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Catalytic Transfer Hydrogenation. In recent years a few labatories have started to employ catalytic transfer hydrogenation (CTH)3. This is a safe and simple operation in which the catalyst and hydrogen gas are replaced with a catalyst and a hydrogen donor such as cyclohexane4, hydrazine5, formic acid6, ammonium formate7, cyclohexdiene8, and phosphinic acid9, sodium hypophosphite10. This type of hydrogenation is usually conducted in flasks fitted with a magnetic stirrer and a reflux condenser. Ethyl alcohol is a widely used solvent for CTH. Recently we11 have demonstrated that catalytic transfer hydrogenation can be conducted very rapidly and in essentially quanitative yield inside an unmodified domestic microwave oven. ...
Microwave-Assisted Reactions. Two pioneering papers12 appeared in 1986 on remarkable acceleration of many organic reactions upon irradition with microwaves (2450 MHz). Since then a number of labatories, inculding our own, have been studying microwave-assisted chemical syntheses13...
... We prefer to conduct experiments in open vessels in inexpensive, unmodified, domestic microwave ovens. A wide variety of compounds have been synthesized using our microwave-induced organic reaction enhancement (MORE) chenistry techniques15.
These techniques are also very convenient for rapid and safe catalytic transfer hydrogenation experiments.
MORE Chemistry Techniques. We have devolpedan unconvential experimential set up for conducting organic reactions to take advantage of the special nature of microwave energy.
Erlenmeyer flasks or beakers with loose covers are preferred reaction vessels for ambient pressure reactions in unmodified domestic microwave ovens. The upper parts of these vessels remain cool since glass is transparent to microwaves. The solvent (microwave transfer agent) should be polar and with a suitably high boiling point at least 20°C or 30°C higher than the projected reaction tempature.
Domestic microwave ovens produce 2450 MHz radition at a rate that is controlled to a moderate degree by an "on-off" cycle. For finer control of the microwave energy input to small-scale reaction mixtures, it is convenient to use a "heat sink"- a beaker of water placed next to the reaction vessels inside the oven. This heat sink with appropriate amounts of water captures a significant amount of the microwave energy thereby reducing the energy supplied to the reaction mixture.
Since microwave energy is absorbed by all of the polar molecules at the same time, no stirrer is required for reaction mixtures in shallow layers. ...
Microwave-Assisted CTH. Ethylene glycol (bp 198°C) or more eco-friendly 1,3-propanediol, bp 210-212°C as the solvent and ammonium formate as the hydrogen donor form an excellent combination for catalytic transfer hydrogenation under microwave irradition. Hydrazine hydrate was used as the hydrogen donor in a few cases but ammonium formate proved to be more convenient. Most of our studies on CTH reactions have been conducted with Pd/C (10%) catalyst. A few experiments were catalyzed with Ra/Ni catalyst. ...
Reduction and Hydrolysis of β-Lactams. ...
... We17 obsevred eariler that, in the presense of a large excess of Raney Nickel catalyst and hydrogen, 3-methoxy-1,4-diphenyl-2-azetidinone under went β-lactam scission to provide a small amount of the anilide of α-methoxy-β-phenylproponic acid (Scheme 5). However under milder conditions, cleaveage of the β-lactam ring does not occur.
Recently we11 have studied microwave assisted catalytic transfer hydrogenlysis at 120-130°C using 10% Pd/C as the catalyst. Rapid scission of 4-phenyl-2-azetidinones was observed in every case. The N-benzyl group of the β-lactam9 was not hydrogenolyzed, but the O-Bn group at C-3 was converted to an OH group; alkenes (11, 13, and 15) were reduced to alkyl groups (scheme 7). The reduction product was obtained in high yield and in a few minutes. It is useful to note that under these conditions Ra/Ni did not cause cleave of the β-lactam ring in 3 (See scheme 2). "
[Paraphrase of scheme 7]
"Scheme 7 ... [where _ is a spacer, Bn = C6H5-CH2, Ph = C6H5, MWI* = microwave irradition]
BnO-HC---CH-Ph HCO2NH4, 10% Pd/C
|___| ------------------->
O=C---N-R Ethlyene Glycol, MWI* - 80-83%
9
HO-HC---CH2-PH
|___|
O=C---NH-R
10
"In summary, we have devised safe, rapid, and effiecent techniques for conducting catalytic hydrogenation and hydrogenolysis useing just beakers and flasks and unmodified domestic microwave ovens. ...
General Procedure for CTH Reactions. ... The reaction vessel should be a beaker or Erlenmeyer flask of fairly large size. A beaker of water should be be placed near this reaction vessel to serve as a "heat sink" to provide a finer control on the amount of microwave energy input into the hydrogenation mixture. Water absorbs microwave energy very efficently and thereby reduces the amount of energy absorbed by the reaction mixture. The approxiamate amount of water to be used can be determined by a trail run involving only the solvent and without the catalyst.
The desired tempature of the solvent should rise to 110-120°C in about 3 min. The catalyst should be quickly introduced into the reaction vessel and covered with the solvent (such as ethylene glycol, bp 198°C) and made into a slurry by gently swirling motion of the beaker or the conical flask. The compound to be reduced is dissolved in the solvent (ethlyene glycol or 1,3-propanediol) and then added to the reaction vessel. The hydrogen donor (such as ammonium formate) is added now. microwave irradition for the predetermained peroid of time to reach a tempature of 110-130°C should be applied. The microwave oven door should be opened, and the tempature of the reaction mixture shloud be checked to be in the desired range.
The oven door should be closed and irraditionwith the microwave should be resumed for another 3-4 min. The microwave oven should be switched off, and the reaction vessel removed from the oven. Careful decantation of the reaction mixture after cooling followed by the addition of glycol to the reaction vessel would preserve the catalyst for the next experiment.
It is customary in our labatory to place a beaker cover or filter funnel on top of the reaction vessel to prevent any accidential spillage. Since glass is nearly transparent to microwaves, the upper parts of the beaker or flask serves as a condenser for any small amounts of vapor formed. ... We have observed that the optimal ratio of the catalyst (10% Pd/C) to substrate is 0.3:1 by wieght for each reducilble group. Five equivalents of ammonium formate for each reducible group gave good results."