Amino microwave effects

This microwave effect is consistent with the fact that the rate-determining step may be certainly the generation of aldimine A from aldehydes and 2-amino 3-pico-line. It is in agreement with the transition state develops a dipole and, consequently more polar than the ground state. To ascertain this hypothesis, it was effectively next shown that the reaction involving reaction with preformed aldimine A, no revealed any microwave effect [119]. 

Primary amino methylene substituents were introduced by a sequence of cya-nodehalogenation and subsequent reduction of the resulting nitrile with borane dimethyl sulfide. To incorporate tertiary aminomethylene substituents into the 2-pyri-done framework, a microwave-assisted Mannich reaction using preformed iminium salts proved to be effective. 

The noticeable rate enhancement due to a microwave-specific effect is consistent with a reaction mechanism in which the kinetic rate-determining step is nucleophilic attack of an amino group on the chloroquinoline ring (Scheme 3.16). 

Mildly basic liquiddiquid conditions with a stoichiometric amount of catalyst prevent hydrolysis during alkylation [101] and, more recently, it has been established that solid-liquid or microwave promoted reactions of dry materials are more effective for monoalkylation [102-106] of the esters and also permits dialkylation without hydrolysis. Soliddiquid phase-transfer catalytic conditions using potassium f-butoxide have been used successfully for the C-alkylation of diethyl acetamido-malonate and provides a convenient route to a-amino acids [105, 107] use of potassium hydroxide results in the trans-esterification of the malonate, resulting from hydrolysis followed by O-alkylation. The rate of C-alkylation of malonic esters under soliddiquid phase-transfer catalytic conditions may be enhanced by the addition of 18-crown-6 to the system. The overall rate is greater than the sum of the individual rates observed for the ammonium salt or the crown ether [108]. 

To carry out the similar MCR involving 5-amino-3-methyl-l-phenylpyrazole, aromatic aldehydes, and 3-cyanoacetyl indoles, Zhu et al. [70] used microwave-assisted synthesis in glygol at 150°C. Application of other solvents was less effective and gave either no reaction products (water medium) or led to the sufficient yield decreasing (EtOH, HOAc, DME). Microwave irradiation was also used by Quiroga et al. [71] to synthesize ether 4-aryl-5-cyano-6-phenylpyrazolo[3,4-b]pyridine-3-ones or their dihydroderivatives under argone atmosphere. 

A common and effective direct approach to unsubstituted or multiply substituted oxazolines is the Lewis acid catalyzed reaction of nitriles with amino alcohols in an alcoholic or aromatic solvent (chlorobenzene) at reflux. The most common Lewis acids employed include ZnCl2, ZnBr2, NiBr2, CuCl2, and kaolinitic clay. Microwave irradiation has also been reported to facilitate the transformation. Alternatively, the condensation can be carried out in the presence of catalytic amounts of potassium carbonate. The method works well for both aliphatic and aromatic nitriles, with retention of stereochemistry. Some representative examples from the recent literature are listed in Table 8.16 (Scheme 3 40),2 35.2oi-2i3... 

Due to the rapid and extensive metabolism of nitrofurans in animals, thermostability studies on residues of the parent compounds are not relevant and not published. Instead, the effect of cooking on the concentrations of both the bound and extractable 3-amino-2-oxazolidinone, tire main furazolidone metabolite, in incurred swine tissues has been investigated (43). Total 3-amino-2-oxazolidinone concentrations were not found to be significantly reduced in liver, kidney, or muscle following frying, grilling, or microwaving. 

The pharmaceutical value ofthe unsubstituted thiazoloquinazolinones maybe limited due to a lack of substituents such as basic amino groups. However, the microwave-assisted multi-step approach (Scheme 3.44) would enable investigation of the effect of introducing various substituents on biological activity. Previously, the same group had reported another microwave multi-step synthesis (six steps) of thiazoloquinazolinone derivatives70. Unfortunately, this pathway was not well adapted for easy introduction of various substituents on the core and only one isomer could be obtained. 

In order to eliminate the influence of temperature on the rate of a chemical reaction, a reaction mixture of phthalic anhydride with amino acids was placed in a block of ice and then irradiated under microwave conditions. Ice was used to cool the reaction mixture because opposite to water it is transparent to microwaves (e 3.2, c" 0.0029 at 25°C for 2.45 GHz) [26]. The reaction product was formed after 3 min. of irradiation while under conventional conditions the reaction was conducted in a boiling toluene solution for 1.5 h. However, since in such a case microwaves interact directly with the reaction mixture and temperature was not monitored during the experiments, it was stated that the increase of the reaction rate is not only due to thermal effects [27]. 

Steroidal, alicyclic or aromatic annulated pyridines were prepared via a microwave-assisted, base-catalyzed Henry reaction of /1-formyl enamides and nitromethane on an alumina support [97]. Highly substituted tri- and tetrasubstituted pyridines were synthesized in a Bohlmann-Rahtz reaction from ethyl /3-amino crotonate and various alkynones. The reaction involved a Michael addition-cyclodehydration sequence and was effected in a single synthetic step under microwave heating conditions [98]. An alternative approach towards polysubstituted pyridines was based on a reaction sequence involving an inverse electron-demand Diels-Alder reaction between various enamines 45 and 1,2,4-triazines 44 (Sect. 3.6), followed by loss of nitrogen and subsequent elimination-aromatization. Enamines 45 were formed in situ from various ketones and piperidine under one-pot microwave dielectric heating conditions [99]. Furthermore, a remarkable acceleration of the reaction speed (from hours and days to minutes) was observed in a microwave-assisted cycloaddition. Unsymmetrically substituted enamines 45 afforded mixtures of regioisomers (Scheme 35). 

Zhang and co-workers [186] reported a microwave-assisted one-pot, three-component [3-f2] cycloaddition reaction of a fluorous amino ester, an aldehyde and a maleimide to afford bicyclic prolines 135 in yields up to 94%. Fluorous solid phase extraction (F-SPE) has been used effectively to separate the product from the reaction mixture (Scheme 105). 

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