· Ammonium Formate
· (MW 63.06)
(used as a source of ammonia;1 a hydrogen source for catalytic transfer hydrogenation reactions;2,7-9,10-13,17,18 hydrogenolysis of functional groups3-6,8,14,15,19,20)
Physical Data: mp 119-121 °C; d 1.27 g cm-3.
Solubility: sol water, alcohols.
Form Supplied in: crystalline solid.
Analysis of Reagent Purity: base titration.
Handling, Storage, and Precautions: hygroscopic.
Source of Ammonia.
Ammonium formate can be used as a source of nonvolatile ammonia (eq 1),1 but much of its use is as a hydrogen transfer agent in conjunction with heterogeneous or homogeneous catalysts.2
Catalytic transfer hydrogenation of N-benzyl protecting groups using 10% Palladium on Carbon as the catalyst and ammonium formate as the hydrogen source generally gives primary and secondary amines in excellent yields.3 In the case of 1-benzyl-2,3-dihydroindoles, the one-pot dehydrodebenzylation gave indoles as the major products along with minor amounts of N-benzylindoles (eq 2).4
Regioselective stepwise debenzylation of 1,3-dibenzyluracils was observed with this catalytic transfer hydrogenation system (eq 3). Functional groups such as esters, alcohols, nonbenzylic ketones or ethers, carboxylic acids, amides, acetals, and nitriles are stable under the reaction conditions.5
Interestingly, even N-((b-phenylethyl)oxy)carbonyl and 2-phenylethyl benzoates can be deblocked with ammonium formate in the presence of 10% Pd/C or Palladium(II) Acetate.6
Aryl ketones are selectively reduced to the secondary alcohols or to the hydrocarbons by careful selection of the reaction temperature and solvent. The alcohol is formed in MeOH at rt7 and the hydrogenolysis product is produced at 110 °C in acetic acid. Diaryl ketones also provided diarylmethanes under the latter reaction conditions.8 Raney Nickel can also participate in the catalytic transfer hydrogenation reaction. The combination of Raney nickel and ammonium formate reduces aryl alkyl ketones to alcohols at rt in >90% yield.9
Nitro groups are readily reduced to amines. Alkyl nitro compounds are reduced to the amines with retention of configuration.10 Certain appropriately substituted nitro compounds do not give amines under the reaction conditions. a,b-Unsaturated nitroalkenes gave oximes (eq 4),11 g-nitro ketones gave cyclic nitrones (eq 5),12 and 2-nitro-b-nitrostyrenes gave indoles (eq 6).13
Azides and pyridine N-oxides are reduced to amines14 and pyridines,15 respectively, with this reaction system. Allyl b-keto carboxylates are decarboxylated to form ketones and propene.16 Alk-2-ynyl carbonates are hydrogenolyzed to 1,2-dienes (allenes).17
Selective reduction of quinoline, isoquinoline, and acridine at the nitrogen containing ring has been reported.18 Concomitant dehalogenation was also observed with chlorinated isoquin-olines.
Hydrogenolysis of allylic compounds such as esters, nitro compounds, halides, phenyl ethers, carbonates, and vinyl epoxides has provided alkenic products.19 The reactions required the use of homogeneous Pd catalysts. Use of Tri-n-butylphosphine as ligand gave excellent selectivity to 1-alkenes. More 2-alkenes were formed (up to 66% in one case) when triarylphosphines or trialkyl phosphites were used.20
- 1. Bossio, R.; Marcaccini, S.; Paoli, P.; Pepino, R.; Polo, C. S 1991, 999.
- 2. For a review see Ram, S.; Ehrenkaufer, R. E. S 1988, 91.
- 3. Bringmann, G.; Geisler, J.-P. S 1989, 608. Purchase, C. F.; Goel, O. P. JOC 1991, 56, 457. Adger, B. M.; Farrell, C.; Lewis, N. J.; Mitchell, M. B. S 1987, 53. Ram, S.; Spicer, L. D. TL 1987, 28, 515.
- 4. Kiguchi, T.; Kuninobu, N.; Takahashi, Y.; Yoshida, Y.; Naito, T., Ninomiya, I. S 1989, 778.
- 5. Botta, M.; Summa, U.; Saladino, R.; Nicoletti, R. SC 1991, 21, 2181.
- 6. Carpino, L. A.; Tunga, A. JOC 1986, 51, 1930.
- 7. Radhakrishna, A. S.; Prasad Rao, K. R. K.; Nigram, S. C.; Bakthavatchalam, R.; Singh, B. B. OPP 1989, 21, 373.
- 8. Ram, S.; Spicer, L. D. TL 1988, 29, 3741.
- 9. Chen, F.-E.; Zhang, H.; Yuan, W.; Zhang, W.-W. SC 1991, 21, 107.
- 10. Ram, S.; Ehrenkaufer, R. E. TL 1984, 25, 3415. Barrett, A. G. M.; Spilling, C. D. TL 1988, 29, 5733.
- 11. Kabalka, G. W.; Pace, R. D.; Wadgaonkar, P. P. SC 1990, 20, 2453.
- 12. Zschiesche, R.; Reissig, H.-U. TL 1988, 29, 1685.
- 13. Rajeswari, S.; Drost, K. J.; Cava, M. P. H 1989, 29, 415.
- 14. Gartiser, T.; Selve, C.; Delpuech, J.-J. TL 1983, 24, 1609.
- 15. Balicki, R. S 1989, 645.
- 16. Tsuji, J.; Nisar, M.; Shimizu, I. JOC 1985, 50, 3416.
- 17. Tsuji, J.; Suguira, T.; Yuhara, M.; Minami, I. CC 1986, 922.
- 18. Balczewski, P.; Joule, J. A. SC 1990, 20, 2815.
- 19. Tsuji, J.; Shimizu, I.; Minami, I. CL 1984, 1017.
- 20. Ono, N.; Hamamoto, I.; Kamimura, A.; Kaji, A. JOC 1986, 51, 3736.
Anthony O. King & Ichiro Shinkai
Merck Research Laboratories, Rahway, NJ, USA
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