demorol
(Hive Bee)
04-19-03 13:54
No 428126
      Nitrostyrenes to oximes in aqueous media
(Rated as: excellent)
    

This procedure probably has no practical value for you, fellow bees, due to high price of indium powder. However, the paper shows that nitrostyrenes can be reduced to oximes in fairly good yields (>75%) using this method.

Indium-Mediated Reduction of β-Nitrostyrenes to Oximes in Aqueous Media
Synlett, No. 10, 1447-1449 (2000)

Abstract
β-Nitrostyrenes are selectively reduced to the corresponding oximes in high yields by indium metal in aqueous methanol under neutral reaction conditions.


General procedure

Method A
To a solution of the beta-nitrostyrene (3 mmol) in MeOH (10mL) was added saturated ammonium chloride solution (10mL) and indium powder (1g). The reaction mixture was stirred under the reflux for an appropriate time. After complete conversion, as indicated by TLC, the reaction mixture was diluted with water and extracted with ethyl acetate (2 15mL). The combined organic layers were dried over anhydrous Na2SO4, concentrated in vacuo and the resulting product was purified by column chromatography on silica gel (Merck, 100-200 mesh, ethyl acetate-hexane, 2:8) gave oxime as as E/Z isomers.

Method B
To a solution of the beta-nitrostyrene (3 mmol) in MeOH (15mL) was added indium powder (1g) and trimethylsilyl chloride (3 mmol) at room temp. The reaction mixture was stirred at 25C under nitrogen atmosphere for an appropriate time. After complete conversion, as indicated by TLC, the reaction mixture was diluted with water and extracted with ethyl acetate (2 15mL). The combined organic layers were dried over anhydrous Na2SO4, concentrated in vacuo and the resulting product was purified by column chromatography on silica gel to afford pure alpha-methoxy oxime as E isomer.



I'm dreaming of the white crystals.
 
 
 
 
    Kinetic
(Hive Bee)
04-19-03 14:54
No 428131
      Nice!     

Using a 3 molar excess of indium does seem a little excessive, but it would be rather a nice method if the indium could be reused. Does the article mention whether it can or not?

Method (b) looks promising for making compounds from the BOX series. The beta-methoxy phenethylamines in PIHKAL don't look too interesting, but if the ether was oxidised to the beta-ketone it could be a nice way to interesting cathinone analogues.

I wish I'd been part of that research group. Imagine the temptations to 'accidentally' overreduce to the amine, especially with the first two entrieslaugh.
 
 
 
 
    Rhodium
(Chief Bee)
09-05-04 18:45
No 529792
      Indium Reduction of Oximes to N-Acetyl-Amines
(Rated as: good read)
    

Indium as a Reducing Agent: Reduction of Oximes
Justin R. Harrison, Christopher J. Moody, Michael R. Pitts
Synlett (11), 1601-1602 (2000)

Abstract
α-Oximino carbonyl compounds can be selectively reduced to the corresponding N-acetyl amine with indium powder, acetic anhydride and acetic acid in THF.


The reduction of oximes and oxime ethers to amines is a useful transformation in organic synthesis, and has been achieved using a range of reagents. The most commonly used conditions include: catalytic hydrogenation,1-3 lithium aluminium hydride,4 sodium borohydride in the presence of various additives,5-7 diborane8 and zinc and acetic acid, often in the presence of acetic anhydride to effect in situ acetylation of the amine.9-12 In continuation of our interest in oxime chemistry,13 we needed to reduce the ketoxime 1b to the corresponding N-acetylamine 2b. Attempts to perform this transformation by catalytic hydrogenation over Pd/C with in situ acetylation with acetic anhydride proved unsatisfactory. Thus, we explored the possibility of extending our new indium metal reduction methodologies for the reduction of oximes.

The potential of indium metal as a reducing agent has only recently been recognised, and is based on its first ionisation potential (5.8 eV),14 which is lower than reducing metals such as zinc (9.4 eV) or tin (7.3 eV) and close to that of strongly reducing alkali metals such as sodium (5.1 eV). In this context we have reported the selective reduction of aromatic nitro groups,15 the heterocyclic ring in quinolines, isoquinolines and quinoxalines,16 and the deprotection of 4-nitrobenzyl ethers and esters with indium metal.17 Subsequently others have shown that indium can be used in the reductive elimination of 1,2-dibromo compounds,18 and in the reduction of α-halocarbonyl compounds and benzyl halides,19 azides,20 and amine N-oxides.21 We now report a new method for reduction of oximes to N-acetyl amines using indium metal in the presence of acetic anhydride and acetic acid in THF.

The reduction was carried out by simply heating the α-oximino carbonyl compound 1 (commercially available or prepared by standard methods) in THF containing 4 equivalents of acetic acid and 2.5 equivalents of acetic anhydride, and a suspension of 4 equivalents of indium powder.22 The reactions were complete in less than 30 min for compounds in which the C=N bond is rendered more reactive by the presence of two carbonyl groups, and within 18 h for monocarbonyl compounds, and gave the required N-acetyl amines 2 in good to excellent yield (Table).23 Hence the reaction can be used to prepare a range of α-acetamido carbonyl compounds including a diester 2a, β-ketoester 2b, β-diketone 2c, ester 2d, ketones 2e, 2f, 2h, and amides 2g; the camphor derived oxime 1h gave a single endo-diastereomer acetamide 2h. It is worth noting that the carbonyl group in all cases was unaffected (reduction with hydride transfer reagents would yield the α-hydroxy amine). The reaction is simple to carry out; there is no need for exclusion of air or the use of dry solvents, and the reaction is worked up by simply quenching with bicarbonate and extraction into organic solvent. In most cases further purification by column chromatography was unnecessary.

In summary, the present work extends the use of indium metal as a reducing agent in organic chemistry, and provides a simple method for the reduction of oximes with in situ acetylation of the resulting amine.


Table
Reduction of oximes 1 to N-acetyl amines 2 using indium metal-acetic anhydride-acetic acid in THF


References and Notes

(1) Boye, O.; Brossi, A.; Yeh, H. J. C.; Hamel, E.; Wegrzynski, B.; Toome, V. Can. J. Chem. 1992, 70, 1237-1249.
(2) Cipolla, L.; Lay, L.; Nicotra, F.; Panza, L.; Russo, G. J. Chem. Soc., Chem. Commun. 1995, 1993-1994.
(3) Booker-Milburn, K. I.; Dunkin, I. R.; Kelly, F. C.; Khalaf, A. I.; Learmonth, D. A.; Proctor, G. R.; Scopes, D. I. C. J. Chem. Soc., Perkin Trans. 1 1997, 3261-3273.
(4) Rahman, M. A.; Fraser-Reid, B. J. Am. Chem. Soc. 1985, 107, 5576-5578.
(5) Lee, G. S.; Kammermeier, T.; Kaiser, A.; Eibler, E.; Wiegrebe, W. Arch. Pharm. 1991, 324, 177-181.
(6) Demir, A. S.; Tanyeli, C.; Sesenoglu, O.; Demiq, S.; Evin, O. Tetrahedron Lett. 1996, 37, 407-410.
(7) Baruah, B.; Dutta, M. P.; Boruah, A.; Prajapati, D.; Sandhu, J. S. Synlett 1999, 409-410.
(8) Feuer, H.; Braunstein, D. M. J. Org. Chem. 1969, 34, 1817-1821.
(9) Zambito, A. J.; Howe, E. E. Org. Synth. 1973, Coll. Vol. 5, 373-375.
(10) Girard, A.; Greck, C.; Ferroud, D.; Genet, J. P. Tetrahedron Lett. 1996, 37, 7967-7970.
(11) Matuszczak, B. J. Prakt. Chem. 1998, 340, 20-25.
(12) Nudelman, A.; Nudelman, A. Synthesis 1999, 568-570.
(13) Hunt, J. C. A.; Lloyd, C.; Moody, C. J.; Slawin, A. M. Z.; Takle, A. K. J. Chem. Soc., Perkin Trans. 1 1999, 3443-3454, and earlier papers in the series.
(14) Cintas, P. Synlett 1995, 1087-1096.
(15) Moody, C. J.; Pitts, M. R. Synlett 1998, 1028.
(16) Moody, C. J.; Pitts, M. R. Synlett 1998, 1029-1030.
(17) Moody, C. J.; Pitts, M. R. Synlett 1999, 1575-1576.
(18) Ranu, B. C.; Guchhait, S. K.; Sarkar, A. J. Chem. Soc. Chem. Commun. 1998, 2113-2114.
(19) Ranu, B. C.; Dutta, P.; Sarkar, A. J. Chem. Soc., Perkin Trans. 1 1999, 1139-1140.
(20) Reddy, G. V.; Rao, G. V.; Iyengar, D. S. Tetrahedron Lett. 1999, 40, 3937-3938.
(21) Yadav, J. S.; Reddy, B. V. S.; Reddy, M. M. Tetrahedron Lett. 2000, 41, 2663-2665.
(22) General Procedure. Indium powder (-100 mesh, 0.92 g, 8.0 mmol) was added to a solution of the oxime 1 (2.0 mmol), acetic anhydride (0.51 g, ~0.47 mL, 5.0 mmol) and acetic acid (0.48 g, ~0.46 mL, 8.0 mmol) in THF (10 mL) and the mixture heated at reflux for 18 h. Saturated aqueous sodium bicarbonate solution (10 mL) was carefully added to the cooled reaction mixture, and stirring continued for 1 h. The resulting mixture was diluted with water (30 mL) and extracted with ethyl acetate (3 x 15 mL). The combined organic layers were dried (MgSO4) and concentrated in vacuo. If necessary, the crude material was purified by flash column chromatography (silica eluting with ~20% ethyl acetate in dichloromethane) to give the N-acetyl amine 2.
(23) 2a, mp 131-132C (lit.@24 mp 130-132C); 2b, mp 38-39C (lit.@25 no mp given); 2c, oil, 2d, mp 37C (lit.@26 mp 34-35C); 2e, mp 89-90C (lit.@27 mp 87-89C); 2f, mp 83C (lit.@28 mp 83-84C); 2g, mp 246-248C (lit.@29 248-249.5C); 2h, mp 115C (from ether) [...] In the reduction of 1b and 1e, the yields obtained with indium were comparable with those obtained using zinc metal under similar conditions.
(24) L'Esperance, R. P.; Ford, T. M.; Jones, M. J. Am. Chem. Soc. 1988, 110, 209-213.
(25) Kuwano, R.; Okuda, S.; Ito, Y. J. Org. Chem. 1998, 63, 3499-3503.
(26) Lee, J. C.; Oh, Y. S.; Cho, S. H.; Lee, J. I. Org. Prep. Proc. Int. 1996, 28, 480-483.
(27) Koga, K.; Yamada, S.-I. Chem. Pharm. Bull. 1972, 20, 539-542.
(28) Yoon, U. C.; Cho, S. J.; Lee, Y.-J.; Mancheno, M. J.; Mariano, P. S. J. Org. Chem. 1995, 60, 2353-2360.
(29) Endler, A. S.; Becker, E. I. J. Am. Chem. Soc. 1955, 77, 6608-6610.

The Hive - Clandestine Chemists Without Borders
 
 
 
 
    Kinetic
(Hive Bee)
09-06-04 03:45
No 529874
      More indium mediated reductions
(Rated as: good read)
    

Indium Mediated Reduction of Nitro and Azide Groups in the Presence of HCl in Aqueous Media
Jung Gyu Lee, Kyung Il Choi, Hun Yeong Koh, Youseung Kim, Yonghan Kang, Yong Seo Cho*
Synthesis
2001, 81-84

Abstract
Indium mediated reduction of azide and nitro groups in the presence of HCl (1.5 equiv based on indium) at room temperature in aqueous THF successfully provided the corresponding amine in high to quantitative yields. Under the same reaction conditions, selective reduction of azide and nitro group in the presence of vinyl group could be accomplished.



Ethyl 4-(2-Aminophenyl)but-2-enoate; Typical Procedure
To a solution of (4-nitrobut-1-enyl)benzene (1; 100 mg, 0.56 mmol) in aq THF (3 mL) was added indium powder (260 mg, 2.26 mmol) and concd HCl (300 L). After stirring for 3 h at r.t., the pH of the reaction mixture was adjusted to 7 with solid NaHCO3, diluted with H2O and extracted with EtOAc, and the organic layer was dried (MgSO4) and concentrated in vacuo. The crude product was purified by a short column chromatography on neutral alumina (Scheme 2).



A Novel, Simple, Chemoselective and Practical Protocol for the Reduction of Azides Using In/NH4Cl
G. Vidyasagar Reddy*, G. Venkat Rao and D.S. Iyengar*
Tetrahedron Letters
40 (1999), 3937-3938

Abstract
A simple, mild and efficient method for the reduction of azides to amines using In / NH4Cl is described



Typical procedure
To a solution of the azide (2 mmol) in ethanol (6 ml) was added indium powder (2 mmol) and NH4Cl (2 mmol). The resulting reaction mixture was heated at reflux with constant stirring (1-3 h). After completion of the reaction (monitored by TLC), the reaction mixture was brought to room temperature, diluted with ethylacetate (10 ml), stirred for 10 min and passed through a short pad of celite to give a clear solution. Removal of solvent under reduced pressure gave the amines in pure form.
 
 
 
 
    Kinetic
(Hive Bee)
09-06-04 12:45
No 529874
      More indium mediated reductions
(Rated as: good read)
    

Indium Mediated Reduction of Nitro and Azide Groups in the Presence of HCl in Aqueous Media
Jung Gyu Lee, Kyung Il Choi, Hun Yeong Koh, Youseung Kim, Yonghan Kang, Yong Seo Cho*
Synthesis
2001, 81-84

Abstract
Indium mediated reduction of azide and nitro groups in the presence of HCl (1.5 equiv based on indium) at room temperature in aqueous THF successfully provided the corresponding amine in high to quantitative yields. Under the same reaction conditions, selective reduction of azide and nitro group in the presence of vinyl group could be accomplished.



Ethyl 4-(2-Aminophenyl)but-2-enoate; Typical Procedure
To a solution of (4-nitrobut-1-enyl)benzene (1; 100 mg, 0.56 mmol) in aq THF (3 mL) was added indium powder (260 mg, 2.26 mmol) and concd HCl (300 L). After stirring for 3 h at r.t., the pH of the reaction mixture was adjusted to 7 with solid NaHCO3, diluted with H2O and extracted with EtOAc, and the organic layer was dried (MgSO4) and concentrated in vacuo. The crude product was purified by a short column chromatography on neutral alumina (Scheme 2).



A Novel, Simple, Chemoselective and Practical Protocol for the Reduction of Azides Using In/NH4Cl
G. Vidyasagar Reddy*, G. Venkat Rao and D.S. Iyengar*
Tetrahedron Letters
40 (1999), 3937-3938

Abstract
A simple, mild and efficient method for the reduction of azides to amines using In / NH4Cl is described



Typical procedure
To a solution of the azide (2 mmol) in ethanol (6 ml) was added indium powder (2 mmol) and NH4Cl (2 mmol). The resulting reaction mixture was heated at reflux with constant stirring (1-3 h). After completion of the reaction (monitored by TLC), the reaction mixture was brought to room temperature, diluted with ethylacetate (10 ml), stirred for 10 min and passed through a short pad of celite to give a clear solution. Removal of solvent under reduced pressure gave the amines in pure form.