Boron Triiodide-Mediated Reduction of Nitroarenes Using Borohydride Reagents

Andrej Ćorković, Thomas Chiarella, Florence J. Williams*

*University of Iowa, Iowa City, Iowa 52242, United States, Email: Florence-Williamsuiowa.edu

A. Ćorković, T. Chiarella, F. J. Williams, Org. Lett., 2023, 25, 8787-8791.

DOI: 10.1021/acs.orglett.3c03257

Abstract

In a reduction of nitroarenes using KBH₄ and I₂, BI₃ is generated in situ and was shown to be the active reductant. Conditions were optimized for BI₃ generation and then applied to a wide range of nitroarenes, including traditionally challenging substrates. The method constitutes a practical reduction option which produces low-toxicity boric acid and potassium iodide upon workup.

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proposed mechanism

General Procedure for Reduction of Nitro Compounds via in situ Generated Boron Triiodide (BI₃)

Potassium borohydride (KBH₄) (43.2 mg, 0.800 mmol, 4.00 equiv) was added to a clean 50 mL RBF and ground with a glass stir rod for 30-60 s. Molecular iodine (I₂) (406.1 mg, 1.600 mmol, 8.000 equiv), cyclohexane (4 mL), and an oven-dried (80 °C) stir bar were subsequently added. The flask was sealed with a rubber septum secured by copper wire. The mixture was heated to 60 °C in a silicon oil bath and stirred at 700 RPM for 1.5 h. The reaction flask was allowed to cool to room temperature (pressure buildup of byproduct gases observed with inflated septum). The septum was simultaneously pierced with two 20-gauge needles, one to evacuate gaseous byproducts and the other to introduce a nitrogen atmosphere. Completed synthesis of BI₃ was usually accompanied with the loss of purple color attributed to iodine. The starting nitro compound (0.20 mmol, 1.0 equiv) was dissolved in cyclohexane (17 mL). This solution was added to the reaction flask containing in situ generated BI₃. The septum was quickly removed, and Amberlite ™ IR120 Na⁺ form (100. mg) was added before quickly recapping the reaction flask with the septum. Nitrogen was introduced to the reaction flask, and the mixture was stirred at room temperature for 2.5 h.

Note: for specific substrates, a cosolvent (trifluorotoluene, DCM, or DCE) was used with cyclohexane.

Workup 1: The mixture was cooled to 0 °C and MeOH (~5.0 mL) was added. DTT (~50 mg) was added to react with excess iodine (A loss of color was accompanied with the addition of the reducing agent. If significant color remained, additional DTT was added until color receded). TEA (~1.0 mL) was added to the mixture, which was then vacuum filtered and concentrated in vacuo.

Workup 2: The mixture was cooled to 0 °C and sat. aq. Na₂S₂O₃ (~10 mL) was added with stirring. The resultant biphasic cloudy solution was added to a separatory funnel, and shaken until both solutions became colorless, or until the organic layer color was observed not to change upon further added sat. aq. Na₂S₂O₃. The aqueous layer was separated and neutralized with NaHCO₃ (solid or sat. aq. solution). Once neutralized, the aqueous layer was added back into the separatory funnel and extracted with EtOAc (3x20 mL), DCM (3x20 mL), or ether (3x20 mL). If cloudy, the organic layers were washed with sat. brine (10 mL), then dried over Na₂SO₄ and concentrated in vacuo.

Key Words

reduction of nitro compounds, potassium borohydride

ID: J54-Y2023