Simple, Mild, and Practical Esterification, Thioesterification, and Amide Formation Utilizing p-Toluenesulfonyl Chloride and N-Methylimidazole

Article abstract of DOI:10.1002/adsc.200303093

We have developed an efficient method for the esterification or thioesterification of equimolar amounts of carboxylic acids and alcohols or thiols using a novel reagent, p-toluenesulfonyl chloride (TsCl) together with N-methylimidazole. The present method is simple, mild, and reactive, uses readily available and economical reagents. The choice of amine is critical for the present method. The amine, N-methylimidazole, has two roles: (i) as an HCl scavenger for the initial smooth generation of mixed anhydrides between carboxylic acids and TsCl and (ii) successive formation of highly reactive ammonium intermediates from mixed anhydrides. This method could be applied to various types of carboxylic acids, alcohols, and thiols: a) several functionalities were tolerated; b) two N-Cbz amino acids were smoothly esterified without racemization; and c) the labile 1β-methylcarbapenem key intermediate and a pyrethroid insecticide, prallethrin, were successfully prepared. The related amide formation between carboxylic acids and primary or secondary amines was also performed. The proposed reaction mechanism involves a novel method for producing the reactive acylammonium intermediates. The production of these intermediates was rationally supported by a careful ¹H NMR monitoring study.

Full text of DOI:10.1002/adsc.200303093

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Simple, Mild, and Practical Esterification, Thioesterification, and
Amide Formation Utilizing p-Toluenesulfonyl Chloride and
N-Methylimidazole
Kazunori Wakasugi, Akira Iida, Tomonori Misaki, Yoshinori Nishii, Yoo Tanabe*
Department of Chemistry, School of Science and Technology, Kwansei Gakuin University, 2 1 Gakuen, Sanda, Hyogo
669 1337, Japan
Fax: ( ‡ 81)-795-65-9077, e-mail: tanabe@kwansei.ac.jp
Received: May 6, 2003; Accepted: August 5, 2003
Supporting information for this article is available on the WWW under http://asc.wiley.vch.de or from the author.
Much effort has been invested in the development of
Abstract: We have developed an efficient method
efficient methods; e.g., the use of DCC,[2] halopyridi-
for the esterification or thioesterification of equi-
nium salts,[3] N,N-carbonyldiimidazole,[4] 2,4,6-trichloro-
molar amounts of carboxylic acids and alcohols or
benzoyl chloride,[5] BOP-Cl,[6] DPC,[7] DPTC,[8]
thiols using a novel reagent, p-toluenesulfonyl chlor-
MNBA,[9] etc.
ide (TsCl) together with N-methylimidazole. The
In view of process chemistry, there remains a strong
present method is simple, mild, and reactive, uses
need for simpler, more reactive, convenient, and inex-
readily available and economical reagents. The
pensive agents. The mixed anhydride method, com-
choice of amine is critical for the present method.
posed of different acids, is a rational process: Use of
The amine, N-methylimidazole, has two roles: (i) as
sulfonic acid as a counter acid moiety is a promising
an HCl scavenger for the initial smooth generation
candidate for an efficient esterification due to its
of mixed anhydrides between carboxylic acids and
simplicity, ready availability and low cost of the re-
TsCl and (ii) successive formation of highly reactive
agents.
ammonium intermediates from mixed anhydrides.
To this end, we focused our attention on the use of an
This method could be applied to various types of
easily accessible reagent, p-toluenesulfonyl chloride
carboxylic acids, alcohols, and thiols: a) several
(TsCl; 1)/a specific amine. Here, we present an efficient
functionalities were tolerated; b) two N-Cbz amino
method for the esterification and thioesterification of
acids were smoothly esterified without racemization;
equimolar amounts of carboxylic acids and alcohols or
and c) the labile 1b-methylcarbapenem key inter-
thiols, respectively, using TsCl (1)/N-methylimidazole
mediate and a pyrethroid insecticide, prallethrin,
(2).[10] The related amide formation between carboxylic
were successfully prepared. The related amide for-
acids and primary or secondary amines was also
mation between carboxylic acids and primary or
successfully performed (vide supra).
secondary amines was also performed. The proposed
A related reagent, CH3SO2Cl, was not suitable due to
reaction mechanism involves a novel method for
the undesirable side sulfene dimerization.[11] The choice
producing the reactive acylammonium intermedi-
of amine is critical for the present method, because the
ates. The production of these intermediates was
amine has two roles: (i) as an HCl scavenger for the
1
rationally supported by a careful H NMR monitor-
initial smooth generation of mixed anhydrides between
ing study.
carboxylic acids and 1 and (ii) the successive formation
Keywords: amide formation; esterification; N-meth-
ylimidazole; synthetic methods; thioesterification; p-
toluenesulfonyl chloride
From the standpoint of elaborate complex natural
product synthesis and process chemistry, direct ester-
ification between equimolar amounts of carboxylic
acids and alcohols is well recognized as an important
Scheme 1. Esterification or thioesterification using readily
unit reaction for a wide range of organic syntheses.[1] available TsCl (1)/N-methylimidazole (2).
Adv. Synth. Catal. 2003, 345, 1209 1214
DOI:10.1002/adsc.200303093
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Table 1. Esterification between equimolar amounts of carboxyl-
ic acids and alcohols using TsCl (1) and N-methylimidazole (2).
of reactive ammonium intermediates from mixed anhy-
drides. We expected that N-methylimidazole (2) would
fulfill both roles.
Indeed, the reaction of 3-phenylpropanoic acid (3)
with 1-octanol (6; 1.0 equiv.) using TsCl (1) (1.2 equivs.)
and N-methylimidazole (2; 3.0 equivs.) in CH3CN at 0
58C resulted in esterification in 93% yield. Table 1 lists
the results of the esterification using various carboxylic
acids and alcohols. As solvents, CH3CN and CH2Cl2
were somewhat superior to toluene and THF. Although
the use of 1/Et3N/catalytic N,N-dimethylaminopyridine
(DMAP) might be expected to fulfill this role, some
comparable experiments under identical conditions
demonstrated the superiority of the present method
(see Supporting Information).
The proposed reaction mechanism, exemplified using
3 and 6, is as follows (Scheme 2). The mixed anhydride 4
between 3 and 1 is initially produced with the formation
of the HCl salt of 2. Anhydride 4 is in turn transformed
into acylammonium salt 5. The highly reactive inter-
mediate 5 immediately condenses with 6 to produce
octyl 3-phenylpropanoate (7). This marked switching
behavior is characteristic of N-methylimidazole 2. Due
to the electron withdrawing effect of the cationic
ammonium, the intermediate 5 is likely to be more
reactive than the corresponding anhydride 4 and
acylimidazole 8, which is a reactive acylating substrate.[4]
Bigg and their coworkers reported that activation of
acylimidazoles with methyl trifluoromethanesulfonate
(CH3OTf) contributes to the aminoacylations.[12] The
advantage of the present protocol is that it eliminates
the use of CH3OTf and generates acylammonium 5 in a
one-pot process.
1
A H NMR monitoring study using 3-phenylpropa-
noic acid 3 and its analogues 4, 5, 8, and 9 rationally
supported the hypothesis of the generation of 5. The
chemical shift of the a-position of these compounds
progressively shifted downfield from acid 3 (d ˆ
2.54 ppm), mixed anhydride 4 (2.74), acylimidazaole 8
(3.05), acyl chloride 9 (3.20), and acylammonium 5
(3.66) (see Supporting Information). This shift is
considered to be proportional to the acylating reactivity
of these analogues.
The salient features of the present esterification are as
follows. (i) Several esters of primary and secondary
alcohols were prepared in good to excellent yield under
mild and practical conditions. (ii) Several functionalities
such as a double or a triple bond, a halogen, and an ester
were tolerated. (iii) N-Cbz alanine (10) and proline (11),
which are prone to racemization under basic conditions,
were smoothly esterified with complete retention of
their chiral centers. (iv) The labile 1b-methylcarbape-
nem key intermediate[13] and a pyrethroid insecticide,
prallethrin,[14] were successfully prepared from azetidi-
none 12 and by the reaction between (1R,3R)-chrysan-
themic acid (13) and (S)-hydroxycyclopentenone 14,
respectively (see Supporting Information). Direct and
[a]
Parentheses indicate the reaction using TsCl (1; 1.2
equivs.)/Et3N (3.0 equivs.)/cat. DMAP (0.1 equiv.) under
identical conditions (see Supporting Information).
2.4 equivalents of N-methylimidazole (2) were used.
Step ii) 20 258C for 2 h.
[b]
[c]
[d]
Step i) 20 258C for 30 min and ii) 20 258C for 2 h.
[e]
In CH2Cl2, i) À 40 to À 35 8C for 30 min and ii) À 40 to
À 358C for 2 h. In all examples, > 99% ee by HPLC
analyses (see Experimental Section).
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Scheme 2. Proposed reaction mechanism.
Table 2. Thioesterification between equimolar amounts of
carboxylic acids and thiols using TsCl (1) and N-methylimi-
dazole (2).
Table 3. Amide formation between equimolar amounts of
carboxylic acids and primary or secondary amines using TsCl
(1) and N-methylimidazole (2).
[a]
Step ii) 20 258C for 2 h.
Step i) 20 258C for 30 min and ii) 20 258C for 2 h.
[b]
DMAP is strongly desired by many process chemists
due to its cost and toxicity. (vi) The reaction of 3 with
tertiary alcohols such as t-butyl alcohol and linalool,
however, resulted in low yields under standard condi-
tions ( < 10%).
[a]
Parentheses indicate the reaction using TsCl (1; 1.2
Compared with a related method using Me2NSO2Cl/
Me2NR/cat. DMAP,[11b, c] the present method has other
merits as well: (i) higher reactivity; (ii) operationally
simpler; (iii) economical (including the elimination of
expensive DMAP during the acylation step, the total
equivs.)/Et3N (3.0 equivs.)/cat. DMAP (0.1 equiv.) under
identical conditions (see Supporting Information).
Step ii) 20 258C for 2 h.
[b]
[c]
Step i) 20 258C for 30 min and ii) 20 258C for 2 h.
mild esterification of these compounds is an important cost of the condensation reagent is reduced to approx-
subject in the fine chemical area. (v) DMAP, a popular imately 10%); and (iv) lower toxicity of TsCl (1)
acylation-step catalyst was not used; avoidance of compared to Me2NSO2Cl.[15]
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purified by silica-gel column chromatography (hexane:ether,
40:1) to give 1-octyl 3-phenylpropanonate;[16] Yield: 243 mg
(93%).
We then extended this protocol to a related thioester-
ification, and amide formation between equimolar
amounts of carboxylic acids and thiols, as well as
primary or secondary amines (Tables 2 and 3).
The present method was successful, while the
Me2NSO2Cl method failed to produce thioesterification
(no reaction). The results of the thioesterification
method using 1/Et3N/cat. DMAP did not reach a
practical revel, as shown in Table 2. The reactivity of
the present amide formation was higher than esterifica-
tion and thioesterification, so that it proceeded with
good to excellent yields.
In conclusion, various carboxylic esters, thioesters,
and amides can be practically and conveniently pre-
pared in good to excellent yield between carboxylic
acids and equimolar amounts of alcohols, thiols, and
amines, respectively, under very mild conditions using a
simple and easily accessible reagent, p-TsCl (1) and N-
methylimidazole (2), wherein the reactions proceed
through a new type of highly reactive acylammonium
intermediate pathway.
N-Carbobenzyloxy-l-alanine Methyl Ester[23]
TsCl (1; 229 mg, 1.2 mmol) in CH2Cl2 (1.0 mL) was added to a
stirred solution of N-Cbz-l-alanine (10; 223 mg, 1.0 mmol) and
N-methylimidazole (2; 246 mg, 3.0 mmol) in CH2Cl2 (1.0 mL)
at À 40 to À 358C under an Ar atmosphere, and the mixture
was stirred for 30 min. CH3OH (32 mg, 1.0 mmol) in CH2Cl2
(1.0 mL) was added to the mixture at À 40 to À 358C, followed
by stirring at the same temperature for 2 h. The reaction
mixture was poured into the stirred ice/water (reverse quench),
which was extracted with ether. The organic phase was washed
with water, brine, dried (Na2SO4), and concentrated. The
obtained crude product was purified by silica-gel column
chromatography (hexane:EtOAc; 4:1) to give the desired
product; yield: 210 mg (89%). HPLC analyses were performed
using Shimadzu HPLC system (consisting of the following:
SLC-10A, DGU-4A, LC-10AD, SIL-10A, CTO-10A, and
detector SPD-10AV, measured at 254 nm) and DAICEL
Chiracel OD column (4.6 mm i.d. Â 25 cm) at 308C (column
oven temperature). > 99% ee by HPLC analysis [flow rate
1.50 mL/min, solvent: n-hexane/2-propanol, 70/30, tR (race-
mic) ˆ 6.18 min and 6.88 min, respectively, tR (N-carbobenzy-
loxy-l-alanine methyl ester) ˆ 6.24 min]. Colorless oil; [a]D23:
Experimental Section
The following esters, thioesters, and amides obtained in this
work are known compounds: 1-octyl 3-phenylpropanoate,[16] 9-
decen-1-yl 3-phenylpropanoate,[11c] 2-hexyn-1-yl 3-phenylpro-
panoate,[11c] 2-phenylethyl 3-phenylpropanoate,[17] benzyl 3-
phenylpropanoate,[18] phenyl 3-phenylpropanoate,[19] 6-chloro-
hexyl 3-phenylpropanoate,[11c] ethyl 6-(3-phenylpropanoyl-
oxy)hexanoate,[11c] 2-octyl 3-phenylpropanoate,[20] l-menthyl
3-phenylpropanoate,[11c] 1-octyl cyclohexanecarboxylate,[21]
2-octyl benzoate,[22] N-carbobenzyloxy-l-alanine methyl es-
ter,[23] N-carbobenzyloxy-l-proline methyl ester,[23] (3S,4S)-
4-[(1R)-1-benzyloxycarbonylethyl]-1-(tert-butoxycarbonylme-
thyl)-3-[(1R)-1-tert-butyldimethylsilyloxyethyl]-2-azetidinone,[13]
S)-2-methyl-4-oxo-3-(2-propynyl)cyclopent-2-enyl (1R,3R)-
chrysanthemate,[14] S-benzyl 3-phenylpropanethioate,[24] S-
phenyl 3-phenylpropanethioate,[25] S-1-octyl cyclohexanecar-
bothioate,[26] S-cyclohexyl cyclohexanecarbothioate,[27] S-1-
octyl benzothioate,[28] S-cyclohexyl benzothioate,[29] N-(3-phe-
nylpropanoyl)-(1S)-phenylethylamine,[11c] N-(3-phenylpropa-
noyl)piperidine,[11c] N-(1,1-dimethylethyl)-3-phenylpropion-
amide,[11c] 5-(methoxycarbonyl)pentanilide,[30] N-(cyclohex-
anecarbonyl)piperidine,[11c] N-(benzoyl)piperidine.[11c]
1
À 33.9 (c 1.00, CH3OH) [lit. [a]D22: À 36 (c 1, CH3OH)]; H
NMR (400 MHz, CDCl3): d ˆ 1.41 (3H, d, J ˆ 7.3 Hz), 3.75
(3H, s), 4.40 (1H, m), 5.09 (1H, d, Jgem ˆ 12.5 Hz), 5.13 (1H, d,
Jgem ˆ 12.5 Hz), 5.32 (1H d, J ˆ 5.4 Hz), 7.29 7.41 (5H, m);
13C NMR (100 MHz, CDCl3): d ˆ 18.63, 49.55, 52.38, 66.87,
128.06, 128.12, 128.48, 136.24, 155.54, 173.41; IR (neat): n ˆ
3343, 2953, 1723, 1530, 1454, 1215, 1071 cmÀ1.
N-Carbobenzyloxy-l-alanine Octyl Ester
A similar reaction using 1-octanol (130 mg, 1.0 mmol) instead
of CH3OH produced the desired product; yield: 290 mg (87%).
> 99% ee by HPLC analysis [flow rate 1.50 mL/min, solvent:
n-hexane/2-propanol, 80/20, tR (racemic) ˆ 3.65 min and
5.11 min, respectively, tR (N-carbobenzoxy-l-alanine octyl
ester) ˆ 3.66 min]. Colorless oil; [a]D23: À 25.6 (c 1.00,
1
CH3OH); H NMR (400 MHz, CDCl3): d ˆ 0.88 (3H, t, J ˆ
6.8 Hz), 1.21 1.38 (10H, m), 1.41 (3H, d, J ˆ 7.1 Hz), 1.56
1.68 (2H, m), 4.13 (2H, t, J ˆ 6.3 Hz), 4.38 (1H, m), 5.09 (1H, d,
Jgem ˆ 12.7 Hz), 5.34 (1H, d, Jgem ˆ 12.7 Hz), 7.28 7.38 (5H, m);
13C NMR (100 MHz, CDCl3): d ˆ 14.05, 18.80, 22.59, 25.75,
28.48, 29.11, 31.73, 49.67, 65.61, 66.85, 128.07, 128.12, 128.49,
136.29, 155.55, 173.02; IR (neat): n ˆ 3345, 2928, 2857, 1728,
1528, 1454, 1211, 1071 cmÀ1. Anal. found: C 59.2, H 5.9, N 6.0%;
calcd. for C11H13NO4: C 59.19, H 5.87, N 6.27%.
Typical Procedure for Esterification
TsCl (1; 229 mg, 1.2 mmol) in CH3CN (1.0 mL) was added to
the stirred solution of 3-phenylpropanoic acid (3; 150 mg,
1.0 mmol) and N-methylimidazole (2; 246 mg, 3.0 mmol) in
CH3CN (1.0 mL) at 0 58C under an Ar atmosphere, and the
mixture was stirred for 30 min. To the stirred mixture 1-octanol
(6;130 mg, 1.0 mmol) in CH3CN (1.0 mL) was added at0 58C,
and the mixture was stirred at the same temperature for 2 h.
Water was added to the stirred mixture, and extracted with
ether. The organic phase was washed with water, brine, dried
(Na2SO4), and concentrated. The obtained crude product was
1H NMR Monitoring Study
1H NMR spectra of 4 and 6 (in situ generated) were measured
for the ratios of 3:1:2 (ˆ1:1:1) and (ˆ1:1:3), respectively, in
1
CDCl3 at 20 258C. These H NMR spectra are available as
PDF files (Supporting Information). Actually, the use of N-
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methylimidazole (2) showed a higher generation of mixed
anhydride 4 than the use of Et3N.
S-Cyclohexyl 5-(Methoxycarbonyl)pentanethioate
Colorless oil; 1H NMR (400 MHz, CDCl3): d ˆ 1.21 1.73
(12H, m), 1.86 1.95 (2H, m), 2.32 (2H, m), 2.53 (2H, m),
3.50 (1H, m), 3.67 (3H, s); 13C NMR (100 MHz, CDCl3): d ˆ
24.19, 25.02, 25.52, 25.91, 33.04, 33.65, 42.20, 43.67, 51.52,
173.68, 198.95; IR (neat): n ˆ 2932, 2855, 1740, 1686, 1449, 997,
700 cmÀ1. Anal. found: C 60.1, H 8.7%; calcd. for C13H22O3S : C
60.43, H 8.58%.
Typical Procedure for Thioesterification
A similar reaction using 1-octanethiol (146 mg, 1.0 mmol)
instead of 1-octanol in the case of esterification resulted in the
production of S-octyl 3-phenylpropionthioate, yield: 252 mg
1
(94%). Colorless oil; H NMR (400 MHz, CDCl3): d ˆ 0.88
(3H, t, J ˆ 6.8 Hz), 1.21 1.38 (10H, m), 1.55 (2H, m), 2.83
2.89 (4H, m), 2.97 (2H, m), 7.16 7.22 (3H, m), 7.25 7.31 (2H,
m); 13C NMR (100 MHz, CDCl3): d ˆ 14.06, 22.62, 28.79, 28.91,
29.06, 29.13, 29.51, 31.49, 31.78, 45.52, 126.28, 128.30, 128.49,
140.14, 198.73; IR (neat): n ˆ 2926, 2855, 1690, 1454, 1047, 974,
698 cmÀ1. Anal. found: C 73.1, H 9.3%; calcd. for C17H26OS: C
73.33, H 9.41%.
(3S,4S)-4-[(1R)-1-Cyclohexylthiocarbonylethyl]-1-
(tert-butoxycarbonylmethyl)-3-[(1R)-1-tert-
butyldimethylsilyloxyethyl]-2-azetidinone
Colorless oil; [a]D23: À 28.5 (c 0.20, CHCl3); 1H NMR
(400 MHz, CDCl3): d ˆ 0.08 (6H, s), 0.87 (9H, s), 1.20 (3H, d,
J ˆ 7.1 Hz), 1.23 (3H, d, J ˆ 6.3 Hz), 1.91 1.32 (2H, m), 1.35
1.44 (4H, m), 1.45 (9H, s), 1.64 1.73 (2H, m), 1.83 1.92 (2H,
m), 2.96 (1H, dd, J ˆ 3.4 Hz, 7.1 Hz), 2.98 (1H, dd, J ˆ 2.1 Hz,
7.1 Hz), 3.47 (1H, m), 3.74 (1H, d, Jgem ˆ 17.8 Hz), 4.04 (1H, dd,
J ˆ 2.1 Hz, 3.4 Hz), 4.09 (1H, d, Jgem ˆ 17.8 Hz), 4.15 (1H, dd,
J ˆ 6.3 Hz, 7.1 Hz); 13C NMR (100 MHz, CDCl3): d ˆÀ 4.76,
À 4.27, 12.37, 17.89, 22.69, 25.46, 25.81, 28.02, 32.75, 32.99,
42.53, 43.38, 49.65, 57.44, 61.10, 66.54, 81.88, 167.24, 167.95,
201.16; IR (neat): n ˆ 2932, 2857, 1767, 1680, 1451, 1370, 1157,
837 cmÀ1. Anal. found: C 60.5, H 9.1, N 2.5%; calcd. for
C26H47NO5SSi: C 60.78, H 9.22, N 2.73%.
Typical Procedure of Amide Formation
A similar reaction using piperidine (85 mg, 1.0 mmol) instead
of 1-octanol in the case of esterification resulted in the
production of N-(3-phenylpropanoyl)piperidine;[11c] yield:
206 mg (95%).
Methyl 2-Octyladipate
Colorless oil; 1H NMR (400 MHz, CDCl3): d ˆ 0.88 (3H, t, J ˆ
6.6 Hz), 1.19 (3H, d, J ˆ 6.3 Hz), 1.22 1.34 (8H, m), 1.41 1.61
(2H, m), 1.63 1.71 (4H, m), 2.26 2.37 (4H, m), 3.67 (3H, s),
4.90 (1H, m); 13C NMR (100 MHz, CDCl3): d ˆ 14.03, 19.97,
22.55, 24.38, 24.50, 25.34, 29.09, 31.71, 33.68, 34.28, 35.91, 51.49,
70.95, 172.95, 173.75; IR (neat): n ˆ 2932, 2861, 1736, 1460,
1437, 1177, 1078 cmÀ1. Anal. found: C 66.8, H 6.0%; calcd. for
C13H14O4: C 66.66, H 6.02%.
N-(5-Methoxycarbonylpentanoyl)piperidine
Colorless oil; 1H NMR (400 MHz, CDCl3): d ˆ 1.49 1.73 (10H
m), 2.30 2.39 (4H, m), 3.36 3.41 (2H m), 3.52 3.57 (2H, m),
3.66 (3H, s); 13C NMR (100 MHz, CDCl3): d ˆ 24.55, 24.74,
24.82, 25.56, 26.52, 32.93, 33.85, 42.61, 46.61, 51.46, 170.76,
173.92; IR (neat): n ˆ 2938, 2857, 1738, 1642, 1439, 1254,
1013 cmÀ1. Anal. found: C 63.2, H 9.2, N 6.0%; calcd. for
C12H21NO3: C 63.41, H 9.31, N 6.16%.
S-Cyclohexyl 3-Phenylpropanethioate
Acknowledgements
Colorless oil; 1H NMR (400 MHz, CDCl3): d ˆ 1.20 1.47 (5H,
m), 1.54 1.62 (1H, m), 1.64 1.74 (2H, m), 1.85 1.94 (2H, m),
2.81 (2H, m), 2.96 (2H, m), 3.52 (1H, m), 7.16 7.22 (3H, m),
7.25 7.31 (2H, m); 13C NMR (100 MHz, CDCl3): d ˆ 25.52,
25.89, 31.49, 33.00, 42.26, 45.61, 126.25, 128.30, 128.47, 140.20,
198.44; IR (neat): n ˆ 2930, 2855, 1686, 1451, 1046, 972,
698 cmÀ1. Anal. found: C 72.1, H 7.9%; calcd. for C15H20OS:
C 72.53, H 8.12%.
This research was partially supported by a Grant-in-Aid for
Scientific Research on Priority Areas (A) ™Exploitation of
Multi-Element Cyclic Molecules∫ from the Ministry of Educa-
tion, Culture, Sports, Science and Technology, Japan. We thank
Sumitomo Chemical Co. Ltd. for the generous gift of 13 and 14.
References and Notes
S-1-Octyl 5-(Methoxycarbonyl)pentanethioate
[1] a) G. Benz, in Comprehensive Organic Synthesis, (Eds.:
B. M. Trost, I. Fleming), Pergamon, Oxford, 1991, Vol. 6,
p. 323; b) T. W. Greene, P. G. Wuts, in Protective Groups
in Organic Synthesis, 3rd ed. Wiley: New York, 1999,
p. 372; c) J. Otera, Esterification, Wiley-VCH, Weinheim,
2003.
[2] a) A. Hassner, V. Alexanian, Tetrahedron Lett. 1978,
4475; b) F. E. Ziegler, G. D. Berger, Synth. Commun.
1979, 9, 539.
Colorless oil; 1H NMR (400 MHz, CDCl3): d ˆ 0.88 (3H, t, J ˆ
6.9 Hz), 1.22 1.39 (10H, m), 1.53 1.59 (2H, m), 1.62 1.74
(4H, m), 2.33 (2H, m), 2.56 (2H, m), 2.86 (2H, t, J ˆ 7.3 Hz),
3.67 (3H, s); 13C NMR (100 MHz, CDCl3): d ˆ 14.05, 22.61,
24.19, 25.03, 28.82, 28.86, 29.05, 29.12, 29.54, 31.76, 33.64, 43.59,
51.52, 173.65, 199.21; IR (neat): n ˆ 2928, 2857, 1742, 1690,
1458, 1437, 995, 666 cmÀ1. Anal. found: C 62.2, H 9.7%; calcd.
for C15H28O3S: C 62.46, H 9.78%.
Adv. Synth. Catal. 2003, 345, 1209 1214
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1214
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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