Synthesis of Mixed Carbonates via a Three-Component Coupling of Alcohols, CO₂, and Alkyl Halides in the Presence of K₂CO₃ and Tetrabutylammonium Iodide

Abstract

Various mixed carbonates can be conveniently prepared in good yields using the corresponding alcohols, alkyl halides under CO₂ atmosphere in the presence of potassium carbonate or sodium carbonate and tetrabutylammonium iodide.

Introduction

Organic carbonates have played very important roles in the area of Synthetic Organic Chemistry, as key intermediates or as novel protecting groups [1]. Common synthetic methods leading to carbonates can be categorized into five classes: 1) alcoholysis of phosgene or its derivatives [2]; 2) exchange of organic carbonates [3]; 3) alkylation of carbon dioxide [4]; and 5) alkylation of inorganic carbonate [5]. However, for the synthesis of mixed (unsymmetrical) alkyl carbonates [ROC(O)OR’], these methods all suffer from two main drawbacks: 1) low selectivity and low yield; (2) the limited scope and availability of the substrates. The lack of facile synthetic methodologies for the preparation of mixed alkyl carbonates [6] promoted us to develop some efficient, convenient, and practical procedures for the synthesis of carbonates [7]. Recently, Jung et. al. reported a cesium carbonate (Cs₂CO₃) and tetrabutylammonium iodide (TBAI) promoted O-alkylation of alcohols for the preparation of mixed alkyl carbonates under a CO₂ atmosphere [8]. Herein, we wish to report the use of cheaper and more readily available potassium carbonate (K₂CO₃) or sodium carbonate (Na₂CO₃) instead of cesium carbonate (Cs₂CO₃) to synthesize the mixed alkyl carbonates via alkylation of carbon dioxide under mild conditions. This facile synthetic method provides a potentially practical way for the utilization of carbon dioxide, a cheap, environmentally benign, natural and abundant reagent, for the synthesis of mixed carbonates [9].

Results and Discussion

First we sought to examine the best reaction conditions for the preparation of unsymmetrical carbonates under a CO₂ atmosphere in the presence of K₂CO₃ using benzyl alcohol and benzyl halides as the substrates (Scheme 1).

Scheme 1.

Scheme 1.

In general, the reaction of benzyl alcohol and benzyl halides under a CO₂ atmosphere with additives gave very poor yields of carbonate (Table 1, entry 1). In the presence of additives such as 18-crown-6, KI or tetrabutylammonium iodide (TBAI), the yields of carbonate can be increased to some extent (Table 1, entries 2-14). Potassium hydroxide (KOH) or DBU is not as good as potassium carbonate (Table 1, entry 7-9). Benzyl bromide gave a higher yield of carbonate than benzyl chloride (Table 1, entries 5-6). We found that when the reaction was carried out at 70 ^oC in the presence of a 5-fold excess of potassium carbonate as base and a 5-fold excess of TBAI as the additive in N,N -dimethylformamide (DMF) solution the yield of carbonate can reach 82% (Table 1, entry 13).

This represent the best reaction conditions found for the preparation of carbonates. Using sodium carbonate (Na₂CO₃) as a base under the same reaction conditions, the yields of carbonate are in general lower than those observed using K₂CO₃ (Table 1, entries 12-14). Thus we have found a highly chemoselective, convenient, and efficient synthetic method for the preparation of carbonates in high yield through the three-component coupling reaction of alcohols, carbon dioxide, and halides. This synthetic method obviously has the potential for industrial use and for the preparation of mixed carbonates (unsymmetrical carbonates).

We next investigated the formation of carbonates using other alcohols and alkyl bromides as the substrates under the optimized conditions described above (Scheme 2).

Table 1. Reactiions of PhCH₂OH (1.0 eq) with PhCH₂X (1.0 eq) (X = Cl, Br) in the presence of additives (0.1 ~ 5.0 eq) under CO₂ atmosphere.

Table 1. Reactiions of PhCH₂OH (1.0 eq) with PhCH₂X (1.0 eq) (X = Cl, Br) in the presence of additives (0.1 ~ 5.0 eq) under CO₂ atmosphere.

Scheme 2.

Scheme 2.

Table 2. Reactiions of akohols with different alkyl bromides CO₂ atmosphere.

Table 2. Reactiions of akohols with different alkyl bromides CO₂ atmosphere.

The results are summarized in Table 2. As can be seen, we found that C₄–C₇ alcohols and benzyl alcohol can react efficiently with various alkyl bromides under a CO₂ atmosphere to give the corresponding carbonates in moderate to good yields. In addition, we also found that in the reaction of n-propylalcohol, isopropylalcohol, 1-dodecanol and 1-tetradecanol with benzyl bromide under the same reaction conditions, the mixed carbonates were obtained in very low yield and major product was PhCH₂OCHO, which is derived from a Vilsmeier-Haack salt [9] in the reaction of benzyl bromide with DMF [8] (Scheme 3).

Scheme 3.

Scheme 3.

It should be emphasized that using C₄H₉Br or C₈H₁₇Br as the electrophile, the mixed carbonate is formed exclusively without the formation of the corresponding ROCHO (R= C₄H₉ or C₈H₁₇).

Conclusions

In summary, we have disclosed a highly efficient three-component coupling reaction using alcohols, carbon dioxide, and alkyl halides as the starting materials in the presence of potassium carbonate and TBAI and leading to the exclusive synthesis of mixed alkyl carbonates. This synthetic method has potential future industrial use as potassium carbonate, a much cheaper and more easily available inorganic base than cesium carbonate, is utilized as the base.

Experimental

General

MPs were obtained with a Yanagimoto micro melting point apparatus and are uncorrected. ¹H-NMR spectra were recorded on a Bruker AM-300 spectrometer for solution in CDCl₃ with tetramethylsilane (TMS) as internal standard; J-values are in Hz. Mass spectra were recorded with a HP-5989 instrument and HRMS was measured by a Finnigan MA+ mass spectrometer. Organic solvents were dried by standard methods when necessary. Analyzed solid compounds reported in this paper gave satisfactory CHN microanalyses using a Carlo-Erba 1106 analyzer. Commercially obtained reagents were used without further purification. All reactions were monitored by TLC using Huanghai GF₂₅₄ silica gel coated plates. Flash column chromatography was carried out using 200-300 mesh silica gel.

Representative Experimental Procedure. To benzyl alcohol (216 mg, 2.0 mmol) in anhydrous N,N-dimethylformamide (10 mL) were added potassium carbonate (1.38 g, 10 mmol, 5.0 eq.) and tetrabutylammonium iodide (3.7 g, 10.0 mmol, 5.0 eq.). Carbon dioxide gas was flushed into the reaction mixture three times, and then alkyl bromide (10 mmol, 5.0 equiv.) was added into suspension. The reaction was carried out under carbon dioxide atmosphere for 48 h, during which time the starting material was consumed. The reaction mixture was then poured into water (30 mL) and extracted with EtOAc (3 x 30 mL). The organic layer was washed with water (2 x 30 mL) and brine (30 mL) and dried over anhydrous sodium sulfate. Evaporation of solvent followed by flash column chromatography (eluent: hexane-EtOAc, 20:1) afforded the carbonate as a colorless oil.

Carbonic acid dibenzyl ester (PhCH₂OCO₂CH₂Ph). A colorless liquid; 277 mg, 60%; IR (CHCl₃) ν 1745 cm^-1 (C=O); ¹H-NMR: δ 5.17 (4H, s, CH₂), 7.35-7.41 (10H, m, Ph); MS (EI) m/z 197 (M⁺-45); [Calc. for C₁₅H₁₄O₃: requires M, 242.0943. Found: 243.1024 (M⁺)].

Dibenzyl ether (PhCH₂OCH₂Ph). A colorless liquid; 217 mg, 16%; IR (CHCl₃) ν 1600, 1445 cm^-1; ¹H-NMR: δ 4.56 (4H, s, CH₂), 7.25-7.39 (10H, m, Ph); MS (EI) m/z 197 (M⁺-1); [Calc. for C₁₄H₁₄O: requires M, 198.1045. Found: 198.1041 (M⁺)].

Carbonic acid benzyl ester hexadecyl ester (PhCH₂OCO₂C₁₆H₃₃). A colorless liquid; 543 mg, 76%; IR (CHCl₃) ν 1737 cm^-1 (C=O); ¹H-NMR: δ 0.90 (3H, t, J = 6.9 Hz, CH₃), 1.22-1.33 (28H, m, CH₂), 1.51-1.60 (2H, m, CH₂), 4.17 (2H, t, J = 6.7 Hz, CH₂), 5.12 (2H, s, CH₂), 7.37-7.42 (5H, m, Ph); MS (EI) m/z 152 (M⁺-224); [Calc. for C₂₄H₄₀O₃: requires M, 376.2979. Found: 376.2966 (M⁺)].

Carbonic acid benzyl ester butyl ester (n-BuOCO₂CH₂Ph). A colorless liquid; 221 mg, 56%; IR (CHCl₃) ν 1718 cm^-1 (C=O); ¹H-NMR: δ 0.90 (3H, t, J = 6.9 Hz, CH₃), 1.37-1.44 (2H, m, CH₂), 1.64-1.69 (2H, m, CH₂), 4.12 (2H, t, J = 6.7 Hz, CH₂), 5.18 (2H, s, CH₂), 7.36-7.42 (5H, m, Ph); MS (EI) m/z 208 (M⁺); [Calc. for C₁₂H₁₆O₃: requires M, 208.1100. Found: 208.1105 (M⁺)].

Carbonic acid benzyl ester hexadecyl ester [CH₃(CH₂)₅CH₂OCO₂CH₂Ph]. A colorless liquid; 301 mg, 60%; IR (CHCl₃) ν 1716 cm^-1 (C=O); ¹H-NMR: δ 0.89 (3H, m, CH₃), 1.29-1.32 (8H, m, CH₂), 1.66 (2H, m, CH₂), 4.15 (2H, t, J = 6.0 Hz, CH₂), 5.16 (2H, s, CH₂), 7.35-7.45 (5H, m, Ph); MS (EI) m/z 250 (M⁺); [Calc. for C₁₅H₂₂O₃: requires M, 250.1570. Found: 250.1576 (M⁺)].

Carbonic acid benzyl ester cyclopentyl ester [PhCH₂OCO₂(CH₂)₅]. A colorless liquid; 167 mg, 40%; IR (CHCl₃) ν 1736 cm^-1 (C=O); ¹H-NMR: δ 1.56-1.93 (8H, m, CH₂), 5.01-5.10 (1H, m, CH), 5.12 (2H, s, CH₂), 7.31-7.45 (5H, m, Ph); MS (EI) m/z 219 (M⁺-1); [Calc. for C₁₃H₁₆O₃: requires M, 220.1100. Found: 220.1094 (M⁺)].

Carbonic acid benzyl ester 3-methylbutyl ester [PhCH₂OCO₂CH₂CH₂CH(CH₃)₂]. A colorless liquid; 219 mg, 52%; IR (CHCl₃) ν 1742 cm^-1 (C=O); ¹H-NMR: δ 0.94 (6H, d, J = 6.7 Hz, CH₃), 1.59 (2H, q, J = 6.9 Hz, CH₂), 1.69-1.76 (1H, m, CH), 4.20 (2H, t, J = 6.9 Hz, CH₂), 5.18 (2H, s, CH₂), 7.34-7.42 (5H, m, Ph); MS (EI) m/z 222 (M⁺); [Calc. for C₁₃H₁₈O₃: requires M, 222.1256. Found: 222.1244 (M⁺)].

Carbonic acid benzyl ester octyl ester (n-C₈H₁₇OCO₂CH₂Ph). A colorless liquid; 301 mg, 60%; IR (CHCl₃) ν 1745 cm^-1 (C=O); ¹H-NMR: δ 0.88 (3H, t, J = 6.9 Hz, CH₃), 1.27-1.43 (10H, m, 5CH₂), 1.62-1.69 (2H, m, CH₂), 4.15 (2H, t, J = 6.9 Hz, CH₂), 5.16 (2H, s, CH₂), 7.33-7.41 (5H, m, Ar); MS (EI) m/z 264 (M⁺); [Calc. for C₁₆H₂₄O₃: requires M, 264.1726. Found: 264.1725 (M⁺)].

Carbonic acid benzyl ester hexyl ester (n-C₆H₁₃OCO₂CH₂Ph). A colorless liquid; 300 mg, 67%; IR (CHCl₃) ν 1744 cm^-1 (C=O); ¹H-NMR: δ 0.88-0.90 (3H, m, CH₃), 1.31-1.41 (6H, m, CH₂), 1.61-1.71 (2H, m, CH₂), 4.10- (2H, t, J = 6.9 Hz, CH₂), 5.16 (2H, s, CH₂), 7.33-7.41 (5H, m, Ar); MS (EI) m/z 236 (M⁺); [Calc. for C₁₄H₂₀O₃: requires M, 236.1412. Found: 236.1372 (M⁺)].

Carbonic acid benzyl ester 3-phenylpropyl ester [Ph(CH₂)₃OCO₂CH₂Ph]. A colorless liquid; 291 mg, 69%; IR (CHCl₃) ν 1723 cm^-1 (C=O); ¹H-NMR: δ 1.98-2.07 (2H, m, CH₂), 2.71-2.78 (2H, m, CH₂), 4.17-4.23 (2H, m, CH₂), 5.19 (2H, s, CH₂), 7.21-7.40 (5H, m, Ar); MS (EI) m/z 208 (M⁺-60); [Calc. for C₁₇H₁₈O₃: requires M, 270.1256. Found: 270.1245 (M⁺)].

Carbonic acid benzyl ester heptyl ester (n-C₇H₁₅OCO₂C₄H₉). A colorless liquid; 238 mg, 58%; IR (CHCl₃) ν 1744 cm^-1 (C=O); ¹H-NMR: δ 0.86-0.96 (6H, m, CH₃), 1.25-1.50 (10H, m, CH₂), 1.60-1.68 (4H, m, CH₂), 4.10-4.16 (4H, m, CH₂); MS (EI) m/z 215 (M⁺-1); [Calc. for C₁₂H₂₄O₃: requires M, 216.1726. Found: 216.1722 (M⁺)].

Carbonic acid dibutyl ester (n-C₄H₉OCO₂C₄H₉). A colorless liquid; 231 mg, 70%; IR (CHCl₃) ν 1745 cm^-1 (C=O); ¹H-NMR: δ 0.88 (6H, t, J = 6.9 Hz, CH₃), 1.20-1.40 (4H, m, CH₂), 1.50-1.65 (4H, m, CH₂), 4.05 (4H, t, J = 6.7 Hz, CH₂); MS (EI) m/z 175 (M⁺+1); [Calc. for C₉H₁₈O₃: requires M, 174.1256. Found: 174.1263 (M⁺)].

Formic acid benzyl ester [PhCH₂OC(O)H]. A colorless liquid; 217 mg, 60%; IR (CHCl₃) ν 1724 cm^-1 (C=O); ¹H-NMR: δ 5.12 (2H, s, CH₂), 7.33-7.41 (5H, m, Ar), 8.14 (1H, s, CH); MS (EI) m/z 136 (M⁺); [Calc. for C₈H₈O₂, M 136.1749: requires C, 70.57; H, 5.92. Found: C, 70.12; H, 6.21].