heated under reflux in triisopropylbenzene (232 °C) for 1.5 to 20 h to provide the basic canthine skeleton 51. Recently, Lindsley et al. reported a rapid MW-mediated procedure for synthesis of 51 [95]. This reaction, performed in a monomode MW reactor at 180 °C, required a reaction time of only 5 min. Even more interesting, treatment of the acryl hydrazide-tethered indole input, with benzil in the presence of 10 equiv. NH4OAC delivered not only the expected triazine 50 but also, directly, the 1,2-diphenyl canthine derivative 51 (Scheme 17.37, reaction path b). The products were formed in a 9 1 ratio of 50 and 51, respectively. In the one-pot reaction, the indole underwent a three-component condensation to generate 50 followed by an intramolecular inverse-electron-demand Diels-Alder reaction and subsequent chelotropic expulsion of N2 to generate the 1,2-diphenyl canthine 51. 

One example of a library synthesized via MW-assisted soHd-phase MCRs is that of Hoel and Nielson [13] (Scheme 2.3-9). The authors performed Ugi-4CC (four component condensation) reactions in a monomodal MW reactor between polymer (TentaGel)-bound amines and various aldehydes, carboxylic acids, and isocyanides to yield a mini library of 18a-acylaminoamides in just 15 minutes per compound. The reaction time was reduced by a factor of three. The yields were variable, but the authors reported highly pure products (>95%). 

Nucleophilic substitutions of pyrimidyl halides 519 with MeSNa, PhSNa, PhONa, MeONa, or EtONa as nucleophiles under irradiation in a monomode MW reactor in the presence of NMP, HMPA, or DMSO gave 69-97% yields of 520 within 0.5-10 min (Scheme 102). On conventional heating in the presence of NMP, 5-bro-mopyrimidine reacted with PhSNa to give only a 7% yield of 5-phenylthiopyrimi-dine when compared to 96% yield under MWI (02T887). 

Chemat and his coworkers [92] have proposed an innovative MW-UV combined reactor (Fig. 14.7) based on the construction of a commercially available MW reactor, the Synthewave 402 (Prolabo) [9[. It is a monomode microwave oven cavity operating at 2.45 GHz designed for both solvent and dry media reactions. A sample in the quartz reaction vessel could be magnetically stirred and its temperature was monitored by means of an IR pyrometer. The reaction systems were irradiated from an external source of UV radiation (a 240-W medium-pressure mercury lamp). Similar photochemical applications in a Synthewave reactor using either an external or internal UV source have been reported by Louerat and Loupy [93],... 

Tab. 6.8. Polyethers from isoidide and 1,8-dimesyloctane. Effect of reaction time on the yields of high-molecular-weight fraction (FP MeOH), low molecular weight fraction (FP Hex), and molecular weight distribution. Mn and Mw are, respectively, the number average and weight average molecular weights of the FP MeOH fraction and the ratio Mw/Mn is the polydispersity index (monomode microwave reactor, 300 W).

Two different kinds of MW reactor are currently emerging - multimode and monomode (also referred to as single mode) (Chapters 1 and 2 in this book). 

MW monomode reactor Ultrasound (cleaning bath) Conventional heating (oil bath)... 

Nucleophilic substitutions of benzyl halides as electrophiles with Ph3P or BU3P as nucleophiles have been conducted under solvent-free conditions with accurate control of the power and temperature using a monomode reactor (Synthewave S402). The results were carefully compared under similar conditions with either MW or A activation [137] (Eq. (50), Table 4.12) ... 

An eflEcient method for ring-closing metathesis [186] was established between solvent-free conditions under the action of MW in a monomode reactor (Eq. 92) ... 

The development of monomode reactors, which focus the electromagnetic waves in an accurately dimensioned wave guide, enables homogeneous distribution of the electric field leading to increased efficiency and reliability. So, the current trend in MAOS is to move away from the multimode MW ovens and use the more dedicated monomode instruments, which have only become available in the last few years [22, 23]. 

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