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dormouse
(Member) 04-20-00 09:02 No 108378 |
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CTH Reductions -Cherrie Baby | Bookmark | |||||
the Hive BB Novel Discourse CTH Reductions profile | register | preferences | faq | search next newest topic | next oldest topic Author Topic: CTH Reductions Cherrie Baby Member posted 06-09-98 04:48 PM ---------------------------------------- CTH - Catalytic Transfer Hydrogenation This looks like a very promising road to explore for reseach. The chemicals involved are just 5% or 10% Pd/C and ammonium formate. How would polymer supported Pd work? The reaction conditions are mild [reflux at 100 C.] The ammonium formate acts as a hydrogen donor (sodium formate works too). This interests me cos' my hardware shop sells ammonium formate solution as kettle descaler. It could interest other bees in the UK. Eg. Ketones were reduced to alkanes [sounds a lot better than Wolff-Kischner or Clemmensen for this.] Alkens are reduced to alkanes. Aromatic nitros to amines. What would happen with aliphatic nitros. Who knows? Nobody has yet written up their reseach. Sounds like a juicy PhD here for someone Rhodium? See J. Chem. Education 74(4), p430 (1997) for starters or Tetr. Lett. 1988, 29, 3741. redxn of nitrocompounds with Pd/C* & HCOOH: "Most of the nitro-compounds reduced have been aromatic or heteroaromatic but 2-nitropropane and beta-nitrostyrene were also reduced under this conditions, the latter yielding phenylacetaldehyde oxime." I have ref about selective redxn of polynitroaromatics with triethylamine/HCOOH in presence of Pd/C. Why not to use hydrazine hydrate/HCOOH? redxn of nitrocompounds with Pd/C* & HCOOH: "Most of the nitro-compounds reduced have been aromatic or heteroaromatic but 2-nitropropane and beta-nitrostyrene were also reduced under this conditions, the latter yielding phenylacetaldehyde oxime." I have ref about selective redxn of polynitroaromatics with triethylamine/HCOOH in presence of Pd/C. Why not to use hydrazine hydrate/HCOOH? General procedure for the reduction of Azides to Amines [from Ref 2.] A mixture of 1 mole of azide, 4 moles of anhydrous ammonium formate and 5% Pd-C (6-15% of the azide by weight) in 100 mL of methanol is stirred for 3-4 hours at ambient temperature. The catalyst is removed by filtration and the product is isolated by standard procedures. Yield 74-93%. General procedure for the reduction of nitro-alkanes. [from Ref 1.] To a stirred suspension of an appropriate nitro compound (5 mmol) and 10% Pd-C (0.2 - 0.3 g) [see Note 1] in dry methanol (10 mL), anhydrous ammonium formate was added (23 mmol) in a single portion. The resulting reaction mixture (slightly exothermic and effervescent) was stirred at room temperature for 3-40 min under argon[see Note 2], the catalyst was removed by filtration through a celite pad and washed with dry methanol (10 mL). The filtrate was evaporated either under reduced or at normal pressure. The resulting residue was triturated with water (10 mL - 25 mL), product was extracted with an organic solvent (i.e. ether, DCM or chloroform) and dried over Na2SO4. The organic layer on evaporation gave the desired amino derivative. Some products were directly converted into the HCl-salt with ethereal-HCl without evaporation of ether layer. In most cases the reaction is over within 15-30 min with nitro-alkanes. These results demonstrate a rapid versatile and selective reducing system for wide variety of nitro-compounds in the presence of other functional groups for e.g. -CN. > C=O, etc. Ammonium formate also has the advantages of being readily available, inexpensive, stable and nontoxic and can be used in conjunction with either Pd-C or Raney-Nickel catalysts. Moreover, it may be added to the reaction in a single portion and products can be easily separated from the reaction mixture. This procedure will therefore be of general use for the preparation of amines specifically in cases where rapid mild reduction is required. A typical procedure for reduction of aldehydes and ketones. [ref. 4] To a stirred suspension of an appropriate aldehyde or ketone (7.5 mmole) and 10% Pd-C (0.350 g) in glacial acetic acid (10 ml), the anhydrous ammonium formate (38 mmole) was added in a single portion under argon. The resulting reaction mixture was stirred at 110°C +/- 5°C for 10-30 min. The progress of reaction was monitored by TLC and GC. After completion of the reaction, 50 ml of CHCl3 was added, and the catalyst was removed by filtration through a celite pad and washed with CHCl3 (20 ml). The combined organic filtrate was washed with water (20 ml x 2), then with saturated sodium bicarbonate solution (20 ml x 2), and dried over anhydrous Na2SO4. The organic filtrate on evaporation, either under reduced pressure or at normal pressure, afforded the desired product, which was further purified by column chromatography over silica gel using an ethyl acetate:hexane mixture as the mobile phase. The phenolic derivatives were obtained by direct evaporation of filtrate after removal of the catalyst. Yields from a variety of methoxy ring-substituted benzaldehydes to the corresponding methoxy-ring substituted toluene varied from 57-70% but benzaldehyde required a longer reduction time and gave only 10% yield of toluene. The reduction of acetophenone was sluggish. After a 30 min reaction time interval, the product/substrate ratio in the reaction mixture was 1/5 observed by GC analysis (as described above, except initial temperature hold time 3 min). However, upon adding an additional amount of HCO2NH4 and increasing the reaction time up to 4 hr. the product/substrate ratio changed to 55/44. In the case of benzaldehyde, 1.5% toluene, 34% benzyl alcohol (retention time 4.9 min) and 60% high boiling by-product (retention time 8.9 min) were observed in the reaction mixture after 20 min at 85°C. Prolonging the reaction time slowly increases the concentration of toluene (Table 1) with reduction of benzyl alcohol. This important observation provides evidence that reduction of aldehydes and ketones to hydrocarbons proceeds via the alcohol intermediate, which is further confirmed by our finding that diphenylmethanol is rapidly converted to diphenylmethane under the experimental conditions reported here. The poor yield of toluene may be due to its low boiling point. These results demonstrate a rapid, mild and selective reduction of a wide variety of aromatic aldehydes and ketones to methylene derivatives under moderate reaction conditions and can be an attractive alternative for Wolff-Kishner or Clemmensen reduction, provided other functionalities such as nitro or halo substituents are not present in the substrate, since these groups are readily reduced or displaced. We have found, however, this procedure is not applicable for reduction of conjugated olefinic carbonyl groups, as the C-C double bond is preferentially reduced. Other Applications of CTH with Amm. Formate are: dehalogenation of aromatic chlorocarbons, deprotection of peptides and reduction of hydrazones and azides to hydrazines. Note 1 - Other catalysts can be used. Polymer supported Pd catalyst should work. Raney Ni often works and Urushibara Ni should work as well [but these are untested]. References: General procedure for the reduction of Azides to Amines [from Ref 2.] A mixture of 1 mole of azide, 4 moles of anhydrous ammonium formate and 5% Pd-C (6-15% of the azide by weight) in 100 mL of methanol is stirred for 3-4 hours at ambient temperature. The catalyst is removed by filtration and the product is isolated by standard procedures. Yield 74-93%. General procedure for the reduction of nitro-alkanes. [from Ref 1.] To a stirred suspension of an appropriate nitro compound (5 mmol) and 10% Pd-C (0.2 - 0.3 g) [see Note 1] in dry methanol (10 mL), anhydrous ammonium formate was added (23 mmol) in a single portion. The resulting reaction mixture (slightly exothermic and effervescent) was stirred at room temperature for 3-40 min under argon[see Note 2], the catalyst was removed by filtration through a celite pad and washed with dry methanol (10 mL). The filtrate was evaporated either under reduced or at normal pressure. The resulting residue was triturated with water (10 mL - 25 mL), product was extracted with an organic solvent (i.e. ether, DCM or chloroform) and dried over Na2SO4. The organic layer on evaporation gave the desired amino derivative. Some products were directly converted into the HCl-salt with ethereal-HCl without evaporation of ether layer. In most cases the reaction is over within 15-30 min with nitro-alkanes. These results demonstrate a rapid versatile and selective reducing system for wide variety of nitro-compounds in the presence of other functional groups for e.g. -CN. > C=O, etc. Ammonium formate also has the advantages of being readily available, inexpensive, stable and nontoxic and can be used in conjunction with either Pd-C or Raney-Nickel catalysts. Moreover, it may be added to the reaction in a single portion and products can be easily separated from the reaction mixture. This procedure will therefore be of general use for the preparation of amines specifically in cases where rapid mild reduction is required. A typical procedure for reduction of aldehydes and ketones. [ref. 4] To a stirred suspension of an appropriate aldehyde or ketone (7.5 mmole) and 10% Pd-C (0.350 g) in glacial acetic acid (10 ml), the anhydrous ammonium formate (38 mmole) was added in a single portion under argon. The resulting reaction mixture was stirred at 110°C +/- 5°C for 10-30 min. The progress of reaction was monitored by TLC and GC. After completion of the reaction, 50 ml of CHCl3 was added, and the catalyst was removed by filtration through a celite pad and washed with CHCl3 (20 ml). The combined organic filtrate was washed with water (20 ml x 2), then with saturated sodium bicarbonate solution (20 ml x 2), and dried over anhydrous Na2SO4. The organic filtrate on evaporation, either under reduced pressure or at normal pressure, afforded the desired product, which was further purified by column chromatography over silica gel using an ethyl acetate:hexane mixture as the mobile phase. The phenolic derivatives were obtained by direct evaporation of filtrate after removal of the catalyst. Yields from a variety of methoxy ring-substituted benzaldehydes to the corresponding methoxy-ring substituted toluene varied from 57-70% but benzaldehyde required a longer reduction time and gave only 10% yield of toluene. The reduction of acetophenone was sluggish. After a 30 min reaction time interval, the product/substrate ratio in the reaction mixture was 1/5 observed by GC analysis (as described above, except initial temperature hold time 3 min). However, upon adding an additional amount of HCO2NH4 and increasing the reaction time up to 4 hr. the product/substrate ratio changed to 55/44. In the case of benzaldehyde, 1.5% toluene, 34% benzyl alcohol (retention time 4.9 min) and 60% high boiling by-product (retention time 8.9 min) were observed in the reaction mixture after 20 min at 85°C. Prolonging the reaction time slowly increases the concentration of toluene (Table 1) with reduction of benzyl alcohol. This important observation provides evidence that reduction of aldehydes and ketones to hydrocarbons proceeds via the alcohol intermediate, which is further confirmed by our finding that diphenylmethanol is rapidly converted to diphenylmethane under the experimental conditions reported here. The poor yield of toluene may be due to its low boiling point. These results demonstrate a rapid, mild and selective reduction of a wide variety of aromatic aldehydes and ketones to methylene derivatives under moderate reaction conditions and can be an attractive alternative for Wolff-Kishner or Clemmensen reduction, provided other functionalities such as nitro or halo substituents are not present in the substrate, since these groups are readily reduced or displaced. We have found, however, this procedure is not applicable for reduction of conjugated olefinic carbonyl groups, as the C-C double bond is preferentially reduced. Other Applications of CTH with Amm. Formate are: dehalogenation of aromatic chlorocarbons, deprotection of peptides and reduction of hydrazones and azides to hydrazines. Note 1 - Other catalysts can be used. Polymer supported Pd catalyst should work. Raney Ni often works and Urushibara Ni should work as well [but these are untested]. References: Contact Us | the Hive Powered by: Ultimate Bulletin Board, Version 5.39a |
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