Download PDF
Synthesis 2009(6): 929-934  
DOI: 10.1055/s-0028-1087986
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

2-Iodoxybenzoic Acid/Tetraethylammonium Bromide/Water: An Efficient Combination for Oxidative Cleavage of Acetals

Chutima Kuhakarn*a, Waraporn Panchana, Supanimit Chiampanichayakula, Natthapol Samakkanada, Manat Pohmakotra, Vichai Reutrakula, Thaworn Jaipetchb
a Department of Chemistry and Center for Innovation in Chemistry, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand
Fax: +66(2)3547151; e-Mail: scckk@mahidol.ac.th;
b Mahidol University, Kanchanaburi Campus, Saiyok, Kanchanaburi 71150, Thailand

Further Information

Publication History

Received 27 June 2008
Publication Date:
02 March 2009 (online)

 PDF Download Permissions and Reprints All articles of this category

Abstract

A simple and efficient procedure has been developed for the oxidation of cyclic and acyclic acetals to the corresponding hydroxyalkyl carboxylic esters and simple esters, respectively. 2-Iodoxybenzoic acid (IBX) in the presence of tetraethylammonium bromide was employed for the reaction in aqueous media. The salient features of the protocol include short reaction time, environmentally benign reagents and solvent, and moderate to high yields.

Key words

o-iodoxybenzoic acid - acetals - oxidations - hydroxyalkyl esters - alcohols

Cyclic acetals are often used in organic synthesis, particularly as carbonyl protecting groups, [¹] as well as for the synthesis of hydroxyalkyl carboxylic esters (Scheme  [¹] ), which are commercially important products serving as the cross-linking agents for polyesters as well as fungicides. [²] A number of oxidizing agents are used for the conversion of cyclic and acyclic acetals, and include molecular oxygen-cobalt(II), [³] di-tert-butyl peroxide, [4] tert-butyl hydroperoxide in combination with transition metals, [5] tert-butyl hydroperoxide-pyridinium dichromate, [6] tert-butyl hydroperoxide-iodine(III) compounds, [7] potassium permanganate, [8] electrochemical oxidation, [9] ozonolysis, [¹0] electrophilic halogen, [¹¹] m-chloroperbenzoic acid in the presence of 2,2′-bipyridinium chlorochromate or boron trifluoride-diethyl ether, [¹²] sodium perborate in acetic anhydride, [¹³] and oxone. [¹4]

Scheme 1 Cleavage of cyclic acetals to form hydroxyalkyl carboxylic esters

Recently, the use of hypervalent iodine reagents in organic synthesis has attracted considerable interest owing to their mild, selective, and environmentally friendly properties. [¹5] 2-Iodoxybenzoic acid (IBX), despite its explosive properties, is a versatile oxidizing reagent due to its stability to air and moisture, mild reaction conditions, efficiency, and ease of preparation. [¹6] The synthetic utility of o-iodoxybenzoic acid as an efficient oxidizing reagent for elegant oxidative transformations has been demonstrated by several groups. [¹7] In continuation of our interest in the development of novel synthetic applications of o-iodoxybenzoic acid, [¹8] we disclose herein an efficient approach to hydroxyalkyl carboxylic esters by oxidative cleavage of cyclic acetals mediated by 2-iodoxybenzoic acid in the presence of tetraethylammonium bromide [¹9] in water.

Initially, the effect of various reaction parameters was examined, and for this 1,3-dioxolane 1a derived from 4-nitrobenzaldehyde was utilized as the model substrate (Table  [¹] ). In the absence of tetraethylammonium bromide (entries 1-8), reactions performed at room temperature under various conditions gave unsatisfactory results, and mostly starting material was recovered (entries 1-5). Significant amounts of hydrolysis product 3a was obtained when the reactions were carried out at elevated temperature in the absence of tetraethylammonium bromide (entries 6-8). Much to our delight, the addition of tetraethylammonium bromide (0.5 equiv) to the reaction mixture dramatically altered the situation; hydroxyalkyl ester 2a formed in moderate to excellent conversion (entries 9-12). More importantly, water can be used as the solvent for this reaction (entry 12), providing the corresponding hydroxyalkyl ester 2a in excellent conversion (97%). When the experiments were performed either at room temperature or with less tetraethylammonium bromide (0.25 equiv), the reactions remained incomplete and significant conversion to hydrolysis product occurred (entries 13 and 16). It should also be mentioned that no reaction took place in aqueous media in the presence of only o-iodoxybenzoic acid or only tetraethylammonium bromide (entries 14 and 15). Additionally, only moderate conversion occurred when the reaction of 1a was carried out under our previously established biphasic conditions (CH2Cl2-H2O, 1:1) (entries 17 and 18). [¹8]

Table 1 Optimization of Reagents and Reaction Conditions for the Oxidation of Acetal 1a

Entry IBX/Et4NBr (equiv) Conditions Conversiona (%)
2a 3a
 1 1.1:0 CH2Cl2-H2O (4:1), r.t., 24 h  0  0
 2 1.1:0 acetone-H2O (4:1), r.t., 24 h  0  0
 3 1.1:0 EtOAc-H2O (4:1), r.t., 24 h  0  2
 4 1.1:0 MeCN-H2O (4:1), r.t., 24 h  0   6
 5 1.1:0 DMSO-H2O (4:1), r.t., 24 h   0  5
 6 1.1:0 MeCN-H2O (4:1), 65 ˚C, 24 h  0 57
 7 1.1:0 DMSO-H2O (4:1), 65 ˚C, 24 h  0 53
 8 1.1:0 DMSO-H2O (4:1), 100 ˚C, 24 h   96
 9 1.1:0.5 MeCN-H2O (3:1), 65 ˚C, 1 h 67   0
10 1.1:0.5 MeCN-H2O (1:3), 65 ˚C, 1 h 93  1
11 1.1:0.5 EtOAc-H2O (1:3), 65 ˚C, 1 h 96  0
12 1.1:0.5 H2O, 65 ˚C, 1 h 97  0
13 1.1:0.5 H2O, r.t., 1 h 41  2
14 0:0.5 H2O, 65 ˚C, 1 h  0  0
15 1.1:0 H2O, 65 ˚C, 1 h  0  0
16 1.1:0.25 H2O, 65 ˚C, 3 h 63 24
17 1.1:0.5 CH2Cl2-H2O (1:1), r.t., 1 h 55  0
18 1.1:0.5 CH2Cl2-H2O (1:1), r.t., 4 h 52  0
a Calculated from ¹H NMR (300 MHz) integration.

The effect of the type of phase-transfer catalyst was also evaluated, as shown in Table  [²] . It is obvious that the type of the halide anion of the phase-transfer reagent has a considerable effect on this conversion. The presence of the bromide anion was found vital for the conversion of 1a into 2a. Tetraethylammonium bromide gave the best conversion (entry 1), while tetrabutylammonium bromide and cetyltrimethylammonium bromide (CTMAB) led to comparatively lower conversions (entries 2 and 3). Unexpectedly, the chloride and iodide anions did not give the expected hydroxyalkyl ester 2a, and the hydrolysis product 3a was obtained in moderate to low yields (entries 4-6).

Table 2 Evaluation of Phase-Transfer Catalysts for the Transformation of 1a into 2a a

Entry Phase-transfer reagent Conversionb (%)
2a 3a
1 Et4NBr 97  0
2 Bu4NBr 89  0
3 CTMABc 75  0
4 Et4NCl  0 56
5 Et4NI  0  1
6 Bu4NI  0  2
a Reagents and conditions: IBX (1.1 equiv), phase-transfer reagent (0.5 equiv).
b Calculated from ¹H NMR (300 MHz) integration.
c CTMAB = cetyltrimethylammonium bromide.

Having established the optimal reaction conditions [IBX (1.1 equiv), Et4NBr (0.5 equiv), H2O, 65 ˚C], we then examined the scope and the generality of the reaction, and the results are summarized in Table  [³] . 1,3-Dioxolane- and 1,3-dioxane-derived aldehydes representing several structural varieties were prepared according to previously reported procedures [²0] and were screened for their reactivity (entries 1-21). In general, aromatic 1,3-dioxolanes underwent oxidative cleavage, yielding β-hydroxyethyl esters in good yields (55-81%, entries 1-7). Oxidation of aliphatic 1,3-dioxolanes gave the corresponding esters in moderate to good yields (entries 8-11). 1,3-Dioxane derivatives reacted with the reagents with almost equal facility, leading to corresponding γ-hydroxypropyl esters in comparable yields (entries 12-21). Unlike the reactions mediated by ozone, [¹0] electrochemical oxidation, [9] and hypervalent iodine(III), [7] the reactions of acyclic dialkyl acetals proceeded readily to give simple alkyl esters in moderate yields (entries 22 and 23). It should also be pointed out that the reaction of 1,3-dioxolane-derived 4-nitroacetophenone under standard conditions exclusively led to simple hydrolysis to the corresponding carbonyl compound.

Table 3 Oxidation of Acetals with o-Iodoxybenzoic Acid and Tetraethylammonium­ Bromide in Watera

Entry Acetal R n Et4NBr (equiv) Time (h) 2 Yieldb (%)
 1 1a 4-O2NC6H4 1 0.5 1 2a 81
 2 1b 2-O2NC6H4 1 0.5 5 2b 71
 3 1c 4-BrC6H4 1 0.5 2 2c 75
 4 1d 3-ClC6H4 1 0.5 1 2d 70
 5 1e 4-FC6H4 1 0.5 1 2e 63
 6 1f Tol 1 1.0 1 2f 55
 7 1g Ph 1 0.5 1 2g 58
 8 1h Bn 1 0.5 2 2h 81
 9 1i CHMePh 1 0.5 1 2i 76
10 1j n-C8H17 1 0.5 1 2j 62
11 1k n-C13H27 1 0.5 1 2k 59
12 1l 4-O2NC6H4 2 1.0 3 2l 50
13 1m 4-BrC6H4 2 0.5 2 2m 78
14 1n 3-ClC6H4 2 0.5 1 2n 78
15 1o 4-FC6H4 2 0.5 1 2o 61
16 1p Tol 2 1.0 1 2p 42
17 1q Ph 2 0.5 1 2q 59
18 1r Bn 2 0.5 2 2r 83
19 1s CHMePh 2 0.5 1 2s 79
20 1t n-C8H17 2 0.5 1 2t 86
21 1u n-C13H27 2 0.5 1 2u 79
22 4a c - - 0.5 1 5a c 60
23 4b c - - 0.5 2.5 5b c 56
a Reagents and conditions: IBX (1.1 equiv), H2O, 65 ˚C, in air.
b Isolated yield.
c Phenylacetaldehyde dimethyl acetal (4a); 2-phenylpropanal dimethyl acetal (4b); methyl phenylacetate (5a), methyl 2-phenylpropanoate (5b).

Oxidation of unsymmetrical cyclic acetals under similar reaction conditions was also evaluated as shown in Scheme  [²] . Even though moderate to good yields were observed, an approximately 1:1 inseparable isomeric mixture of the hydroxyalkyl esters was obtained.

Scheme 2 Oxidation of unsymmetrical acetals

On the basis of the experimental results and literature precedents on similar acetal cleavage, a plausible reaction pathway for the formation of hydroxyalkyl esters is assumed to involve the following steps: (a) oxidation of the bromide anion by 2-iodoxybenzoic acid to give electrophilic bromine; (b) oxidation of the acetal carbon to provide stabilized acetal carbocation A; (c) nucleophilic attack by water to give hemiorthoester B; and (d) ring opening of hemiorthoester B to provide, finally, hydroxyalkyl ester 2 (Scheme  [³] ).

Scheme 3 Plausible reaction pathway for 2-iodoxybenzoic acid/tetraethylammonium­ bromide mediated oxidative cleavage of acetals

In summary, we have developed an efficient and simple method for the oxidative cleavage of cyclic and acyclic acetals to their corresponding hydroxyalkyl carboxylic esters and simple esters, respectively, using the combination of 2-iodoxybenzoic acid and tetraethylammonium bromide in water. The method has general scope, and a clean reaction occurs, giving the products in moderate to high yields; the short reaction time in aqueous media can be of great synthetic utility in organic synthesis. The oxidative hydrolysis of acetals and ketals by 2-iodoxybenzoic acid as well as other hypervalent iodine(III) reagents is currently being investigated and will be reported in due course.

All known compounds were characterized by ¹H and ¹³C NMR, IR, and mass spectroscopy, and their spectroscopic data were identical to those reported in the literature. All new compounds were characterized by ¹H and ¹³C NMR, IR, and high-resolution mass spectroscopy. ¹H and ¹³C NMR spectra were run on Bruker DPX-300 and Bruker Avance 500 spectrometers. IR spectroscopy was carried out on a Perkin Elmer GX FT-IR System spectrometer, and HRMS was carried out on a Bruker micro TOF spectrometer.

Hydroxyalkyl Carboxylic Esters 2; General Procedure

IBX (154 mg, 0.55 mmol) was added to a suspension of acetal 1 or 4 (0.5 mmol) and Et4NBr (52.5 mg, 0.25 mmol) in H2O (2 mL), and the reaction mixture was vigorously stirred at 65 ˚C for the time period shown in Table  [³] . Upon completion of the reaction, the reaction mixture was quenched by the addition of sat. aq Na2S2O3 (5 mL), and basified with sat. aq NaHCO3 (5 mL); further stirring was followed by extraction with EtOAc (3 × 5 mL). The combined organic extracts were washed with H2O (10 mL) and brine (10 mL), dried (Na2SO4), filtered, and concentrated (aspirator). The residue was purified by column chromatography (silica gel) to furnish the analytically pure product.

2-Hydroxyethyl 4-Bromobenzoate (2c)

Compound 2c was prepared by the general procedure from 1c (114.5 mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2 cm; hexanes-EtOAc, 1:0 to 7:3) gave the title compound.

Yield: 92.0 mg (75%); colorless liquid; R f  = 0.26 (hexanes-EtOAc, 7:3).

IR (neat): 3419 (O-H), 1722 (C=O) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 7.91 (d, J = 8.5 Hz, 2 H), 7.58 (d, J = 8.5 Hz, 2 H), 4.45 (t, J = 4.7 Hz, 2 H), 3.96 (t, J = 4.7 Hz, 2 H), 2.05 (br s, 1 H).

¹³C NMR (75 MHz, CDCl3): δ = 166.2, 131.8, 131.2, 128.8, 128.3, 66.8, 61.3.

HRMS (ESI-TOF): m/z [M + Na+] calcd for C9H9BrO3Na: 266.9633; found: 266.9659.

2-Hydroxyethyl 3-Chlorobenzoate (2d)

Compound 2d was prepared by the general procedure from 1d (92.3 mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2 cm; hexanes-EtOAc, 1:0 to 3:2) gave the title compound.

Yield: 70.0 mg (70%); pale yellow liquid; R f  = 0.30 (hexanes-EtOAc, 7:3).

IR (neat): 3419 (O-H), 1723 (C=O) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 8.04 (t, J = 1.8 Hz, 1 H), 7.95 (ddd, J = 7.9, 1.5, 1.1 Hz, 1 H), 7.55 (ddd, J = 7.9, 2.1, 1.1 Hz, 1 H), 7.39 (td, J = 7.9, 0.3 Hz, 1 H), 4.47 (t, J = 4.7 Hz, 2 H), 3.97 (t, J = 4.7 Hz, 2 H), 2.42 (br s, 1 H).

¹³C NMR (75 MHz, CDCl3): δ = 165.7, 134.5, 133.1, 131.6, 129.68, 129.66, 127.8, 66.9, 61.1.

HRMS (ESI-TOF): m/z [M + Na+] calcd for C9H9ClO3Na: 223.0138; found: 223.0145.

2-Hydroxyethyl 4-Fluorobenzoate (2e)

Compound 2e was prepared by the general procedure from 1e (84.0 mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2 cm; hexanes-EtOAc, 1:0 to 1:1) gave the title compound.

Yield: 58.0 mg (63%); pale yellow liquid; R f  = 0.26 (hexanes-EtOAc, 7:3).

IR (neat): 3424 (O-H), 1719 (C=O) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 8.11-8.04 (m, 2 H), 7.15-7.09 (m, 2 H), 4.44 (t, J = 4.7 Hz, 2 H), 3.94 (t, J = 4.7 Hz, 2 H), 2.73 (br s, 1 H).

¹³C NMR (75 MHz, CDCl3): δ = 165.9, 165.8 (d, J = 252.9 Hz), 132.2 (d, J = 9.4 Hz), 126.1 (d, J = 2.9 Hz), 115.5 (d, J = 21.9 Hz), 66.6, 61.2.

HRMS (ESI-TOF): m/z [M + Na+] calcd for C9H9FO3Na: 207.0433; found: 207.0444.

2-Hydroxyethyl 2-Phenylethanoate (2h)

Compound 2h was prepared by the general procedure from 1h (72.9 mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2 cm; hexanes-EtOAc, 1:0 to 7:3) gave the title compound.

Yield: 73.0 mg (81%); pale yellow liquid; R f  = 0.22 (hexanes-EtOAc, 7:3).

IR (neat): 3418 (O-H), 1732 (C=O) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 7.38-7.27 (m, 5 H), 4.25 (t, J = 4.7 Hz, 2 H), 3.81 (t, J = 4.7 Hz, 2 H), 3.70 (s, 2 H), 2.10 (br s, 1 H).

¹³C NMR (75 MHz, CDCl3): δ = 171.9, 133.8, 129.2, 128.6, 127.2, 66.4, 61.0, 41.2.

HRMS (ESI-TOF): m/z [M + Na+] calcd for C10H12O3Na: 203.0684; found: 203.0667.

2-Hydroxyethyl 2-Phenylpropanoate (2i)

Compound 2i was prepared by the general procedure from 1i (89 mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2 cm; hexanes-EtOAc, 9:1 to 7:3) gave the title compound.

Yield: 73.7 mg (76%); colorless liquid; R f  = 0.24 (hexanes-EtOAc, 7:3).

IR (neat): 3426 (O-H), 1732 (C=O) cm-¹.

¹H NMR (500 MHz, CDCl3): δ = 7.37-7.32 (m, 4 H), 7.30-7.26 (m, 1 H), 4.24-4.16 (m, 2 H), 3.79 (q, J = 7.2 Hz, 1 H), 3.76-3.71 (m, 2 H), 2.19 (br s, 1 H), 1.53 (d, J = 7.2 Hz, 3 H).

¹³C NMR (125 MHz, CDCl3): δ = 174.8, 140.4, 128.6, 127.3, 127.2, 66.2, 60.9, 45.4, 18.4.

HRMS (ESI-TOF): m/z [M + Na+] calcd for C11H14O3Na: 217.0841; found: 217.0892.

2-Hydroxyethyl Nonanoate (2j)

Compound 2j was prepared by the general procedure from 1j (93.0 mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2 cm; hexanes-EtOAc, 1:0 to 7:3) gave the title compound.

Yield: 62.6 mg (62%); colorless liquid; R f  = 0.23 (hexanes-EtOAc, 7:3).

IR (neat): 3423 (O-H), 1737 (C=O) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 4.19 (t, J = 4.7 Hz, 2 H), 3.81 (t, J = 4.7 Hz, 2 H), 2.75 (br s, 1 H), 2.33 (t, J = 7.6 Hz, 2 H), 1.70-1.55 (m, 2 H), 1.40-1.20 (m, 10 H), 0.87 (t, J = 6.6 Hz, 3 H).

¹³C NMR (75 MHz, CDCl3): δ = 174.2, 65.8, 61.1, 34.1, 31.7, 29.11, 29.05, 29.01, 24.8, 22.5, 14.0.

HRMS (ESI-TOF): m/z [M + Na+] calcd for C11H22O3Na: 225.1467; found: 225.1466.

2-Hydroxyethyl Tetradecanoate (2k)

Compound 2k was prepared by the general procedure from 1k (128.0 mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2 cm; hexanes-EtOAc, 7:3) gave the title compound.

Yield: 80.2 mg (59%); colorless solid; mp 44-45 ˚C; R f  = 0.32 (hexanes-EtOAc, 7:3).

IR (KBr): 3367 (O-H), 1737 (C=O) cm-¹.

¹H NMR (500 MHz, CDCl3): δ = 4.23 (t, J = 4.7 Hz, 2 H), 3.85 (t, J = 4.7 Hz, 2 H), 2.37 (t, J = 7.6 Hz, 2 H), 1.70-1.55 (m, 2 H), 1.40-1.20 (m, 21 H), 0.90 (t, J = 6.9 Hz, 3 H).

¹³C NMR (125 MHz, CDCl3): δ = 174.2, 65.9, 61.3, 34.2, 31.9, 29.64, 29.61, 29.57, 29.43, 29.32, 29.23, 29.12, 24.9, 24.7, 22.7, 14.1.

HRMS (ESI-TOF): m/z [M + Na+] calcd for C16H32O3Na: 295.2249; found: 295.2299.

3-Hydroxypropyl 4-Nitrobenzoate (2l)

Compound 2l was prepared by the general procedure from 1l (104.5 mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2 cm; hexanes-EtOAc, 1:0 to 3:2) gave the title compound.

Yield: 56.3 mg (50%); pale yellow liquid; R f  = 0.14 (hexanes-EtOAc, 7:3).

IR (neat): 3416 (O-H), 1724 (C=O) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 8.29 (d, J = 8.7 Hz, 2 H), 8.21 (d, J = 8.7 Hz, 2 H), 4.54 (t, J = 6.1 Hz, 2 H), 3.81 (t, J = 6.1 Hz, 2 H), 2.05 (quin, J = 6.1 Hz, 2 H), 2.03 (br s, 1 H).

¹³C NMR (75 MHz, CDCl3): δ = 164.9, 150.5, 135.5, 130.7, 123.5, 62.8, 59.0, 31.6.

HRMS (ESI-TOF): m/z [M + Na+] calcd for C10H11NO5Na: 248.0535; found: 248.0533.

3-Hydroxypropyl 3-Chlorobenzoate (2n)

Compound 2n was prepared by the general procedure from 1n (99.3 mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2 cm; hexanes-EtOAc, 1:0 to 1:1) gave the title compound.

Yield: 83.7 mg (78%); pale yellow liquid; R f  = 0.27 (hexanes-EtOAc, 7:3).

IR (neat): 3423 (O-H), 1720 (C=O) cm-¹.

¹H NMR (500 MHz, CDCl3): δ = 8.00 (t, J = 1.8 Hz, 1 H), 7.92 (dt, J = 7.9, 1.1 Hz, 1 H), 7.54 (ddd, J = 7.9, 2.1, 1.1 Hz, 1 H), 7.39 (t, J = 7.9 Hz, 1 H), 4.49 (t, J = 6.2 Hz, 2 H), 3.79 (t, J = 6.2 Hz, 2 H), 2.45 (br s, 1 H), 2.02 (quin, J = 6.2 Hz, 2 H).

¹³C NMR (125 MHz, CDCl3): δ = 165.7, 134.5, 133.0, 131.8, 129.7, 129.6, 127.7, 62.2, 59.0, 31.7.

HRMS (ESI-TOF): m/z [M + Na+] calcd for C10H11ClO3Na: 237.0294; found: 237.0286.

3-Hydroxypropyl 4-Fluorobenzoate (2o)

Compound 2o was prepared by the general procedure from 1o (91 mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2 cm; hexanes-EtOAc, 1:0 to 1:1) gave the title compound.

Yield: 60.5 mg (61%); colorless liquid; R f  = 0.26 (hexanes-EtOAc, 7:3).

IR (neat): 3407 (O-H), 1716 (C=O) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 8.07-8.02 (m, 2 H), 7.14-7.08 (m, 2 H), 4.47 (t, J = 6.1 Hz, 2 H), 3.77 (t, J = 6.1 Hz, 2 H), 2.47 (br s, 1 H), 2.01 (quin, J = 6.1 Hz, 2 H).

¹³C NMR (75 MHz, CDCl3): δ = 165.9, 165.8 (d, J = 252.6 Hz), 132.1 (d, J = 9.3 Hz), 126.3 (d, J = 3.0 Hz), 115.5 (d, J = 21.9 Hz), 62.0, 59.0, 31.8.

HRMS (ESI-TOF): m/z [M + H+] calcd for C10H12O3F: 199.0770; found: 199.0740.

3-Hydroxypropyl 2-Phenylethanoate (2r)

Compound 2r was prepared by the general procedure from 1r (89 mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2 cm; hexanes-EtOAc, 1:0 to 1:1) gave the title compound.

Yield: 80.6 mg (83%); colorless liquid; R f  = 0.21 (hexanes-EtOAc, 7:3).

IR (neat): 3416 (O-H), 1731 (C=O) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 7.34-7.28 (m, 5 H), 4.24 (t, J = 6.1 Hz, 2 H), 3.64 (s, 2 H), 3.61 (t, J = 6.1 Hz, 2 H), 2.49 (br s, 1 H), 1.84 (quin, J = 6.1 Hz, 2 H).

¹³C NMR (75 MHz, CDCl3): δ = 171.8, 133.8, 129.0, 128.4, 126.9, 61.8, 58.8, 41.2, 31.4.

HRMS (ESI-TOF): m/z [M + Na+] calcd for C11H14O3Na: 217.0841; found: 217.0833.

3-Hydroxypropyl 2-Phenylpropanoate (2s)

Compound 2s was prepared by the general procedure from 1s (96 mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2 cm; hexanes-EtOAc, 9:1 to 4:1) gave the title compound.

Yield: 82.2 mg (79%); colorless liquid; R f  = 0.27 (hexanes-EtOAc, 7:3).

IR (neat): 3416 (O-H), 1732 (C=O) cm-¹.

¹H NMR (500 MHz, CDCl3): δ = 7.36-7.26 (m, 5 H), 4.26-4.19 (m, 2 H), 3.75 (q, J = 7.2 Hz, 1 H), 3.59-3.51 (m, 2 H), 2.15 (br s, 1 H), 1.81 (quin, J = 6.1 Hz, 2 H), 1.52 (d, J = 7.2 Hz, 3 H).

¹³C NMR (125 MHz, CDCl3): δ = 174.9, 140.4, 128.5, 127.3, 127.1, 61.7, 58.9, 45.5, 31.5, 18.2.

HRMS (ESI-TOF): m/z [M + Na+] calcd for C12H16O3Na: 231.0997; found: 231.1049.

3-Hydroxypropyl Nonanoate (2t)

Compound 2t was prepared by the general procedure from 1t (100 mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2 cm; hexanes-EtOAc, 1:0 to 3:2) gave the title compound.

Yield: 93.0 mg (86%); colorless liquid; R f  = 0.24 (hexanes-EtOAc, 7:3).

IR (neat): 3425 (O-H), 1737 (C=O) cm-¹.

¹H NMR (300 MHz, CDCl3): δ = 4.22 (t, J = 6.1 Hz, 2 H), 3.68 (t, J = 6.1 Hz, 2 H), 2.36 (br s, 1 H), 2.30 (t, J = 7.5 Hz, 2 H), 1.86 (quin, J = 6.1 Hz, 2 H), 1.70-1.52 (m, 2 H), 1.40-1.15 (m, 10 H), 0.87 (t, J = 6.6 Hz, 3 H).

¹³C NMR (75 MHz, CDCl3): δ = 174.3, 61.1, 59.1, 34.3, 31.7 (2 C), 29.13, 29.07, 29.03, 24.9, 22.5, 14.0.

HRMS (ESI-TOF): m/z [M + Na+] calcd for C12H24O3Na: 239.1623; found: 239.1606.

3-Hydroxypropyl Tetradecanoate (2u)

Compound 2u was prepared by the general procedure from 1u (135.0 mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2 cm; hexanes-EtOAc, 85:15) gave the title compound.

Yield: 113.0 mg (79%); colorless liquid; R f  = 0.30 (hexanes-EtOAc, 7:3).

IR (neat): 3297 (O-H), 1736 (C=O) cm-¹.

¹H NMR (500 MHz, CDCl3): δ = 4.24 (t, J = 6.1 Hz, 2 H), 3.69 (t, J = 6.1 Hz, 2 H), 2.32 (t, J = 7.6 Hz, 2 H), 1.87 (quin, J = 6.1 Hz, 2 H), 1.65-1.59 (m, 2 H), 1.36-1.23 (m, 21 H), 0.88 (t, J = 6.8 Hz, 3 H).

¹³C NMR (125 MHz, CDCl3): δ = 174.3, 61.1, 59.1, 34.3, 31.9, 31.7, 29.62 (2 C), 29.58, 29.54, 29.4, 29.3, 29.2, 29.1, 24.9, 22.6, 14.0.

HRMS (ESI-TOF): m/z [M + Na+] calcd for C17H34O3Na: 309.2406; found: 309.2404.

Methyl 2-Phenylpropanoate (5b)

Compound 5b was prepared by the general procedure from 4b (90 mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2 cm; hexanes-EtOAc, 1:0 to 3:2) gave the title compound.

Yield: 46.0 mg (56%); pale yellow liquid; R f  = 0.44 (hexanes-EtOAc, 9:1).

IR (neat): 1738 (C=O) cm-¹.

¹H NMR (500 MHz, CDCl3): δ = 7.38-7.26 (m, 5 H), 3.75 (q, J = 7.2 Hz, 1 H), 3.69 (s, 3 H), 1.53 (d, J = 7.2 Hz, 3 H).

¹³C NMR (125 MHz, CDCl3): δ = 175.0, 140.6, 128.6, 127.5, 127.1, 52.0, 45.4, 18.6.

HRMS (ESI-TOF): m/z [M + Na+] calcd for C10H12O2Na: 187.0735; found: 187.0728.

Acknowledgment

We thank the Thailand Research Fund (RMU5180040), Center for Innovation in Chemistry (PERCH-CIC), and the Commission on Higher Education (CHE-RES-RG) for financial support.

   Permissions and Reprints All articles of this category

Scheme 1 Cleavage of cyclic acetals to form hydroxyalkyl carboxylic esters

Scheme 2 Oxidation of unsymmetrical acetals

Scheme 3 Plausible reaction pathway for 2-iodoxybenzoic acid/tetraethylammonium­ bromide mediated oxidative cleavage of acetals