Influence of Carboxylic Acids on the Synthesis of Chlorohydrin Esters ...

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from 1,3-Butanediol. Jonh Jairo Méndez. Chemistry Department, Universitat de Lleida, Lleida, Spain and Chemistry Department, Tolima University, Colombia.

Synthetic Communicationsw, 36: 1167–1175, 2006 Copyright # Taylor & Francis Group, LLC ISSN 0039-7911 print/1532-2432 online DOI: 10.1080/00397910500514055

Influence of Carboxylic Acids on the Synthesis of Chlorohydrin Esters from 1,3-Butanediol Jonh Jairo Me´ndez Chemistry Department, Universitat de Lleida, Lleida, Spain and Chemistry Department, Tolima University, Colombia

Jordi Eras Chemistry Department, Universitat de Lleida, Lleida, Spain

Merce` Balcells and Ramon Canela Chemistry Department and Centre Udl-IRTA, Universitat de Lleida, Lleida, Spain

Abstract: The influence of diverse carboxylic acid on the preparation of chlorohydrin esters using a one-pot esterification – chlorination reaction, in which one of the reagents (chlorotrimethylsilane) acts as solvent, is described. Whereas the acid with low pKa provided higher amounts of the 2-chloro regioisomer, the ones with higher pKa rendered the 1-chloro regioisomer in 80% yield. These results are in accordance with the mechanism proposed in a previous article. Keywords: Carboxylic acids, chlorohydrin esters, chlorotrimethylsilane, diol, halogenation, regioselectivity

Chlorohydrin esters have been used in the preparation of epichlorohydrins and chloroalcohols.[1] Both can be used as building blocks in the synthesis of drugs,[2] surfactants,[3] epoxides,[4] and chiral ionic liquids.[5] In a previous article, we described the preparation of chlorohydrin esters from diols, chlorotrimethylsilane (CTMS), and palmitic acid using a one-pot Received in Poland July 15, 2005 Address correspondence to Ramon Canela, Departament de Quı´mica, Universitat de Lleida Av., Alcalde Rovira Roure, 191, 25198 Lleida, Spain. Tel.: þ 34 973 702843; Fax: þ34 973 238264; E-mail: [email protected] 1167

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esterification –chlorination reaction, in which CTMS acts as a solvent. We showed that the reaction can be carried out with diols separated by up to six carbons. The reaction was stereospecific, and its regioselectivity depended on the distance between the two hydroxyl groups. Thus, 1,3-butanediol (1) produced halohydrin esters with the chlorine atom in the primary position (3m) as the major compound. The other regioisomer (4m) was present to the extent of about 25% (Scheme 1).[6] The compound (3m) could be a precursor of (R)-4-chloro-2-butanol, a building block for the preparation of lactones.[7] The putative application of this methodology as the starting step in the synthesis of such a building block has prompted us to investigate this reaction further. Thus, the effect of the structure of the acid in the regioselectivity of the reaction is now presented. Also, a more friendly process using the addition of the CTMS at once is also described. The developed methodology was applied to a set of different acids to determine their regioselectivity and scope (Scheme 2). Assays were carried out mixing all the reagents at once, avoiding the previous requirement to add the CTMS slowly.[6] When acids with an alkyl chain longer than 12 carbons were used (2l, n), halohydrin esters with the chlorine atom in the primary position (3l, n) were obtained mainly. The other regioisomers (4l, n) were present in amounts below 25%. Lauric (2k) and pivalic (2j) acids produced this regioisomer (4k and 4j) to the extent of about 27%. The percentage of this regioisomer increased as the alkyl chain became shorter. Hence, acetic acid (2d) produced both chlorohydrin ester regioisomers (3d and 4d) in a near 1 : 1 proportion. Subsequently, chloroacetic acid (2c) produced a higher proportion of the ester presenting the chlorine atom in the secondary position (4c). Finally, dichloroacetic acid (2b) and trichloroacetic acid (2a) produced mainly the ester presenting the chlorine atom in the secondary position (4a and 4b) (Table 1). This set of results could confirm the mechanism proposed for this one-pot esterification –chlorination in our previous publication. The diol could be transformed into monoesters followed by the formation of a dioxygenated ring, 5a –n (Figure 1), similar to those proposed by several authors.[4,8,9] These intermediates could react with chloride ions present in the medium through a nucleophilic opening process. This chloride attack would produce the corresponding chlorohydrin esters (3a –n and 4a– n) bringing the reaction to completion.

Scheme 1.

Conditions: 80 8C, 48 h.

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Scheme 2. Conditions: 808C, 48 h. a, R ¼ CCl3 b, R ¼ CHCl2 c, R ¼ CH2Cl d, R ¼ CH3 e, R ¼ CH2C(CH3)3 f, R ¼ C3H7 g, R ¼ C5H11 h, R ¼ C7H15 i, R ¼ C9H19 j, R ¼ C(CH3)3 k, R ¼ C11H23 l, R ¼ C13H27 m, R ¼ C15H31 n, R ¼ C17H35.

This mechanism could explain the observed decrease of preference of the chloride ion for the primary position as the charge density of carboxylic carbon increases. We assume that inductive effects are likely to be present. Thus, supporting oxygen atoms could hardly be influenced by the charge density of the carboxylic carbon. As the pKa of the acid increases, the chloride preference for the primary position decreases. Consequently, the primary ester would be predominant for the most acidic acid, whereas the secondary ester would be predominant for the less acidic ones. In summary, we have shown that the developed methodology can be carried out with diverse carboxylic acids, adding the CTMS at once. The regioselectivity of the reaction depends on the pKa of the carboxylic acid. Table 1. Influence of the acid on the regioisomeric rate Yield (%)a Entry a b c d e f g h i j k l m n

R

3

4

CCl3 CHCl2 CH2Cl CH3 CH2C(CH3)3 C3H7 C5H11 C7H15 C9H19 C(CH3)3 C11H23 C13H27 C15H31 C17H35

21 27 37 40 52 57 55 59 60 62 63 62 64 69

66 61 51 46 34 34 32 27 31 27 28 24 22 18

a Determined by GC using tridecane as internal standard.

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Figure 1. R ¼ CCl3, CHCl2, CH2Cl, CH3, (CH3)3CCH2, C3H7, C5H11, C7H15, C9H19, (CH3)3C, C11H23, C13H27, C15H31, C17H35.

The results would confirm the mechanism already proposed in our previous publication.[6]

EXPERIMENTAL General Procedure for the Synthesis of Chlorohydrin Esters The corresponding acid (1.56 mmol), 1,3-butanediol (1 mmol), and chlorotrimethylsilane (30 mmol) were added to a screw-cap vial with a Teflon-faced rubber liner. The reaction mixture was stirred at 80 8C for 48 h under the pressure generated by the system, quenched with saturated sodium bicarbonate solution, and then extracted with hexane. The organic extract was washed with water, dried over MgSO4, and concentrated in vacuo to give the chlorohydrin ester product. The residues were purified either by column chromatography (silica gel H60, hexane/ethyl acetate) or by distillation (acetic acid and butyric acid derivatives) to yield the expected compounds.

Data 4-Chloro-2-butyl trichloroacetate (3a) and 3-chloro-1-butyl trichloroacetate (4a): 3a regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 1.2 (d, 3J ¼ 6.4 Hz, 3 H), 3.53 (dt, 3J ¼ 6.6 Hz, 2J ¼ 1.1 Hz, 2 H), 5.0 –5.1 (m, 1 H). 13C NMR (75 MHz) d 40, 67.9. All other NMR signals are hidden by the signals of the 4a regioisomer. MS (EI, 70 eV) m/z: 254 (M þ 1)þ, 252 (M 2 1)þ, 162, 156, 92, 90, 55. 4a regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 1.55 (d, 3J ¼ 6.6 Hz, 3H) 1.70 –2.01 (m, 2 H) 4.06 –4.41 (m, 3 H). 13C NMR (75 MHz) d 20.7, 38.7, 54.2, 61.5, 90, 173.3. MS (EI, 70 eV) m/z: 348 (M þ 1)þ, 346 (M-1)þ, 256, 239, 55. Calcd. for C6H8Cl4O2: C, 28.38; H, 3.18; Cl, 55.84; O, 12.60. Found: C, 28.25; H, 3.22. 4-Chloro-2-butyl dichloroacetate (3b) and 3-chloro-1-butyl dichloroacetate (4b): 3b regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 1.2

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(d, 3J ¼ 6.4 Hz, 3 H), 3.53 (dt, 3J ¼ 6.6 Hz, 2J ¼ 1.1 Hz, 2 H), 5.0 – 5.1 (m, 1 H). 13C NMR (75 MHz) d 40.7, 67.9. All other NMR signals are hidden by the signals of the 4b regioisomer. MS (EI, 70 EV) m/z: 219 (M þ 1)þ, 217 (M1)þ, 128, 112, 92, 90, 55. 4b regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 1.55 (d, 3J ¼ 6.6 Hz, 3H) 1.70 –2.01 (m, 2 H) 4.06– 4.41 (m, 3 H). 5.9 (s, 1 H). 13C NMR (75 MHz) d 20.7, 38.7, 54.2, 61.5, 64.2, 173.3. MS (EI, 70 EV) m/z: 219 (M þ 1)þ, 217(M-1)þ, 128, 112, 55. Calcd. for C6H9Cl3O2: C, 32.83; H, 4.13; Cl, 48.46; O, 14.58. Found: C, 32.76; H, 4.18. 4-Chloro-2-butyl chloroacetate (3c) and 3-chloro-1-butyl chloroacetate (4c): 3c regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 1.2 (t, 3J ¼ 6.4 Hz, 3 H), 3.53 (dt, 3J ¼ 6.6 Hz, 2J ¼ 1.1 Hz, 2 H), 5.05– 5.15 (m, 1 H). 13C NMR (75 MHz) d 40.7, 67.9. All other NMR signals are hidden by the signals of the 4c regioisomer. MS (EI, 70 EV) m/z: 186 (M þ 1)þ, 184 (M 2 1)þ, 94, 78, 92, 90, 55. 4c regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 1.55 (d, 3J ¼ 6.6 Hz, 3H), 1.90 – 2.14 (m, 2 H), 4.05 (d, 3J ¼ 14.1 Hz, 2 H), 4.16 –4.41 (m, 3 H). 13C NMR (75 MHz) d 21.1, 38.7, 40.1, 54.2, 61.5, 173.3. MS (EI, 70 EV) m/z: 186 (M þ 1)þ, 184 (M 2 1)þ, 94, 78, 55. Calcd. for C6H10Cl2O2: C, 38.94; H, 5.45; Cl, 38.32; O, 17.29. Found: C, 38.77; H, 5.52. 4-Chloro-2-butyl acetate (3d) and 3-chloro-1-butyl acetate (4d): 3d regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 1.31 (d, 3J ¼ 6.4 Hz, 3 H), 1.90–2.14 (m, 2 H), 1.97 (s, 3 H) 3.53 (dt, 3J ¼ 6.6 Hz, 2J¼ 1.1 Hz, 2 H), 5.05–5.58 (m, 1 H). 13C NMR (75 MHz) d 19.9, 21.1, 38.7, 40.7, 67.9, 173.3. MS (EI, 70 EV) m/z: 152 (M þ 1)þ, 150 (M-1)þ, 60, 44, 92, 90, 55. 4d regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 1.55 (d, 3J ¼ 6.6 Hz, 3H), 4.06– 4.41 (m, 3 H). 13C NMR (75 MHz) d 54.2, 61.5. All other NMR signals are hidden by the signals of the 3d regioisomer. MS (EI, 70 EV) m/z: 152 (M þ 1)þ, 150 (M 2 1)þ, 60, 44, 55. Bp 72–79 8C/17 mm. (Reported Bp 73– 78 8C/16 mm).[10] 4-Chloro-2-butyl-3,3-dimethylbutanoate (3e) and 3-chlorobutyl-3,3dimethylbutanoate (4e): 3e regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 1.07 (s, 9 H) 1.31 (d, 3J ¼ 6.4 Hz, 3 H) 1.90 – 2.14 (m, 2 H), 2.29 (s, 2 H), 3.53 (dt, 3J ¼ 6.6 Hz, 2J ¼ 1.1 Hz, 2 H), 5.05– 5.18 (m, 1 H). 13C NMR (75 MHz) d 19.9, 29.1, 29.2, 38.7, 40.7, 67.9, 173.3. MS (EI, 70 EV) m/z: 208 (M þ 1)þ, 206 (M 2 1)þ, 116, 100, 92, 90, 55. 4e regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 1.55 (d, 3J ¼ 6.6 Hz, 3H), 4.06– 4.41 (m, 3 H). 13C NMR (75 MHz) d 54.2, 61.5. All other NMR signals are hidden by the signals of the 3e regioisomer. MS (EI, 70 EV) m/z: 208 (M þ 1)þ, 206 (M 2 1)þ, 116, 100, 55. Calcd. for C10H19ClO2: C, 58.10; H, 9.26; Cl, 17.15; O, 15.48. Found: C, 57.95; H, 9.31.

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4-Chloro-2-butyl butanoate (3f) and 3-chloro-1-butyl butanoate (4f): 3f regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 0.88 (t, 3J ¼ 6.4 Hz, 3 H) 1.31 (d, 3J ¼ 6.4 Hz, 3 H) 1.58 – 1.66 (m, 2 H), 1.90 –2.14 (m, 2 H), 2.29 (t, 3J ¼ 7.3 Hz, 2 H), 3.53 (dt, 3J ¼ 6 Hz, 2J ¼ 1.1 Hz, 2 H), 5.05 –5.28 (m, 1 H). 13C NMR (75 MHz) d 14.1, 19.9, 22.7, 25.0, 31.9, 34.5, 38.7, 40.7, 67.9, 173.3. MS (EI, 70 EV) m/z: 180 (M þ 1)þ, 178 (M 2 1)þ, 88, 72, 92, 90, 55. 4f regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 1.55 (d, 3J ¼ 6.6 Hz, 3H), 4.06 –4.41 (m, 3 H). 13C NMR (75 MHz) d 54.2, 61.5. All other NMR signals are hidden by the signals of the 3f regioisomer. MS (EI, 70 EV) m/z: 180 (M þ 1)þ, 178 (M 2 1)þ, 88, 72, 55. Bp 76 – 82 8C/ 7 mm. Calcd. for C8H15ClO2: C, 53.78; H, 8.46; Cl, 19.84; O, 17.91. Found: C, 53.54; H, 8.48. 4-Chloro-2-butyl hexanoate (3g) and 3-chloro-1-butyl hexanoate (4g): 3g regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 0.88 (t, 3J ¼ 6.4 Hz, 3 H), 1.31 (d, 3J ¼ 6.4 Hz, 3 H), 1.58– 1.66 (m, 4 H), 1.90 –2.14 (m, 2 H), 2.29 (t, 3J ¼ 7.3 Hz, 2 H), 3.53 (dt, 3J ¼ 6.6 Hz, 2J ¼ 1.1 Hz, 2 H), 5.05 –5.15 (m, 1 H). 13C NMR (75 MHz) d 14.1, 19.9, 22.7, 25.0, 31.9, 34.5, 38.7, 40.7, 67.9, 173.3. MS (EI, 70 EV) m/z: 208 (M þ 1)þ, 206 (M 2 1)þ, 116, 100, 92, 90, 55. 4g regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 1.55 (d, 3J ¼ 6.6 Hz, 3H), 4.06 –4.41 (m, 3 H). 13C NMR (75 MHz) d 54.2, 61.5. All other NMR signals are hidden by the signals of the 3g regioisomer. MS (EI, 70 EV) m/z: 208 (M þ 1)þ, 206 (M 2 1)þ, 116, 100, 55. Calcd. for C10H19ClO2: C, 58.10; H, 9.26; Cl, 17.15; O, 15.48. Found: C, 57.95; H, 9.31. 4-Chloro-2-butyl octanoate (3h) and 3-chloro-1-butyl octanoate (4h): 3h regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 0.88 (t, 3J ¼ 6.4 Hz, 3 H), 1.20– 1.35 (m, 11 H), 1.58– 1.66 (m, 2 H), 1.90– 2.14 (m, 2 H), 2.29 (t, 3J ¼ 7.3 Hz, 2 H), 3.53 (dt, 3J ¼ 6 Hz, 2J ¼ 1.1 Hz, 2 H), 5.05 –5.58 (m, 1 H). 13C NMR (75 MHz) d 14.1, 19.9, 22.7, 25.0, 29.1, 29.2, 31.9, 34.5, 38.7, 40.7, 67.9, 173.3. MS (EI, 70 EV) m/z: 236 (M þ 1)þ, 234 (M 2 1)þ, 144, 128, 92, 90, 55. 4h regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 1.55 (d, 3J ¼ 6.6 Hz, 3H), 4.06– 4.41 (m, 3 H). 13C NMR (75 MHz) d 54.2, 61.5. All other NMR signals are hidden by the signals of the 3h regioisomer. MS (EI, 70 EV) m/z: 236 (M þ 1)þ, 234 (M 2 1)þ, 144, 128, 55. Calcd. for C12H23ClO2: C, 61.39; H, 9.87; Cl, 15.10; O, 13.63. Found: C, 61.33; H, 9.92. 4-Chloro-2-butyl decanoate (3i) and 3-chloro-1-butyl decanoate (4i): 3i regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 0.88 (t, 3J ¼ 6.4 Hz, 3 H), 1.20– 1.35 (m, 15 H), 1.58– 1.66 (m, 2 H), 1.90– 2.14 (m, 2 H), 2.29 (t, 3J ¼ 7.3 Hz, 2 H), 3.53 (dt, 3J ¼ 6.6 Hz, 2J ¼ 1.1 Hz, 2 H), 5.05 –5.28 (m, 1 H). 13C NMR (75 MHz) d 14.1, 19.9, 22.7, 25.0, 29.1, 29.2, 29.3, 31.9, 34.5, 38.7, 40.7, 67.9, 173.3. MS (EI, 70 EV) m/z: 264 (M þ 1)þ, 262 (M 2 1)þ, 172, 156, 92, 90, 55. 4i regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 1.55 (d, 3J ¼ 6.6 Hz, 3H), 4.06– 4.41 (m, 3 H). 13C NMR

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(75 MHz) d 54.2, 61.5. All other NMR signals are hidden by the signals of the 3i regioisomer. MS (EI, 70 EV) m/z: 264 (M þ 1)þ, 262 (M 2 1)þ, 172, 156, 55. Calcd. for C14H27ClO2: C, 63.98; H, 10.35; Cl, 13.49; O, 12.18. Found: C, 63.79; H, 10.40. 4-Chloro-2-butyl dimethylpropionate (3j) and 3-chloro-1-butyl dimethylpropionate(4j): 3j regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 1.17 (s, 9 H) 1.31 (d, 3J ¼ 6.4 Hz, 3 H), 1.90– 2.14 (m, 2 H), 3.53 (dt, 3 J ¼ 6.6 Hz, 2J ¼ 1.1 Hz, 2 H), 5.05– 5.27 (m, 1 H). 13C NMR (75 MHz) d 27.2, 38.7, 39.9, 40.7, 67.9, 178. MS (EI, 70 EV) m/z: 194 (M þ 1)þ, 192 (M 2 1)þ, 102, 86, 92, 90, 55. 4j regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 1.55 (d, 3J ¼ 6.6 Hz, 3H), 4.06 –4.41 (m, 3 H). 13C NMR (75 MHz) d 54.2, 61.5. All other NMR signals are hidden by the signals of the 3j regioisomer. MS (EI, 70 EV) m/z: 194 (M þ 1)þ, 192 (M 2 1)þ, 102, 86, 55. Calcd. for C9H17ClO2: C, 56.10; H, 8.89; Cl, 18.40; O, 16.61. Found: C, 56.00; H, 8.95. 4-Chloro-2-butyl laurate (3k) and 3-chloro-1-butyl laurate (4k): 3k regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 0.88 (t, 3J ¼ 6.4 Hz, 3 H), 1.20– 1.35 (m, 19 H), 1.58–1.66 (m, 2 H), 1.90–2.14 (m, 2 H), 2.29 (t, 3J ¼ 7.3 Hz, 2 H), 3.53 (dt, 3J ¼ 6.6 Hz, 2J ¼ 1.1 Hz, 2 H), 5.05–5.30 (m, 1 H). 13C NMR (75 MHz) d 14.1, 19.9, 22.7, 25.0, 29.1, 29.2, 29.3, 29.4, 31.9, 34.5, 38.7, 40.7, 67.9, 173.3. MS (EI, 70 EV) m/z: 292 (M þ 1)þ, 290 (M 2 1)þ, 200, 184, 92, 90, 55. 4k regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 1.55 (d, 3J ¼ 6.6 Hz, 3H), 4.06–4.41 (m, 3 H). 13C NMR (75 MHz) d 54.2, 61.5. All other NMR signals are hidden by the signals of the 3k regioisomer. MS (EI, 70 EV) m/z: 292 (M þ 1)þ, 290 (M 2 1)þ, 200, 184, 55. Calcd. for C16H31ClO2: C, 66.07; H, 10.74; Cl, 12.19; O, 11.00. Found: C, 65.90; H, 10.78. 4-Chloro-2-butyl myristate (3l) and 3-chloro-1-butyl myristate (4l): 3l regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 0.88 (t, 3J ¼ 6.4 Hz, 3 H), 1.20 –1.35 (m, 23 H), 1.58 – 1.66 (m, 2 H), 1.90– 2.14 (m, 2 H), 2.29 (t, 3J ¼ 7.3 Hz, 2 H), 3.53 (dt, 3J ¼ 6 Hz, 2J ¼ 1.1 Hz, 2 H), 5.05– 5.58 (m, 1 H). 13C NMR (75 MHz) d 14.1, 19.9, 22.7, 25.0, 29.1, 29.2, 29.3, 29.4, 29.6, 31.9, 34.5, 38.7, 40.7, 67.9, 173.3. MS (EI, 70 EV) m/z: 320 (M þ 1)þ, 318 (M 2 1)þ, 228, 212, 92, 90, 55. 4l regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 1.55 (d, 3J ¼ 6.6 Hz, 3H), 4.06 – 4.41 (m, 3 H). 13 C NMR (75 MHz) d 54.2, 61.5. All other NMR signals are hidden by the signals of the 3l regioisomer. MS (EI, 70 EV) m/z: 320 (M þ 1)þ, 318 (M 2 1)þ, 228, 212, 55. Calcd for C18H35ClO2: C, 67.79; H, 11.06; Cl, 11.12; O, 10.03. Found: C, 67.74; H, 11.10. 4-Chloro-2-butyl palmitate (3m) and 3-chloro-1-butyl palmitate (4m):[6] 3m regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 0.86 (t, 3J ¼ 6.4 Hz) 1.20– 1.35 (m, 27 H) 1.58–1.66 (m, 2 H), 1.90–2.14 (m, 2 H), 2.29 (t, 3J ¼ 7.3 Hz, 2 H), 3.53 (dt, 3J ¼ 6.6 Hz, 2J ¼ 1.1 Hz, 2 H), 5.05–5.15 (m, 1 H). 13C NMR

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(75 MHz) d 14.1, 20.3, 22.6, 24.9, 29.1, 29.2, 29.3, 29.4, 29.6, 29.7, 31.9, 34.5, 38.8, 39.6, 67.9, 173.1. MS (EI, 70 EV) m/z: 376 (M þ 1)þ, 374 (M 2 1)þ, 284, 268, 92, 90, 55. 4m regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 1.55 (d, 3J ¼ 6.6 Hz, 3H), 4.06–4.41 (m, 3H). 13C NMR (75 MHz) d 54.2, 61.5. All other NMR signals are hidden by the signals of the 3m regioisomer. MS (EI, 70 EV) m/z: 348 (M þ 1)þ, 346 (M 2 1)þ, 256, 240, 55. 4-Chloro-2-butyl stearate (3n) and 3-chloro-1-butyl stearate (4n): 3n regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 0.88 (t, 3J ¼ 6.4 Hz, 3 H), 1.20– 1.35 (m, 31H), 1.58 –1.66 (m, 2 H), 1.90 –2.14 (m, 2 H), 2.29 (t, 3J ¼ 7.3 Hz, 2 H), 3.53 (dt, 3J ¼ 6.6 Hz, 2J ¼ 1.1 Hz, 2 H), 5.05– 5.58 (m, 1 H). 13C NMR (75 MHz) d 14.1, 19.9, 22.7, 25.0, 29.1, 29.2, 29.3, 29.4, 29.6, 29.7, 31.9, 34.5, 38.7, 40.7, 67.9, 173.3. MS (EI, 70 EV) m/z: 376 (M þ 1)þ, 374 (M 2 1)þ, 284, 268, 92, 90, 55. 4n regioisomer: 1H NMR (300 MHz, CDCl3, 25 8C) d 1.55 (d, 3J ¼ 6.6 Hz, 3H), 4.06 –4.41 (m, 3H). 13C NMR (75 MHz) d 54.2, 61.5. All other NMR signals are hidden by the signals of the 3n regioisomer. MS (EI, 70 EV) m/z: 376 (M þ 1)þ, 374 (M 2 1)þ, 284, 268, 55. Calcd. for C22H43ClO2: C, 70.46; H, 11.56; Cl, 9.45; O, 8.53. Found: C, 70.16; H, 11.58. Confirmation of the structure of new esters was undertaken by reducing purified compounds according the procedure described by Wilen et al.[9] The corresponding alcohols were identified by GC and GC-MS using external standards. General Procedure for the Prepartion of Standards of 4-Chloro-2butanol (5) and 3-Chloro-1-butanol (6) 4-Chloro-2-butanyl and 3-chloro-1-butanyl acetates were hydrolysed to the corresponding 4-chloro-2-butanol and 3-chloro-1-butanol respectively as Wilen et al. described.[9] 5: 1H NMR (300 MHz, CDCl3, 25 8C) d 1.20 (t, 3J ¼ 6.4 Hz, 3 H), 1.70 –2.01 (m, 2 H), 3.53 (dt, 3J ¼ 6.6 Hz, 2J ¼ 1.1 Hz, 2 H), 4.0 –4.1 (m, 1 H). 13C NMR (75 MHz) d, 24.2, 38.7, 42.7, 65.9 MS (EI, 70 EV) m/z: 110 (M þ 1)þ, 108 (M 2 1)þ, 92, 90, 55. Bp 67 8C (20 mm).[11] 6: 1H NMR (300 MHz, CDCl3, 25 8C) d 1.55 (d, 3J ¼ 6.6 Hz, 3H), 4.06– 4.41 (m, 3 H). 13C NMR (75 MHz) d 55,58. All other NMR signals are hidden by the signals of the 5 regioisomer. MS (EI, 70 EV) m/z: 110 (M þ 1)þ, 108 (M 2 1)þ, 55. Bp 68 –70 8C/17 mm. (Reported Bp 70– 71 8C/17 mm).[11] ACKNOWLEDGMENTS The authors are grateful to Secretarı´a de Estado de Polı´tica Cientı´fica y Tecnolo´gica of the Spanish Ministerio de Educacio´n y Ciencia (PPQ2003-02871) and Departament d’Universitats, Recerca i Societat de la Informacio´ (DURSI)

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(2001SGR00309) for financial support. We thank Montserrat Llovera for GC/MS measurements.

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