Imines, synthesis using microwave irradiation

Formation of the imine and subsequent reduction can often be achieved in one pot . Thus, a microwave-assisted reductive amination-cyclisation domino reaction was used as the key step in the synthesis of perhydrocyclo-penta[ij]quinolizines from 1,5,9-triketones. This type of heterocycle is an important structural element in a series of alkaloids. The reaction of the triketone with ammonium formate in PEG-200 was performed within 1 min using microwave irradiation of370 W in a domestic microwave oven. Amixture oftwo ofthree possible stereoisomers was obtained in 87% overall yield (Scheme 4.29)52. 

To address issues of high temperatures, extended reaction times, and expensive catalysts, Jun et al. [107] proposed two alternative methodologies. An optimized solvent-free, microwave-assisted combined imine formation, and ortho alkylation was first developed (Scheme 19.74). In this one-pot synthesis, the use of ZnCl2 was found to improve the yield of imine formation under microwave irradiation. 

The Pictet-Spengler reaction has mainly been investigated as a potential source of polycyclic heterocycles for combinatorial apphcations or in natural product synthesis [149]. Tryptophan or differently substituted tryptamines are the preferred substrates in a cyclocondensation that involves also aldehydes or activated ketones in the presence of an acid catalyst. Several versions of microwave-assisted Pictet-Spengler reactions have been reported in the hter-ature. Microwave irradiation allowed the use of mild Lewis acid catalysts such as Sc(OTf)3 in the reaction of tryptophan methyl esters 234 with different substituted aldehydes (aliphatic or aromatic) [150]. Under these conditions the reaction was carried out in a one-pot process without initial formation of the imine (Scheme 86). 

The synthesis of /Mactams from diazoketones and imines can be realized not only by using photochemical reaction conditions but also under the action of microwave irradiation. When the reaction was performed in o-dichlorobenzene at 180 °C, however, the rates of thermal and microwave-assisted formations of -lactams were shown to be identical within the limits of experimental error (80-85% conversion after 5 min) [30]. 

Rapid monoalkylations are achieved in good yield compared with classical methods. Of particular interest is the synthesis of ot-amino acids by alkylation of aldimines with microwave activation. Subsequent acidic hydrolysis of the alkylated imine provides leucine, serine, or phenylalanine in preparatively useful yields within 1-5 min [50], Alkylation of phenylacetonitrile was performed by solid-liquid PTC in 1-3 min under microwave irradiation (Eq. 36 and Tab. 5.14). The nitriles obtained can subsequently be quickly hydrolyzed in a microwave oven to yield the corresponding amides or acids [56]. 

This methodology has also been used by Bose, who described the synthesis of the thienamycin side chain [119], the first step of which was a [2+2] cycloaddition under microwave irradiation. Likewise, Khajavi described the reaction of trichloroacetic anhydride with imines [120] with classical heating the reaction requires the use of Fe2(CO)9 as a catalyst, whereas under microwave irradiation a catalyst is not required. 

Reduction ofimines using formates Ammonium formates and formic acid have been employed as reducing agents in the synthesis of secondary amines from imines. By simple mixing of the reagents and microwave irradiation without solvent, the amines were produced in good yields within 2.5-10 min (Scheme 4.28)51. 

The use of domestic microwave and automated oven in organic synthesis is well established (Microwave activation has become a very popular and useful technology in organic and medicinal chemistry. For some recent examples, see [128-131]). This is particularly very noteworthy because of the unconventional set up necessary for conducting the reaction. Microwave irradiation of a solution of imines 21, 23, and 29 with acetoxyacetyl chloride in chlorobenzene using a domestic and... 

When irradiated in a microwave oven using chlorobenzene and triethylamine, cis (3-lactams 44 and 47 did not isomerize to trims (3-lactams 43 and 46. These experiments clearly established that there is no isomerization of the cis (3-lactams to the more stable tram (3-lactams during reaction of imines with acid chlorides at a high temperature and under microwave irradiation. Irradiation of 21, 23, and 29 with 17 under identical conditions afforded the trans product 22a, 24a, and 30a as the only isomers. Therefore, the present study clearly indicated that microwave irradiation can accelerate the synthesis of (3-lactams (e.g., see [132-139]). No... 

In summary, we have described a general, simple and efficient methodology for the synthesis of A r-(/m-butvlsul-finyl)imines by using a heterogeneous polymer-supported catalyst (amberlist-15) under microwave irradiation. This method is useful for the synthesis of A-(fer -butylsulfi-nyl)imines (racemic and chiral) from aromatic as well as aliphatic aldehydes. This method can also be applied for the preparation of A-(ferf-butylsulfinyl)imines on a gram scale. 

Diels-Alder cyclizations are thermal reactions, and recent significant developments in the use of microwave irradiation to pyridine synthesis have been reported, including a series of pyrazolo[3,4- ]pyridines from nitroalkenes and pyrazolylimines with reaction times of 5-10min (Equation 115) <2000T1569>. This method appears to be general to this bicyclic class for example, replacement of the substituent on the imine allows for a C-2-unsubstituted pyridine. A range of cyclic and acyclic dienes have also been reported. 

Synthesis of thiazolidinones [PEG -RMIM]X ionic liquids have been used for rapid synthesis of a small library of amido 4-thiazolidinones from amine, aldehyde, and mercaptoacid components (Scheme 7.22) [74]. In an initial feasibility study, acid-functionalized benzaldehydes were first coupled to the [PEG -RMIM]X ionic liquids. Imines were formed by reaction of the supported aldehydes with primary amines. The reactions were run in open vessels. Optimum results were obtained by irradiating the reaction mixture with low power at 100 °C for 20 min. The imines were then condensed with mercaptoacids to give the desired thiazolidinones which were then cleaved from the ionic liquid support by amide formation. Microwave irradiation was again used in this cleavage step. The procedure entailed addition of a small amount of solid potassium tert-butoxide to a premixed mixture of the amine and supported thiazolidinone and microwave exposure for 10-20 min at 100 or 150 °G depending on the amine used. In another study, a series of one-... 

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