Synthesis, characterization, and intramolecular Diels-Alder reaction tandem dehydroaromatization of a diene-diyne

Article abstract of DOI:10.1246/cl.2005.938

5-(2-Methylthio-4-methyl-5-pyrimidinyl)-2,4-pentadiynyl sorbate 2 was synthesized and characterized. It had two conjugating systems, which made its 5J and 6J ¹H-¹³C correlating signals be obtained in gHMBC spectra. Intramolecular Diels-Alder reaction tandem dehydroaromatization of diene-diyne 2 under heating and irradiating resulted in formation of benzolactone. The reaction underwent the two steps: thermochemistry and photochemistry. The intermediate was confirmed using C₆₀ as an intermediate catcher. This reaction represents a rare example of intramolecular Diels-Alder reaction tandem dehydroaromatization of diene-diyne under mild conditions without catalyst and oxidant. Copyright

Full text of DOI:10.1246/cl.2005.938

9
38
Chemistry Letters Vol.34, No.7 (2005)
Synthesis, Characterization, and Intramolecular Diels–Alder Reaction Tandem
Dehydroaromatization of a Diene-diyne
ꢀ
y
yy
Shu-Zhi Liu, Guang-Shi Tang, Jing Wang, and Xue-Hua Li
The Key Laboratory of Science and Technology of Controllable Chemical Reactions, Ministry of Education,
Beijing University of Chemical Technology, Beijing 100029, P. R. China
y
Research Institute of Petroleum Processing, SINOPEC, Beijing 100083, P. R. China
Beijing Institute of Microchemistry Analytical Center, Beijing 100091, P. R. China
yy
(Received April 6, 2005; CL-050457)
5
-(2-Methylthio-4-methyl-5-pyrimidinyl)-2,4-pentadiynyl
sorbate 2 was synthesized and characterized. It had two conju-
THF
CH3CH=CHCH=CHCOOH + SOCl2
CH3CH=CHCH=CHCOCl + HOCH2C
CH3CH=CHCH=CHCOCl
N
reflux, 2h
1
13
gating systems, which made its 5J and 6J H– C correlating
signals be obtained in gHMBC spectra. Intramolecular Diels–
Alder reaction tandem dehydroaromatization of diene-diyne 2
under heating and irradiating resulted in formation of benzolac-
tone. The reaction underwent the two steps: thermochemistry
and photochemistry. The intermediate was confirmed using
C60 as an intermediate catcher. This reaction represents a rare
example of intramolecular Diels–Alder reaction tandem dehy-
droaromatization of diene-diyne under mild conditions without
catalyst and oxidant.
THF
C
C
C
SCH3
2
63 K
N
1
CH3
N
CH3CH=CHCH=CHCO2CH2C
C
C
C
SCH3
N
2
CH3
Scheme 1.
8.48
1.88
6.21 5.81
.21 7.33
N
N
O
2.568
C
C
C
C
S
6
4.91
O
1H NMR
2.571
Intramolecular Diels–Alder reactions were efficient meth-
ods for the synthesis of many polycyclic compounds. The meth-
odology was particularly effective for the construction of highly
166.23
1
59.71
171.68
140.72 117.39
29.65 146.65
N
18.77
81.24*
72.39
O
C
70.36
C
C
C
S 14.26
1
52.23
1
79.22*
N
strained bridgehead bicycle[3.n.1]alkenes and complex poly-
2
O
111.7
23.31
13C NMR
169.98
cyclic molecules. Cycloaromatization of (Z)-1,2,4-heptatrien-
6-ynes underwent mild thermal cyclization to form the biradical
Figure 1. Chemical shifts, peak assignments of 2 in 13C and
H NMR (CDCl3, TMS). The symbol ꢀ denots exchanging of
3
4
ꢀ
,3-didehydrotoluene, and some cycloaromatizations and
1
5
dehydroaromatizations were carried out under the efficient
catalysts or oxidants. For example, Shim et al. reported in-
tramolecular ionic Diels–Alder reaction of ꢀ-acetylenic acetals
under acid catalysts, and the cyclization product bicyclodienal
gave an aromatic compound by slow aromatization.
chemical shifts.
1
13
and H– C gHMBC spectra (Figure 1). Efforts to obtain a sin-
gle crystal suitable for an X-ray crystal structure had not as yet
been successful.
6
The intramolecular dehydro Diels–Alder reactions between
7
Diene-diyne 2 in chlorobenzene, when heated and irradiat-
ed, gave 311 as the sole product in 93% yield. A proposed mech-
anism of producing 3 was shown in Scheme 2. In order to con-
firm the proposed mechanism, a solution of 2 in chlorobenzene
was irradiated at room temperature for 3 days but failed to give
any 3, then the reaction solution was stirred at 398 K in the dark
for 48 h resulting in unobserved formation of 3. It showed that
neither heating in the absence of irradiating nor irradiating in
the absence of heating resulted in formation of 3. It suggested
that 3 is formed either by the dehydrogenation of intermediate
4 or by a stepwise pathway through 5 or 6 (Scheme 2). The three
medium-ring bicyclic lactones containing two bridgehead dou-
ble bonds were one of the more highly strained representatives
of this family of molecules. So they were instable, and none of
4, 5 and 6 were obtained by column chromatography.
To confirm the presence of the intermediates in the reaction,
C60, as an intermediate catcher with 1.1-fold excess, and 2 in
chlorobenzene was stirred at 398 K being exposed in room light
for several days, but the reaction gave only trace amounts of C60
derivative and 3 was isolated as the major product. In contrast,
reaction of C60 with 2 at 398 K in the dark for 48 h produced 7
in 2% yield and another C60 derivative 8 in 15% yield, and no
alkynes and arenynes had been well-reported as methods for the
synthesis of polycyclic aromatic compounds. These reactions
evolved to intermediate 1,2,4-cyclohexatrienes which formed
8
aromatic products by isomerization.
Herein, we reported a novel example of intramolecular
Diels–Alder cycloaddition that resulted in formation of a bicy-
cle[4.3.0]diene intermediate, a highly strained class of bridge-
head dienes, followed by dehydroaromatization of the intermedi-
ate leading to a benzolactone.
The diene-diyne precursor 2, 5-(2-methylthio-4-methyl-5-
pyrimidinyl)-2,4-pentadiynyl sorbate, was synthesized as out-
lined in Scheme 1. 5-(2-Methylthio-4-methyl-5-pyrimidinyl)-
9
2
,4-pentadiyn-1-ol 1 reacted with sorbyl chloride in anhydrous
1
1
0
1
THF and resulted in 37% yields of 2. The H– H gCOSY of 2
gave three correlating signals: ꢁ 1.875 coupling with ꢁ 6.21, ꢁ
7
.33 coupling with ꢁ 5.804 and ꢁ 6.21, respectively. Interesting-
ly, diene-diyne 2 had two conjugating systems, which made its
1
13
5
J and 6J H– C correlating signals obtained in gHMBC spec-
tra: ꢁ 1.875 coupling with ꢁ 117.39, ꢁ 4.910 coupling with ꢁ
2.39 and ꢁ 111.66 respectively. NMR signals of 2 were as-
7
1
1
1
13
signed on the basis of DEPT, H– H gCOSY, H– C gHSQC,
Copyright Ó 2005 The Chemical Society of Japan

Chemistry Letters Vol.34, No.7 (2005)
939
CH3
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O
O
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O
6
5
4
2
C60
[
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O
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N
N
N
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C
C
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9
7
3
4
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0 Synthesis of 2: To a stirred solution of 5-(2-methylthio-4-methyl-
Scheme 2.
was detected by TLC in the reaction mixture. Unfortunately,
1
3
the structure of 8 is not established for its poor NMR spectra.
However, the spectra of 8 suggests that it contains fragments
of 2 and C60 in 1:1 ratio. The isolation of 7 strongly suggested
that the aromatization of 2 occurred via cyclohexadiene 4 or 5.
The reaction conditions for formation of 7 showed that 2 under-
went a mild thermal cyclization to form 4 and 5 at 398 K without
irradiation, although no intermediate was obtained. Strangely, no
9 was isolated, albeit 6 is supposed to be more stable then 5 due
to the lack of bridgehead double bonds.
5
6
These results indicated that formation of 3 underwent the
two steps: thermochemistry and photochemistry. In the first step,
thermolysis of the diene-diyne 2 resulted in intramolecular
Diels–Alder reaction to form intermediates 4, 5, or 6. Then, pho-
todehydrogenation of 4, 5, or 6 produced benzolactone 3. The
conjugated aromatic diene-diyne system was in favor of absorb-
ing the light, and could lead to a lower barrier to cycloaromati-
zation of 2. This barrier may be further reduced by N and S
atoms with lone-pair electrons contributing to the p system.
This reaction was strongly influenced by temperature,
shown in the results as follows: 403 K (93%, 48 h), 398 K
7
8
9
1
(
84%, 48 h), 383 K (20%, 48 h), and at 339 K the product was
5
-pyrimidinyl)-2,4-pentadiyn-1-ol 1 (4.8 g, 22 mmol) in anhydrous
THF (50 mL) was added sorbyl chloride (4.0 g, 30.7 mmol) in THF
20 mL) dropwise over 10 min. The mixture was stirred for 6 h at
not obtained at all, even after a prolonged reaction time. The
reaction proved to be quite luminous sensitive, even under the
room light at 398 K, the reaction was carried out easily and gave
3 in modest yield (53%). And the reaction was not affected by
aerobic or anaerobic condition.
In conclusion, this reaction apparently represented a rare
example of intramolecular Diels–Alder reaction tandem dehy-
droaromatization of diene-diyne under mild conditions. Dehy-
droaromatization was accomplished simply by heating and
irradiating without catalyst and oxidant. Further investigation
of the reaction was in progress.
(
room temperature, then a solution KOH (2.24 g, 40 mmol) in
ꢂ
2
0 mL water was added dropwise slowly at ꢁ10 C, The cold bath
was removed and the solution warmed to room temperature. After
stirring for 12 h at room temperature, the mixture was poured into
water and filtered. The crude product was purified by column
chromatography on silica gel; elution with ethyl acetate–petrole-
um ether (1:6, Rf ¼ 0:6) afforded 2 (2.52 g, 8.08 mmol, 37%) as
a white solid.
1
1 Synthesis of 3: A solution of diene-diyne 2 (0.25 g) in chloroben-
zene (50 mL) was heated under gentle reflux with stirring and was
irradiated with a 500 W medium-pressure mercury UV-lamp for
48 h. The reaction mixture was then concentrated and purified by
column chromatography on silica gel. Elution with toluene–ethyl
We thank the National Foundation of Natural Science of
China for financial support. (No. 59902001).
acetate (8:1, Rf ¼ 0:48) gave 3 (0.23 g, 93%) as a white solid.
1
References and Notes
3: H NMR (CDCl3, TMS, 500 MHz) ꢁ 8.531 (s, 1H), 7.7955 (d,
1
a) K. J. Shea and S. Wise, J. Am. Chem. Soc., 100, 6519 (1978).
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P. D. Davis, J. W. Gilman, and A. C. Greeley, J. Am. Chem.
Soc., 104, 5708 (1982). d) K. J. Shea and L. D. Burke, J. Org.
J ¼ 8, 1H), 7.449 (d, J ¼ 8, 1H), 5.356 (s, 2H), 2.656 (s, 3H),
2.640 (s, 3H), 2.596 (s, 3H). 13C NMR (CS2, 125.6 MHz), ꢁ:
14.217, 20.925, 23.341, 69.210, 91.175, 92.751, 112.383,
117.163, 124.028, 125.527, 130.887, 146.692, 148.958, 158.416,
168.156, 170.394, 171.77.
Published on the web (Advance View) June 4, 2005; DOI 10.1246/cl.2005.938