Zinc-activation procedures reaction

Since the free carbene ( CH2) is not thought to be present, the reagent (40) is termed a carbenoid. The activity of the zinc surface is of crucial importance to the smoothness and success of the reaction. Failure to ensure appropriate activation procedures may cause the reaction to fail, or the onset of the exothermic reaction may be delayed and then proceed with excessive vigour. The recent use of ultrasonic activation of the zinc surface from the outset of the reaction results in a smoother, less unpredictable reaction rate, and leads to satisfactory yields.118 Furthermore, sonication enables the cheaper dibromomethane to be employed.1 lb... 

This Section will cover these new developments as well as the older, more traditional, ones. As was the case with magnesium and lithium in the previous Sections, it should be mentioned that also not all the examples of zinc-activation presented here have been applied in Zn-Barbier reactions. Several of them come from other organic synthetic procedures such as the Reformatsky or the Simmons-Smith reaction. 

A major benefit of the use of DMCs compared with that of conventional base-catalyzed systems in these reactions is that they produce high-molecular-weight polymers, with very narrow molecular weight distributions, very low levels of unsaturation, and lower viscosities. The downside to using DMCs however is that they require an activation period at elevated temperatures in the presence of initiator molecules, which causes an induction period at the start of the polymerization process [10]. After this induction period, the polymerization process proceeds very rapidly, making it a very important parameter to control. The CAs play an important role in the catalytic activity of the DMCs and in the activation procedure. The zinc sites with bound CAs can be seen as dormant catalytic sites [11]. After exchange of the CA, preferably rerr-butanol, with initiator molecules such as polyfpropylene glycol), the dormant sites are converted into the very active catalytic sites. 

A modified procedure" uses activated zinc together with dry gaseous hydrogen chloride in an organic solvent, e.g. acetic acid, as reducing agent. Under those conditions the reaction occurs at lower temperatures as with the original procedure. 

With special techniques for the activation of the metal—e.g. for removal of the oxide layer, and the preparation of finely dispersed metal—the scope of the Refor-matsky reaction has been broadened, and yields have been markedly improved." The attempted activation of zinc by treatment with iodine or dibromomethane, or washing with dilute hydrochloric acid prior to use, often is only moderately successful. Much more effective is the use of special alloys—e.g. zinc-copper couple, or the reduction of zinc halides using potassium (the so-called Rieke procedure ) or potassium graphite. The application of ultrasound has also been reported. ... 

The chemistry of indium metal is the subject of current investigation, especially since the reactions induced by it can be performed in aqueous solution.15 The selective reductions of ethyl 4-nitrobenzoate (entry 1), 2-nitrobenzyl alcohol (entry 2), l-bromo-4-nitrobenzene (entry 3), 4-nitrocinnamyl alcohol (entry 4), 4-nitrobenzonitrile (entry 5), 4-nitrobenzamide (entry 6), 4-nitroanisole (entry 7), and 2-nitrofluorenone (entry 8) with indium metal in the presence of ammonium chloride using aqueous ethanol were performed and the corresponding amines were produced in good yield. These results indicate a useful selectivity in the reduction procedure. For example, ester, nitrile, bromo, amide, benzylic ketone, benzylic alcohol, aromatic ether, and unsaturated bonds remained unaffected during this transformation. Many of the previous methods produce a mixture of compounds. Other metals like zinc, tin, and iron usually require acid-catalysts for the activation process, with resultant problems of waste disposal. 

Recently, the required heteroaromatic organozinc halides for the Negishi reaction have also been prepared using microwave irradiation [23]. Suna reported that a Zn - Cu couple (activated Zn), prepared using a slightly modified LeGoff procedure from Zn dust and cupric acetate monohydrate, allowed the smooth preparation of (3-pyridinyl)zinc iodide and (2-thienyl)zinc iodide... 

The reaction between acyl halides and alcohols or phenols is the best general method for the preparation of carboxylic esters. It is believed to proceed by a 8 2 mechanism. As with 10-8, the mechanism can be S l or tetrahedral. Pyridine catalyzes the reaction by the nucleophilic catalysis route (see 10-9). The reaction is of wide scope, and many functional groups do not interfere. A base is frequently added to combine with the HX formed. When aqueous alkali is used, this is called the Schotten-Baumann procedure, but pyridine is also frequently used. Both R and R may be primary, secondary, or tertiary alkyl or aryl. Enolic esters can also be prepared by this method, though C-acylation competes in these cases. In difficult cases, especially with hindered acids or tertiary R, the alkoxide can be used instead of the alcohol. Activated alumina has also been used as a catalyst, for tertiary R. Thallium salts of phenols give very high yields of phenolic esters. Phase-transfer catalysis has been used for hindered phenols. Zinc has been used to couple... 

The cyclopropanation of 1-trimethylsilyloxycyclohexene in the present procedure is accomplished by reaction with diiodomethane and diethylzinc in ethyl ether." This modification of the usual Simmons-Smith reaction in which diiodomethane and activated zinc are used has the advantage of being homogeneous and is often more effective for the cyclopropanation of olefins such as enol ethers which polymerize readily. However, in the case of trimethylsilyl enol ethers, the heterogeneous procedures with either zinc-copper couple or zinc-silver couple are also successful. Attempts by the checkers to carry out Part B in benzene or toluene at reflux instead of ethyl ether afforded the trimethylsilyl ether of 2-methylenecyclohexanol, evidently owing to zinc iodide-catalyzed isomerization of the initially formed cyclopropyl ether. The preparation of l-trimethylsilyloxybicyclo[4.1.0]heptane by cyclopropanation with diethylzinc and chloroiodomethane in the presence of oxygen has been reported. "... 

Procedure B. Finely cut (0.15 g, 22.0 mmol) and a stoichiometrical amount of naphthalene (2.80 g, 22.0 mmol) were weighed into a 100-ml flask, and ZnCl2 (1.5 g, 11.0 mmol) was weighed into a 50-ml flask. The Lithium and naphthalene were dissolved in THF (20 ml) in ca. 2h. ZnCl2 was dissolved in THF (20 ml) and the solution was transferred into the flask with lithium naphthalide via cannula over 10 min. The reaction mixture was further stirred for 1 h, and the resulting black suspension of active zinc thus prepared was ready for use. 

Mossy zinc is activated by conversion to zinc amalgam by brief immersion in a dilute aqueous solution of mercuric chloride and decantation of the solution before the reaction proper (40 g of mossy zinc, 4g of mercuric chloride, 4 ml of concentrated hydrochloric acid and 40 ml of water [759]). This type of activation is especially used in the Clemmensen reduction which converts carbonyl groups to methylene groups [160 Procedure 31, p. 213). 

This structural change is suppressed by the addition of tetrahydrothiophene (THT)19b. It prevents the formation of polymethylene zinc, i.e. (—CH2Zn—) . Without THT, a solution of 3 in THF yields polymethylene zinc at 60 °C. Monomeric bis(iodozincio)methane (3) is much more active for methylenation as compared to polymethylene zinc. As shown in Table 3 (entry 3), the addition of THT to the reaction mixture at 60 °C improved the yield of the alkene dramatically. Practically, however, its stinking property makes the experimental procedure in large scale uncomfortable. Fortunately, an ionic Uquid, l-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF6]), plays the same role. Ionic liquid also stabilizes the monomeric structure of 3 even at 60 °C and maintains it during the reaction at the same temperature. The method can be applied to various ketones as shown in Scheme 14.4... 

Metal-substitution studies, especially those in which Co11 replaces Zn11, have proved to be an important tool in the study of zinc metalloenzymes the Con-substituted species often have activities approaching those of the Zn11 enzyme in its in vivo reaction. These modification procedures have been the subject of a recent review,1265 which, however, focusses in particular on the use of substitution-inert metal ions. A recent innovation in metal-substitution techniques is the replacement of Znn in zinc metalloenzymes by 113Cdn, which can then be examined by Cd NMR. The results of a recent such investigation1266 indicate that the u3Cdn can serve as an... 

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