Indium(III)-Catalyzed Synthesis of Primary Carbamates and N-Substituted Ureas

Abstract

An indium triflate-catalyzed synthesis of primary carbamates from alcohols and urea as an ecofriendly carbonyl source has been developed. Various linear, branched, and cyclic alcohols were converted into the corresponding carbamates in good to excellent yields. This method also provided access to N-substituted ureas by carbamoylation of amines. All the products were obtained by simple filtration or crystallization, without the need for chromatographic purification. Mechanistic investigations suggest that the carbamoylation reaction proceeds through activation of urea by O-coordination with indium, followed by nucleophilic attack by the alcohol or amine on the carbonyl center of urea. The inexpensive and easily available starting materials and catalyst, the short reaction times, and the ease of product isolation highlight the inherent practicality of the developed method.

Key words

carbamates - alcohols - ureas - indium catalysis - nucleophilic substitution

Publication History

Received: 20 September 2021

Accepted: 09 October 2021

Article published online:
11 November 2021

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• 43 Carbamates and N-Substituted Ureas 3a–t; General ProcedureIn(OTf)₃ (5 mol%) was added to a stirred solution of urea (1 mmol) and the appropriate alcohol or amine (3 mmol) in 1,4-dioxane in a sealed tube, and the mixture was stirred at 150 °C until the reaction was complete (TLC). In the case of alcohols, the mixture was extracted with CH₂Cl₂ (3 × 10 mL) and the organic layers were combined, dried (Na₂SO₄), filtered, and concentrated to give a product that was purified by crystallization from CH₂Cl₂. In(OTf)₃ was recovered by evaporating the aqueous layer to dryness and subsequent co-distillation with toluene; the resulting In(OTf)₃ was then dried under reduced pressure for reuse in further carbamoylation reactions. In the case of amines, the desired products were precipitated with CH₂Cl₂ and separated by simple filtration.Hexyl Carbamate (3a)White solid; yield: 104 mg (80%); mp 62.4–63 °C. IR (KBr): 3416 (N–H), 1694 (C=O), 1339 (C–N) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 4.99 (br s, 2 H), 4.06–4.02 (t, J = 6.7 Hz, 2 H), 1.64–1.57 (m, 2 H), 1.38–1.25 (m, 6 H), 0.90–0.87 (t, J = 5.2 Hz, 3 H). ¹³C NMR (100 MHz, DMSO): δ = 157.3, 65.3, 31.4, 28.8, 25.4, 22.5, 13.9. EI-MS (70 eV): m/z = 146 [M]⁺, 102 [C₃H₆OCONH₂]⁺, 74 [M – OCONH₂]⁺.Octyl Carbamate (3b)White solid; yield: 97 mg (83%); mp 67.7–67.9 °C. IR (KBr): 3426 (N–H), 1699 (C=O), 1349 (C–N) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 4.62 (br s, 2 H), 4.07–4.04 (t, J = 5.4 Hz, 2 H), 1.33–1.28 (m, 12 H), 0.90–0.86 (m, 3 H). ¹³C NMR (100 MHz, DMSO): δ = 157.2, 65.3, 31.7, 29.1–28.9, 25.8, 22.6, 14.0. EI-MS (70 eV): m/z = 87 [C₂H₄OCONH₂]⁺, 60 [OCONH₂]⁺.