TBAF-mediated dimerization reaction of β,γ-unsaturated arylketones

Article abstract of DOI:10.1002/jccs.200800003

A simple and high-yield method for the synthesis of several 1,5-diaryl-1,5-dicarbonyl compounds has been established starting from TBAF-mediated isomerization and dimerization reaction of β,γ- unsaturated arylketones (allyl arylketones) with mono-, di-, and tri-methoxy groups, which is derived from allylation of commercially available different benzaldehydes and followed by oxidation of the resulting secondary alcohols.

Full text of DOI:10.1002/jccs.200800003

Journal of the Chinese Chemical Society, 2008, 55, 9-12
9
Communication
TBAF-Mediated Dimerization Reaction of b,g-Unsaturated Arylketones
Meng-Yang Changa* (
), Chin-Yi Hunga (
) and Shiang-Tsern Linb (
)
aDepartment of Applied Chemistry, National University of Kaohsiung,
Kaohsiung 811, Taiwan, R.O.C.
bDepartment of Nutrition, Chung-Ho Memorial Hospital, Kaohsiung Medical University,
Kaohsiung 807, Taiwan, R.O.C.
Asimple and high-yield method for the synthesis of several 1,5-diaryl-1,5-dicarbonyl compounds has
been established starting from TBAF-mediated isomerization and dimerization reaction of b,g-unsatu-
rated arylketones (allyl arylketones) with mono-, di-, and tri-methoxy groups, which is derived from
allylation of commercially available different benzaldehydes and followed by oxidation of the resulting
secondary alcohols.
Keywords: TBAF; Dimerization; b,g-Unsaturated arylketones.
INTRODUCTION
RESULTS AND DISCUSSION
Among the fluoride ion sources, tetra-n-butylammo-
nium fluoride (TBAF) is the most popular candidate for
various synthetic proposes. The fluoride anion could be an
efficacious basic activator in different reactions. Accord-
ingly, some new and efficient fluoride-promoted methods
warrant attention.1,2 Recently, DeShong and co-worker
demonstrated the superiority of tetra-n-butylammonium
triphenyldifluorosilicate (TBAT) over TBAF as a fluoride
source for various reactions.3a,b Fry and coworker have also
reported that the dimerization reaction of methyl crotonate
by TBAT afforded a 7:1 E/Z mixture in 74% yield at reflux
temperature for 4 h under a nitrogen system.3c The pro-
posed mechanism has been studied well. Although TBAT
was a more efficient reagent than TBAF in different reac-
tions, the commercially available TBAF is still more con-
venient and cheaper than freshly prepared TBAT.
To improve the yield and reactivity of the TBAF-me-
diated dimerization reaction of a,b-unsaturated com-
pounds, we turned to the examination of vinylketones. Af-
ter treatment of vinylketones with a¢-aliphatic groups
(methyl and benzyl) and a¢-aromatic groups (phenyl and
3,4-dimethoxyphenyl) by TBAF, the starting material was
recycled as the major product.
For exploring a more applicable substrate toward the
TBAF-mediated dimerization reaction, we found that al-
lylketone with 4-methoxyphenyl group was the better sub-
strate, and the resultant sole Z-isomer was obtained in 93%
yield at rt for 2 h without an atmosphere of nitrogen and dry
solvent system. During the course of our investigation,
these dimerization reactions of other allylketones with aro-
matic substitutents (e.g. phenyl, 4-fluorophenyl-, 2-furan-
yl, 2-pyridinyl, 2-indolyl and 2-quinolinyl) with TBAF
were unsuccessful under different conditions. The differ-
ence between a,b-unsaturated arylketone and b,g-unsatu-
rated arylketone was not further investigated.
In order to reinvestigate this dimerization reaction,
TBAF was chosen as the starting fluoride ion source. With
the related dimerization literature reports of a,b-unsatu-
rated esters by different initiators (e.g. metal ion complex,
trialkylphosphine, tetra-alkylammonium cyanide, TBAT)
in hand,3c,4 we tried to examine the TBAF-mediated di-
merization reaction of methyl crotonate and methyl cinna-
mate (b-methyl and b-phenyl vinylesters). However, the
desired dimers were obtained in trace yields.
Although the dimerization process of a,b-unsatu-
rated ester has been developed by Fry’s group, the present
work toward TBAF-mediated dimerization reaction of
b,g-unsaturated arylketone is complementary to existing
methodology. As shown in Table 1, it became apparent that
many substituted 1,5-dicarbonyl compounds having 1,5-

10 J. Chin. Chem. Soc., Vol. 55, No. 1, 2008
Chang et al.
Table 1. TBAF-mediated dimerization of ketones 1a-k and the
good yields of the Z-isomers 2a-ka
The proposed dimerization mechanism of
Scheme I
aryl allylketones 1a-k with TBAF
O
O
O
TBAF, THF
rt, 2 h
Ar
Ar
Ar
1
2
Entry
1, Ar
2, Yielda
1
1a, 2-CH3OC6H4
1b, 3-CH3OC6H4
1c, 4-CH3OC6H4
1d, 3,4-CH2O2C6H3
1e, 3,4-(CH3O)2C6H3
2a, 90%
2b, 94%
2c, 93%
2d, 95%
2e, 95%
2f, 94%
2g, 89%
2h, 93%
2i, 92%
2j, 94%
2k, 90%
2
3
4
5
6
1f, 3-C4H9O-4-CH3OC6H3
1g, 3-C10H21O-4-CH3OC6H3
7
8
1h, 3-CH=CH2CH2O-4-CH3OC6H3
1i, 3-C6H5CH2O-4-CH3OC6H3
1j, 3,4,5-(CH3O)3C6H2
9
10
11
1k, 3-F-4-OCH3C6H3
a The yields of compounds 2a-k was adjusted based on isolated
products.
force between the two methyl groups under thermody-
namic equilibration. In comparison with a related literature
report,3c the structural assignment of vinyl b-proton quar-
tets was made as the Z-isomer (q, d 5.90~6.20). It is worthy
of note that 1,5-dicarbonyl compounds 2a-k could be use-
ful building blocks in the search for various multi-substi-
tuted pyridines with different applications.6 Dimers 2a-k
with an a,b-unsaturated system could be applied in the
preparation of the related analogs with potential biological
activities.7
diaryl substitutents with a methoxy donating group re-
quired by us could not be obtained in satisfactory yields
following reported methods.
Herein, we report a simple and high-yield method to-
ward 1,5-dicarbonyl compounds 2a-k via TBAF-mediated
dimerization reaction of different b,g-unsaturated arylke-
tones 1a-k with mono-, di- and tri-methoxy groups. These
experimental results are summarized in Table 1.5 In view of
the experimental simplicity, the yield of compound 2a
(3.24 g, 90%) was also provided in a multigram scale from
compound 1a (1.8 g, 10 mmole).
In summary, we have developed a simple and high-
yield approach toward the 1,5-diaryl-1,5-diketone deriva-
tives via the dimerization of b,g-unsaturated arylketones
with TBAF. Further novel TBAF-mediated methodologies
and related applications are now underway.
How are Z-form dimers 2a-k generated under the
TBAF-mediated dimerization condition? Mechanically it
is not clear if the reaction follows the same pathway
(Scheme I).3c The most likely explanation would be that
isomerization of compounds 1a-k is controlled by involve-
ment of the fluoride ion to form the equilibrium of interme-
diates I and II. Because of the weaker basicity of fluoride
ion and the presence of starting ketone as a proton source,
the overall event may be considered to yield intermediate
III via the self-dimerization of the intermediate I and II
and followed by tautomerization. By a series of prototropic
shifts, the more stable Z-form dimers 2a-k can be generated
as the sole product.
ACKNOWLEDGMENTS
The authors would like to thank the National Science
Council (NSC-95-2113-M-390-003-MY2) of the Republic
of China for financial support.
Received May 8, 2007.
REFERENCES AND NOTES
During the specific dimerization process, the other
possible isomer analogs were not observed. For generating
the sole Z-isomer, the major reason should be the repulsion
1.
Crouch, R. D. Tetrahedron 2004, 60, 5833.
2. (a) Amantini, D.; Beleggia, R.; Frenguelli, F.; Pizzo, F.;

TBAF-Mediated Dimerization of b,g-Unsaturated Ketones
J. Chin. Chem. Soc., Vol. 55, No. 1, 2008 11
Vaccaro, L. J. Org. Chem. 2004, 69, 2896. (b) Nakamura,
H.; Aoyagi, K.; Yamamoto, Y. J. Am. Chem. Soc. 1998, 120,
1167. (c) Kuduk, S. D.; DiPardo, R. M.; Bock, M. G. Org.
Lett. 2005, 7, 577. (d) Seganish, W. M.; Mowery, M. E.;
Riggleman, S.; DeShong, P. Tetrahedron 2005, 61, 2117. (e)
Kang, S. K.; Kim, T. H.; Pyun, S. J. J. Chem. Soc., Perkin
Trans. 1 1997, 797. (f) Heuft, M. A.; Collins, S. K.; Yap, G. P.
A.; Fallis, A. G. Org. Lett. 2001, 3, 2883.
(125 MHz, CDCl3) d 199.77, 199.10, 159.72, 159.28,
144.32, 140.71, 139.92, 138.57, 129.47, 128.91, 122.25,
120.85, 119.54, 117.98, 113.87, 112.08, 55.36, 55.32, 43.42,
29.25, 19.37, 14.06. For compound 2c: HRMS (ESI) m/z
calcd for C22H25O4 (M++1) 353.1753, found 353.1756; H
1
NMR (500 MHz, CDCl3) d 7.96 (d, J = 8.5 Hz, 2H), 7.69 (d, J
= 8.5 Hz, 2H), 6.89 (d, J = 8.5 Hz, 2H), 6.87 (d, J = 8.5 Hz,
2H), 6.07 (q, J = 7.0 Hz, 1H), 3.85 (s, 6H), 3.61-3.54 (m,
1H), 3.42 (dd, J = 7.5, 17.0 Hz, 1H), 3.26 (dd, J = 7.0, 17.0
Hz, 1H), 1.92 (d, J = 7.0 Hz, 3H), 1,30 (d, J = 7.0 Hz, 3H);
13C NMR (125 MHz, CDCl3) d 198.62, 198.37, 163.32,
162.71, 144.37, 136.95 (2x), 132.00 (2x), 131.79, 130.41
(2x), 113.57 (2x), 113.24 (2x), 55.40, 55.39, 43.04, 29.55,
19.47, 13.83. For compound 2d: HRMS (ESI) m/z calcd for
C22H21O6 (M++1) 381.1338, found 381.1337; 1H NMR (500
MHz, CDCl3) d 7.57 (dd, J = 1.5, 8.0 Hz, 1H), 7.42 (d, J = 1.5
Hz, 1H), 7.26 (dd, J = 1.5, 8.0 Hz, 1H), 7.20 (d, J = 1.5 Hz,
1H), 6.79 (d, J = 8.0 Hz, 1H), 6.77 (d, J = 8.0 Hz, 1H), 6.07
(q, J = 7.0 Hz, 1H), 6.00 (s, 4H), 3.57-3.50 (m, 1H), 3.38 (dd,
J = 7.5, 17.0 Hz, 1H), 3.19 (dd, J = 6.5, 17.0 Hz, 1H), 1.91 (d,
J = 7.0 Hz, 3H), 1.27 (d, J = 7.0 Hz, 3H); 13C NMR (125
MHz, CDCl3) d 197.96, 197.72, 151.55, 150.92, 148.02,
147.55, 144.13, 137.12, 133.48, 132.13, 126.04, 124.46,
109.54, 107.81, 107.72, 107.43, 101.70, 101.61, 43.07,
29.52, 19.41, 13.81. For compound 2f: HRMS (ESI) m/z
3. (a) Pilcher, A. S.; Ammon, H. L.; DeShong, P. J. Am. Chem.
Soc. 1995, 117, 5166. (b) Pilcher, A. S.; DeShong, P. J. Org.
Chem. 1996, 61, 6901. (c) Xuan, J. X.; Fry, A. J. Tetrahedron
Lett. 2001, 21, 3275.
4. (a) Saegusa, T.; Ito, Y.; Tomita, S.; Kinoshita, H. J. Org.
Chem. 1970, 35, 670. (b) White, D. A.; Baizer, M. M. J.
Chem. Soc., Perkin Trans. 1 1973, 2230. (c) Ikeda, M.;
Hirano, T.; Tsuruta, T. Tetrahedron 1974, 30, 2217. (d)
Shabtai, J.; Ney-Igner, E. J. Org. Chem. 1981, 46, 3795. (e)
Chuit, C.; Corriu, R. J. P.; Reye, C. Synthesis 1983, 294. (f)
Komiya, S.; Oyasato, N.; Furukawa, T. Bull. Chem. Soc.
Jpn. 1989, 62, 4078.
5.
TBAF-mediated dimerization of b,g-unsaturated arylke-
tones 1a-k into 1,5-diaryl-1,5-diketones 2a-k is as follows:
A solution of tetra-n-butylammonium fluoride (1.0 M in
tetrahydrofuran, 0.52 mL, 0.52 mmol) in tetrahydrofuran (2
mL) was added to a solution of b,g-unsaturated arylketones
1a-k (0.5 mmol) in tetrahydrofuran (5 mL) at rt. The reaction
mixture was stirred at rt for 2 h, poured into aqueous ammo-
nium chloride solution (15%, 2 mL), and concentrated. The
residue was extracted with ethyl acetate (3 ´ 20 mL). The
combined organic layers were washed with brine, dried, fil-
tered and evaporated to afford crude product. Purification on
silica gel (hexane/ethyl acetate = 8/1~10/1) afforded com-
pounds 2a-k. Representative data for compound 2a: HRMS
(ESI) m/z calcd for C22H25O4 (M++1) 353.1753, found
1
calcd for C30H41O6 (M++1) 497.2903, found 497.2902; H
NMR (500 MHz, CDCl3) d 7.60 (dd, J = 2.0, 8.5 Hz, 1H),
7.51 (d, J = 1.5 Hz, 1H), 7.32 (d, J = 2.0 Hz, 1H), 7.26 (dd, J
= 1.5, 8.5 Hz, 1H), 6.82 (d, J = 8.5 Hz, 1H), 6.79 (d, J = 8.5
Hz, 1H), 6.07 (q, J = 7.0 Hz, 1H), 4.08-4.02 (m, 4H), 3.90 (s,
6H), 3.61-3.54 (m, 1H), 3.44 (dd, J = 7.5, 17.0 Hz, 1H), 3.21
(dd, J = 6.5, 17.0 Hz, 1H), 1.92 (d, J = 7.0 Hz, 3H), 1.86-1.80
(m, 4H), 1.53-1.45 (m, 4H), 1.30 (d, J = 7.0 Hz, 3H), 0.98 (t,
J = 7.0 Hz, 3H), 0.97 (t, J = 7.0 Hz, 3H); 13C NMR (125 MHz,
CDCl3) d 198.76, 198.47, 153.48, 152.87, 148.40, 148.20,
144.14, 136.71, 131.74, 130.45, 124.58, 122.80, 113.10,
111.47, 110.14, 109.77, 68.65, 68.62, 56.01 (2x), 42.94,
31.11, 31.07, 29.74, 19.54, 19.16 (2x), 13.85, 13.83, 13.81.
For compound 2g: HRMS (ESI) m/z calcd for C42H65O6
1
353.1755; H NMR (500 MHz, CDCl3) d 7.61 (dd, J = 2.0,
7.5 Hz, 1H), 7.42 (ddd, J = 2.0, 7.5, 9.0 Hz, 1H), 7.33 (ddd, J
= 2.0, 7.5, 9.0 Hz, 1H), 7.12 (dd, J = 2.0, 7.5 Hz, 1H), 6.97
(dt, J = 1.0, 7.5 Hz, 1H), 6.94 (d, J = 8.0 Hz, 1H), 6.91 (dd, J
= 1.0, 7.5 Hz, 1H), 6.88 (d, J = 8.0 Hz, 1H), 6.20 (q, J = 7.0
Hz, 1H), 3.88 (s, 3H), 3.72 (s, 3H), 3.62-3.53 (m, 2H), 3.38-
3.31 (m, 1H), 1.89 (d, J = 7.0 Hz, 3H), 1.34 (d, J = 7.0 Hz,
3H); 13C NMR (125 MHz, CDCl3) d 202.64, 198.73, 158.29,
156.85, 146.37, 142.92, 132.90, 130.62, 130.55, 129.92,
129.12, 128.96, 120.42, 119.99, 111.49, 111.22, 55.55,
55.46, 48.08, 28.53, 19.18, 14.46. For compound 2b: HRMS
(ESI) m/z calcd for C22H25O4 (M++1) 353.1753, found
353.1757; 1H NMR (500 MHz, CDCl3) d 7.57 (d, J = 8.0 Hz,
1H), 7.49 (dd, J = 2.0, 2.5 Hz, 1H), 7.33 (t, J = 8.0 Hz, 1H),
7.28 (t, J = 8.0 Hz, 1H), 7.19-7.17 (m, 2H), 7.07 (dd, J = 2.5,
8.5 Hz, 1H), 7.02 (dd, J = 2.5, 8.5 Hz, 1H), 6.20 (q, J = 7.0
Hz, 1H), 3.84 (s, 3H), 3.82 (s, 3H), 3.61-3.54 (m, 1H), 3.54
(dd, J = 7.0, 17.0 Hz, 1H), 3.30 (dd, J = 6.5, 17.0 Hz, 1H),
1.94 (d, J = 7.0 Hz, 3H), 1.33 (d, J = 7.0 Hz, 3H); 13C NMR
1
(M++1) 665.4781, found 665.4784; H NMR (500 MHz,
CDCl3) d 7.60 (dd, J = 2.0, 8.5 Hz, 1H), 7.51 (d, J = 2.0 Hz,
1H), 7.32 (d, J = 1.5 Hz, 1H), 7.26 (dd, J = 2.0, 8.5 Hz, 1H),
6.82 (d, J = 8.5 Hz, 1H), 6.79 (d, J = 8.5 Hz, 1H), 6.07 (q, J =
7.0 Hz, 1H), 4.06-4.01 (m, 4H), 3.90 (s, 6H), 3.61-3.55 (m,
1H), 3.44 (dd, J = 7.5, 17.0 Hz, 1H), 3.22 (dd, J = 7.0, 17.0
Hz, 1H), 1.92 (d, J = 7.0 Hz, 3H), 1.87-1.81 (m, 4H), 1.46-
1.42 (m, 4H), 1.39-1.21 (m, 27H), 0.88 (t, J = 7.0 Hz, 6H).
For compound 2h: HRMS (ESI) m/z calcd for C28H33O6
1
(M++1) 465.2277, found 465.2278; H NMR (500 MHz,
CDCl3) d 7.61 (dd, J = 2.0, 8.5 Hz, 1H), 7.52 (d, J = 2.0 Hz,
1H), 7.31 (d, J = 1.5 Hz, 1H), 7.28 (dd, J = 1.5, 8.5 Hz, 1H),
6.83 (d, J = 8.5 Hz, 1H), 6.81 (d, J = 8.5 Hz, 1H), 6.12-6.03
(m, 2H), 6.05 (q, J = 7.0 Hz, 1H), 5.45-5.39 (m, 2H), 5.31-

12 J. Chin. Chem. Soc., Vol. 55, No. 1, 2008
Chang et al.
5.28 (m, 2H), 4.64-4.61 (m, 4H), 3.90 (s, 6H), 3.58-3.53 (m,
1H), 3.43 (dd, J = 7.0, 16.5 Hz, 1H), 3.19 (dd, J = 7.0, 16.5
Hz, 1H), 1.91 (d, J = 7.0 Hz, 3H), 1.29 (d, J = 7.0 Hz, 3H);
13C NMR (125 MHz, CDCl3) d 198.59, 198.28, 153.47,
152.83, 147.71, 147.42, 144.04, 136.79, 132.83, 132.75,
131.65, 130.35, 124.73, 123.08, 118.41, 118.40, 113.81,
112.01, 110.19, 109.88, 69.67, 69.66, 55.97 (2x), 42.88,
29.71, 19.54, 13.79. For compound 2i: HRMS (ESI) m/z
(2x), 60.86 (2x), 56.20 (2x), 56.16 (2x), 42.90, 29.80, 19.67,
13.98. For compound 2k: HRMS (ESI) m/z calcd for
1
C22H23F2O4 (M++1) 389.1565, found 389.1566; H NMR
(500 MHz, CDCl3) d 7.75 (ddd, J = 1.0, 2.0, 8.5 Hz, 1H),
7.70 (dd, J = 2.0, 12.0 Hz, 1H), 7.46 (d, J = 10.0 Hz, 2H),
6.95 (d, J = 8.0 Hz, 1H), 6.92 (d, J = 8.0 Hz, 1H), 6.10 (q, J =
7.0 Hz, 1H), 3.93 (s, 6H), 3.58-3.52 (m, 1H), 3.44 (dd, J =
7.5, 17.0 Hz, 1H), 3.19 (dd, J = 6.5, 17.0 Hz, 1H), 1.94 (d, J =
7.0 Hz, 3H), 1.29 (d, J = 7.0 Hz, 3H); 13C NMR (125 MHz,
CDCl3) d 197.66, 197.12, 152.95, 151.79, 151.08, 150.59,
143.81, 137.87, 131.96, 130.58, 127.08, 125.54, 117.42,
115.72, 112.16, 111.96, 56.25, 56.24, 42.89, 29.50, 19.48,
13.92.
calcd for C36H37O6 (M++1) 565.2590, found 565.2593; H
1
NMR (500 MHz, CDCl3) d 7.62 (dd, J = 2.0, 8.5 Hz, 1H),
7.59 (d, J = 2.0 Hz, 1H), 7.47-7.43 (m, 4H), 7.38-7.28 (m,
8H), 6.85 (d, J = 8.5 Hz, 1H), 6.84 (d, J = 8.5 Hz, 1H), 5.95
(q, J = 7.0 Hz, 1H), 5.20-5.11 (m, 4H), 3.92 (s, 3H), 3.91 (s,
3H), 3.56-3.49 (m, 1H), 3.38 (dd, J = 7.5, 16.5 Hz, 1H), 3.16
(dd, J = 6.5, 16.5 Hz, 1H), 1.84 (d, J = 7.0 Hz, 3H), 1.27 (d, J
= 7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3) d 198.58,
198.21, 153.71, 153.06, 147.90, 147.46, 143.93, 136.72,
136.63, 136.56, 131.62, 130.34, 128.54 (2x), 128.52 (2x),
127.95, 127.92, 127.53 (2x), 127.38 (2x), 124.76, 123.23,
114.58, 112.58, 110.35, 110.15, 70.80, 70.76, 56.00 (2x),
42.86, 29.75, 19.53, 13.75. For compound 2j: HRMS (ESI)
m/z calcd for C26H33O8 (M++1) 473.2176, found 473.2180;
1H NMR (500 MHz, CDCl3) d 7.22 (s, 2H), 6.89 (s, 2H), 6.16
(q, J = 7.0 Hz, 1H), 3.89 (s, 6H), 3.88 (s, 6H), 3.87 (s, 3H),
3.84 (s, 3H), 3.60-3.53 (m, 2H), 3.18-3.12 (m, 1H), 1.95 (d, J
= 7.0 Hz, 3H), 1.34 (d, J = 7.0 Hz, 3H); 13C NMR (125 MHz,
CDCl3) d 198.89, 198.58, 152.94 (2x), 152.59 (2x), 143.95,
142.45, 141.51, 138.55, 134.32, 132.42, 107.16 (2x), 105.56
6.
7.
(a) Henry, G. D. Tetrahedron 2004, 60, 6043. (b) Jones, G. In
Comprehensive Heterocyclic Chemistry; Katritzky, A. R.,
Rees, C. W., Ed.; Pergamon: New York, 1984; Vol. 2, p 395.
(c) Katritzky, A. R.; Abdel-Fattah, A. A. A.; Tymoshenko,
D. O.; Essawy, S. A. Synthesis 1999, 2114. (d) Chiu, C. F.;
Tang, Z. L.; Ellingboe, J. W. J. Comb. Chem. 1999, 1, 1.
(a) Eun, J. K.; Ko, S. Y. Bioorg. Med. Chem. 2005, 13, 4103.
(b) Patra, A.; Batra, S.; Kundu, B.; Joshi, B. S.; Roy, R.;
Bhaduri, A. P. Synthesis 2001, 276. (c) Pontikis, R.; Dolle,
V.; Guillaumel, J.; Dechaux, E.; Note, R.; Nguyen, C. H.;
Legraverend, M.; Bisagni, E.; Aubertain, A.-M.; Grierson,
D. S.; Monneret, C. J. Med. Chem. 2000, 43, 1927. (d)
Kobayashi, J.; Sekiguchi, M.; Shigemori, H.; Ohsaki, A. J.
Nat. Prod. 2000, 63, 375.