Reduction by dissolving metals
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- 2. www.scifysolution.com 1 Reduction by dissolving Metals Chemical methods of reduction can take place by addition of electrons to the unsaturated compound followed by transfer of protons or can take place by addition of hydride ion followed by protonation. Reductions that follow the first path are generally effected by a metal, the source of the electrons, and a proton donor, which may be water, an alcohol or an acid. However, in absence of proton source it can undergo dimerization or polymerization. The metals commonly employed in these reductions include the alkali metals, calcium, zinc, magnesium, tin and iron. The alkali metals are often used in solution in liquid ammonia or as suspensions in inert solvents such as ether or toluene, frequently with addition of an alcohol or water to act as a proton source. Reduction of carbonyl compounds Reduction of ketones to secondary alcohols can be effected by catalytic transfer hydrogenation or by complex hydrides or by sodium and an alcohol.
- 3. www.scifysolution.com 2 One feature of the sodium–alcohol method is that with cyclic ketones it normally gives rise exclusively or predominantly thermodynamically more stable alcohol. Trans Cis (More stable) (Less stable) The ratios of the more-stable (trans) product (equatorial substituents) and the cis product formed by reduction of 2-methylcyclohexanone with different reducing agents are given in Table below The ketone 4-tert-butylcyclohexanone similarly gives the more stable trans-4- tertbutylcyclohexanol almost exclusively on reduction with lithium and propanol in liquid ammonia. The high proportion of the more-stable product (equatorial hydroxyl group) formed in the reduction with a metal–alcohol is thought to arise from the preference for the intermediate radical anion (or other intermediate) to adopt the configuration with the equatorial oxygen atom. .Na . EtOH - Na EtOH
- 4. www.scifysolution.com 3 The reductive coupling of two aldehydes or ketones is referred to as the McMurry or pinacol coupling reaction and gives rise to a 1,2-diol (a pinacol) or an alkene (McMurry) Pinacol Coupling 2 Mg,HgCl2 McMurry Coupling 2 TiCl4,Zn Dioxane Reflux Carboxylic esters can be reduced by sodium and alcohols to form primary alcohols, known as the Bouveault–Blanc reaction, but has now been largely replaced by reduction with lithium aluminium hydride. When the reaction is carried out in the absence of a proton donor, for example with sodium in xylene or liquid ammonia, dimerization takes place known as Acyloin condensation, resulting in medium and large rings ring. Na Xylene Reflux H3O+ The Clemmensen reduction of aldehydes and ketones to methyl or methylene groups takes place by heating with zinc and hydrochloric acid. A non-miscible solvent can be used and serves to keep the concentration in the aqueous phase low, and thus prevent bimolecular condensations at the metal surface.
- 5. www.scifysolution.com 4 Zinc, HCl Reduction of conjugated double bond with metal and ammonia or an amine Reduction of conjugated double bond possible because the intermediate anion can be stabilized by electron delocalization. The best reagent is a solution of an alkali metal in liquid ammonia, with or without addition of an alcohol called as Birch reduction conditions. Under these conditions conjugated alkenes, α, β unsaturated ketones and even aromatic rings can be reduced to dihydro derivatives. Birch reductions are usually carried out with solutions of lithium or sodium in liquid ammonia. Any added alcohol can act as a proton donor to buffer against the accumulation of the strongly basic amide ion. Solutions of alkali metals in liquid ammonia contain solvated metal cations and electrons. Conjugated dienes are readily reduced to the 1,4-dihydro derivatives with metal–ammonia reagents in the absence of added proton donors. The protons required to complete the reduction are supplied by the ammonia. Na,NH3 Reduction of α, β unsaturated ketones gives the saturated ketone or saturated alcohol, depending on the conditions. In absence of alcohol as proton source saturated ketone is obtained, however in presence of ethanol as proton source, the saturated alcohol is obtained.
- 6. www.scifysolution.com 5 NH4Cl EtOH Li,NH3, 80% Li,NH3,Ether 92% Reduction of aromatic compounds with metal and ammonia One of the most useful synthetic applications of metal–ammonia–alcohol reducing agents is in the reduction of benzene rings to 1,4-dihydro derivatives. The presence of an alcohol as a proton donor is necessary in these reactions, for the initial radical anion is an insufficiently strong base to abstract a proton from ammonia. The alcohol also acts to prevent the accumulation of the strongly basic amide ion, which might bring about isomerization of the 1,4-dihydro compound to the conjugated 1,2-dihydro isomer (which would be further reduced to tetrahydrobenzene). EtOH . - . Li,NH3, EtOH Li,NH3, - Particularly useful synthetically is the reduction of methoxy- or amino substituted benzenes to dihydro compounds, which are readily hydrolyzed to cyclohexenones. The Birch reduction of benzenes containing electron-donating substituents takes place to give the 1,4-dihydro compounds in which the two new hydrogen atoms avoid the carbon atoms to which the electron-donating substituents are attached. This selectivity can be rationalized in terms of the relative electron densities of the carbon atoms in the intermediate radical anion. An electron-donating substituent destabilizes an adjacent negative charge and therefore the site of highest electron density is not alpha to such substituents.
- 7. www.scifysolution.com 6 EtOH. - . Li or Na EtOH Liq.NH3, Li or Na Liq.NH3, - The reduction of benzene rings substituted by electron-withdrawing carbonyl groups gives rise to 1, 4-dihydrobenzoic acid derivatives, in which the intermediate anion is alpha to the anion-stabilizing substituent. These intermediate carbanions can be alkylated in the alpha position to the carbonyl group. H3O+ -Na H3O+ Liq.NH3, C7H15Br Selective reduction of a benzene ring in the presence of another reducible group is possible if the other group is first protected in some way. Ketones, for example, may be converted to acetals or enol ethers to protect them from reduction. Selective reduction of less-electron-rich aromatic rings occurs in bicyclic aromatic compounds. EtOH Li,NH3,Ether 98% Stereo selective Birch reduction is possible and a number of examples have been reported, particularly for selective alkylation of the intermediate enolate anion
- 8. www.scifysolution.com 7 i)K, NH3,tBuOH ii) EtI Reduction of alkynes with metal and ammonia Alkynes are reduced to alkenes with metal-ammonia as reducing agents. The reduction is completely stereoselective and the only product from a disubstituted alkyne is the corresponding E-alkene. Na,NH3 THF THANK YOU www.scifysolution.com Free Mock Test - Quality Study Notes- Exam Update