Photolytic cleavage and condensation reactions of cyclohexa-2,4-dienones with diamines

Article abstract of DOI:10.3390/50700961

Cyclohexa-2,4-diene-1-one sulfone derivative undergoes ring cleavage to afford bis-amides containing a diene moiety on irradiation with visible light in the presence of various diamines.

Full text of DOI:10.3390/50700961

Molecules 2000, 5, 961-966
molecules
ISSN 1420-3049
© 2000 by MDPI
http://www.mdpi.org
Photolytic Cleavage and Condensation Reactions of
Cyclohexa-2,4-dienones with Diamines
Young Mee Kim1, Suk Jin Song1, Tae Woo Kwon1* and Sung Kee Chung2
1Department of Chemistry, Kyungsung University, Pusan 608-736, Korea
(ꢀPDLOꢁꢂWZNZRQ#VWDUꢃN\XQJVXQJꢃDFꢃNU
2Department of Chemistry, Pohang University of Science Technology, Pohang 790-784, Korea
Received: 29 April 2000 / Accepted: 29 June 2000 / Published: 23 July 2000
Abstract: Cyclohexa-2,4-diene-1-one sulfoneꢂ GHULYDWLYHꢂ XQGHUJRHVꢂ ULQJꢂ FOHDYDJHꢂ WRꢂ DIIRUG
bis-amidesꢂFRQWDLQLQJꢂDꢂdieneꢂmoietyꢂRQꢂLUUDGLDWLRQꢂZLWKꢂYLVLEOHꢂOLJKWꢂLQꢂWKHꢂSUHVHQFHꢂRIꢂYDULꢀ
RXVꢂdiamines.
Keywords: Fyclohexa-2,4-diene-1-one, diamines, ketene, photolytic cleavage.
Introduction
We previously reported that the photochemical ring cleavage of cyclohexa-2,4-dienones represents a
new and high yielding method for labeling the terminal amino functionality of amino acids and peptides
[1]. Since the pioneering work of Barton and Quinkert [2], it has been established that the cleavage of
cyclohexa-2,4-dien-1-ones by photolysis using UV light generates ketenes [3]. For the cleavage of the
dienones of type 1, it was found that UV light can be replaced by visible light, a highly desirable feature
for ketene generation in the presence of light sensitive chromophores in peptides or in DNA [4].
We have also shown that the photolysis of 1 in EtOH in the presence of amines resulted in the for-
mation of amides [5]. However, one drawback of the parent dienones 1 and 2 is their sensitivity to acid
and, resultant conversion to the aromatic compounds 4 and 5 [6] (Scheme 1). Oxidation of sulfone 3
obviated the stability problem. We have been interested in the synthesis of symmetrical bis-
cyclohexadienones of the type 6, in which two units of chromophores are linked via varying lengths of
carbon tether. These type of compounds may be envisaged as a molecular measuring rod for nucleo-
philic functionalities on a polypeptide or DNA fragment. The photolytic coupling reactions of 3 were
studied with dibasic functionality such as diamines, in order to test whether ketenes derived from 3
could react with diamines to produce symmetrical bis-amides without any problems such as polymeriza-
tion. Herein we wish to report the results of the photochemical coupling reactions (Scheme 2).

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Molecules 2000, 5
O
O
OH
O
CH2SCH3
CH2R
CH3
H3C
H3C
H3C
CH2R
O
CH3
CH3
O
CH2R'
(CH2)n
CH2R'
O
1. R=SCH3, R'=H
2. R=SCH3, R'=CO2H
3. R=SO2CH3, R'=H
H3C
4. R=H, R'=H
5. R=H, R'=CO2H
CH2SCH3
O
6
(Target Molecules)
Scheme 1.
Results and Discussion
The sulfone 3 was prepared by treating mesitol with Me2S-N-chlorosuccinimide followed by oxida-
tion using m-chloroperbenzoic acid [5, 7 and 8]. Photolysis of 3 with a tungsten lamp in the presence of
diamines afforded the corresponding bis (amide) products 8 from the reaction of two molecules of the
ketene from 3 in ethanol or ethanol-DMSO below 38oC and the results are summarized in Table 1.
The reactions were over within 5-8 hr and the major products (8) were obtained in 43-70%. Longer
reaction time did not increase the yields. The ring cleavage led to both cis and trans isomers which were
difficult to separate by flash column chromatography. A trace amount of terminal amine products (9;
n=2, 3, 4, 8 and 10) from monoacylation were also detected by TLC and compared with authentic sam-
ples (n=3) [7]. For the preparation of 8d and 8e, we carried out the reaction in EtOH/DMSO, which
provided enough solubility for the diamines.
Table 1. Photolysis of cyclohexa-2,4-dienone (3, 2.3 equiv.) in the presence of diamine (1equiv.).
Product (8)
Product
No.
Reaction
Time
Diaminesa
Solvent
EtOH
Rfb
n
2
Yielde
69%
1,2-Diaminoethane
1,3-Diaminopropane
5 hr
8 hr
0.26c
8a
8b
EtOH
EtOH
0.13d
0.12d
0.15d
0.17d
3
4
6
8
43%
61%
70%
47%
1,4-Diaminobutane
1,8-Diaminooctane
1,10-Diaminodecane
5 hr
5 hr
7 hr
8c
8d
8e
EtOH/DMSO
1:1
EtOH/DMSO
1:1
aDiamines were purchased from Aldrich and used without further purification. TLC plates were made
b
c
d
with E. Merck AB Darmstadt Silica gel 60 F254. 90% Et2O/10% MeOH. 95% Et2O / 5% MeOH.
eYields of isolated product based on 3 after flash column chromatography.

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Molecules 2000, 5
O
O
CH2 S CH3
H3C
O
3
CH3
CH3
hv
CH3
H3C
CH3
H3C
O
O
O C
H2N(CH2)nNH2
C O
CH3
S CH3
O
H3C
H3C S
O
7
H2N(CH2)nNH2
Visible light
CH3
H3C
O
O
CH3
H3C
O
C
O
C
S CH3
O
H3C
CH3
H3C S
O
HN(CH2)nNH
8
+
H3C
O
H3C
O
H3C S
O
C
9
H3C
HN(CH2)nNH2
Scheme 2.
Conclusion
In summary, photolytic cleavage and condensation reactions between sulfone 3 and various diamines
were found to yield the corresponding bis-amide products in moderate yields. These results augur well
for the potential utility of the symmetric bichromophoric cyclohexadienones (6) as molecular measuring
rods. Additional studies on the preparation and uses of 6 are in progress and results will be communi-
cated in due course.
Acknowledgments: Dedicated to the memory of Sir Derek H. R. Barton (deceased March 16th, 1998).
This research was supported by the Non Directed Research Fund, Korea Research Foundation (1998)
and the Kyungsung University Research Grants in 2000.

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Molecules 2000, 5
Experimental
General
A typical experimental procedure for the photolysis of 3 is as follows: A tungsten lamp (220 W) was
employed to irradiate 3 (345 mg, 1.51 mmole) in 5 mL of absolute ethyl alcohol in the presence of 1,2-
diaminoethane (39 mg, 0.66 mmole) under argon atmosphere. The solution was irradiated at a distance
of 2 cm and the temperature kept below 38ÛC with a water cooling bath. The reactions were monitored
by TLC. Irradiation was continued for 5 hr. The volatiles were removed in vacuo and the crude product
was diluted with 20 mL of CH2Cl2. The organic layer was washed with 10% HCl (2×10mL) and dried
over MgSO4, filtered and evaporated in vacuo. The residue was subjected to flash chromatography
(MeOH : Et2O = 5 : 95) over silica gel to give 8a (540 mg, 1.04 mmol, 69%) as an oil.
Spectral Data
7-Methanesulfonyl-2,4,6-trimethylhepta-3,5-dienoic acid [2-(7-methanesulfonyl-2,4,6-trimethylhepta-
3,5-dienoylamino)-ethyl]-amide, 8a
1H NMR (300 MHz, CDCl3) 6.75 (2H, two NH, broad t), 6.00 (2H, two =CH, s), 5.32-5.28 (2H,
two =CH, d, J=9.54 Hz), 3.76 (4H, two CH2SO2, s), 3.24 (4H, two NCH2, m), 3.03 (2H, two CHCO,
m), 2.97 (6H, two SO2CH3, s), 1.79 (6H, two CH3C=, s), 1.75 (6H, two CH3C=, s), 1.13 (6H, two
CH3-CH, d); IR (neat); 3392.3 (amide), 2980.2, 1644.0, 1540.3, 1448.4, 1380.1, 1297.6, 1131.6 cm-1
HRMS; m/z Calcd for C24H40N2O6S2; [M+H]+=517.3582 /Found 517.3578.
7-Methanesulfonyl-2,4,6-trimethylhepta-3,5-dienoic acid [3-(7-methanesulfonyl-2,4,6-trimethylhepta-
3,5-dienoylamino)-propyl]-amide, 8b
1H NMR (300 MHz, CDCl3) 6.63 (2H, two NH, broad t), 6.05 (2H, two =CH, s), 5.37-5.34 (2H,
two =CH, d, J=9.60 Hz), 3.78 (4H, two CH2SO2, s), 3.16 (4H, two NCH2, m), 3.03 (2H, two CHCO,
m), 2.94 (6H, two SO2CH3, s), 1.84 (6H, two CH3C=, s), 1.78 (6H, two CH3C=, s), 1.54 (4H, -CH2-,
m), 1.17 (6H, two CH3-CH, dd); IR (neat); 3390.4, 2975.1, 2933.6, 1646.9, 1540.1, 1448.4, 1378.8,
1297.0, 1131.6 cm-1 HRMS; m/z Calcd for C25H42N2O6S2; [M+H]+=531.3743 /Found 531.3735.
7-Methanesulfonyl-2,4,6-trimethylhepta-3,5-dienoic acid [4-(7-methanesulfonyl-2,4,6-trimethylhepta-
3,5-dienoylamino)-butyl]-amide, 8c
1H NMR (300 MHz, CDCl3) 6.43 (2H, two NH, broad t), 5.99 (2H, two =CH, s), 5.37-5.33 (2H,
two =CH, d, J=9.78 Hz), 3.77 (4H, two CH2SO2, s), 3.15 (4H, two NCH2, m), 3.14 (2H, two CHCO,
m), 2.99 (6H, two SO2CH3, s), 1.82 (6H, two CH3C=, s), 1.75 (6H, two CH3C=, s), 1.43 (4H, two -
CH2-, m), 1.16 (6H, two CH3-CH, d); IR (neat); 3375.4, 2977.0, 2933.9, 1648.9, 1542.6, 1448.2,
1378.4, 1299.6, 1128.3, 1097.5 cm-1 HRMS; m/z Calcd for C26H44N2O6S2; [M+H]+=545.3897 /Found
545.3871.

ꢀꢁꢅ
Molecules 2000, 5
7-Methanesulfonyl-2,4,6-trimethylhepta-3,5-dienoic acid [8-(7-methanesulfonyl-2,4,6-trimethylhepta-
3,5-dienoylamino)-octyl]-amide, 8d
1H NMR (300 MHz, CDCl3) 6.23 (2H, two NH, broad t), 5.96 (2H, two =CH, s), 5.35-5.32 (2H,
two =CH, d, J=9.68 Hz), 3.74 (4H, two CH2SO2, s), 3.10 (4H, two NCH2, m), 3.10 (2H, two CHCO,
m), 2.96 (6H, two SO2CH3, s), 1.79 (6H, two CH3C=, s), 1.73 (6H, two CH3C=, s), 1.38 (12H, -
(CH2)6-, m), 1.16, 1313 (6H, two CH3-CH, d, J=6.80 Hz); IR (neat); 3393.2, 2933.3, 2874.1, 1654.0,
1540.1, 1437.5, 1378.6, 1298.5, 1139.4cm-1 HRMS; m/z Calcd for C28H48N2O6S2; [M+H]+=573.4096/
Found 573.4075.
7-Methanesulfonyl-2,4,6-trimethylhepta-3,5-dienoic acid [10-(7-methanesulfonyl-2,4,6-trimethylhepta-
3,5-dienoylamino)-decyl]-amide, 8e
1H NMR (300 MHz, CDCl3) 6.16 (2H, two NH, broad t), 5.99 (2H, two =CH, s), 5.38-5.35 (2H,
two =CH, d, J=9.82 Hz), 3.74 (4H, two CH2SO2, s), 3.13 (4H, two NCH2, m), 3.05 (2H, two CHCO,
m), 2.98 (6H, two SO2CH3, s), 1.83 (6H, two CH3C=, s), 1.76 (6H, two CH3C=, s), 1.45 (4H, two -
CH2-, m), 1.24 (12H, -(CH2)6-, m), 1.19-1.16 (6H, two CH3-CH, d, J=6.81 Hz); IR (neat); 3295,
3368.4, 2930.2, 2856.0, 1649.7, 1540.8, 1448.3, 1375.3, 1301.0, 1132.6, 1083.2 cm-1 HRMS; m/z
Calcd for C32H56N2O6S2; [M+H]+=629.4837 /Found 629.4912.
(3,5-Dimethyl-3-methylsulfonylmethyl-4-oxo-cyclohexa-1,5-dienyl)-acetic acid, 2
Rf=0.18 (50% hexane/50% Ethyl acetate). 1H NMR (300 MHz, D2O/CDC3OD) 6.95 (1H, s), 6.01
(1H, s), 3.04 (2H, s, CH2C=O), 2.84 (1H, d), 2.61 (1H, d), 1.91 (3H, s, CH3-S), 1.75 (3H, s, CH3-C=),
1.08 (3H, s, CH3) ppm; IR(neat); 3650-2700, 1628, 1560, 1379, 1250 cm-1 HRMS; m/z Calcd for
C12H16O3S; [M+H]+=241.0609 /Found 241.0621.
(4-Hydroxy-3,5-dimethylphenyl)-acetic acid, 5
1H NMR (300 MHz, CDCl3) 6.85 (2H, s, Ar-H), 3.49 (2H, s, Ar- CH2-), 2.21 (6H, s, two CH3);
13CNMR (300 MHz, CDCl3) ; 178.10, 151.64, 129.61, 124.90, 123.42, 39.98, 15.59 ppm; IR(neat);
3440, 2997, 2970, 1680, 1290, 1189, 923 cm-1. mp = 145-147oC.
References and Notes
1. Barton, D. H. R.; Kwon, T. W.; Taylor, D. K.; Tajbakhsh, M. Bioorg. Med. Chem. 1995, 3, 79-84.
2. (a) Barton, D. H. R.; Quinkert, G. Proc. Chem. Soc. 1958, 197-198; (b) Barton, D.H.R.; Quinkert,
G. J. Chem. Soc. 1960, 1, 1-9.
3. (a) Quinkert, G. Angew. Chem. Int. Ed. Engl. 1975, 14, 790-802; (b) Quinkert, G. Angew. Chem.
Int. Ed. Engl. 1972, 11, 1072-1087; (c) Quinkert, G. Pure Appl. Chem. 1973, 33, 285-316.
4. Barton, D. H. R.; Chung, S. K.; Kwon, T. W. Tetrahedron Lett. 1996, 37, 3631-3634.
5. Barton, D. H. R.; Chung, S. K.; Kim, Y. M.; Kwon, T. W. Bioorg. Med. Chem. Lett. 1997, 7, 733-
738.
6. For example, saponification of dienone 10 with aqueous NaOH afforded the carboxylate salt quan-

ꢀꢁꢁ
Molecules 2000, 5
titatively. However, neutralization attempts with 10% aqueous HCl gave the phenol 5, although
compound 2 could be obtained by careful neutralization with NH4Cl;
O
CH2SCH3
CH3
H3C
(i) aq. NaOH
(ii) NH4Cl
(i) aq. NaOH
2
5
(ii) 10% aq. HCl
10
CH2CO2Et
7. Kim, Y. M.; Kwon, T. W.; Chung, S. K.; Barton, D. H. R. Bioorg. Med. Chem. Lett.ꢂ1999, 9,
1175-1178.
8. Katayama, S.; Watanabe, T.; Yamauchi, M. Chem. Pharm. Bull.ꢂ1993, 41, 439-444.
Sample Availability: Not available.
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