Connecting metalation and intramolecular inverse Diels-Alder strategies of 1,2,4-triazines: A short and efficient synthesis of 1-azafluorenones

Article abstract of DOI:10.1055/s-2001-17524

A short high yield synthesis of polysubstituted l-azafluorenones from 1,2,4-triazines using the metalation and intramolecular Diels-Alder reaction is described.

Full text of DOI:10.1055/s-2001-17524

1800
PAPER
Connecting Metalation and Intramolecular Inverse Diels–Alder Strategies of
1,2,4-Triazines: A Short and Efficient Synthesis of 1-Azafluorenones
Intramolecular
D
h
iels–Alder
o
S
trategie
s
of
m
1,2,4-Triazines. Sy
a
nthesis of
1
s
-AzafluorenonesHundsdorf, Hans Neunhoeffer*
Darmstadt University of Technology, Institute of Organic Chemistry, Petersenstrasse 22, 64287 Darmstadt, Germany
Fax +49(6151) 163278; E-mail: di88@hrzpub.tu-darmstadt.de
Received 30 April 2001; revised 6 July 2001
Abstract: A short high yield synthesis of polysubstituted 1-azaflu-
orenones from 1,2,4-triazines using the metalation and intramolec-
ular Diels–Alder reaction is described.
Key words: 1,2,4-triazines, p-deficient heterocycles, 1-azafluo-
renones, metalations, intramolecular Diels–Alder reactions
Studies aimed to establish synthetic links between metala-
tion strategies and other prominent methods, e.g., transi-
tion metal catalyzed cross-coupling reactions1 and olefin
metathesis,2 have been reported both in the field of carbo-
and heteroaromatics for the construction of a variety of
bioactive substances.3,4 In the chemistry of p-deficient
heterocycles, metalation5 and inverse Diels–Alder
strategies6,7 are undoubtedly of high synthetic value. Sur-
prisingly, no investigations have been undertaken to de-
velop synthetic connections of the metalation and
intramolecular inverse Diels–Alder reactions.
Based on our work on 1,2,4-triazines,8,9 we reasoned that
a synthetic link of metalation reactions to the intramolec-
ular inverse Diels–Alder strategy may open a short path-
way for the synthesis of condensed heterocyclic systems.
In view of the natural occurrence and the biological activ-
ity of various fluorenones,10,11 the azafluorenone system
appeared an useful target for application of this concept.
Starting from metalation of 1,2,4-triazines, we developed
a short and efficient synthesis, which represents a practi-
cal synthetic protocol for polysubstituted 1-azafluo-
renones.
Scheme
In a typical procedure, the 1,2,4-triazines 1 (1a,14 1b15),
when subjected to standard metalation with LiTMP at
–100 °C, followed by the addition of several 2-bromoben-
Diels–Alder precursors 5, and final products 7 of this
zaldehydes 2, afforded the benzylalcohols 3 (60–83%
yield). Oxidation of 3 using MnO2 in THF furnished the
ketones 4 (69–94% yield). Subsequent Sonogashira
coupling12 of 4 under PdCl2(PPh3)2–CuI catalyzed condi-
tions led to 5, which upon intramolecular Diels–Alder re-
action in triisopropylbenzene (TIPB) gave the 4-
trimethylsilyl-1-azafluorenones 6 in high yields (81–
89%). Desilylation of 6 under TBAF-conditions resulted
in the 1-azafluorenones 7 in excellent overall yields of
31–37%. The metalation products (benzylalcohols 3),
route are summarized in the Table.
To the best of our knowledge, there are only a few previ-
ous reports13 on 1-azafluorenone syntheses. However,
these methods need hard reaction conditions (KMnO4, hot
aqueous KOH;13a-e I2O5, hot aqueous KOH13f). As report-
ed herein, our concept illustrates a new methodology for
1-azafluorenone ring formation, which, by virtue of its
high overall yields, may complement and (or) supersede
those classical methods.
In summary, a new and efficient synthetic route for the
construction of 1-azafluorenones, based on metalation
and intramolecular Diels–Alder reactions of 1,2,4-tria-
zines has been developed. This procedure allows access to
substituted systems, which are difficult to prepare by clas-
Synthesis 2001, No. 12, 25 09 2001. Article Identifier:
1437-210X,E;2001,0,12,1800,1805,ftx,en;T03001ss.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

PAPER
Intramolecular Diels–Alder Strategies of 1,2,4-Triazines: Synthesis of 1-Azaflourenones
1801
Table Metalation Products 3, Intramolecular Inverse Diels–Alder Precursors 5, and Final Products 7
Entry 1,2,4-Triazine
Benzylalcohol
Alkyne
1-Azafluorenone
Overall Yield
(%)
1
36
1a14
7a
7b
7c
3a
5a
2
37
31
1b15
3b
5b
3
1b15
5c
3c
4
31
1b15
7d
3d
5d
with concd HCl–MeOH–THF (1:1:4) (4.5 mL), and allowed to
warm to r.t. Saturated NaHCO3 was added until pH 8, the organic
solvent was removed under vacuum (40 °C), and the remaining so-
lution extracted with CH2Cl2 (3 ¥ 30 mL). The organic layer was
dried (MgSO4), the solvent removed under vacuum, and the crude
residue purified as specified below.
sical approaches. Further investigations on the synthesis
of 2-azafluorenones are in progress and will be reported in
due course.
Metalation experiments were carried out under Ar in THF, which
was freshly distilled from sodium benzophenone ketyl under Ar pri-
or to use. Solvents used in all other experiments (oxidation, Sono-
gashira coupling, Diels–Alder reaction, desilylation) were dried
over molecular sieves. IR spectra were obtained on a Nicolet impact
3-(2-Bromo-a-hydroxybenzyl)-5,6-diphenyl-1,2,4-triazine (3a)
tA = 3.5 min; column chromatography (cyclohexane–EtOAc, 2:1);
light yellow crystals; yield: 60%.
1
400 spectrometer. H and 13C NMR spectra were recorded on a
Mp 118 °C.
Bruker AC-300 or ARX-300 spectrometer. MS were determined on
a Varian 212 instrument at 70 eV. Elemental analysis were obtained
on a Perkin-Elmer CHN 240 A or 240 B.
IR (KBr): 3206, 3058, 2926, 1505, 1449, 1388, 1016, 756,
700 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.20 (s, 1 H, OH), 6.56 (s, 1 H,
CH-OH), 7.11 (m, 1 H, Ph), 7.32 (m, 7 H, Ph), 7.51 (m, 6 H, Ph).
13C NMR (75.4 MHz, CDCl3): d = 74.12, 123.87, 127.84, 128.68,
128.82, 129.31, 129.60, 129.80, 130.02, 130.14, 131.34, 133.26,
135.02, 135.14, 140.26, 156.26, 156.77, 165.64.
EIMS: m/z (%) = 419 (M+, 1; 81Br), 417 (M+, 1; 79Br), 338 (73), 178
(100), 152 (9), 77 (9).
3-(2-Bromo-a-hydroxybenzyl)-1,2,4-triazines 3; General
Procedure
To cooled (–60 °C) THF (40 mL) were added 2,2,6,6-tetramethylpi-
peridine (TMPH) (0.80 mL, 4.7 mmol) and 2.5 M n-BuLi solution
(1.60 mL, 4.0 mmol). The mixture was allowed to warm to r.t.,
stirred for 30 min, and cooled to –100 °C. The 1,2,4-triazine 114,15
(1.0 mmol) in THF (5 mL) was added in portions while keeping the
internal temperature below –95 °C. After 3–10 min (accumulation
time; tA), 2-bromobenzaldehyde 2 (4.0 mmol) was added and the so-
lution was stirred for 60 min (T £ –95 °C). The mixture was treated
Anal. Calcd for C22H16BrN3O: C, 63.17; H, 3.86; N, 10.05. Found:
C, 63.43; H, 3.95; N, 9.97.
Synthesis 2001, No. 12, 1800–1805 ISSN 0039-7881 © Thieme Stuttgart · New York

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T. Hundsdorf, H. Neunhoeffer
PAPER
3-(2-Bromo-a-hydroxybenzyl)-5,6-dimethoxy-1,2,4-triazine
(3b)
3-(2-Bromobenzoyl)-5,6-diphenyl-1,2,4-triazine (4a)
Column chromatography (cyclohexane–EtOAc, 2:1); light yellow
tA = 10 min; column chromatography (cyclohexane–EtOAc, 1:1);
colorless crystals; yield: 83%.
crystals; yield: 93%.
Mp 165 °C.
Mp 88–89 °C.
IR (KBr): 3078, 3058, 1709, 1495, 1439, 1368, 1286, 1205, 1093,
1006, 853, 761, 751, 700 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.35 (m, 8 H, Ar-H), 7.58 (m, 5
H, Ar-H), 7.62 (m, 1 H, Ar-H).
EIMS: m/z (%) = 417 (M+, 1; 81Br), 415 (M+, 1; 79Br), 336 (90), 178
(100), 155 (14), 76 (13).
IR (KBr): 3267, 3030, 2956, 2921, 1551, 1510, 1403, 1255, 1011,
746, 593 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.93 (s, 3 H, OMe), 4.08 (s, 3 H,
OMe), 4.45 (s, 1 H, OH), 6.22 (s, 1 H, CH-OH), 7.07 (m, 1 H, Ar-
H), 7.22 (m, 1 H, Ar-H), 7.39 (m, 1 H, Ar-H), 7.49 (m, 1 H, Ar-H).
13C NMR (75.4 MHz, CDCl3): d = 55.10, 55.54, 73.36, 123.77,
127.69, 128.85, 129.53, 132.97, 140.47, 154.55, 155.23, 161.57.
Anal. Calcd for C22H14BrN3O: C, 63.48; H, 3.39; N 10.09. Found:
C, 63.44; H, 3.33; N, 10.04.
FDMS: m/z (%) = 328 (M+ +1, 43; 81Br), 326 (M+ +1, 37; 79Br), 246
(100), 43 (16).
3-(2-Bromobenzoyl)-5,6-dimethoxy-1,2,4-triazine (4b)
Column chromatography (cyclohexane–EtOAc, 1:1); colorless
crystals; yield: 77%.
Anal. Calcd for C12H12BrN3O3: C, 44.19; H, 3.71; N, 12.88. Found:
C, 44.16; H, 3.72; N, 12.81.
Mp 147–148 °C.
3-(2-Bromo-a-hydroxy-4,5-dimethoxybenzyl)-5,6-dimethoxy-
1,2,4-triazine (3c)
tA = 10 min; column chromatography (cyclohexane–EtOAc, 1:2);
colorless crystals; yield: 68%.
IR (KBr): 3027, 2966, 1704, 1576, 1546, 1500, 1408, 1377, 1265,
1214, 991, 889, 766, 700, 624 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.15 (s, 3H, OMe), 4.17 (s, 3H,
OMe), 7.34 (m, 2H, Ar-H), 7.52 (m, 2H, Ar-H).
EIMS: m/z (%) = 324 (M+–1, 1; 81Br), 322 (M+–1, 1; 79Br), 244
(100), 201 (15), 185 (65), 183 (64), 159 (54), 157 (59), 155 (60),
144 (16), 86 (22), 76 (54), 75 (52), 50 (39), 43 (41).
Mp 102 °C.
IR (KBr): 3420, 3007, 2951, 2849, 1551, 1500, 1403, 1266, 1159,
1026, 991, 731, 594 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.75 (s, 3 H, OMe), 3.80 (s, 3 H,
OMe), 3.97 (s, 3 H, OMe), 4.09 (s, 3 H, OMe), 4.52 (s, 1 H, OH),
6.14 (s, 1 H, CH-OH), 6.93 (s, 1 H, Ar-H), 6.95 (s, 1 H, Ar-H).
Anal. Calcd for C12H10BrN3O3: C, 44.47; H, 3.11; N, 12.96. Found:
C, 44.24; H, 3.12; N, 12.78.
13C NMR (75.4 MHz, CDCl3): d = 55.19, 55.57, 56.12, 56.24,
73.13, 110.78, 113.70, 115.33, 132.23, 148.76, 149.32, 154.53,
155.38, 161.80.
3-(2-Bromo-4,5-dimethoxybenzoyl)-5,6-dimethoxy-1,2,4-
triazine (4c)
Column chromatography (cyclohexane–EtOAc, 1:2); yellow crys-
tals; yield: 94%.
EIMS: m/z (%) = 387 (M+, 1; 81Br), 385 (M+, 1; 79Br), 306 (100),
274 (13), 168 (22), 140 (17).
Mp 173–174 °C.
Anal. Calcd for C14H16BrN3O5: C, 43.54; H, 4.18; N, 10.88. Found:
C, 43.50; H, 4.04; N, 11.13.
IR (KBr): 3058, 3002, 2966, 2839, 1688, 1602, 1571, 1546, 1510,
1403, 1398, 1261, 1204, 1174, 1026, 991, 853, 777, 619 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.85 (s, 3 H, OMe), 3.87 (s, 3 H,
OMe), 4.14 (s, 3 H, OMe), 4.18 (s, 3 H, OMe), 6.97 (s, 1 H, Ar-H),
7.14 (s, 1 H, Ar-H).
EIMS: m/z (%) = 386 (M++1, 1; 81Br), 384 (M++1, 1; 79Br), 304
(100), 243 (12), 204 (13).
3-(2-Bromo-a-hydroxy-4,5-methylenedioxybenzyl)-5,6-
dimethoxy-1,2,4-triazine (3d)
tA = 5 min; 6-bromopiperonal (4.5 mmol); column chromatography
(cyclohexane–EtOAc, 1:1); colorless crystals; yield: 71%.
Mp 130–131 °C.
Anal. Calcd for C14H14BrN3O5: C, 43.77; H, 3.67; N 10.94. Found:
C, 43.96; H, 3.74; N, 10.95.
IR (KBr): 3414, 3007, 2956, 2905, 1551, 1499, 1480, 1398, 1235,
1113, 1037, 934, 843, 568 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.03 (s, 3 H, OMe), 4.16 (s, 3 H,
3-(2-Bromo-4,5-methylenedioxybenzoyl)-5,6-dimethoxy-1,2,4-
triazine (4d)
2
OMe), 4.33 (s, 1 H, OH), 5.95 (d, 2 H, J = 1.3 Hz), 6.22 (s, 1 H,
CH-OH), 6.92 (s, 1 H, Ar-H), 7.01 (s, 1 H, Ar-H).
Column chromatography (cyclohexane–EtOAc, 1:1); colorless
crystals; yield: 69%.
13C NMR (75.4 MHz, CDCl3): d = 55.10, 55.54, 73.20, 101.92,
108.33, 112.68, 114.39, 133.73, 147.76, 148.23, 154.59, 155.37,
161.68.
Mp 147–148 °C.
IR (KBr): 3053, 3007, 2956, 2910, 1688, 1617, 1545, 1505, 1480,
1398, 1250, 1133, 1031, 1001, 863, 782, 588 cm–1.
FDMS: m/z (%) = 371 (M+, 90; 81Br), 369 (M+, 100; 79Br).
Anal. Calcd for C13H12BrN3O5: C, 42.19; H, 3.27; N, 11.35. Found:
C, 42.39; H, 3.35; N, 11.09.
1H NMR (300 MHz, CDCl3): d = 4.14 (s, 3 H, OMe), 4.18 (s, 3 H,
OMe), 5.99 (s, 2 H, O-CH2-O), 6.97 (s, 1 H, Ar-H), 7.03 (s, 1 H,
Ar-H).
3-(2-Bromobenzoyl)-1,2,4-triazines 4; General Procedure
To a solution of 3 (0.5 mmol) in THF (20 mL) was added MnO2
(0.87 g, 10.0 mmol), and the suspension was stirred at r.t. for 5 h.
The mixture was filtrated, the solvent evaporated under vacuum,
and the crude residue was purified as specified below.
FDMS: m/z (%) = 369 (M+, 72; 81Br), 367 (M+, 100; 79Br), 144 (12).
Anal. Calcd for C13H10BrN3O5: C, 42.42; H, 2.74; N, 11.41. Found:
C, 42.42; H, 2.79; N, 11.60.
3-[2-(Trimethylsilylethynyl)-benzoyl]-1,2,4-triazines 5;
General Procedure
To a solution of 4 (0.25 mmol) in DMF (2.0 mL) and Et3N (2.0 mL)
were added CuI (2.0 mg, 11 mmol) and PdCl2(PPh3)2 (7.0 mg, 10
Synthesis 2001, No. 12, 1800–1805 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Intramolecular Diels–Alder Strategies of 1,2,4-Triazines: Synthesis of 1-Azaflourenones
1803
mmol), and the solution was stirred for 20 min at r.t. Then, trimethyl-
silylacetylene (70 mL, 0.50 mmol) was added, and the mixture
stirred for 3–7 h (TLC control) at r.t. H2O (10 mL) and Et2O (10
mL) were added, and the reaction mixture was extracted with
CH2Cl2 (3 ¥ 20 mL). The organic layers were separated, dried
(MgSO4), and purified as specified below to afford 5.
EIMS: m/z (%) = 385 (M+, 100), 370 (82), 354 (100), 342 (67), 311
(15), 288 (50), 256 (17), 245 (36), 231 (16), 187 (20), 115 (37), 89
(18), 73 (35), 43 (41).
HRMS: m/z calcd. for C18H19N3O5Si: 385.1094. Found: 385.1139.
4-Trimethylsilyl-1-azafluorenones 6; General Procedure
A solution of the alkyne 5 (0.15 mmol) in triisopropylbenzene
(TIPB) (3 mL) was heated until the reaction was complete (TLC
control). The mixture was cooled, the solvent removed under high
vacuum (0.1 mbar), and the crude residue purified as specified be-
low.
5,6-Diphenyl-3-[2-(trimethylsilylethynyl)-benzoyl]-1,2,4-
triazine (5a)
Column chromatography (cyclohexane–EtOAc, 2:1); yellow crys-
tals; yield: 82%.
Mp 138–139 °C.
2,3-Diphenyl-4-trimethylsilyl-1-azafluorenone (6a)
The mixture was heated to 140 °C (1 h); column chromatography
(cyclohexane–EtOAc, 2:1); yellow crystals; yield: 83%.
IR (KBr): 3058, 2961, 2895, 2157, 1688, 1602, 1495, 1454, 1378,
1250, 1199, 1011, 879, 843, 777, 711 cm–1.
1H NMR (300 MHz, CDCl3): d = –0.15 (s, 9 H, SiMe3), 7.37 (m, 9
H, Ar-H), 7.57 (m, 4 H, Ar-H), 7.76 (m, 1 H, Ar-H).
Mp 220–221 °C.
IR (KBr): 3063, 3053, 2951, 1724, 1607, 1546, 1347, 1255, 1184,
970, 869, 762, 716 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.00 (s, 9 H, SiMe3), 7.14 (m, 10
H, Ar-H), 7.30 (m, 1 H, Ar-H), 7.49 (m, 1 H, Ar-H), 7.63 (m, 1 H,
Ar-H), 7.72 (m, 1 H, Ar-H).
13C NMR (75.4 MHz, CDCl3): d = 1.36, 124.59, 126.19, 127.46,
127.53, 128.09, 128.16, 129.41, 129.98, 131.33, 133.37, 134.66,
139.92, 141.09, 143.93, 145.14, 145.75, 145.92, 150.79, 157.87,
192.89.
EIMS: m/z (%) = 433 (M+, 21), 405 (40), 390 (24), 336 (10), 201
(10), 178 (100), 73 (16).
HRMS: m/z calcd. for C27H23N3OSi: 433.1610. Found: 433.1644.
5,6-Dimethoxy-3-[2-(trimethylsilylethynyl)-benzoyl]-1,2,4-
triazine (5b)
Column chromatography (cyclohexane–EtOAc, 1:1); colorless
crystals; yield: 85%.
Mp 104–105 °C.
EIMS: m/z (%) = 405 (M+, 88), 390 (99), 332 (36), 178 (48), 73
(100), 45 (28).
IR (KBr): 3073, 3012, 2956, 2895, 2162, 1693, 1545, 1500, 1403,
1255, 996, 909, 843, 767, 619 cm–1.
Anal. Calcd for C27H23NOSi: C, 79.96; H, 5.72; N, 3.45. Found: C,
79.77; H, 5.84; N, 3.25.
1H NMR (300 MHz, CDCl3): d = –0.07 (s, 9 H, SiMe3), 4.24 (s, 3
H, OMe), 4.29 (s, 3 H, OMe), 7.50 (m, 3 H, Ar-H), 7.76 (m, 1 H,
Ar-H).
EIMS: m/z (%) = 341 (M+, 72), 326 (91), 310 (100), 298 (61), 244
(51), 201 (36), 187 (33), 143 (57), 89 (39), 73 (27), 43 (61).
2,3-Dimethoxy-4-trimethylsilyl-1-azafluorenone (6b)
The mixture was heated to 170 °C (1.5 h); column chromatography
(cyclohexane–EtOAc, 5:1); light orange crystals; yield: 83%.
HRMS: m/z calcd. for C17H19N3O3Si: 341.1196. Found: 341.1188.
Mp 131–132 °C.
IR (KBr): 3084, 3017, 2982, 2946, 2900, 1724, 1608, 1520, 1459,
1383, 1347, 1266, 1123, 1001, 853, 772, 731 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.44 (s, 9 H, SiMe3), 3.79 (s, 3 H,
OMe), 4.03 (s, 3 H, OMe), 7.14 (m, 1 H, Ar-H), 7.35 (m, 2 H, Ar-
H), 7.56 (m, 1 H, Ar-H).
13C NMR (75.4 MHz, CDCl3): d = 1.56, 54.22, 60.99, 124.10,
124.25, 128.20, 133.14, 134.32, 137.26, 141.52, 143.03, 144.45,
152.19, 158.16, 192.18.
5,6-Dimethoxy-3-[4,5-dimethoxy-2-(trimethylsilylethynyl)-
benzoyl]-1,2,4-triazine (5c)
Column chromatography (cyclohexane–EtOAc, 2:1); yellow crys-
tals; yield: 55%.
Mp 50–51 °C.
IR (KBr): 3084, 3002, 2996, 2931, 2859, 2152, 1683, 1597, 1541,
1495, 1398, 1271, 1138, 1001, 858, 751, 599 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.00 (s, 9 H, SiMe3), 3.95 (s, 3 H,
OMe), 3.98 (s, 3 H, OMe), 4.18 (s, 3 H, OMe), 4.24 (s, 3 H, OMe),
6.96 (s, 1 H, Ar-H), 7.39 (s, 1 H, Ar-H).
EIMS: m/z (%) = 313 (M+, 100), 298 (29), 270 (11), 255 (20), 240
(19), 225 (29), 212 (11), 197 (17), 89 (23), 73 (84), 59 (37), 45 (22).
Anal. Calcd for C17H19NO3Si: C, 65.15; H, 6.11; N, 4.47. Found: C,
64.89; H, 5.89; N, 4.19.
EIMS: m/z (%) = 401 (M+, 52), 386 (75), 373 (71), 370 (100), 358
(49), 343 (15), 328 (18), 312 (14), 304 (14), 295 (12), 272 (12), 261
(44), 228 (12), 203 (20), 169 (12), 123 (17), 89 (32), 73 (40).
2,3,6,7-Tetramethoxy-4-trimethylsilyl-1-azafluorenone (6c)
The mixture was heated to 150 °C (1.5 h); column chromatography
(cyclohexane–EtOAc, 3:1); orange-red crystals; yield: 89%.
HRMS: m/z calcd. for C19H23N3O5Si: 401.1407. Found: 401.1382.
5,6-Dimethoxy-3-[4,5-methylenedioxy-2-(trimethylsilyl-
ethynyl)-benzoyl]-1,2,4-triazine (5d)
Mp 154–155 °C.
Column chromatography (cyclohexane–EtOAc, 1:1); colorless
crystals; yield: 90%.
IR (KBr): 3007, 2956, 2900, 2859, 2839, 1725, 1597, 1505, 1464,
1373, 1240, 1093, 1016, 873, 756, 675, 568 cm–1.
Mp 144–145 °C.
1H NMR (300 MHz, CDCl3): d = 0.48 (s, 9 H, SiMe3), 3.77 (s, 3 H,
OMe), 3.85 (s, 3 H, OMe), 3.88 (s, 3 H, OMe), 4.02 (s, 3 H, OMe),
7.00 (s, 1 H, Ar-H), 7.14 (s, 1 H, Ar-H).
13C NMR (75.4 MHz, CDCl3): d = 1.82, 54.17, 56.40, 56.41, 60.94,
107.82, 108.94, 126.19, 136.00, 137.96, 140.67, 145.15, 148.71,
151.65, 153.64, 157.48, 191.48.
IR (KBr): 3084, 3017, 2971, 2956, 2147, 1693, 1541, 1495, 1393,
1250, 1128, 1031, 996, 858, 594 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.01 (s, 9 H, SiMe3), 4.19 (s, 3 H,
OMe), 4.25 (s, 3 H, OMe), 6.08 (s, 2 H, O-CH2-O), 6.95 (s, 1 H, Ar-
H), 7.30 (s, 1 H, Ar-H).
EIMS: m/z (%) = 373 (M+, 100), 358 (12), 73 (28).
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T. Hundsdorf, H. Neunhoeffer
PAPER
Anal. Calcd for C19H23NO5Si: C, 61.10; H, 6.21; N, 3.75. Found: C,
60.85; H, 6.00; N, 3.71.
IR (KBr): 3073, 3007, 2992, 2941, 2849, 1704, 1607, 1576, 1480,
1408, 1250, 1098, 991, 767, 604 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.92 (s, 3 H, OMe), 4.01 (s, 3 H,
OMe), 4.02 (s, 3 H, OMe), 4.11 (s, 3 H, OMe), 6.86 (s, 1 H, Ar-H),
7.08 (s, 1 H, Ar-H), 7.19 (s, 1 H, Ar-H).
2,3-Dimethoxy-6,7-methylenedioxy-4-trimethylsilyl-1-
azafluorenone (6d)
The mixture was heated to 150 °C (0.75 h); column chromatogra-
phy (cyclohexane–EtOAc, 3:1); red crystals; yield: 81%.
EIMS: m/z (%) = 301 (M+, 100), 286 (22), 215 (11).
Anal. Calcd for C16H15NO5: C, 63.79; H, 5.02; N, 4.64. Found: C,
63.70; H, 5.27; N, 4.36.
Mp 185–186 °C.
IR (KBr): 3099, 3017, 2961, 2931, 2900, 1729, 1607, 1515, 1474,
1373, 1230, 1026, 869, 762, 650 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.43 (s, 9 H, SiMe3), 3.76 (s, 3 H,
OMe), 4.14 (s, 3 H, OMe), 5.98 (s, 2 H, O-CH2-O), 6.90 (s, 1 H, Ar-
H), 7.04 (s, 1 H, Ar-H).
13C NMR (75.4 MHz, CDCl3): d = 1.70, 54.22, 61.00, 102.27,
105.56, 106.44, 127.74, 136.49, 140.10, 140.44, 144.95, 147.18,
151.67, 152.66, 157.46, 190.75.
2,3-Dimethoxy-6,7-methylenedioxy-1-azafluorenone (7d)
Column chromatography (CH2Cl2–EtOAc, 1:1); light red crystals;
yield: 88%.
Mp >300 °C.
IR (KBr): 3078, 3012, 2982, 2946, 1709, 1576, 1480, 1413, 1261,
1220, 1062, 1037, 884, 792 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.00 (s, 3 H, OMe), 4.10 (s, 3 H,
OMe), 6.04 (s, 2 H, O-CH2-O), 6.81 (s, 1 H, Ar-H), 7.02 (s, 1 H, Ar-
H), 7.08 (s, 1 H, Ar-H).
EIMS: m/z (%) = 357 (M+, 100), 327 (11), 223 (11), 73 (32), 59
(12).
Anal. Calcd for C18H19NO5Si: C, 60.51; H, 5.36; N, 3.92. Found: C,
60.24; H, 5.16; N, 3.84.
EIMS: m/z (%) = 285 (M+, 100), 270 (10), 256 (27), 242 (21), 214
(28), 199 (29).
Anal. Calcd for C15H11NO5: C, 63.16; H, 3.89; N, 4.91. Found: C,
63.31; H, 3.86; N, 4.80.
1-Azafluorenones 7; General Procedure
To a solution of 6 (0.10 mmol) in THF (10 mL) was added tetrabu-
tylammoniumfluoride (TBAF) on silica gel (1.1 mmol F–/g silica
gel; 112 mg, 0.123 mmol) and the solution was stirred for 3 h. The
silica gel was separated by filtration, H2O (3 mL) was added, and
the mixture was extracted with CH2Cl2 (3 ¥ 20 mL). The organic
layer was dried (MgSO4) and the solvent removed in vacuum. The
crude product was chromatographed as specified below.
Acknowledgement
We are grateful to Deutsche Forschungsgemeinschaft (DFG) for fi-
nancial support to T. H.
2,3-Diphenyl-1-azafluorenone (7a)
Column chromatography (cyclohexane–EtOAc, 1:1); yellow crys-
tals; yield: 94%.
References
(1) (a) Chauder, B. A.; Kalinin, A. V.; Taylor, N. J.; Snieckus,
V. Angew. Chem.Int. Ed. 1999, 38, 1435. (b) Mohri, S.-I.;
Stefinovic, M.; Snieckus, V. J. Org. Chem. 1997, 62, 7072.
(2) Stefinovic, M.; Snieckus, V. J. Org. Chem. 1998, 63, 2808.
(3) Snieckus, V. Chem. Rev. 1990, 90, 879.
Mp 192–193 °C.
IR (KBr): 3084, 3058, 3033, 1729, 1592, 1403, 1184, 955, 767, 706
cm–1.
(4) Gray, M.; Tinkl, M.; Snieckus, V.In Comprehensive
Organometallic Chemistry II, Vol. 11; Abel, E. W.; Stone, F.
G. A.; Wilkinson, G., Eds.; Pergamon: Oxford, 1995, 1–92,
and literature cited therein.
(5) Quéguiner, Q.; Marsais, F.; Snieckus, V.; Epsztajn, J. Adv.
Heterocycl. Chem. 1991, 52, 187.
(6) Boger, D. L.; Weinreb, S. M. Hetero Diels-Alder
Methodology in Organic Synthesis; Academic Press: New
York, 1987, 323–335.
1H NMR (300 MHz, CDCl3): d = 7.24 (m, 11 H, Ar-H), 7.50 (m, 2
H, Ar-H), 7.71 (m, 1 H, Ar-H), 7.80 (s, 1 H, Ar-H).
EIMS: m/z (%) = 333 (M+, 86), 332 (M+ - 1, 100), 303 (16), 276
(13), 166 (10), 152 (16).
Anal. Calcd for C24H15NO: C, 86.46; H, 4.54; N, 4.20. Found: C,
86.45; H, 4.50; N, 3.99.
2,3-Dimethoxy-1-azafluorenone (7b)
(7) (a) Ceder, O.; v. Angerer, S.; Bohle, M .In Houben-Weyl, 4th
ed., Vol. E9b/1; Schaumann, E., Ed.; Thieme: Stuttgart,
1998, 250–372, and literature cited therein. (b) Stanovnik,
B. In Houben-Weyl, 4th ed., Vol. E9a; Schaumann, E., Ed.;
Thieme: Stuttgart, 1997, 557–682, and literature cited
therein. (c) Neunhoeffer, H. In Houben-Weyl, 4th ed., Vol.
E9c; Schaumann, E., Ed.; Thieme: Stuttgart, 1998, 582–666,
and literature cited therein. (d) Neunhoeffer, H. In Houben-
Weyl, 4th ed., Vol. E9c; Schaumann, E., Ed.; Thieme:
Stuttgart, 1998, 870–916, and literature cited therein.
(8) Plé, N.; Turck, A.; Quéguiner, G.; Glassl, B.; Neunhoeffer,
H. Liebigs Ann. Chem. 1993, 583.
Column chromatography (cyclohexane–EtOAc, 1:1); yellow-or-
ange crystals; yield: 84%.
Mp 197 °C.
IR (KBr): 3099, 3073, 3017, 2941, 2859, 1714, 1607, 1581, 1480,
1408, 1368, 1271, 1225, 1128, 1021, 802, 726 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.96 (s, 3 H, OMe), 4.06 (s, 3 H,
OMe), 7.10 (s, 1 H, Ar-H), 7.17 (m, 1 H, Ar-H), 7.25 (m, 1 H, Ar-
H), 7.36 (m, 1 H, Ar-H), 7.51 (m, 1 H, Ar-H).
EIMS: m/z (%) = 241 (M+, 100), 226 (25), 212 (58), 198 (17), 170
(33), 155 (30), 147 (18), 127 (43), 76 (13).
(9) Neunhoeffer, H.; Glassl, B.; Sinks, U. Heterocyclic
Commun. 1996, 513.
Anal. Calcd for C14H11NO3: C, 69.71; H, 4.60; N, 5.80. Found: C,
69.67; H, 4.61; N, 5.61.
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29, 2135.
2,3,6,7-Tetramethoxy-1-azafluorenone (7c)
Column chromatography (CH2Cl2–EtOAc, 1:1); light red crystals;
yield: 99%.
Mp 209 °C.
Synthesis 2001, No. 12, 1800–1805 ISSN 0039-7881 © Thieme Stuttgart · New York

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Intramolecular Diels–Alder Strategies of 1,2,4-Triazines: Synthesis of 1-Azaflourenones
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Synthesis 2001, No. 12, 1800–1805 ISSN 0039-7881 © Thieme Stuttgart · New York