M. S. Manhas

Highly Accelerated Reactions in a Microwave Ovem: Synthesis of Heterocycles

Efficient synthesis of a wide variety of heterocycles on 0.1 to 200 g scale was conducted in organic solvents in a commercial microwave oven in a few minutes at a low energy level. Erlenmeyer flasks were adequate reaction vessels since neither high pressure nor high temperature were involved. Fast monitoring of synthetic reactions was achieved by tlc separation and transfer of tlc spot material directly to a solids probe of a chemical ionization mass spectrometer. Microwave oven-induced reaction enhancement (MORE) chemistry is not due to thermolysis: one reaction was conducted successfully in a reaction vial encased in a block of ice.

Studies on lactams—V : 3-azido-2-azetidinones

Abstract A convenient synthesis of α-amino-β-lactams has been devised with the aim of preparing derivatives and analogs of penicillin and cephalosporin C. It has been found that α-azido-β-lactams can be obtained from the reaction of α-azido acid chlorides with imines in presence of triethylamine. The azido group undergoes facile catalytic reduction to afford α-amino-β-lactams. The sequence of addition of the reactants influences the stereochemistry of the azido-β-lactam formed. The slow addition of azidoacetyl chloride to a solution of benzaliniline and triethylamine in methylene chloride favors the cis product, while the trans stereochemistry is favored when triethylamine is added to a mixture of the Schiff base and azidoacetyl chloride. Prolonged heating in presence of triethylamine did not result in the interconversion of cis- and trans- 1-phenyl-3-azido-4-(p-nitrophenyl)-azetidin-2-one. 1-Cholestanyl-3,3-dimethylazetidine-2-one has been prepared as an analog of the β-lactam-substituted steroid alkaloids reported recently.

Stereocontrol of β-lactam formation using microwave irradiation

Abstract Formation of β-lactams by the reaction of an acid chloride, a Schiff base and a tertiary amine seems to involve multiple pathways some of which are very fast at higher temperatures. When β-lactam formation is conducted in open vessels in unmodified domestic microwave ovens, high level irradiation leads to preferential formation of trans β-lactams in several cases when the Schiff base is derived from an aryl aldehyde rather than glyceraldehyde acetonide.

Microwave-Induced Organic Reaction Enhancement (More) Chemistry: Techniques for Rapid, Safe and Inexpensive Synthesis

Synthetic organic reactions have been conducted under microwave irradiation in open vessels in unaltered domestic microwave ovens. Reaction times vary from a few seconds for sub-milligram reactions to about 15 minutes for reactions carried out on a scale of hundreds of grams. Promising results have been obtained for several condensations, as well as the Bischler-Napieralski reaction, the Wolff-Kishner reduction, free radical dehalogenation reactions, and other standard synthetic operations. Rapid catalytic transfer hydrogenation using ammonium formate as the source of hydrogen has been conducted at about 100-130 °C under microwave irradiation.Meaningful, safe and inexpensive synthetic experiments for undergraduate and pre-college students have been developed and tested. The MORE chemistry techniques make it possible to use simple apparatus and very short reaction times.Commercial microwave ovens are now essential equipment in our research and teaching laboratories [1-3]. These ovens are relatively inexpensive, easy to move from one laboratory and set up in another, and safe to operate. Glass, plastics, and ceramics are essentially transparent to microwaves whereas many organic compounds are dipolar in nature and absorb microwave energy readily. We have found that untraditional experimental arrangements are possible for conducting a wide variety of organic reactions in open vessels inside domestic microwave ovens. Depending on the quantity of reactants, most reactions (on a scale of milligrams to several grams) can be completed in minutes instead of hours. One important element of our “Microwave-induced Organic Reaction Enhancement” (MORE) chemistry is the proper choice of a microwave energy transfer agent as the reaction medium.

Microwave-assisted rapid synthesis of α-amino-β-lactams

Abstract A rapid and convenient approach to α-amino-β-lactams has been developed using the tetrachlorophthalimido group as a masked amino substituent. Reaction between glycine and tetrachlorophthalic anhydride in DMF for about 90 sec in a domestic microwave oven led to an imidoacetic acid in high yield; the corresponding acid chloride reacted with Schiff bases to provide mixtures of trans and cis β-lactams. Nearly exclusive formation of trans β-lactams could be achieved in some cases in a few minutes by conducting β-lactam formation under strong microwave irradiation. Facile conversion to α-amino-β-lactams was realized in 5–10 minutes via solventless reaction of these α-amino-β-lactams with ethylenediamine at room temperature.

Polyhydroxy Amino Acid Derivatives via β-Lactams Using Enantiospecific Approaches and Microwave Techniques

Abstract Enantiospecific synthesis has been developed for α-hydroxy β-lactams of predictable absolute configuration starting with readily available carbohydrates. Stereospecific approaches and microwave assisted chemical reactions have been utilized for the preparation of these 3-hydroxy-2-azetidinones and their conversion to natural or non-natural enantiomeric forms of intermediates for gentosamine, 6-epi-lincosamine, γ-hydroxythreonine, and polyoxamic acid.

Microwave-induced organic reaction enhancement chemistry.4 convenient synthesis of enantiopure α-hydroxy-β-lactams1

Abstract A convenient and rapid synthesis of enantiopure α-hydroxy-β-lactams using microwave-induced organic reaction enhancement chemistry has been developed. Reactions in domestic microwave ovens, which are very convenient and economical for small scale work in research or teaching laboratories, can also be conducted on a preparative scale of 100–500g in simple beakers or flasks.

Stereoregulated synthesis of β-lactams from schiff bases derived from threonine esters

Abstract A variety of optically active 3-substituted-2-azetidinones has been prepared by the annelation of Schiff bases derived from cinnamaldehyde and D-threonine esters and their absolute configuration determined. When the β-hydroxyl group of threonine is unprotected, both enantiomeric forms of N-unsubstituted 3,4-disubstituted-2-azetidinones can be prepared from a single β-lactam-forming reaction. On the other hand, by converting the hydroxyl group of D-threonine to a bulky group (e.g., triphenylsilyl ether), very high diastereoselectivity can be induced. The multiple functional groups on these β-lactams can be easily modified to generate useful synthons for optically active sugars, alkaloids, and monocyclic and bicyclic β-lactam antibiotics.

Environ-friendly approaches to densely functionalized β-lactams

Abstract A convenient approach to densely functionalized α-allyl-β-lactams has been developed using organometallic reagents and α-keto-β-lactams. Indium mediated Barbier reaction in aqueous media proceeded with a higher level of diastereoselectivity and chemical yield than zinc mediated Barbier reaction in anhydrous organic solvents.

Enantiospecific synthesis of β-lactams via cycloaddition

Enantiospecific synthesis of variously substituted cis-β-lactams can be achieved by the annelation of Schiff bases from optically active ketal aldehydes derived from D-threonine. Similar annelation of Schiff bases from the triphenylsilyl ether of D-threonine ester and cinnamaldehyde leads to cis-β-lactams with high diastereofacial selectivity.