Elsevier

Tetrahedron

Volume 91, 2 July 2021, 132195
Tetrahedron

Neutral reducing agents supported on merrifield resin obtained by solid phase organic synthesis

https://doi.org/10.1016/j.tet.2021.132195Get rights and content

Abstract

An efficient methodology for the synthesis of neutral reducing agents supported on Merrifield resin has been developed. The process was carried out under mild conditions, varying the linker length, the bidentate chelating amine and the alkali metal tetrahydroborate. Fluorescence and infrared spectroscopies and thermogravimetric analysis were used for monitoring the chemical modifications. The developed methodology proved to be successful in obtaining a library of 40 neutral reducing agents supported on Merrifield resin in high yields (90–95%), with the potential to reduce carbonyl compounds and to be reusable.

Graphical abstract

A chemically and thermally stable library of neutral reducing agents supported on Merrifield resin was readily obtained with high yields using an efficient methodology under mild conditions. The stability, high yields and easy preparation of the neutral supported reducing complexes make them attractive as reducing agents in heterogeneous organic synthesis.

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Introduction

Solid-phase organic synthesis (SPOS) allows for the obtaining of compounds with high yields, at low cost, easily purified, recyclable, and using eco-friendly procedures [[1], [2], [3], [4], [5]]. Furthermore, reaction conditions can yield moderate to mild or even high reaction rates [4,6,7]. This technique has found many applications, which in the field of synthetic organic chemistry allows for the evaluation of quantitative reactions at each step [2,4,7]. Thus, it has been used to support biological and organic reagents [2]a), [6], [8], [9]. SPOS is expected to improve the synthesis, stability, and selectivity of reducing agents. Alkali metal tetrahydroborates (LiBH4 and NaBH4) are some of the most widely used reducing agents, as they are inexpensive and easy to use. Both can reduce a wide variety of functional groups that contain a carbon-oxygen double bond (Cdouble bondO) without reducing, for example, a carbon-carbon double bond (Cdouble bondC) [[10], [11], [12], [13]]. In order to improve the selectivity of the reducing agents (i.e. the alkali metal tetrahydroborates), various synthetic strategies, structural changes, solvents, etc, have been explored [1,5,[14], [15], [16], [17]]. One such strategy has been to support them into polymeric resins to then use them in reducing reactions. Fig. 1 shows some supported reducing agents, derived from boron hydrides obtained from good yields. The reduction times displayed by a-d and conversion percentages shown by a and c are higher, in comparison to the reported values using tetrahydroborates (NaBH4 reduction time 5–50 min and conversion of 80–90%) [11,17]. However, in materials a-c chemical liability is an issue, as they tend to form ammonium salts that decrease both the solvation, or swelling capacity of the resin, and the availability of the reducing groups, effectively requiring an extra amount of reducing agent to complete the reaction. This synthetic drawback could be avoided by using bidentate chelating amines (as in the case of the reducing agent d), as they have the advantage of working as chelating agents without the formation of ammonium salts, favoring reducing reactions [[14], [15], [16]]. Following on from our previous research regarding the synthesis of reducing agents [17,18], with this work we aimed to provide an efficient methodology to prepare a library of neutral reducing agents by modifying Merrifield resin with alkyl diamines of different chain lengths (as linkers) and different chelating amines (as ligands) to improve the use of the resins in organic solvents and the availability of the reducing groups. Lithium and sodium tetrahydroborates were used to form the supported reducing agents. The coordination mode of the [BH4]- group was analyzed due to its influence on chemical stability and its reducing properties as reducing agents [19].

Section snippets

Materials

Merrifield resin 98%, 1% linked with divinylbenzene with 0.8 mmol/g loading, terephthalic acid, sodium sulfate, triphosgene, triphenylphosphine (TPP), terephthalaldehyde, ether, tetrahydrofuran (THF), methanol (MeOH) and dicloromethane (DCM) were used (all from Sigma). Ethane-1,2-diamine, propane-1,3-diamine, butane-1,4-diamine, hexane-1,6-diamine, octane-1,8-diamine, 1,2-phenylendiamine, 2,2′-dipyridylamine, 2(aminomethyl)pyridine, sodium and lithium tetrahydoborates were from Sigma-Aldrich,

Results and discussion

The synthesis of the reducing agents started with the incorporation of alkyl diamines [ethane-1,2-diamine (a), propane-1,3-diamine (b), butane-1,4-diamine (c), hexane-1,6-diamine (d) and octane-1,8-diamine (e)] into the Merrifield resin 1 (0.8 mmol, 1% divinylbenzene) using K2CO3 in DMF to obtain the new resins 1 (a-e). Then, terephthalaldehyde (TPTD) was supported to form the imine products 2 (a-e) using Na2SO4 as a dehydrating agent and THF as a solvent. The imines-aldehydes resins 2 (a-e)

Conclusions

The methodology for the synthesis of neutral reducing agents reported here allows for the easy gathering of a library of 40 neutral reducing agents supported on the Merrifield resin, with a modified linker with high yields and good swelling in THF. The supported reducing agents showed more chemical and thermal stability than the free alkali metal tetrahydroborate. The stability, high yields and easy preparation of the neutral supported reducing complexes presented here make them attractive as

Declaration of competing interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Juan-Carlos Galvez-Ruiz reports financial support was provided by National Council for Science and Technology of Mexico (CONACYT-Mexico).

Acknowledgements

The authors acknowledge M. Sc. Christian Javier Salas-Juárez for processing TGA data, Dr. Eduardo Ruíz Bustos for the critical reading of the manuscript and the National Council for Science and Technology of Mexico (CONACYT-México) for both the scholarship awarded to JTVD and for partially supporting this research (Grant 418361).

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