6
96
M. Nagel, H.-J. Hansen
LETTER
4
(
6
(
sept, 1 H); 2.58 (s, 6 H); 2.30 (s, 6 H); 1.50 (d, J = 6.9 Hz,
(23) Data of selected azulenes: For 14, 33 and 34, see ref. . NMR
H). 13C NMR (75 MHz, CDCl ): 157.2, 142.6 (2 s), 139.7
data (standard conditions: 300/75.5 MHz, in CDCl /TMS):
1,4,6,8-Tetramethylazulene(23): (violet-blue cyrstals) H
3
3
1
d), 138.6, 130.2 (2 s), 111.7, 30.0 (2 d), 26.8, 23.9, 21.1 (3
+·
3
3
q). EI-MS: 226.0 (100, M ), 211.0 (65, M – 15).
NMR: 7.44 [d, J {H-C(3)} = 4 Hz, H-C(2)]; 7.24 [d, J {H-
C(2)} = 4 Hz, H-C(3)]; 6.86 [br s, H-C(5,7)]; 3.02 [s, CH3-
C(8)]; 2.81 [s, CH -C(4)]; 2.56 [br s, 6 H, CH -C(1), CH -
C(6)]. C NMR: 147.1 [C(8)], 145.7 [C(6)]; 144.9 [C(4)];
136.7 [C(3a)]; 136.5 [C(2)]; 132.9 [C(8a)]; 127.7 [C(7)];
(
16) (a) The well-established Ziegler–Hafner procedure, starting
from the corresponding trimethylpyrylium salt and sodium
cyclopentadienide, delivers optimized yields of 20 in the
order of 45–65%: Hafner, K.; Kaiser, H. Liebigs Ann. Chem.
3
3
3
1
3
1958, 618, 140. (b) cf. also: Org. Synth. Coll. Vol. V; J.
126.8 [C(1)]; 125,6 [C(5)]; 114.6 [C(3)]; 28.4 [CH -C(8)];
3
Wiley and Sons: New York, 1964, 1088–1091. (c) For
NMR data, see also: Braun, S.; Kinkeldei, J. Tetrahedron
27.7 [CH -C(6)]; 25.3 [CH -C(4)]; 19.7 [CH -C(1)]. EI-MS
3
3
3
+·
+·
(GC-MS): 184 (100, M ), 169 (85, [M – CH ] ). 2,4,6,8-
3
1
1977, 33, 1827–1832; and references therein.. (d) Cf.:
Tetramethylazulene (25): (blue-violet crystals) H NMR:
Matsubara, Y.; Takekuma, S.; Yokoi, K.; Yamamoto, H.;
Nozoe, T. Bull. Chem. Soc. Jpn. 1987, 60, 1415.
7.12 [s, H-C(1,3)]; 7.02 [s, H-C(5,7)]; 2.82 [s, H C-C(4,8)];
3
1
3
2.61, 2.598 [2 s, H C-C(6), H C-C(2)]. C NMR: 145.0,
3 3
(
e) Collins, M. J.; Sternhell, S.; Tansey, C. W. Aust. J.
144.0, 143.0, 136.5 [4 q, C(2,3a/8a,4/8,6)]; 127.2 [d, H-C(5/
7)]; 116.3 [d, H-C(5/7)]; 28.4 [q, H C-C(6)]; 24.8 [q, H C-
Chem. 1990, 43, 1541. (f) Fallahpour, R.-A.; Hansen, H.-J.
Helv. Chim. Acta 1995, 78, 1419.
3
3
C(4/8)]; 16.4 [q, H C-C(2)]. EI-MS (GC-MS): 184 (100,
3
+·
+·
(
17) Hafner's synthesis (cf. ref.16a) leads to badly separable
mixtures of 1,4,6,8- and 2,4,6,8-tetramethylazulene (23, and
M ), 169 (65, [M – CH ] ). 2-Ethyl-4,6,8-trimethylazulene
(28): H NMR (taken from the 1:1 mixture with known 27):
3
1
2
5, respectively): Anderson, A. G.; Anderson, R. G.;
7.12 [s, H-C(1,3)]; 6.99 [(H-C(5,7)]; 3.03 [q, J = 7.4 Hz,
Me-CH -C(2)]; 2.81 [s, CH -C(4,8)]; 2.60 [s, CH -C(6)];
5
c
Hollander, G. T. J. Org. Chem. 1965, 30, 131; cf. also ref. .
18) For further literature, including spectroscopic
2
3
3
(
1.32 [t, J = 7.4 Hz, CH -CH -C(2)]. EI-MS (GC-MS): 198
3
2
+
+
characterizations, see: (a) Chen, Y.; Kunz, R. W.; Uebelhart,
P.; Weber, R. H.; Hansen, H.-J. Helv. Chim. Acta 1992, 75,
(100, M ), 183 (75, [M – CH ] ). 1-Ethyl-4,6,8-
3
1
3
trimethylazulene (30): H NMR: 7.52 [d, J = 4 Hz, H-C(2)];
7.28 [d, J = 4 Hz, H-C(3)]; 6.86 [br s, H-C(5,7)]; 3.25 (q, J
= 7.4 Hz, H CCH ); 2.98, 2.80, 2.53 (3 s, 3 CH ); 1.36 (t, J
2447. (b) Fallahpour, R. A.; Hansen, H.-J. Helv. Chim. Acta
1992, 75, 2210. (c) Rippert, A. J. Ph. D. Thesis; University
2
3
3
1
3
of Zürich: Switzerland, 1994.
= 7.4 Hz, H CCH ). C NMR: 146.7, 145.6, 144.9, 136.8
2 3
(
(
19) Cf. ref.1g and references cited therein.
(4s, arom C); 134,6 [d, H-C(2)]; 133.8 132.0 (2 s, arom. C);
20) For the preparation of pyrrolidine enamines from aminals
cf.: (a) Mannich, G.; Davidsen, H. Ber. Deutsch. Chem. Ges.
128.1, 125.9, 115.1 (3 d, H-C); 28.4, 27.5, 25.5 (3 q, CH );
3
25.3 (t, CH CH ); 17.1 (q, CH ). EI-MS (GC-MS): 198 (35,
2
3
3
+
·
+·
1936, 69, 2106. (b) Opitz, G.; Hellmann, H.; Schubert, H.
M ), 183 (100, [M – CH ] ). 1-Isopropyl-4,6,8-
trimethylazulene (32): (blue oil) H NMR: 7.69 [d, J = 4.2
3
1
W. Liebigs Ann. Chem. 1959, 623, 112. (c) Igarashi, M.;
Tada, M. J. Heterocyclic Chem. 1995, 32, 807; and
references therein. (d) In situ aminal thermolysis (general
method): Finely powdered, dry K CO (1.2–2 mol equiv)
Hz, H-C(2)]; 7.33 [d, J = 4.2 Hz, H-C(3)]; 6.98, 6.88 [2 s, H-
C(5), H-C(7)]; 3.91 [sept, J = 6.7 Hz, H-C(CH ) ]; 3.03,
3
2
2.82, 2.54 (3 s, 3 CH ); 1.38 [d, J = 6.7 Hz, H-C(CH ) ]. 13C
2
3
3
3 2
was suspended in toluene, and pyrrolidine (2 mol equiv) was
added. The aldehyde (1 mol equiv) was added with stirring
at 0–5 °C and the suspension stirred for 12 h at r.t. (inert gas
atmosphere). After filtration (or centrifugation) the slightly
yellowish ‘aminal solutions’ were used without further
purification. The cyclohepta[b]furan-2(2H)-ones 12 were
dissolved in TEGDME (or NMP or toluene, respectively)
and heated with stirring together with about 5–7 mol equiv
of the ‘aminal solution’ to 120–140 °C in a stainless steel
autoclave or Schlenk flask, respectively. Within 12–36 h the
mixture changed the color from yellow to reddish brown and
NMR: 146.2, 145.3, 144.8, 139.2, 136.7 (5 s), 131.8 (d),
130.9 (s); 128.5, 126.0, 115.5 (3 d, arom C-H); 28.5 [d, H-
C(CH ) ]; 28.3, 28.1, 26.0, 25.9, 25.6 (5 q, CH ). EI-MS
3
2
3
+
·
+·
(GC-MS): 212 (25, M ), (100, [M – CH ] ). 4,5,7,8-
3
1
Tetramethylazulene (36) (blue oil): H NMR: 7.70 [t, J = 4.0
Hz, H-C(2)]; 7.66 [s, H-C(6)]; 7.39 [d, J = 4.0 Hz, H-C(1,3)];
1
3
2.83 (s, 2 CH ); 2.60 (s, 2 CH ). C NMR: 144.8 [s,
3
3
C(3a,8a)]; 141,3 [d, H-C(6)]; 138.4 [s, C(4,8)]; 133.3 [d, H-
C(2)]; 130,2 [s, C(5,7)]; 114.2 [d, H-C(1,3)]; 26.8, 21.4 (2
+
·
+·
q). EI-MS (GC-MS): 184 (100, M ), 169 (85, [M – CH ] ).
3
1
1,4,5,7,8-Pentamethylazulene (37): H NMR: 7.60 [d, J =
finally to violet with a slight evolution of gas (CO ). The
4.1 Hz, H-C(2)]; 7.37 [d, J = 4.1 Hz, H-C(3)]; 2.79, 2.60,
2
1
3
formation of the azulenes was monitored by TLC analyses
after acidic work-up of aliquot parts of the product mixture.
Finally, the mixtures were poured in diluted HCl solution
2.54 (3 s, CH ); 2.33 (s, 2 CH ). C NMR: 146.6, 143.8 [2
3
3
q, C(3a), C(8a)]; 140.8 [d, H-C(6)]; 140.0 (q, arom C); 138.1
[d, H-C(2)]; 136.5, 134.7, 130.0, 128.9 (4 q, arom C), 114.1
(pH ca. 4–5) and the organic phase dissolved in hexane. The
[d, H-C(3)]; 27.2, 26.4, 23.1, 21.4, 20.5 (5 q, CH ). 1-
3
intensely blue-green to red-violet colored organic layers
were washed several times with diluted HCl solutions and
brine, and filtered through a pad of silica gel or alox. The
Isopropyl-4,5,7,8-tetramethylazulene (38): (dark blue oil)
H NMR: 7.72 [d, J = 4.4 Hz, H-C(2)]; 7.44 [s, H-C(6)]; 7.27
1
[d, J = 4.4 Hz, H-C(3)]; 3.80 [sept, J = 6.9 Hz, H-C(CH ) ];
3
2
now blue or violet organic phases were dried (NaSO ) and
2.83, 2.76 (2 s, CH ); 2.51 (s, 2 CH ); 1.37 [d, J = 6.7 Hz, H-
4
3
3
+·
the solvent removed. The azulenes were subsequently
purified by column chromatography on alox (basic, act. IV)
or on silica gel with hexane as eluent.
C(CH ) ]. EI-MS (GC-MS): 226 (30, M ), 211 (100, [M –
3
·
2
+
1f
CH ] ). 4,5,6,7,8-Pentamethylazulene (40) (blue crystals):
3
1
H NMR: 7.56 [t, J = 4.3 Hz, H-C(2)]; 7.25 [d, J ~ 4 Hz, H-
(21) (a) Hafner, K. Angew. Chem. 1958, 70, 419. (b) Hafner, K.;
Stephan, A.; Bernhard, C. Liebigs Ann. Chem. 1961, 650,
C(1,3)]; 2.84 (br s, 6 H, 2 CH ); 2.52 (s, 3 H, CH ); 2.47 (s,
6 H, 2 CH3). C NMR: 145.3, 144.4, 137.6 (3 s); 132.1 [d,
3
3
1
3
4
2. (c) Hafner, K.; Stephan, A.; Bernhard, C. Liebigs Ann.
C(2)]; 130.5 (s); 113.9 [d, C(1,3)]; 24.5, 22.7, 22.5 (3 q).
1,4,5,6,7,8-Hexamethylazulene (39): (blue-violet oil) H
1
Chem. 1961, 650, 62.
(
22) For azulene formation from 12e by cycloaddition with itself
or with other cyclohepta[b]furan-2(2H)-ones such as 12a or
NMR: 7.20 [d, J = 3.9 Hz, H-C(2)]; 6.99 [d, J = 3.9 Hz, H-
C(3)]; 2.75, 2.70, 2.68, 2.37 (4 s, 4 CH ); 2.33 (br s, 2 CH ).
3
3
1
2c, see ref.1f
Synlett 2002, No. 5, 692–696 ISSN 0936-5214 © Thieme Stuttgart · New York