Ndze D. Jumbam

Siyavuya Makaluza

Wayiza Masamba

English

South East Academic Libraries System (SEALS)

Bull. Chem. Soc. Ethiop. 2018, 32(1), 179-184.                                                             ISSN 1011-3924  2018 Chemical Society of Ethiopia and The Authors                                           Printed in Ethiopia              DOI: https://dx.doi.org/10.4314/bcse.v32i1.18  __________ *Corresponding author. E-mail: njumbam@wsu.ac.za This work is licensed under the Creative Commons Attribution 4.0 International License SHORT COMMUNICATION  POLYMETHYLHYDROSILOXANE REDUCTION OF CARBONYL FUNCTION CATALYSED BY TITANIUM TETRACHLORIDE  Ndze D. Jumbam*, Siyavuya Makaluza and Wayiza Masamba  Department of Chemical and Physical Sciences, Walter Sisulu University, Nelson Mandela Drive, Mthatha 5117, South Africa  (Received October 11, 2017; Revised January 22, 2018; Accepted January 23, 2018)  ABSTRACT. Reduction of aromatic aldehydes and ketones into the corresponding methylene derivatives by polymethylhydrosiloxane in the presence of titanium tetrachloride as catalyst was achieved in good to excellent yields ranging from 55-90%. The reaction took place under relatively mild conditions and smoothly led to the desired target molecules in the presence of other functional groups such as halogens, hydroxyl, nitro and methoxy groups. However, in the reduction of the substrate with two methoxy groups in close proximity (1,2-positions), the reaction necessitated a larger amount of the titanium catalyst and a longer reaction time to complete the reduction of the carbonyl function due to a likely complex formation of titanium tetrachloride with the methoxy groups.   KEY WORDS: Carbonyl reduction, Polymethylhydrosiloxane, Titanium tetrachloride, Catalyst, Hydride transfer INTRODUCTION  The reduction of the carbonyl function of aldehydes and ketones to methylene is an important reaction that has found wide applications in organic syntheses both in research laboratories and also in the chemical industry. Various methods have been employed for this chemical transformation but the Clemmensen [1] and Wolff–Kishner [2] reduction processes have thus far exhibited the most general utility [3]. However, the drastic reaction conditions of both processes have given rise to various other methods, all in an effort to find milder reaction conditions. Some of the alternative methods include catalytic hydrogenation [4-5], reductions using Raney nickel in hydroxide media [6], reductions using PtO2 [7], HI-phosphorus [8-9], NaBH4-CF3COOH [10-11], NaCNBH3-BF3Et2O [12], LAH-AlCl3 [13]. While these methods offer some advantages, they also suffer from some disadvantages. A good number of the methods are limited to aromatic systems, others require the use of pyrophoric hydride source for reduction, and some are prone to long reaction hours coupled with tedious workup and are associated with low yields. Since silanes undergo hydride transfer to relatively stable carbenium ions, they have been used to convert carbonyl function to methylene [3]. More recently, however, catalytic reduction of the carbonyl group has been carried out in the presence of polymethylhydrosiloxane (PMHS), an excellent hydride donor and cheap by-product of the silicone industry, which is easy to handle and claimed to be environmentally friendly [14].  Jaxa-Chamiec and co-workers [15] reported the conversion of carbonyl group to methylene using AlCl3 in the presence of PMHS. The inherent environmental problems associated with the workup of AlCl3 reaction systems, render this process unsustainable. A rapid defunctionalisation of carbonyl group to methylene has been described by Chandrasekhar and co-workers using B(C6F5)3 as a nonconventional Lewis acid to activate PMHS [16]. Although the authors claimed that the method reduced aromatic as well as aliphatic carbonyl compounds in good yields, the high cost of B(C6F5)3 is prohibitive. A promising alternative was the microwave induced Ndze D. Jumbam et al.   Bull. Chem. Soc. Ethiop. 2018, 32(1) 180FeCl3.6H2O-catalysed reduction of ketones and aldehydes to alkane compounds developed by Campagne and co-workers [14, 16] in which aromatic and aliphatic carbonyl compounds were reduced in good yields. South Africa has the world’s second deposits of titanium after Australia [17]. The east coast of the country, more specifically much of Pondoland is awash with titanium sands. It could be the gateway metal to a new golden age for South Africa. However, while titanium finds varied applications in industry, its use in organic syntheses remains largely unexplored especially as a reduction catalyst. Buchwald and co-workers [18] were able to reduce ketones and methyl esters using a titanocene catalyst in the presence of PMHS. Reduction of the carbonyl functional group of various substrates catalysed by titanium tetrachloride (tickle) in the presence of PMHS as a hydride source in dichloroethane (DCE) is herein described by the authors of this paper for the first time. EXPERIMENTAL  General. All chemicals were obtained from commercial sources and were used without further purification unless stated otherwise. Products were characterised by 1H- and 13C-NMR spectroscopy using a Varian spectrometer at 400 and 100 MHz for proton and carbon-13, respectively. Spectra were recorded from CDCl3 solutions employing TMS as an internal reference. All spectra are reported as  (ppm) values.  Representative procedure (compound 2). A solution of 2-chloro-1-[4-(propan-2-yl)phenyl]ethanone (1 g, 5.1 mmol) in dichloroethane (DCE) (10 mL) was placed in a 50 mL three-mouth round-bottomed flask equipped with a reflux condenser, a calcium chloride drying tube, a thermometer and a magnetic stirring bar. To the stirred reaction solution at room temperature, tickle (0.115 mL, 25%) followed by PMHS (0.7 g, 12.2 mmol) were added from a syringe. The reaction mixture was heated to reflux and progress of the reaction monitored by thin layer chromatography (tlc) and stopped after three hours. The gelatinous reaction mixture was taken up in hexane (15 mL) and filtered under a plug of celite. The filter cake was washed with hexane (50 mL) and the filtrate concentrated in vacuo. The crude product was purified by column chromatography on silica gel to give an oily product (0.75 g, ~79.4%); b.p.: 140 oC/2.6 mm Hg.   1H-NMR of 2. CDCl3): 1.11 (d, 6H, J = 7.14), 2.77 (sept, 1H, J = 7.01), 3.01 (t, 2H, J = 7.69), 3.42 (t, 2H, J = 7.69), 7.01 (d, 2H, J = 8.24), 7.06 (d, 2H, J = 8.24). 13H-NMR; CDCl3): 23.96, 33.01, 33.71, 39.07, 126.63, 128.53, 136.20, 147.48; HRMS (EI+): calc. for C11H15Br, 226.0357; found 226.0361.  1H-NMR of 4. CDCl3): 1.16 (d, 6H, J = 7.14), 2.81 (sept, 1H, J = 7.03), 2.96 (t, 2H, J = 7.56), 3.62 (t, 2H, J = 7.41), 7.06 (d, 2H, J = 8.24), 7.11 (d, 2H, J = 8.24). 13H-NMR; CDCl3): 24.34, 34.08, 39.18, 45.41, 121.97, 129.07, 135.73, 147.81; HRMS (EI+): calc. for C11H15Cl, 182.0822; found 182.0777. All products listed in Table 1 were prepared analogously to the representative procedure.     Short Communication Bull. Chem. Soc. Ethiop. 2018, 32(1) 181   Reference        This work    This work    [19]   [20-21]    [20-21]    [22]    [23-24]    [25]    [26]    [27]    RESULTS AND DISCUSSION  The reduction of carbonyl function by PMHS activated by tickle occurred smoothly and the formation of a gelatinous precipitate signified the end of the reaction, which was confirmed by Ndze D. Jumbam et al.   Bull. Chem. Soc. Ethiop. 2018, 32(1) 182TLC. The reaction was complete in less than an hour with the use of 50% tickle. The tickle concentration of 25% was maintained throughout the investigations and the reactions never exceeded three hours.  Results of this reduction reaction are summarised in Table 1. Good to excellent yields were achieved using this method. Entries 1, 2, 3, 7, and 8 indicate that the presence of halogens did not interfere with the reduction reaction. It is noteworthy that reactions in entries 2 and 3 leading to the formation of compounds 4 and 6, respectively, could be carried out at room temperature affording the same products and yields. The high reactivity of the two substrates (3 and 5) may be attributed to the activation of the carbonyl function by the halogen atoms. In the case of substrate 3, two products were observed, irrespective of the reaction conditions utilised. Compound 2 most likely originated from the attack by a chlorine ion from tickle on the intermediate as outlined in Scheme 1 below:  BrOCH3CH3BrOTiClClClCH3CH3 Cl-2TiCl4  Scheme 1  The reduction of 3 afforded a mixture of 2 and 4 in 73 and 27% yields, respectively. This was found to be true when the reaction took place at room temperature and at refluxing temperature. The identity of 2 was confirmed independently by the reaction of 4 with excess sodium chloride in DMSO to afford the product in 90% yield. An attempt to carry out this reaction in DMF resulted in substantial elimination of the halogen to form the corresponding styrene derivative. However the best method to access compound 2 was through the reduction of substrate 1 using the same methodology as shown in entry 1. To the best of our knowledge, compounds 2 and 4 have not been described before. It is also relevant to note that there is no direct conversion of compounds 5 and 15 to the corresponding reduction products 6 and 16, respectively. Reduction of 5 by hydrogen transfer reaction with formic acid in the presence of a ruthenium catalyst led only to the corresponding chlorohydrin (2-chloro-1-phenylethanol [28]. Even though one methoxy group did not interfere in the reduction as shown in entry 4, the two ether groups in close proximity (Entry 6) appeared to slow down the reaction but did not completely inhibit it. The reaction required 60% of tickle and took six hours to complete, due likely to the formation of a chelation complex with tickle that slowed down the reduction process. Surprisingly however, the nitro group in substrate 17 did not inhibit the reaction despite the fact that its two oxygen atoms could potentially chelate the titanium ion. Unlike in all the other entries in table 1, the reaction led to the formation of two products: the expected methylene derivative and the corresponding alcohol. This is an indication that the reaction takes place in a two-step process with the alcohol as the intermediate. This implies that with the use of appropriate reaction conditions, it should be possible to stop the reaction at the alcohol stage or, if so desired, carried on to the final step. The formation and isolation of the alcohol intermediate may open up a new avenue for this reaction. For example, carbonyl derivatives such as imines may be selectively reduced to the corresponding amines. The Clemensen and Wolff–Kishner reductions on the other hand operate with completely different reaction mechanisms. Short Communication Bull. Chem. Soc. Ethiop. 2018, 32(1) 183Although the halogens have an inductive electron-withdrawing ability, substrates 1, 3, 5, 13, and 15 revealed no noticeable influence on the outcome of the reaction.  The herein described PMHS reduction of aromatic aldehydes and ketones into the corresponding methylene derivatives catalysed by tickle compared to the classical Wolff-Kishner and Clemmensen processes has proven to be the method of choice. Its simplicity, safety of operation, low cost and functional group compatibility outweighs those of other known methods. CONCLUSION  Carbonyl compounds were successfully reduced to the corresponding methylene derivatives using the polymethylhydrosiloxane–tickle system as the reducing agent. The mild reaction conditions, namely the ease of handling of the reagents, low reaction temperature, functional group compatibility and easy reaction workup may pave the way for possible industrial applications of this reduction reaction. The unexpected isolation of an alcohol intermediate in one example gives insight into the possible reaction steps involved in the process.  In future investigations, attempts will be made to expand the scope of this reduction reaction and perhaps determine its limitations by utilising a range of aliphatic and aromatic carbonyl compounds with a variety of functional groups.   ACKNOWLEDGMENT  We thank the Directorate of Research Development at Walter Sisulu University for financial support. REFERENCES  1. Martin, E.L. The Clemmensen Reduction in Organic Reactions, John Wiley and Sons, Inc.: 2004. 2. Todd, D. The Wolff-Kishner Reduction in Organic Reactions, John Wiley and Sons, Inc.: 2004. 3. West, C.T.; Donnelly, S.J.; Kooistra, D.A.; Doyle, M.P. Silane reductions in acidic media. II. Reductions of aryl aldehydes and ketones by trialkylsilanes in trifluoroacetic acid. Selective method for converting the carbonyl group to methylene. J. Org. Chem. 1973, 38, 2675-2681. 4. Lee, W.Y.; Park, C.H.; Kim, H.J.; Kim, S. Orthocyclophanes. 3. Ketonands, novel ketonic crowns of polyoxo[1n]orthocyclophane constitution. J. Org. Chem. 1994, 59, 878-884. 5. Lee, W.Y.; Park, C.H.; Kim, Y.D. Orthocyclophanes. 1. Synthesis and characterization of [14]- and [15]orthocyclophanes and bicyclic biscyclophanes. J. Org. Chem. 1992, 57, 4074-4079. 6. Cook, P.L. The reduction of aldehydes and ketones with nickel—Aluminum alloy in aqueous alkaline solution. J. Org. Chem. 1962, 27, 3873-3875. 7. Rao, A.V.R.; Mehendale, A.R.; Reddy, K.B. A simple and regiospecific synthesis of (±) 11-deoxydaunomycinone. Tetrahedron Lett. 1982, 23, 2415-2418. 8. Riemschneider, R.; Kassahn, H.G. Acylderivate cyclischer verbindungen, V. Zur herstellung von o-diacetyl-benzol und 4-nitro-1.2-diacetyl-benzol. Chem. Ber. 1959, 92, 1705-1709. 9. Bradsher, C.K.; Vingiello, F.A. Aromatic cyclodehydration. XXI. ortho- and para-(9-anthryl)benzoic acids. J. Org. Chem. 1948, 13, 786-789. 10. Ketcha, D.M.; Lieurance, B.A.; Homan, D.F.J.; Gribble, G.W. Synthesis of alkyl-substituted N-protected indoles via acylation and reductive deoxygenation. J. Org. Chem. 1989, 54, 4350-4356. Ndze D. Jumbam et al.   Bull. Chem. Soc. Ethiop. 2018, 32(1) 18411. Gribble, G.W.; Kelly, W.J.; Emery, S.E. Reactions of sodium borohydride in acidic media; VII. Reduction of diaryl ketones in trifluoroacetic acid. Synthesis 1978, 1978, 763-765. 12. Srikrishna, A.; Viswajanani, R.; Sattigeri, J.A.; Yelamaggad, C.V. Chemoselective reductive deoxygenation of α,β-unsaturated ketones and allyl alcohols. Tetrahedron Lett. 1995, 36, 2347-2350. 13. Paquette, L.A.; Maleczka, R.E. Enantioselective construction of natural (+)-pallescensin A. A sigmatropic pathway to furanosesquiterpenes. J. Org. Chem. 1992, 57, 7118-7122. 14. Dal Zotto, C.; Virieux, D.; Campagne, J.M. FeCl3-catalyzed reduction of ketones and aldehydes to alkane compounds. Synlett 2009, 2009, 276-278. 15. Jaxa-Chamiec, A.; Shah, V.P.; Kruse, L.I. Aromatic acylation/reduction: An efficient Friedel-Crafts alkylation reaction. J. Chem. Soc., Perkin Trans. I 1989,  1705-1706. 16. Chandrasekhar, S.; Reddy, C.R.; Babu, B.N. Rapid defunctionalization of carbonyl group to methylene with polymethylhydrosiloxane−B(C6F5)3. J. Org. Chem. 2002, 67, 9080-9082. 17. Hugo, V.E. A study of titanium-bearing oxides in heavy mineral deposits along the east coast of South Africa. PhD Thesis, University of Natal, South Africa, 1993. 18. Berk, S.C.; Kreutzer, K.A.; Buchwald, S.L. A catalytic method for the reduction of esters to alcohols. J. Am. Chem. Soc. 1991, 113, 5093-5095. 19. Kelly, B.D.; Lambert, T.H. Aromatic cation activation of alcohols: Conversion to alkyl chlorides using dichlorodiphenylcyclopropene. J. Am. Chem. Soc. 2009, 131, 13930-13931. 20. Wang, H.; Li, L.; Bai, X.F.; Shang, J.Y.; Yang, K.F.; Xu, L.W. Efficient palladium-catalyzed CO hydrogenolysis of benzylic alcohols and aromatic ketones with polymethylhydrosiloxane. Adv. Synth. Catal. 2013, 355, 341-347. 21. Zuidema, D.R.; Williams, S.L.; Wert, K.J.; Bosma, K.J.; Smith, A.L.; Mebane, R.C. Deoxygenation of aromatic ketones using transfer hydrogenolysis with raney nickel in 2-propanol. Synth. Commun. 2011, 41, 2927-2931. 22. Takahashi, T.; Yoshimura, M.; Suzuka, H.; Maegawa, T.; Sawama, Y.; Monguchi, Y.; Sajiki, H., Chemoselective hydrogenation using molecular sieves-supported Pd catalysts: Pd/MS3A and Pd/MS5A. Tetrahedron 2012, 68, 8293-8299. 23. Gavara, L.; Boisse, T.; Rigo, B.; Hénichart, J.P. A new method of bromination of aromatic rings by an iso-amyl nitrite/HBr system. Tetrahedron 2008, 64, 4999-5004. 24. Surya Prakash, G.K.; Do, C.; Mathew, T.; Olah, G.A. Reduction of carbonyl to methylene: Organosilane-Ga(OTf)3 as an efficient reductant system. Catal. Lett. 2011, 141, 507-511. 25. Raya, B.; Biswas, S.; RajanBabu, T.V. Selective cobalt-catalyzed reduction of terminal alkenes and alkynes using (EtO)2Si(Me)H as a stoichiometric reductant. ACS Catal. 2016, 6, 6318-6323. 26. Mack, J.; Fulmer, D.; Stofel, S.; Santos, N. The first solvent-free method for the reduction of esters. Green Chem. 2007, 9, 1041-1043. 27. Onitsuka, S.; Jin, Y.Z.; Shaikh, A.C.; Furuno, H.; Inanaga, J. Silica gel-mediated organic reactions under organic solvent-free conditions. Molecules 2012, 17, 11469-11483. 28. Hodgkinson, R.; Jurčík, V.; Zanotti-Gerosa, A.; Nedden, H.G.; Blackaby, A.; Clarkson, G. J.; Wills, M. Synthesis and catalytic applications of an extended range of tethered ruthenium(II)/η6-arene/diamine complexes. Organometallics 2014, 33, 5517-5524.  

POLYMETHYLHYDROSILOXANE REDUCTION OF CARBONYL FUNCTION CATALYSED BY TITANIUM TETRACHLORIDE

http://vital.seals.ac.za:8080/vital/access/services/Download/vital:44054/SOURCE1

POLYMETHYLHYDROSILOXANE REDUCTION OF CARBONYL FUNCTION CATALYSED BY TITANIUM TETRACHLORIDE

Abstract

Similar works

Full text

Available Versions

South East Academic Libraries System (SEALS)