Easy access to cis-3-(benzoxazol-2-yl)cyclopentanecarboxylic acids from camphorquinone and o-aminophenols via an unexpected opening of camphor ring

Article abstract of DOI:10.1080/00397911.2012.696302

An unexpected formation of cis-1,2,2-trimethyl-3-(benzoxazol-2-yl) cyclopentanecarboxylic acids was observed as the result of an oxidative C-C bond cleavage of the camphor ring in the intermediate imine during the condensation reactions between camphoroqu

Full text of DOI:10.1080/00397911.2012.696302

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Easy Access to cis-3-(Benzoxazol-2-
yl)cyclopentanecarboxylic Acids from
Camphorquinone and o-Aminophenols
via an Unexpected Opening of Camphor
Ring
Joanna Nowicka-Scheibe a
a West Pomeranian University of Technology , Szczecin, Institute of
Chemistry and Environmental Protection , Szczecin , Poland
Accepted author version posted online: 05 Mar 2013.Published
online: 03 Jun 2013.
To cite this article: Joanna Nowicka-Scheibe (2013): Easy Access to cis-3-(Benzoxazol-2-
yl)cyclopentanecarboxylic Acids from Camphorquinone and o-Aminophenols via an Unexpected
Opening of Camphor Ring, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 43:16, 2198-2207
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Synthetic Communications1, 43: 2198–2207, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2012.696302
EASY ACCESS TO cis-3-(BENZOXAZOL-2-
YL)CYCLOPENTANECARBOXYLIC ACIDS FROM
CAMPHORQUINONE AND o-AMINOPHENOLS VIA AN
UNEXPECTED OPENING OF CAMPHOR RING
Joanna Nowicka-Scheibe
West Pomeranian University of Technology, Szczecin, Institute of Chemistry
and Environmental Protection, Szczecin, Poland
GRAPHICAL ABSTRACT
Abstract An unexpected formation of cis-1,2,2-trimethyl-3-(benzoxazol-2-yl)cyclopenta-
necarboxylic acids was observed as the result of an oxidative C-C bond cleavage of the
camphor ring in the intermediate imine during the condensation reactions between camphor-
oquinone and o-aminophenols conducted under open air conditions.
Supplemental materials are available for this article. Go to the publisher’s online edition
of Synthetic Communications1 to view the free supplemental file.
Keywords Air oxidation; benzoxazole; caphoroquinone; condensation; o-aminophenols;
ring opening
INTRODUCTION
The reactions of 1,2-diketones with amino alcohols were investigated by several
research groups.[1] Depending on the molar ratio of the reagents used, structures of
1,2-diketones and N,O-binucleophiles or reaction conditions condensation reactions
proceeding usually via Schiff bases lead to monocyclic oxazines or oxazolidines,[1]
bicyclic,[2] or tricyclic[3,4] oxazino-oxazines or bisoxazolidines, belonging to the
so-called propellanes.
In previous publications we reported a synthetic and structural study on pro-
pellanes derived from 1,2-cyclohexanedione and o-aminophenols and we demon-
strated that the condensation reaction between 4-substituted 1,2-cyclohexanedione
Received February 20, 2012.
Address correspondence to Joanna Nowicka-Scheibe, West Pomeranian University of Technology,
´
Szczecin, Institute of Chemistry and Environmental Protection, Al. Piastow 42, PL-71065 Szczecin,
Poland. E-mail: joannans@zut.edu.pl
2198

cis-CYCLOPENTANECARBOXYLIC ACIDS
2199
and substituted o-aminophenols yields, in a regio- and stereoselective manner,
dibenzodioxadiaza[4.4.4]propellanes as single diastereoizomers (Scheme 1).[5]
RESULTS AND DISCUSSION
In the present communication an unexpected formation of cis-1,2,2-
trimethyl-3-(benzoxazol-2-yl)cyclopentanecarboxylic acids 4 in the reaction between
camphoroquinone and a variety of substituted o-aminophenols is reported.
In the primary experiment performed in typical conditions (not air-protected
reflux in EtOH solution) using 2-aminophenol (2a) and D,L-camphoroquinone (1)
in 2:1 molar ratio, cis-1,2,2-trimethyl-3-(benzoxazol-2-yl)cyclopentanecarboxylic
acid derivative (4a) was obtained in 47% yield after column chromatography
(Scheme 2). Further experiments performed using D,L-camphoroquinone (1), enan-
tiomerically pure isomers, and other derivatives of 2-aminophenols (2b–e) supported
3-(benzoxazol-2-yl)cyclopentanecarboxylic acid derivative formation in these con-
ditions, although an influence of both factors such as substitution pattern in the
o-aminophenol ring and different molar ratio of the reagents used on the yield of
the product 4 was observed (Scheme 2). In general, an application of o-aminophenol
with electron-withdrawing groups and using 1:2 molar ratio of reagents (1:2a–g) led
to the better yields. Moreover, the twice-performed experiments revealed that opti-
cally active substrates 1R and 1S gave optically active products 4c (1R,3S)
([a]D ¼ ꢀ29.33) and 4c (1S,3R) ([a]D ¼ þ27.35) in 36 and 33% yields, respectively.
In contrast to these results, a condensation performed in oxygen-free con-
ditions (argon balloon) led to the regioselective formation of imine 3A, which
nevertheless was easily transformed to corresponding 3-(benzoxazol-2-yl)cyclopenta-
necarboxylic acid during purification in air conditions. These results indicated an
oxidative process, in which aromatization leading to benzoxazole ring acts as a driv-
ing force for C-C bond cleavage of the camphor ring. This process starts from imine
3A, which is formed regioselectively from the less hindered carbonyl group. The
likely reaction pathway is shown in Scheme 2.
A synthesis of benzoxazoles from aldehydes and o-aminophenols via Schiff
bases in oxidative conditions is well defined. In this approach 2,3-dichloro-5,6-
dicyanobenzoquinone (DDQ),[6] PhI(OAc)2,[7] ThClO4,[8] and BaMnO4 were used
[9]
as oxidants. Recently catalytic 4-metoxy-2,2,6,6-tetramethylpiperidine 1-oxyl (4-Me-
TEMPO)[10] was used as well. There are also reports that benzoxazole can be formed
from aldehydes under oxygen over carbon[11] or even under air.[12] Besides, Schiff
bases derived from aldehydes or ketones were transformed into benzoxazoles under
Scheme 1. Synthesis of dibenzodioxadiaza[4.4.4]propellanes.

2200
J. NOWICKA-SCHEIBE
Scheme 2. Synthesis of 4a–g in the condensation reaction of camphoroquinones 1 and o-aminophenols
(2a–g). aYield obtained by using 1:2 ratio of reagents (1:2a–g). bYield obtained by using 1:1 ratio of
reagents (1:2a–e) is given in the parentheses.
photochemical conditions.[13] Among the reactions studied under these conditions,
the condensation between 1,2-dibenzoil and o-aminophenol proceeds with C-C bond
cleavage toward 2-phenylbenzoxazole. However, the formation of benzoxazoles
from cyclic 1,2-diones was hitherto unreported.
Because it was established that the transformation of intermediate imine 3A to
monocyclic acid 4 required oxidative conditions, the attempts to find the best
oxidant to optimize the yield of 4 were taken. Various typical oxidants as H2O2,
DDQ, SeO2, and Oxone did not give positive results. The attempts resulted in a
lot of by-products. It was impossible to isolate the main compound from the reaction
mixture. An application of oxygen in the presence of activated carbon (Darco KB)[11]
improved yields only slightly (4c, yield 36%).
A screening of common organic solvents [CH3OH, EtOH, n-propyl and
isopropyl alcohol, EtOAc, toluene, CH3CN, EtOH with catalytic amount of
P-toluenesulfonic acid (PTSA)] was also performed to find the best solvent and
reaction time. Ethanol was the best solvent for imine formation, while ethyl acetate
was good enough to form 4. The best reaction times were 2 h under reflux in ethanol
in an air atmosphere and 4 h under reflux in ethyl acetate followed by stand-
ing at room temperature for 3 days in an open flask. After this time, the
products were purified on silica gel by using column chromatography (ethyl
acetate–hexane 3:7).
1
All the products were characterized by H NMR, 13C NMR, infrared (IR)
spectra, gas chromatography–mass spectrometry (GC=MS), electrospray ionization
(ESI)–MS, and elemental analyses. The structures of unstable imines 3A were
confirmed by comparing 13C NMR spectrum of crude 3A(b) with 13C NMR
spectrum of referenced crude imine derived from D,L-camphoroquinone (1) and
o-anisidine.[14] Characteristic 13C NMR chemical shifts (205.5 ppm, 175.2 ppm,
and 206.0 ppm, 175.2 ppm respectively for 3A(b) and referenced imine) can be
=
=
assigned to C O and C N. The structure of 4c was determined by x-ray diffraction
(Fig. 1).[15] Additionally, the 1H, 15N HMBC NMR were used as techniques
for distinguishing benzoxazole ring or imine groups. By applying these methods,
chemical shifts of nitrogen atoms (referenced to nitromethane) for compounds 4a

cis-CYCLOPENTANECARBOXYLIC ACIDS
2201
Figure 1. X-ray structure of 4c.
and 4b were detected at ꢀ136 ppm, indicating the nitrogen atom of benzoxazole.[16]
The structures of 4a and b and 4d–g were proved by comparing their 13C NMR
spectra to the 13C NMR spectra of 4c.
To sum up, the condensation reactions of D,L-camphoroquinone, its
enantiomerically pure antipodes, and a variety of substituted o-aminophenols
conducted in unprotected conditions led to cis-1,2,2-trimethtyl-3-(benzoxazol-2-
yl)cyclopentanecarboxylic acids. The obtained cis-bifunctionalizedcyclopentanes
may be useful compounds as building blocks in drug discovery because benzoxa-
zoles,[17] especially 2-cyclopentylbenzoxazoles,[18] were recognized as pharmaco-
phores. Moreover, it is necessary to point out that easy access to both
enantiomerically pure acids, possessing nonenolizable carboxyl groups, obtained
from commercially available, enantiomerically pure camphoroquinones opens
new possibilities in asymmetric synthesis (e.g., in the field of ligand design). These
compounds could also expand the set of compounds applied as chiral derivatizing
agents.
EXPERIMENTAL
1
Melting points were determined on a Boetius hot-stage apparatus. H, 13C
NMR spectroscopic measurements were performed on a Bruker DPX 400 spec-
trometer equipped with a 5-mm 1H=BB inverse probehead, operating at 400.13
and 100.62 MHz. Purity and molecular mass determinations were carried out by
GC-MS on a Hewlett-Packard instrument (model HP 6890) equipped with a mass
detector HP 5973. The analytical procedure was developed on 30-m-long capillary
column, 0.2 mm in diameter, with methyl-siloxane modified with phenyl groups
(5% Ph, Me siloxane) in the 0.25-mm active phase layer. The ESI mass spectra
were obtained on a Waters=Micromass (Manchester, UK) ZQ2000 mass spec-
trometer (single quadrupole type instrument, Z-spray, software Mass Lynx
V3.5). The sample solutions were prepared in methanol. The concentration of 1
and 2 compounds was 1 ꢁ 10ꢀ4 M. The sample solutions were infused into the
ESI source using a Harvard pump at a flow rate of 80 mL=min. The ESI source
potentials were capillary 3 kV, lens 0.5 kV, extractor 4 V, and cone voltage 10 V.
Nitrogen was used as the nebulizing and desolvating gas at flow rates of 100
and 300 L=h, respectively.

2202
J. NOWICKA-SCHEIBE
Silica gel (0.04–0.063 mm, Merck) was used for preparative column chromato-
graphy. Infrared (IR) spectra were taken with a Specord M80 instrument. Elemental
analyses were performed on EuroEA 3000 series, EuroVector CHNS-O Elemental
instrument.
The x-ray diffraction studies were performed on a Kuma KM4 CCD x-axis
four-circle diffractometer equipped with an Oxford Cryosystem Cooler using graph-
ite monochromatedMoKa radiation. The data were corrected for Lorentz and polar-
ization effects as well as for absorption. The structure was solved by direct methods
(SHELXS-97) and refined by the full-matrix least-squares methods using the
SHELXL-97 program.[19] The crystal data and structure refinement are summarized
o
˚
in Table 1. Selected bond lengths (A) and angles ( ) are summarized in Table 2 and
possible hydrogen bonds and short contacts in Table 3. Crystallographic data for the
structural analysis have been deposited with the Cambridge Crystallographic Data
Centre as supplementary publication number CCDC 8252.
General Procedure for Synthesis of 4a–g
A solution of camphoroquinone (0.166 g, 0.001 mol) and corresponding 2-ami-
nophenol (0.002 mol) in ethanol (10 mL) was refluxed for 2 h, and the solvent was
removed under reduced pressure. The residue was dissolved in ethyl acetate and stir-
red under reflux for 4 h. The reaction mixture was left standing in an air atmosphere
for 3 days. After this time, the solvent was removed, and the crude product was pur-
ified by column chromatography on silica gel with ethyl acetate=hexane (3:7) as a
solvent and crystallized.
Data
Compound 4a, (1RS,3SR)-3-(benzoxazol-2-yl)-1,2,2-trimethylcyclopen-
tanecarboxylic acid. White solid, mp 208–210 ꢂC from n-hexane–ethyl acetate.
IR (KBr pellet): n ¼ 3020 (v br), 2972, 2650 (v br), 1692 (s), 1564 (m), 1456 (m),
1292 (m), 1246 (m), 1158 (m), 952 (w), 764 (w), 750 (m) cmꢀ1 1H NMR
;
(400.1 MHz, CDCl3–DMSO-d6 ¼ 5:1) d ¼ 0.76 (3 H, s, 1-CH3), 1.34 (3 H, s,
2-CH3), 1.35 (3 H, s, 2-CH3), 1.63 (1 H, ddd, J ¼ 13.7, 9.5, 4.2 Hz, CHH-5),
2.07–2.20 (1 H, m, CHH-4), 2.47–2.61 (1 H, m, CHH-4), 2.71 (1H, ddd, J ¼ 13.7,
12.2, 6.8 Hz, CHH-5), 3.46 (1 H, t, J ¼ 9.8 Hz, CH-3), 7.28–7.34 (2 H, m, C6H4),
7.50–7.55 (1 H, m, C6H4), 7.64–7.69 (1 H, m, C6H4); 13C NMR (100.6 MHz,
CDCl3–DMSO-d6 ¼ 5:1): d ¼ 21.05 (1-CH3), 21.97, 22.44 (2 ꢁ 2-CH3), 23.58 (CH2-
4), 32.33 (CH2-5), 47.38 (C-2), 47.84 (CH-3), 55.73 (C-1), 110.29, 119.31, 123.96,
=
=
124.40, 140.90, 150.59 (C6H4), 167.64 (C N), 177.53 (C O); GC-MS (EI, 70 eV):
m=z ¼ 273 (69, Mþ.), 258 (12), 228 (100), 212 (14), 200 (11), 187 (33), 186 (33), 172
(16), 158 (21), 146 (83), 133 (60), 120 (12), 109 (55), 65 (10), 41 (11). Found: C,
70.20; H, 6.94; N, 5.06. C16H19NO3 requires C, 70.31; H, 7.01; N, 5.12%.
Compound 4b, (1RS,3SR)-1,2,2-trimethyl-3-(5-nitrobenzooxazol-2-
yl)cyclopentanecarboxylic acid. Yellow solid, mp 229–231 ꢂC from n-hexane–
ethyl acetate. IR (KBr pellet): n ¼ 3432 (br), 3108 (w), 2972 (vbr), 1692 (vs), 1614
(s), 1562 (S), 1526 (vs), 1458 (m), 1440 (m), 1350 (s), 1264 (m), 1154 (m), 1122

cis-CYCLOPENTANECARBOXYLIC ACIDS
2203
(m), 962 (m), 896 (m), 824 (m), 736 (s), 692 (m) cmꢀ1
;
1H NMR (400.1 MHz,
DMSO-d6) d ¼ 0.67 (3 H, s, 1-CH3), 1.28 (3 H, s, 2-CH3), 1.30 (3 H, s, 2-CH3),
1.57 (1 H, ddd, J ¼ 13.6, 9.6, 3.9 Hz, CHH-5), 2.08–2.20 (1 H, m, CHH-4),
2.36–2.48 (1 H, m, CHH-4), 2.59 (1 H, ddd, J ¼ 13.6, 12.7, 6.8 Hz, CHH-5), 3.61
(1 H, t, J ¼ 9.8 Hz, CH-3), 7.97 (1 H, d, J ¼ 9.0 Hz, Ar), 8.30 (1 H, dd, J ¼ 9.0,
2.3 Hz, Ar), 8.61 (1 H, d, J ¼ 2.3 Hz, Ar), 12.40 (1 H, v br s, COOH); 13C NMR
(100.6 MHz, DMSO-d6 ¼ 5): d ¼ 21.11 (1-CH3), 21.81, 22.50 (2 ꢁ 2-CH3), 23.35
(CH2-4), 32.28 (CH2-5), 47.35 (C-2), 47.45 (CH-3), 55.65 (C-1), 111.60, 115.55,
=
121.09, 141.11, 144.88, 154.21, 171.28 (Ar), 176.81 (C O); ESI-MS m=z ¼ 318.
Found: C, 60.45; H, 5.77; N, 8.48. C16H18N2O5 requires C, 60.37; H,5.70; N, 8.80%.
Compound 4c, (1RS,3SR)-1,2,2-trimethyl-3-(6-methyl-benzooxazol-
2-yl)cyclopentanecarboxylic acid. White solid, mp 188–190 ꢂC from n-hexane–
ethyl acetate. IR (KBr pellet): n ¼ 3432 (br), 2968 (vbr), 1718 (vs), 1608 (m), 1562
(s), 1460 (m), 1242 (s), 1156 (m), 1116 (m), 864 (m), 810 (s), 734 (m), 692 (m) cmꢀ1
;
1H NMR (400.1 MHz, DMSO-d6) d ¼ 0.63 (3 H, s, 1-CH3), 1.27 (3 H, s, 2-CH3),
1.29 (3 H, s, 2-CH3), 1.53 (1 H, ddd, J ¼ 13.5, 9.6, 4.0 Hz, CHH-5), 2.02–2.13
(1 H, m, CHH-4), 2.34–2.48 (4 H, m, CH3, CHH-4), 2.56 (1 H, ddd, J ¼ 13.5,
12.2, 7.1 Hz, CHH-5), 3.50 (1 H, t, J ¼ 9.6 Hz, CH-3), 7.16 (1 H, br d, J ¼ 7.7 Hz,
Ar), 7.50 (1 H, br s, Ar), 7.84 (1 H, d, J ¼ 8.1 Hz, Ar), 12.29 (1 H, v br s, COOH);
13C NMR (100.6 MHz, DMSO-d6): d ¼ 21.07 (1-CH3), 21.30 (CH3), 21.83, 22.53
(2 ꢁ 2-CH3), 23.34 (CH2-4), 32.24 (CH2-5), 46.97 (C-2), 47.23 (CH-3), 55.49
=
(C-1), 110.71, 118.85, 125.39, 134.68, 138.58, 150.68, 166.98 (Ar), 176.89 (C O);
GC-MS (EI, 70 eV): m=z ¼ 287 (84, Mþ), 269 (23), 242 (100), 224 (17), 201 (83),
183 (20), 160 (89), 142 (73), 123 (74), 95 (12), 77 (27), 59 (4), 41 (32). Found: C,
71.28; H, 7.15, N, 4.34. C17H21NO3 requires C, 71.06; H, 7.37; N, 4.87%.
Compound 4c (1R,3S), (1R,3S)-1,2,2-trimethyl-3-(6-methyl-benzooxa-
zol-2-yl)cyclopentanecarboxylic acid. [a]D ¼ ꢀ29.33. White solid, mp
1
188–190 ꢂC from n-hexane–ethyl acetate. H and 13C NMR spectral data for this
product were identical with those reported for 4c.
Compound 4c (1S,3R), (1S,3R)-1,2,2-trimethyl-3-(6-methyl-benzooxa-
zol-2-yl)cyclopentanecarboxylic acid. [a]D ¼ þ27.35. White solid, mp
1
187–191 ꢂC from n-hexane–ethyl acetate. H and 13C NMR spectral data for this
product were identical with those reported for 4c.
Compound 4d, (1RS,3SR)-3-(5-chlorobenzooxazol-2-yl)-1,2,2-trimethyl-
cyclopentanecarboxylic acid. Yellow solid, mp 209–211 ꢂC from n-hexane–ethyl
acetate. IR (KBr pellet): n ¼ 3436 (br), 2968 (vbr), 1692 (vs), 1608 (w), 1558 (s),
1452 (s), 1376 (m), 1288 (m), 1260 (m), 1156 (m), 1122 (m), 1056 (m), 964 (m),
1
922 (m), 800 (s), 704 (m) cmꢀ1; H NMR (400.1 MHz, DMSO-d6) d ¼ 0.65 (3 H, s,
1-CH3), 1.26 (3 H, s, 2-CH3), 1.27 (3 H, s, 2-CH3), 1.55 (1 H, ddd, J ¼ 13.4, 9.5,
3.3 Hz, CHH-5), 2.04–2.17 (1 H, m, CHH-4), 2.34–2.46 (1 H, m, CHH-4), 2.58
(1 H, ddd, J ¼ 13.4, 12.2, 6.8 Hz, CHH-5), 3.54 (1 H, t, J ¼ 9.5 Hz, CH-3), 7.41
(1 H, dd, J ¼ 8.6, 2.0 Hz, Ar), 7.75 (1 H, d, J ¼ 8.6 Hz, Ar), 7.84 (1 H, d, J ¼ 2.0 Hz,
Hz, Ar), 12.30 (1 H, v br s, COOH); 13C NMR (100.6 MHz, DMSO-d6): d ¼ 21.08
(1-CH3), 21.83, 22.51 (2 ꢁ 2-CH3), 23.33 (CH2-4), 32.26 (CH2-5), 47.17 (C-2),
47.35 (CH-3), 55.56 (C-1), 112.09, 119.30, 124.92, 128.68, 142.09, 149.22, 169.44

2204
J. NOWICKA-SCHEIBE
þ
=
(Ar), 176.83 (C O); GC-MS (EI, 70 eV): m=z ¼ 307 (37, M ), 281 (1), 262 (9), 236
(3), 218 (2), 194 (16), 169 (13), 143 (38), 109 (100), 91 (35), 67 (28), 50 (26), 41
(33). Found: C, 62.60; H, 5.41; Cl, 11.06, N, 4,12. C16H18ClNO3 requires C,
62.44; H, 5.89; Cl, 11.52; N, 4.55%.
Compound 4e, (1RS,3SR)-3-(6-chloro-5-nitro-benzooxazol-2-yl)-1,2,
2-trimethyl-cyclopentanecarboxylic acid. Yellow solid, mp 216–218 ꢂC from
n-hexane–ethyl acetate. IR (KBr pellet): n ¼ 3420 (br), 2972 (vbr), 1690 (vs), 1608
(w), 1554 (vs), 1536 (vs), 1448 (vs), 1408 (w), 1344 (m), 1260 (m), 1146 (m), 1118
1
(m), 1004 (m), 960 (m), 882 (m), 836 (m) cmꢀ1; H NMR (400.1 MHz, DMSO-d6)
d ¼ 0.66 (3 H, s, 1-CH3), 1.28 (3 H, s, 2-CH3), 1.29 (3 H, s, 2-CH3), 1.56 (1 H, ddd,
J ¼ 13.6, 9.6, 3.9 Hz, CHH-5), 2.07–2.20 (1 H, m, CHH-4), 2.33–2.46 (1 H, m,
CHH-4), 2.58 (1 H, ddd, J ¼ 13.6, 12.1, 7.1 Hz, CHH-5), 3.62 (1 H, t, J ¼ 9.5 Hz,
CH-3), 8.21 (1 H, s, Ar), 8.64 (1 H, s, Ar), 12.34 (1 H, v br s, COOH); 13C NMR
(100.6 MHz, DMSO-d6): d ¼ 21.05 (1-CH3), 21.78, 22.44 (2 ꢁ 2-CH3), 23.34 (CH2-
4), 32.26 (CH2-5), 47.51 (C-2, CH-3), 55.64 (C-1), 109.13, 121.24, 121.68, 144.36,
ꢀ
=
144.56, 148.23, 173.35 (Ar), 176.71 (C O); ESI-MS m=z ¼ 353 [M-H] . Found: C,
54.76; H, 4.30; Cl, 9.89; N, 7.26%. C16H17ClN2O5 requires C, 54.48; H, 4.86; Cl,
10.05; N, 7.94%.
Compound 4f, (1RS,3SR)-1,2,2-trimethyl-3-naphtho[2,3-d]oxazol-2-yl-
cyclopentanecarboxylic acid. Yellow solid, mp 223–225 ꢂC from n-hexane–ethyl
acetate. IR (KBr pellet): n ¼ 3412 (vbr), 3040 (w), 2976 (vbr), 1692 (vs), 1650 (w),
1626 (m), 1568 (s), 1506 (m) 1444 (m), 1406 (s), 1310 (m), 1288 (s), 1248 (s), 1178
1
(m), 1118 (m), 956 (m), 868 (s), 742 (s) cmꢀ1; H NMR (400.1 MHz, DMSO-d6)
d ¼ 0.70 (3 H, s, 1-CH3), 1.26 (3 H, s, 2-CH3), 1.30 (3 H, s, 2-CH3), 1.58 (1 H, ddd,
J ¼ 13.2, 9.6, 3.8 Hz, CHH-5), 2.14 (1 H, dtd, J ¼ 13.4, 9.5, 6.9 Hz, CHH-4),
2.43–2.54 (1 H, m, CHH-4), 2.61 (1 H, ddd, J ¼ 13.2, 12.1, 6.8 Hz, CHH-5), 3.59
(1 H, t, J ¼ 9.4 Hz, CH-3), 7.48–7.56 (2 H, m, Ar), 8.02-8.10 (2 H, m, Ar), 8.18
(1 H, s, Ar), 8.26 (1 H, s, Ar), 12.30 (1 H, v br s, COOH); 13C NMR (100.6 MHz,
DMSO-d6) d ¼ 21.14 (1-CH3), 21.80, 22.61 (2 ꢁ 2-CH3), 23.31 (CH2-4), 32.32
(CH2-5), 47.21 (C-2), 47.49 (CH-3), 55.62 (C-1), 106.32, 116.61, 124.79, 125.51,
=
128.00, 128.42, 130.93, 131.07, 140.85, 149.29, 170.22 (Ar), 176.84 (C O); GC-MS
(EI, 70 eV): m=z ¼ 323 (0), 295 (M-CO), 262 (28), 244 (23), 204 (17), 183 (14), 159
(7), 141 (5), 115 (17), 88 (4), 67 (3), 43 (17);
Found: C, 74.61; H, 6.40; N, 4.02%. C20H21NO3 requires C, 74.28; H, 6.55; N,
4.33%.
Compound 4g, (1RS,3SR)-(1,2,2-trimethyl-3-(5-phenyl-benzooxazol-
2-yl)-cyclopentanecarboxylic acid. White solid, mp 217–219 ꢂC from n-hexane:
ethyl acetate. IR (KBr pellet): n ¼ 3444 (br), 2968 (vbr), 2336 (w), 1720 (vs), 1560
(s), 1470 (s). 1422 (m), 1380 (m), 1262 (m), 1210 (m), 1156 (m), 1112 (m), 956 (m),
820 (m), 760 (s), 696 (s) cmꢀ1
;
1H NMR (400.1 MHz, CDCl3: DMSO-d6 ¼ 3:1)
(¼0.78 (3 H, s, 1-CH3), 1.34 (3 H, s, 2-CH3), 1.36 (3 H, s, 2-CH3), 1.63 (1 H, ddd,
J ¼ 13.2, 9.5, 3.5 Hz, CHH-5), 2.08–2.21 (1 H, m, CHH-4), 2.47–2.63 (1 H, m,
CHH-4), 2.71 (1 H,td, J ¼ 13.2, 6.6 Hz, CHH-5), 3.48 (1 H, t, J ¼ 9.5 Hz, CH-3),
7.31–7.38 (1 H, m, C6H5), 7.45 (2 H, t, J ¼ 7.6 Hz, C6H5), 7.54 (1 H, dt, J ¼ca. 8.4,
1.7 Hz, C6H3), 7.57–7.63 (3 H, m, C6H3, C6H5), 7.85 (1 H, br s, C6H3); 13C NMR

cis-CYCLOPENTANECARBOXYLIC ACIDS
2205
(100.6 MHz, CDCl3 : DMSO-d6 ¼ 3 : 1): (¼20.79 (1-CH3), 21.67, 22.19 (2 ꢁ 2-CH3),
23.29 (CH2-4), 32.06 (CH2-5), 47.11 (C-2), 47.58 (CH-3), 55.41 (C-1), 110.15, 117.31,
=
123.52, 126.84, 128.52, 137.24, 140.45, 141.34, 149.87 (C6H3, C6H4), 168.05 (C N),
=
177.06 (C O); GC-MS (EI, 70 eV): m=z ¼ 305 (36, M-CO2), 276 (39), 259 (21), 237
(27), 209 (100), 139 (59), 115 (9), 41 (24); Found: C, 75.68; H, 6.34; N, 3.92%.
C22H23NO3 requires C, 75.62; H, 6.63; N, 4.01.
All additional data (e.g., X-ray, 1H, 13C NMR data) are available as
Supplementary Matarial online.
ACKNOWLEDGMENTS
The author thanks Wanda Sawka-Dobrowolska (Faculty of Chemistry,
University of Wrocław, Poland) for performing x-ray measurements and Jacek G.
´
Sosnicki (West Pomeranian University of Technology, Szczecin, Poland) for helpful
discussions.
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