New method for the synthesis of β-tropolones: Structures of condensation products of o-quinones with 2-methylquinolines and the mechanism of their formation

Russian Chemical Bulletin, International Edition, Vol. 55, No. 11, pp. 2032—2055, November, 2006

2032

New method for the synthesis of βꢀtropolones:

structures of condensation products of oꢀquinones with 2ꢀmethylquinolines

and the mechanism of their formation*

c

a

V. I. Minkin,^a,bS. M. Aldoshin, V. N. Komissarov, I. V. Dorogan, Yu. A. Sayapin,

ꢀ

V. V. Tkachev,^cand A. G. Starikov^b

^aInstitute of Physical and Organic Chemistry, Rostov State University,

194/2 prosp. Stachki, 344090 RostovꢀonꢀDon, Russian Federation.

Fax: +7 (863) 243 4667. Eꢀmail: minkin@ipoc.rsu.ru

^bSouthern Scientific Center, Russian Academy of Sciences,

41 ul. Chekhova, 344006 RostovꢀonꢀDon, Russian Federation.

Fax: +7 (863)266 5677. Eꢀmail: andr@ipoc.rsu.ru

^cInstitute of Problems of Chemical Physics, Russian Academy of Sciences,

14 Institutskii prosp., 142432 Chernogolovka, Moscow Region, Russian Federation.

Eꢀmail: sma@icp.ac.ru

A new method was developed for the synthesis of functionalized βꢀtropolones based on

acidꢀcatalyzed condensation of 2ꢀmethylquinoline derivatives with 3,5ꢀdi(tertꢀbutyl)ꢀ1,2ꢀbenꢀ

zoquinone and 4,6ꢀdi(tertꢀbutyl)ꢀ3ꢀnitroꢀ1,2ꢀbenzoquinone (14). The mechanism of the mulꢀ

tistep reaction giving rise to βꢀtropolones and their tautomerism were studied by quantum

chemical methods (DFT B3LYP/6ꢀ31G**). The reaction of 2ꢀmethylquinoline derivatives

containing the tertiary amino group at position 4 with quinone 14 is accompanied by the

formation of derivatives of a new heterocyclic system, viz., 4,6ꢀdioxoꢀ2ꢀazabicyclo[3.3.0]octaꢀ

2,7ꢀdiene Nꢀoxide. The molecular and crystal structures of two 5,7ꢀdi(tertꢀbutyl)ꢀ3ꢀhydroxyꢀ

2ꢀ(quinolinꢀ2ꢀyl)tropolones and two dioxoazabicyclooctadiene Nꢀoxides, as well as of the

preparatively isolated intermediate of the first condensation step and of the byꢀproduct of the

reaction were established by Xꢀray diffraction.

Key words: βꢀtropolones, intramolecular hydrogen bond, quantum chemical calculations,

Xꢀray diffraction study, tautomerism.

Due to the unique structure and properties of

the sevenꢀmembered tropolone ring and a broad specꢀ

trum of biological activities, natural compounds of the

tropolone series (colchicine, colchamine, αꢀ, βꢀ, and

γꢀthujaplicins, etc.) and their synthetic analogs have atꢀ

tracted considerable attention.¹Most of the alreadyꢀ

known tropolones belong to αꢀtropolones, i.e., 2ꢀhydroxyꢀ

tropone derivatives. βꢀTropolones (3ꢀhydroxytropones)

are much less studied, although they include biologically

active compounds, such as stipitatic acid (1) and puberuꢀ

lic acid (2).

The latter fact is primarily because convenient proceꢀ

dures for the synthesis of βꢀtropolone derivatives are lackꢀ

ing. Unsubstituted βꢀtropolone isolated as picrate was preꢀ

pared for the first time in very low yield by decarboxylaꢀ

tion of 3,5ꢀdimethoxycycloheptaꢀ1,3,5ꢀtrienecarboxylic

acid followed by bromination of the resulting 3,5ꢀdiꢀ

methoxycycloheptatriene giving rise to βꢀmethoxytropone

and demethylation of the latter.²A more general approach

to the synthesis of βꢀtropolone derivatives is based on the

multistep transformation of 3,4,5ꢀtrimethoxybenzoic acid

involving its reduction to 3,5ꢀdimethoxyꢀ1,4ꢀdihydroꢀ

benzyl alcohol, the preparation of its tosyl derivative, and

the formation of a mixture of 1,3ꢀdimethoxycycloꢀ

heptatrienes (as a result of thermal expansion of the sixꢀ

membered ring) followed by their oxidation.³Unsubꢀ

stituted βꢀtropolone was also prepared by photooxyꢀ

genation of cycloheptaꢀ1,3,5ꢀtriene with singlet oxygen

followed by methanolysis of the resulting isomeric enꢀ

* Dedicated to Academician O. M. Nefedov on the occasion of

his 75th birthday.

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1956—1977, November, 2006.

Synthesis of βꢀtropolones

Russ.Chem.Bull., Int.Ed., Vol. 55, No. 11, November, 2006 2033

doperoxides giving rise to 1,2ꢀdihydroꢀ3ꢀhydroxytropone

and oxidation of the latter with chromium oxide.⁴

βꢀTropolone derivatives containing substituents in the

vicinal position with respect to both functional groups are

preparatively more accessible and more interesting in view

of their biological properties. 2ꢀCarboxyꢀβꢀtropolones

were synthesized in low yields by a series of transformaꢀ

tions based on condensation of diazoacetic ester with

1,2ꢀdimethoxybenzene or 1,2,4ꢀtrimethoxybenzene.^5,6

Recently, a more convenient fourꢀstep method has

been developed based on the cycloaddition reaction of

2ꢀmethylfuran with symmetrical tetrachloroacetone proꢀ

ducing 2ꢀalkoxyꢀβꢀtropolones in 20—37% yields.⁷2ꢀAcylꢀ

βꢀtropolones were synthesized in moderate yields

(12—66%) by the reactions of in situ generated triphenylꢀ

bismuthonium ylides with oꢀquinones.⁸The reaction of

tetrachloroꢀoꢀbenzoquinone with acetone also produces

βꢀtropolone derivatives.⁹Earlier, the structure of an

αꢀtropolone derivative has been assigned to this reaction

product.¹⁰

lier, we have found¹²that when fusing 3,5ꢀdi(tertꢀbutyl)ꢀ

1,2ꢀbenzoquinone (3) with 2ꢀmethylquinolines 4 in

the presence of pꢀtoluenesulfonic acid at 160—170 °C

(method A) or refluxing their solution in oꢀxylene for

3—6 h (method B), 2ꢀ(quinolinꢀ2ꢀyl)ꢀβꢀtropolones 6

(Scheme 1) instead of the expected aldol condensation

products, viz., oꢀmethylenequinones 5, were prepared in

7—43% yields. The highest yields were achieved with the

use of a twofold excess of quinone 3, which acts as an

oxidizing agent in the final step of the transformation

(Scheme 2).

In the present study, we demonstrated that condensaꢀ

tion of oꢀquinones with 2ꢀmethylquinolines can be perꢀ

formed under milder conditions (storage of a solution of

the components in acetic acid at room temperature for

1—4 days, method C), βꢀtropolones 6 and 7 being preꢀ

pared in substantially higher yields. The structures of

1

compounds 6 and 7 were confirmed by H NMR and

IR spectroscopy and mass spectrometry (Tables 1—4).

The molecular structures of βꢀtropolones (6e and 7a) were

established by Xꢀray diffraction (Figs 1 and 2, Table 5).

Xꢀray diffraction study demonstrated that compounds

6e and 7a exist as sꢀcis conformers with respect to the

C(2)—C(8) bond. This conformation provides the formaꢀ

tion of exclusively stable intramolecular O—H...N (see

Fig. 1) or O...H—N hydrogen bonds (see Fig. 2). The

O...N distances in compounds 6e and 7a are more than

0.5 Å shorter than the corresponding van der Waals conꢀ

tact and are the shortest bonds in all known systems with

this type of intramolecular hydrogen bonds.^13,14The

hydrogen nuclei involved in intramolecular hydrogen

bonds in compounds 6e and 7a are strongly deshielded

and are observed in the ¹H NMR spectra at very low field

(at δ 18—20, see Table 2). These values are comparable

with the chemical shifts (19.1—19.7 ppm) of the protons

of conjugated acids of proton sponges.¹⁵It is known^14,15

In the present study, we developed a new general

method for the synthesis of βꢀtropolone derivatives based

on acidꢀcatalyzed condensation of oꢀquinones with

2ꢀmethylquinolines. The structures and the mechanism

of formation of the major reaction products, intermediꢀ

ates, and byꢀproducts were studied by Xꢀray diffraction

and quantum chemical methods.

Results and Discussion

Synthesis and structures of 5,7ꢀdi(tertꢀbutyl)ꢀ3ꢀ

hydroxyꢀ2ꢀ(quinolinꢀ2ꢀyl)tropones. The reactions of carꢀ

bonyl compounds with methyleneꢀactive substrates

are among the most widely used methods for the carꢀ

bon—carbon bond formation.¹¹However, the behavior of

quinones in these transformations is poorly known. Earꢀ

Scheme 1

2034

Russ.Chem.Bull., Int.Ed., Vol. 55, No. 11, November, 2006

Minkin et al.

Table 1. Yields, melting points, and elemental analysis data for 5,7ꢀdi(tertꢀbutyl)ꢀ3ꢀhydroxyꢀ2ꢀ(quinolinꢀ2ꢀyl)tropones 6 and 7

Comꢀ

pound

R¹

R²R³R⁴R⁵

Yield (%)

Method

M.p.

/°C

Found

Calculated

Molecular

formula

(%)

C

H

Cl

—

N

6a

6b

6c

6d

6e

H

NO₂

H

10(B)

37(C)

11(B)

126—128 79.61 7.40

79.74 7.53

3.72 C₂₄H₂₇NO₂

3.87

172—174 70.74 6.33

70.92 6.45

223—225 71.54 6.73

71.41 6.71

173—175 75.31 6.32

75.41 6.33

—

7.02 C₂₄H₂₆N₂O₄

6.89

6.82 C₂₅H₂₈N₂O₄

6.66

3.06 C₂₈H₂₈ClNO₂

3.14

Me

Cl

NO₂

H

7,8ꢀBenzo

7.84

7.95

8.62

8.65

8.12

8.36

8.14

8.36

8.48

8.32

7.84

7.79

7.40

7.56

7.52

7.56

H

Me 11(A), 23(B),

60(C)

189—191 73.22 6.71

73.25 6.88

3.44 C₂₅H₂₈ClNO₂

3.42

6f

Cl

H

Me

H

Me 15(A), 26(B),

70(C)

198—201 73.61 7.02

73.66 7.08

174—176 73.58 7.07

73.66 7.13

157—159 70.56 6.72

70.49 6.63

210—212 65.93 5.92

66.00 5.98

223—225 66.64 6.21

66.59 6.23

234—236 66.62 6.13

66.59 6.23

3.20 C₂₆H₃₀CINO₂

3.30

3.14 C₂₆H₃₀CINO₂

3.30

3.40 C₂₅H₂₈ClNO₃

3.29

6.03 C₂₅H₂₇CIN₂O₄

6.16

5.92 C₂₆H₂₉ClN₂O₄

5.97

5.93 C₂₆H₂₉CIN₂O₄

5.97

6g

6h

6i

Me Me 12(A), 24(B),

63(C)

H

OMe

H

13(B)

NO₂

Me

11(A), 20(B)

13(A), 21(B)

6j

NO₂Me

6k

NO₂

H

Me Me 11(A), 22(B),

43(C)

7a

7b

7c

7d

7e

7f

H

Me

H

Me 34(B), 89(D)

Me 26(B), 92(D)

200—202 75.52 7.72

75.62 7.88

222—224 75.94 7.95

75.92 8.07

227—229 75.84 7.99

75.92 8.07

187—189 73.14 7.55

73.08 7.61

211—213 77.47 7.25

77.39 7.31

272—274 68.87 6.88

68.89 6.98

203—205 69.33 7.07

69.34 7.18

264—266 69.30 7.10

69.34 7.18

—

5.99 C₂₉H₃₆N₂O₃

6.08

5.81 C₃₀H₃₈N₂O₃

5.90

5.93 C₃₀H₃₈N₂O₃

5.90

5.98 C₂₉H₃₆N₂O₄

5.88

5.71 C₃₂H₃₆N₂O₃

5.64

8.26 C₂₉H₃₅N₃O₅

8.31

8.11 C₃₀H₃₇N₃O₅

8.09

8.05 C₃₀H₃₇N₃O₅

8.09

H

Me Me 29(B), 95(D)

H

OMe

H

94(D)

89(D)

H

7,8ꢀBenzo

NO₂

H

Me 26(B), 88(D)

Me 24(B), 76(D)

7g

7h

NO₂Me

NO₂

H

Me Me 22(B), 86(D)

7i

H

Me

H

Me

6(B), 96(D)

81(D)

144—146 78.48 8.17

78.56 8.35

191—193 78.55 8.47

78.77 8.53

169—171 78.80 8.41

78.77 8.53

244—246 71.48 7.27

71.54 7.40

—

6.13 C₃₀H₃₈N₂O₂

6.11

6.18 C₃₁H₄₀N₂O₂

5.93

5.81 C₃₁H₄₀N₂O₂

5.93

8.54 C₃₀H₃₇N₃O₄

8.34

8.02 C₃₁H₃₉N₃O₄

8.12

7j

7h

7l

H

Me Me

8(B), 86(D)

NO₂

H

Me 10(B), 74(D)

Me 8(B), 82(D)

7m

NO₂Me

198—200 71.79 7.41

71.93 7.59

(to be continued)

Synthesis of βꢀtropolones

Table 1 (continued)

Russ.Chem.Bull., Int.Ed., Vol. 55, No. 11, November, 2006 2035

Comꢀ

pound

R¹

R²R³R⁴R⁵

Yield (%)

Method

M.p.

/°C

Found

Calculated

Molecular

formula

(%)

C

H

Cl

—

N

7n

NO₂

H

Me Me 10(B), 78(D)

223—225 71.85 7.47

71.93 7.59

8.03 C₃₁H₃₉N₃O₄

8.12

7o

7p

7q

H

Me

H

Me

94(D)

95(D)

98(D)

264—265 74.55 7.47

74.62 7.89

238—240 74.75 7.97

74.97 8.09

270—272 74.86 7.91

74.97 8.09

—

6.63 C₂₇H₃₄N₂O₃

6.45

6.53 C₂₈H₃₆N₂O₃

6.24

6.38 C₂₈H₃₆N₂O₃

6.24

Me Me

7r

7s

7t

H

Me

H

Me

93(D)

90(D)

9(B)

162—164 75.86 7.96

75.78 8.11

190—192 75.96 8.16

76.07 8.30

194—195 76.02 8.12

76.07 8.30

—

9.38 C₂₉H₃₇N₃O₂

9.14

9.18 C₃₀H₃₉N₃O₂

8.87

9.06 C₃₀H₃₉N₃O₂

8.87

H

Me Me

Me

Me Me

7u NHC₆H₃(OMe)₂ꢀ2,5

H

235—237 75.33 7.17

75.26 7.27

220—222 73.54 6.73

73.44 6.91

5.23 C₃₃H₃₈N₂O₄

5.32

7.82 C₃₃H₃₇N₃O₄

7.79

7v

NHC₆H₄Meꢀ4

NO₂

H

7(B)

7w

7x

7y

7z

NO₂Me

H

Me

7(B), 74(D)

84(D)

262—264 69.32 6.21

69.58 6.44

190—191 76.32 7.01

76.16 7.08

191—193 76.22 7.14

76.45 7.30

204—206 76.34 7.18

76.45 7.30

—

11.29 C₂₉H₃₂N₄O₄

11.19

9.49 C₂₈H₃₁N₃O₂

9.52

9.39 C₂₉H₃₃N₃O₂

9.22

9.43 C₂₉H₃₃N₃O₂

9.22

H

Me

H

86(D)

Me Me

93(D)

1

Table 2. H NMR spectroscopic data for 5,7ꢀdi(tertꢀbutyl)ꢀ3ꢀhydroxyꢀ2ꢀ(quinolinꢀ2ꢀyl)tropones 6 and 7

Comꢀ

pound

δ (J/Hz)

6a

6b

1.25 (s, 9 H, Bu^t(5)); 1.39 (s, 9 H, Bu^t(7)); 6.62 (d, 1 H, H(4), J = 1.5); 6.69 (d, 1 H, H(6), J = 1.5);

7.44—8.18 (m, 6 H, quinoline); 19.3 (br.s, 1 H, C(3)ОH)

1.27 (s, 9 H, Bu^t(5)); 1.41 (s, 9 H, Bu^t(7)); 6.67 (d, 1 H, H(4), J = 1.7); 6.82 (d, 1 H, H(6), J = 1.7); 7.78

(t, 1 H, H(7´)); 8.15 (d, 1 H, H(3´), J = 8.4); 8.24—8.30 (m, 2 H, H(6´), H(8´)); 8.89 (d, 1 H, H(4´),

J = 8.4); 18.25 (s, 1 H, C(3)ОH)

6c

1.25 (s, 9 H, Bu^t(5)); 1.39 (s, 9 H, Bu^t(7)); 2.72 (s, 3 H, Me(4´)); 6.71 (d, 1 H, H(4), J = 1.7); 6.73 (d, 1 H,

H(6), J = 1.7); 7.56 (t, 1 H, H(6´)); 8.05 (s, 1 H, H(3´)); 8.19 (d, 1 H, H(5´), J = 8.0); 8.43 (d, 1 H, H(7´),

J = 8.0); 17.96 (s, 1 H, C(3)ОH)

6d

6e

1.30 (s, 9 H, Bu^t(5)); 1.44 (s, 9 H, Bu^t(7)); 6.77 (d, 1 H, H(4), J = 1.76); 6.84 (d, 1 H, H(6), J = 1.76);

7.7—8.9 (m, 6 H, arom.); 8.41 (s, 1 H, H(3´)); 19.35 (s, 1 H, C(3)ОH)

1.24 (s, 9 H, Bu^t(5)); 1.37 (s, 9 H, Bu^t(7)); 2.72 (s, 3 H, Me(8´)); 6.65 (d, 1 H, H(4), J = 1.7);

6.72 (d, 1 H, H(6), J = 1.7); 7.41 (t, 1 H, H(6´), J = 7.7); 7.54 (d, 1 H, H(7´), J = 7.6); 7.95 (d, 1 H, H(5´),

J = 7.6); 8.23 (s, 1 H, H(3´)); 19.12 (s, 1 H, C(3)ОH)

(to be continued)

2036

Russ.Chem.Bull., Int.Ed., Vol. 55, No. 11, November, 2006

Minkin et al.

Table 2 (continued)

Comꢀ

pound

δ (J/Hz)

6f

1.23 (s, 9 H, Bu^t(5)); 1.37 (s, 9 H, Bu^t(7)); 2.51 (s, 3 H, Me(6´)); 2.68 (s, 3 H, Me(8´));

6.65 (d, 1 H, H(4), J = 1.88); 6.73 (d, 1 H, H(6), J = 1.88); 7.43 (s, 1 H, H(7´)); 7.78 (s, 1 H, H(5´));

8.23 (s, 1 H, H(3´)); 19.19 (s, 1 H, C(3)ОH)

6g

6h

1.23 (s, 9 H, Bu^t(5)); 1.37 (s, 9 H, Bu^t(7)); 2.52 (s, 3 H, Me(7´)); 2.63 (s, 3 H, Me(8´)); 6.64 (d, 1 H, H(4),

J = 1.86); 6.68 (d, 1 H, H(6), J = 1.86); 7.37 (d, 1 H, H(6´); J = 8.5); 7.89 (d, 1 H, H(5´), J = 8.5);

8.20 (s, 1 H, H(3´)); 19.31 (s, 1 H, C(3)ОH)

1.26 (s, 9 H, Bu^t(5)); 1.41 (s, 9 H, Bu^t(7)); 3.97 (s, 3 H, OMe(6´)); 6.65 (d, 1 H, H(4), J = 1.8);

6.80 (d, 1 Н, H(6), J = 1.8); 7.38 (d, 1 H, H(7´), J = 9.0); 7.41 (d, 1 H, H(5´), J = 2.6); 7.78 (d, 1 H, H(8´),

J = 9.0); 8.22 (s, 1 H, H(3´)); 18.53 (s, 1 H, C(3)ОH)

6i

1.23 (s, 9 H, Bu^t(5)); 1.37 (s, 9 H, Bu^t(7)); 2.73 (s, 3 H, Me(8´)); 6.68 (d, 1 H, H(4), J = 1.82);

6.83 (d, 1 H, H(6), J = 1.82); 7.57—7.64 (m, 2 H, H(6´), H(7´)); 8.32 (s, 1 H, H(3´)); 18.02 (s, 1 H, C(3)ОH)

1.25 (s, 9 H, Bu^t(5)); 1.38 (s, 9 H, Bu^t(5)); 2.40 (s, 3 H, Me(6´)); 2.70 (s, 3 H, Me(8´)); 6.68 (d, 1 H, H(4),

J = 1.82); 6.82 (d, 1 H, H(6), J = 1.82); 7.50 (s, 1 H, H(7´)); 8.28 (s, 1 H, H(3´)); 18.02 (s, 1 H, C(3)ОH)

1.24 (s, 9 H, Bu^t(5)); 1.39 (s, 9 H, Bu^t(7)); 2.54 (s, 3 H, Me(7´)); 2.65 (s, 3 H, Me(8´)); 6.67 (d, 1 H, H(4),

J = 1.87); 6.81 (d, 1 H, H(6), J = 1.87); 7.51 (s, 1 H, H(6´)); 8.25 (s, 1 H, H(3´)); 18.30 (s, 1 H, C(3)ОH)

1.23 (s, 9 H, Bu^t(5)); 1.38 (s, 9 H, Bu^t(7)); 2.74 (s, 3 H, Me(8´)); 3.29 (t, 4 H, C(4´)N(СH₂)₂);

3.99 (t, 4 H, C(4´)(СH₂)₂O); 6.62 (s, 2 H, H(4), H(6)); 7.35 (t, 1 H, H(6´), J = 7.8); 7.5 (d, 1 H, H(7´),

J = 7.7); 7.73 (s, 1 H, H(3´)); 7.78 (d, 1 H, H(5´), J = 7.7); 19.15 (br.s, 1 H, C(3)ОH)

1.23 (s, 9 H, Bu^t(5)); 1.38 (s, 9 H, Bu^t(7)); 2.47 (s, 3 H, Me(6´)); 2.67 (s, 3 H, Me(8´));

3.25 (t, 4 H, morpholine); 3.98 (t, 4 H, morpholine); 6.62 (s, 2 H, H(4,6)); 7.37 (s, 1 H, H(7´));

7.52 (s, 1 H, H(5´)); 7.65 (s, 1 H, H(3´)); 19.09 (br.s, 1 H, C(3)ОH)

6j

6k

7a

7b

7c

7d

1.24 (s, 9 H, Bu^t(5)); 1.37 (s, 9 H, Bu^t(7)); 2.50 (s, 3 H, Me(7´)); 2.62 (s, 3 H, Me(8´)); 3.28 (t, 4 H,

morpholine); 3.98 (t, 4 H, morpholine); 6.61 (s, 2 H, H(4), H(6)); 7.24 (d, 1 H, H(6´), J = 10.33); 7.65 (d, 1 H,

H(5´), J = 10.33); 7.66 (s, 1 H, H(3´)); 18.93 (br.s, 1 H, C(3)ОH)

1.24 (s, 9 H, Bu^t(5)); 1.39 (s, 9 H, Bu^t(7)); 3.25 (t, 4 H, morpholine); 3.98 (t, 4 H, morpholine), 3.97 (s, 3 H,

C(6´)OMe); 6.59 (d, 1 H, H(4), J = 1.8); 6.69 (d, 1 H, H(6), J = 1.8); 7.23 (d, 1 H, H(5´), ¹J = 2.7); 7.30 (dd,

2

1 H, H(7´), ¹J = 2.7, J = 9.0); 7.70 (d, 1 H, H(8´), J = 9.0); 7.70 (s, 1 H, H(3´)); 19.11 (br.s, 1 H, C(3)ОH)

7e

7f

1.28 (s, 9 H, Bu^t(5)); 1.42 (s, 9 H, Bu^t(7)); 3.32 (t, 4 H, morpholine); 4.02 (t, 4 H, morpholine); 6.72 (s, 1 H,

H(4)); 6.73 (s, 1 H, H(6)); 7.70—8.00 (m, 6 H, arom.); 8.75 (d, 1 H, H(3´), J = 8.0); 20.05 (s, 1 H, C(3)ОH)

1.24 (s, 9 H, Bu^t(5)); 1.39 (s, 9 H, Bu^t(7)); 2.78 (s, 3 H, Me(8´)); 2.80—3.20 (m, 4 H, morpholine); 3.70—3.97

(m, 4 H, morpholine); 6.70 (d, 1 H, H(4), J = 1.8); 6.78 (d, 1 H, H(6), J = 1.8); 7.50—7.60 (m, 2 H, H(6´), H(7´));

7.92 (s, 1 H, H(3´)); 18.9 (br.s, 1 H, C(3)ОH)

7g

7h

7i

1.27 (s, 9 H, Bu^t(5)); 1.43 (s, 9 H, Bu^t(7)); 2.42 (s, 3 H, Me(6´)); 2.70 (s, 3 H, Me(8´)); 2.80—3.10 (m, 4 H,

morpholine); 3.70—3.85 (m, 4 H, morpholine); 6.67 (d, 1 H, H(4), J = 1.70); 6.80 (d, 1 H, H(6), J = 1.70);

7.44 (s, 1 H, H(7´)); 7.98 (s, 1 H, H(3´)); 18.80 (s, 1 H, C(3)ОH)

1.26 (s, 9 H, Bu^t(5)); 1.4 (s, 9 H, Bu^t(7)); 2.54 (s, 3 H, Me(7´)); 2.65 (s, 3 H, Me(8´)); 2.82—3.22 (m, 4 H,

morpholine); 3.64—3.98 (m, 4 H, morpholine); 6.66 (d, 1 H, H(4), J = 1.86); 6.75 (d, 1 H, H(6), J = 1.86);

7.46 (s, 1 H, H(6´)); 7.84 (s, 1 H, H(3´)); 19.05 (s, 1 H, C(3)ОH)

1.24 (s, 9 H, Bu^t(5)); 1.38 (s, 9 H, Bu^t(7)); 1.60—2.00 (m, 6 H, piperidine); 2.71 (s, 3 H, Me(8´)); 3.20—3.40

(m, 4 H, piperidine); 6.60 (s, 2 H, H(4,6)); 7.29 (t, 1 H, H(6´), J = 7.7); 7.45 (d, 1 H, H(7´), J = 7.8);

7.67 (s, 1 H, H(3´)); 7.73 (d, 1 H, H(5´), J = 7.8); 18.84 (br.s, 1 H, C(3)ОH)

7j

1.23 (s, 9 H, Bu^t(5)); 1.37 (s, 9 H, Bu^t(7)); 1.60—2.00 (m, 6 H, piperidine); 2.47 (s, 3 H, Me(6´)); 2.67 (s, 3 H,

Me(8´)); 3.2—3.4 (m, 4 H, piperidine); 6.59 (d, 1 H, H(4), J = 1.8); 6.60 (d, 1 H, H(6), J = 1.8); 7.31 (s, 1 H,

H(7´)); 7.50 (s, 1 H, H(5´)); 7.66 (s, 1 H, H(3´)); 18.89 (s, 1 H, C(3)ОH)

7k

7l

1.23 (s, 9 H, Bu^t(5)); 1.37 (s, 9 H, Bu^t(7)); 1.60—2.00 (m, 6 H, piperidine); 2.49 (s, 3 H, Me(7´)); 2.61 (s, 3 H,

Me(8´)); 3.20—3.40 (m, 4 H, piperidine); 6.57 (d, 1 H, H(4), J = 1.73); 6.60 (d, 1 H, H(6), J = 1.73); 7.22

(d, 1 H, H(6´), J = 8.53); 7.63 (d, 1 H, H(5´), J = 8.53); 7.63 (s, 1 H, H(3´)), 18.72 (br.s, 1 H, C(3)ОH)

1.25 (s, 9 H, Bu^t(5)); 1.39 (s, 9 H, Bu^t(7)); 1.60—3.20 (m, 10 H, piperidine); 2.72 (s, 3 H, Me(8´)); 6.64 (d, 1 H,

H(4), J = 1.8); 6.72 (d, 1 H, H(6), J = 1.8); 7.49 (d, 1 H, H(7´), J = 7.7); 7.55 (d, 1 H, H(6´), J = 7.7);

7.85 (s, 1 H, H(3´)); 19.0 (br.s, 1 H, C(3)ОH)

1.25 (s, 9 H, Bu^t(5)); 1.39 (s, 9 H, Bu^t(7)); 1.60—3.20 (m, 10 H, piperidine); 2.39 (s, 3 H, Me(6´)); 2.68

(s, 3 H, Me(8´)); 6.65 (d, 1 H, H(4), J = 1.42); 6.74 (d, 1 H, H(6), J = 1.42); 7.39 (s, 1 H, H(7´));

7.96 (s, 1 H, H(3´)); 18.96 (br.s, 1 H, C(3)ОH)

7m

(to be continued)

Synthesis of βꢀtropolones

Table 2 (continued)

Russ.Chem.Bull., Int.Ed., Vol. 55, No. 11, November, 2006 2037

Comꢀ

pound

δ (J/Hz)

7n

7o

7p

7q

7r

7s

7t

1.24 (s, 9 H, Bu^t(5)); 1.38 (s, 9 H, Bu^t(7)); 1.60—3.20 (m, 10 H, piperidine); 2.51 (s, 3 H, Me(7´)); 2.62

(s, 3 H, Me(8´)); 6.62 (d, 1 H, H(4), J = 1.76); 6.68 (d, 1 H, H(6), J = 1.76); 7.47 (s, 1 H, H(6´)), 7.79

(s, 1 H, H(3´)); 19.08 (br.s, 1 H, C(3)ОH)

1.22 (s, 9 H, Bu^t(5)); 1.31 (s, 9 H, Bu^t(7)); 2.60 (s, 3 H, Me(8´)); 3.22 (m, 2 H, СH₂); 3.73 (m, 2 H, СH₂);

4.71 (t, 1 H, ОH); 6.33 (d, 1Н, H(4), J = 1.8); 6.43 (d, 1 H, H(6), J = 1.8); 7.10—7.50 (m, 4 H, arom.);

7.46 (m, 1 H, NH); 8.05 (d, 1 H, H(3´)); 18.28 (s, 1 H, C(3)ОH)

1.22 (s, 9 H, Bu^t(5)); 1.31 (s, 9 H, Bu^t(7)); 2.52 (s, 3 H, Me(6´)); 2.60 (s, 3 H, Me(8´)); 3.34 (m, 2 H, СH₂);

3.73 (m, 2 H, СH₂); 4.70 (t, 1 H, ОH); 6.35 (d, 1 H, H(4), J = 1.8); 6.44 (d, 1 H, H(6), J = 1.8); 7.18

(s, 1 H, H(7´)); 7.24 (s, 1 H, H(5´)); 7.34 (m, 1 H, NH); 7.86 (s, 1 H, H(3´)); 18.30 (s, 1 H, C(3)ОH)

1.22 (s, 9 H, Bu^t(5)); 1.31 (s, 9 H, Bu^t(7)); 2.48 (s, 3 H, Me(7´)); 2.51 (s, 3 H, Me(8´)); 3.37 (m, 2 H, СH₂);

3.73 (m, 2 H, СH₂); 4.70 (t, 1 H, ОH); 6.33 (d, 1 H, H(4), J = 1.8); 6.41 (d, 1 H, H(6), J = 1.8); 7.05—7.15

(m, 2 H, H(5´), H(6´)); 7.37 (m, 1 H, NH); 7.94 (d, 1 H, H(3´)); 18.16 (s, 1 H, C(3)ОH)

1.23 (s, 9 H, Bu^t(5)); 1.37 (s, 9 H, Bu^t(7)); 2.71 (s, 3 H, Me(8´)); 3.16 (t, 4 H, piperazine); 3.26 (t, 4 H,

piperazine); 6.60 (s, 2 H, H(4,6)); 7.32 (t, 1 H, H(6´), J = 7.8); 7.48 (d, 1 H, H(7´), J = 7.8); 7.68

(s, 1 H, H(3´)); 7.76 (d, 1 H, H(5´), J = 7.8); 18.95 (br.s, 1 H, C(3)ОH)

1.23 (s, 9 H, Bu^t(5)); 1.40 (s, 9 H, Bu^t(7)); 2.48 (s, 3 H, Me(6´)); 2.67 (s, 3 H, Me(8´)); 3.17 (t, 4 H,

piperazine); 3.24 (t, 4 H, piperazine); 6.61 (s, 2 H, H(4), H(6)); 7.33 (s, 1 H, H(7´)); 7.53 (s, 1 H, H(5´));

7.68 (s, 1 H, H(3´)); 19.00 (br.s, 1 H, C(3)ОH)

1.23 (s, 9 H, Bu^t(5)); 1.36 (s, 9 H, Bu^t(7)); 2.50 (s, 3 H, Me(7´)); 2.61 (s, 3 H, Me(8´)); 3.15 (m, 4 H,

piperazine); 3.25 (t, 4 H, piperazine); 6.58 (d, 1 H, H(4), J = 1.8); 6.60 (d, 1 H, H(6), J = 1.8); 7.23

(d, 1 H, H(6´), J = 8.3); 7.65 (d, 1 H, H(5´), J = 8.3); 7.70 (s, 1 H, H(3´)); 18.84 (s, 1 H, C(3)ОH)

1.22 (s, 9 H, Bu^t(5)); 1.27 (s, 9 H, Bu^t(7)); 2.72 (s, 3 H, Me(8´)); 3.89 (s, 3 H, C(5´)OMe); 3.98 (s, 3 H,

C(2´)ОMe); 6.57 (d, 1 H, H(4), J = 1.3); 6.59 (d, 1 H, H(6), J = 1.3); 6.68 (dd, 1 H, H(4´), J₁= 8.9, J₂= 2.7);

6.92 (d, 1 H, H(3´), J = 8.9); 7.29 (s, 1 H, C(4´)NH); 7.38 (t, 1 H, H(6´), J = 7.6); 7.39 (d, 1 H, H(6″), J = 2.7);

7.55 (d, 1 H, H(7´), J = 6.95); 7.75 (d, 1 H, H(5´), J = 8.32); 7.97 (s, 1 H, H(3´)); 18.80 (br.s, 1 H, C(3)ОH)

1.16 (s, 9 H, Bu^t(5)); 1.22 (s, 9 H, Bu^t(7)); 2.38 (s, 3 H, Me(4″)); 2.56 (s, 3 H, Me(7´)); 2.67 (s, 3 H, Me(8´));

6.59 (d, 1 H, H(4), J = 1.3); 6.62 (d, 1 H, H(6), J = 1.3); 6.89 (s, 1 H, C(4´)NH); 7.05 (d, 2 H, H(3″), H(5″),

J = 8.3); 7.21 (d, 2 H, H(2″), H(6″), J = 8.3); 7.55 (s, 1 H, H(6´)); 7.61 (s, 1 H, H(3´)); 18.98 (s, 1 H, ОH(3))

1.29 (s, 9 H, Bu^t(5)); 1.37 (s, 9 H, Bu^t(7)); 2.42 (s, 3 H, Me(6´)); 2.80 (s, 3 H, Me(8´)); 6.77 (d, 1 H, H(4),

J = 1.7); 6.88 (d, 1 H, H(6), J = 1.7); 7.08 (s, 1 H, H(7´)); 7.25 (d, 1 H, H(4″), J = 8.55); 7.57 (d, 1 H, H(5″),

J = 8.55); 7.59 (s, 1 H, H(3´)); 8.12 (s, 1 H, H(2″)); 17.85 (s, 1 H, C(3)ОH)

7u

7v

7w

7x

7y

7z

1.27 (s, 9 H, Bu^t(5)); 1.38 (s, 9 H, Bu^t(7)); 2.78 (s, 3 H, Me(8´)); 6.71 (d, 1 H, H(4), J = 1.7); 6.78 (d, 1 H,

H(6), J = 1.7); 7.34 (s, 2 H, H(4″), H(5″)); 7.45 (t, 1 H, H(6´)); 7.62 (d, 1 H, H(7´), J = 8.4); 7.65 (d, 1 H,

H(5´), J = 8.4); 7.85 (s, 1 H, H(3´)); 8.14 (s, 1 H, H(2″)); 19.01 (s, 1 H, C(3)ОH)

1.27 (s, 9 H, Bu^t(5)); 1.37 (s, 9 H, Bu^t(7)); 2.46 (s, 3 H, Me(6´)); 2.75 (s, 3 H, Me(8´)); 6.71 (d, 1 H, H(4),

J = 1.7); 6.79 (d, 1 H, H(6), J = 1.7); 7.33 (s, 1 H, H(7´)); 7.35 (s, 1 H, H(4″)); 7.36 (s, 1 H, H(5″)); 7.49

(s, 1 H, H(5´)); 7.84 (s, 1 H, H(3´)); 8.11 (s, 1 H, H(2″)); 19.10 (s, 1 H, C(3)ОH)

1.27 (s, 9 H, Bu^t(5)); 1.37 (s, 9 H, Bu^t(7)); 2.56 (s, 3 H, Me(7´)); 2.69 (s, 3 H, Me(8´)); 6.70 (d, 1 H, H(4),

J = 1.7); 6.75 (d, 1 H, H(6), J = 1.7); 7.32 (s, 1 H, H(4″)); 7.33 (s, 1 H, H(5″)); 7.36 (d, 1 H, H(6´),

J = 8.5); 7.51 (d, 1 H, H(5´), J = 8.5); 7.84 (s, 1 H, H(3´)); 8.08 (s, 1 H, H(2″)); 19.25 (s, 1 H, C(3)ОH)

that the downfield shifts of protons involved in hydrogen

bonds linearly correlate with the strength of this bond.

Therefore, intramolecular O—H...N and O...H—N hydroꢀ

gen bonds in the conjugated chelate sixꢀmembered rings

in the 2ꢀ(quinolinꢀ2ꢀyl)ꢀβꢀtropolone molecules (6 and 7)

are among the strongest bonds, the soꢀcalled resonance

assisted hydrogen bonds (RAHB).^14,16The sixꢀmembered

ring formed with the involvement of the intramolecuꢀ

lar hydrogen bond, the quinoline fragment, and the

C(1)—C(4) atoms of the tropolone ring are in a single

plane (the C(4) atom slightly deviates from this plane),

whereas the sevenꢀmembered tropolone ring is bent

along the C(1)—C(4) line (see Figs 1 and 2). In both

compounds (6e and 7a), the dihedral angles between

the C(1)C(2)C(3)C(4) and C(4)C(5)C(6)C(7) planes

are 37.9°.

Quantum chemical calculations by the density funcꢀ

tional theory (DFT) method at the B3LYP/6ꢀ31G** level

well reproduce the experimental geometry of molecules

6e and 7a, such as the shortened O...N distances and

the puckering of the sevenꢀmembered ring along the

C(1)—C(4) line (Fig. 3, Table 6). The differences beꢀ

tween the calculated and experimental bond lengths are,

on the average, no larger than 0.01 Å. In the crystals

2038

Russ.Chem.Bull., Int.Ed., Vol. 55, No. 11, November, 2006

Minkin et al.

Table 4. Massꢀspectrometric data (EI, 70 eV) for 5,7ꢀdi(tertꢀ

butyl)ꢀ3ꢀhydroxyꢀ2ꢀ(quinolinꢀ2ꢀyl)tropones 6 and 7

(Xꢀray diffraction data) and the gas phase (DFT calculaꢀ

tions), 2ꢀ(quinolinꢀ2ꢀyl)ꢀβꢀtropolone (6e) containing the

electronꢀwithdrawing substituent (R¹= Cl) at position 4

Comꢀ

pound

m/z (I_rel(%))

Table 3. IR spectroscopic data for 5,7ꢀdi(tertꢀbutyl)ꢀ3ꢀhydroxyꢀ

2ꢀ(quinolinꢀ2ꢀyl)tropones 6 and 7

6a

6d

6e

6f

361 (4) [М]⁺, 333 (62), 318 (100), 290 (29),

57 (23), 40 (80)

445 (7) [М]⁺, 417 (53), 402 (70), 190 (40),

91 (30), 57 (85), 41 (100)

Comꢀ

pound

ν/cm^–1

409 (10) [М]⁺, 381 (90), 366 (100), 350 (40),

338 (40), 310 (45), 57 (40), 41 (50)

423 (8) [М]⁺, 395 (88), 380 (100), 352 (25),

57 (50), 41 (45)

423 (2) [М]⁺, 395 (88), 380 (100), 352 (28),

338 (12.5), 57 (35), 41 (37.5)

454 (7) [М]⁺, 426 (92), 411 (100), 383 (28),

365 (38), 57 (46), 41 (48)

6a

6c

1633, 1607, 1593, 1553, 1447, 1367, 1300

1620, 1513, 1500, 1460, 1447, 1367, 1353,

1327, 1300, 1233

6e

6f

6g

6j

6k

7a

1660, 1647, 1607, 1580, 1513, 1473, 1420

1606, 1580, 1460, 1313, 1300, 1233

1633, 1607, 1580, 1500, 1447, 1367, 1220

1647, 1620, 1567, 1527, 1460

1647, 1607, 1580, 1527, 1460

1633, 1620, 1593, 1513, 1500, 1460, 1447,

1415, 1380, 1367

6g

6i

6j

468 (5) [М]⁺, 440 (75), 425 (75), 397 (20),

379 (18), 91 (33), 57 (90), 41 (100)

468 (5) [М]⁺, 440 (75), 425 (75), 397 (20),

379 (18), 91 (33), 57 (90), 41 (100)

460 (8) [М]⁺, 432 (100), 417 (75), 401 (15),

375 (18), 115 (15), 91 (18), 57 (48), 41 (52)

474 (8) [М]⁺, 446 (100), 431 (65), 415 (10),

403 (18), 45 (18)

6k

7a

7b

7f

7b

7h

1633, 1607, 1580, 1460, 1447, 1367, 1273

1633, 1620, 1593, 1527, 1460, 1447,

1367, 1353

7o

7p

7r

7t

3420, 3260, 1633, 1607, 1580, 1513, 1447,

1393, 1367, 1353, 1340

3340, 3180, 1633, 1593, 1540, 1460, 1367,

1260, 1233

3328, 1593, 1580, 1553, 1500, 1460, 1407,

1367, 1313, 1273, 1233

3353, 1607, 1593, 1553, 1513, 1460, 1407,

1367, 1273, 1233

505 (8) [М]⁺, 477 (100), 462 (44), 83 (18),

57 (10), 41 (10)

7h

7k

7l

519 (8) [М]⁺, 491 (100), 476 (50), 448 (19),

57 (48), 41 (50)

472 (8) [М]⁺, 444 (100), 429 (70), 413 (14),

387 (20), 57 (52), 41 (75)

7v

7w

7x

3380, 1633, 1580, 1500, 1433, 1367,

1353, 1233

1620, 1593, 1580, 1513, 1447, 1367,

1353, 1300

1633, 1607, 1500, 1460, 1407, 1367 1340,

1300, 1260, 1233

503 (8) [М]⁺, 475 (100), 460 (44), 432 (15),

45 (15)

7n

7w

517 (8) [М]⁺, 489 (100), 474 (44), 446 (20),

57 (68), 41 (80)

500 (8) [М]⁺, 472 (100), 457 (72), 429 (20),

91 (25), 57 (72), 41 (90)

Table 5. Selected bond lengths (d) and bond angles (ω) for (2ꢀquinolinꢀ2ꢀyl)ꢀβꢀtropolones 6e and 7a

Bond

d/Å

Bond

d/Å

Angle

ω/deg

Compound 6e

O(1)—C(1)

O(2)—C(3)

O(2)—H(2)

N—C(8)

C(1)—C(2)

C(1)—C(7)

C(2)—C(3)

1.225(2)

1.317(3)

1.040(3)

1.340(3)

1.476(3)

1.400(3)

C(2)—C(8)

C(3)—C(4)

C(4)—C(5)

C(5)—C(6)

C(6)—C(7)

C(8)—C(9)

1.462(3)

1.453(3)

1.350(3)

1.451(3)

1.342(3)

1.423(3)

C(3)—O(2)—H(2)

C(8)—N—H(2)

103.8(13)

101.5(9)

127.2(2)

120.7(2)

119.4(2)

122.0(2)

117.5(2)

O(1)—C(1)—C(2)

C(3)—C(2)—C(1)

C(3)—C(2)—C(8)

O(2)—C(3)—C(2)

N—C(8)—C(2)

Compound 7a

O(1)—C(1)

O(2)—C(3)

N(1)—H(1)

N(1)—C(8)

C(1)—C(2)

C(1)—C(7)

C(2)—C(3)

1.233(4)

1.305(4)

0.99(4)

1.341(4)

1.465(5)

1.504(4)

1.376(4)

C(2)—C(8)

C(3)—C(4)

C(4)—C(5)

C(5)—C(6)

C(6)—C(7)

C(8)—C(9)

1.468(4)

1.470(4)

1.333(4)

1.441(5)

1.333(4)

1.401(4)

C(3)—O(2)—H(1)

C(8)—N(1)—H(1)

O(1)—C(1)—C(2)

C(3)—C(2)—C(1)

C(3)—C(2)—C(8)

O(2)—C(3)—C(2)

N—C(8)—C(2)

100(2)

108(2)

122.9(3)

121.9(3)

120.3(3)

122.3(3)

115.9(3)

Synthesis of βꢀtropolones

Russ.Chem.Bull., Int.Ed., Vol. 55, No. 11, November, 2006 2039

C(22)

C(17)

C(15)

C(17)

a

O(2)

C(22)

C(18)

C(5)

O(2)

C(14)

C(21)

C(20)

C(18)

C(4)

H(2)

N(1)

C(15)

C(16)

C(14)

H(1)

N(1)

C(4)

C(3)

C(21)

C(3)

C(2)

C(8)

C(13)

C(12)

C(5)

C(6)

C(13)

C(16)

C(20)

C(8)

C(2)

C(1)

O(1)

C(7)

C(11)

C(10)

C(6)

C(7)

C(1)

C(12)

C(9)

C(11)

Cl

C(9)

N(2)

C(29)

O(1)

C(25)

C(24)

C(10)

C(19)

C(26)

C(25)

C(19)

C(23)

C(24)

C(27)

O(3)

C(28)

C(25)

C(23)

b

Fig. 2. Molecular structure of 5,7ꢀdi(tertꢀbutyl)ꢀ3ꢀhydroxyꢀ2ꢀ

(8ꢀmethylꢀ4ꢀmorpholinoquinolinꢀ2ꢀyl)tropone (7a). Displaceꢀ

ment ellipsoids are drawn at the 50% probability level. The

O(2)...N(1) distance is 2.446 Å.

C(19)

C(24)

C(7)

C(21)

C(17)

C(16)

C(11)

N(1)

C(14)

C(13)

C(8)

C(2)

C(1)

C(6)

C(5)

C(22)

C(15)

C(18)

C(20)

C(10)

C(12)

C(9)

O(2)

C(3)

O(1)

Cl

C(4)

favorable for 2ꢀ(quinolinꢀ2ꢀyl)ꢀβꢀtropolone (7a) containꢀ

ing the electronꢀdonating substituent R¹= NR´R″.

The nucleophilic substitution of the chlorine atom in

2ꢀ(quinolinꢀ2ꢀyl)ꢀβꢀtropolones 6 (R¹= Cl) occurs in

nearly quantitative yields on heating of a mixture of 6 with

aliphatic, aromatic, or heterocyclic amines at 120—130 °C

for 1—3 h (method D, see Table 1).

Fig. 1. Two stereo projections of the molecular structure of

5,7ꢀdi(tertꢀbutyl)ꢀ2ꢀ(4ꢀchloroꢀ8ꢀmethylquinolinꢀ2ꢀyl)ꢀ3ꢀhydrꢀ

oxytropone (6e) established by Xꢀray diffraction. Displacement

ellipsoids are drawn at the 50% probability level. The O(2)...N(1)

distance is 2.455 Å.

Reaction mechanism. The multistep mechanism of the

reaction giving rise to 2ꢀ(quinolinꢀ2ꢀyl)ꢀβꢀtropolones 6

and 7 is presented in Scheme 2. In the initial step, aldol

condensation of 2ꢀmethylquinolines 4 with 3,5ꢀdi(tertꢀ

butyl)ꢀ1,2ꢀbenzoquinone (3) affords intermediate adꢀ

ducts 8. Some of these intermediates were preparatively

Table 6. Interplanar angles and the total (E_tot) and relative (∆E )

energies of tautomers of (2ꢀquinolinꢀ2ꢀyl)ꢀβꢀtropolones 6e

and 7a

Comꢀ

pound

ψ/deg

E_tot/au

∆Ε/kcal mol^–1

1

isolated, and their structures were established by H and

¹³C NMR spectroscopy and mass spectrometry. The moꢀ

lecular structure of 2,4ꢀdi(tertꢀbutyl)ꢀ6ꢀ(4ꢀchloroꢀ7,8ꢀ

dimethylquinolinꢀ2ꢀylmethylene)ꢀ6ꢀhydroxyꢀ2,4ꢀcycloꢀ

hexadienꢀ1ꢀone (8, R¹= Cl, R²= R³= H, R⁴= R⁵=

Me) was established by Xꢀray diffraction (Fig. 4, Table 7).

Intermediates 8 undergo cyclization to form norcaraꢀ

diene derivatives 9, which are rearranged into dihydroꢀ

tropolones 10. Oxidation of dihydrotropolones 10 with an

6e (OH)

6e (NH)

7a (OH)

7a (NH)

32.2

33.8

32.1

33.6

–1634.973603

–1634.972014

–1461.986964

–1461.987154

0

1.0

0

–0.12

of the quinoline ring exists as the hydroxyvinylimine (OH)

tautomer. On the contrary, the aminoenone (NH) form is

Table 7. Experimental (Xꢀray diffraction) and calculated (B3LYP/6ꢀ31G**) bond lengths (d) and bond angles (ω) for compound 8

Bond

d/Å

Bond

d/Å

Angle

ω/deg

Experiment Calculations

O(1)—C(1)

O(2)—C(6)

C(6)—C(7)

C(7)—C(8)

C(8)—N

1.207

1.402

1.579

1.511

1.294

1.392

1.424

1.231

1.417

1.580

1.511

1.320

1.365

1.422

C(1)—C(2)

C(2)—C(3)

C(3)—C(4)

C(4)—C(5)

C(6)—C(5)

C(1)—C(6)

C(10)—Cl

1.449

1.365

1.463

1.356

1.451

1.552

1.731

1.474

1.361

1.469

1.346

1.498

1.539

1.758

C(6)—C(7)—C(8)

C(1)—C(6)—C(7)

C(5)—C(6)—C(7)

N—C(8)—C(7)

C(8)—N—C(15)

O(1)—C(1)—C(6)

O(2)—C(6)—C(5)

113.7

102.8

111.4

117.4

118.2

117.5

109.6

114.3

104.5

109.2

116.9

119.5

116.6

110.3

N—C(15)

C(8)—C(9)

2040

Russ.Chem.Bull., Int.Ed., Vol. 55, No. 11, November, 2006

Minkin et al.

a

c

1.430

1.236

1.340

1.435

1.358

1.238

1.499

1.504

1.480

2.465

1.478

1.406

1.442

2.454

1.357

1.448

1.474

1.448

1.071

1.353

1.506

1.031

1.446

1.484

1.467

1.330

1.457

1.274

1.360

1.355

6e (OH)

6e (NH)

b

d

1.424

1.341

1.237

1.500

1.426

1.358

1.241

1.505

1.484

2.451

1.477

1.407

1.449

2.462

1.471

1.447

1.357

1.448

1.353

1.479

1.042

1.065

1.502

1.447

1.469

1.456

1.328

1.273

1.359

1.354

7a (OH)

7a (NH)

Fig. 3. Molecular geometry of the hydroxyvinylimine (a, b) and aminoenone (c, d) tautomers of 2ꢀ(quinolinꢀ2ꢀyl)ꢀβꢀtropolones 6e (a, c)

and 7a (b, d), calculated by the B3LYP/6ꢀ31G** method. The bond lengths are given in Å; the C(1)C(2)C(3)C(4)—C(4)C(5)C(6)C(7)

interplanar angles (ψ) are listed in Table 6.

excess of 3,5ꢀdi(tertꢀbutyl)ꢀ1,2ꢀbenzoquinone (3) affords

5,7ꢀdi(tertꢀbutyl)ꢀ2ꢀ(quinolinꢀ2ꢀyl)ꢀβꢀtropolones 6 and 7

C(26)

C(25)

as the final products. In an acetic acid solution, intermeꢀ

C(24)

C(18)

C(20)

diate adducts 8 are in equilibrium with the starting comꢀ

pounds. The involvement of these adducts in the reaction

mechanism is confirmed by the fact that storage of soluꢀ

tions of preisolated compounds 8 in air at room temperaꢀ

ture for 10—12 days or heating of these solutions at

40—50 °C for 20 h leads to their transformation into

2ꢀ(quinolinꢀ2ꢀyl)ꢀβꢀtropolones 6 and 7 in 60—80% yields.

The role of excess quinone 3 as an oxidizing agent is

confirmed by the fact that tosyl ether of the correspondꢀ

ing pyrocatechol was isolated from the reaction mixture.¹⁷

Condensation of 2ꢀmethylquinolines 4 at another carꢀ

bonyl group of quinone 3 is sterically hindered by the

presence of the tertꢀbutyl group adjacent to this carbonyl,

C(17)

C(13)

C(3)

C(19)

C(23)

C(4)

C(5)

C(14)

C(15)

C(2)

N

C(22)

C(12)

C(11)

C(8)

C(1)

O(1)

C(21)

C(6)

O(2)

C(7)

C(9)

C(16)

C(10)

Cl

Fig. 4. Molecular structure of 2,4ꢀdi(tertꢀbutyl)ꢀ6ꢀ[(4ꢀchloroꢀ

quinolinꢀ2ꢀyl)ꢀ7,8ꢀdimethylmethylene]ꢀ6ꢀhydroxyꢀ2,4ꢀcycloꢀ

hexadienꢀ1ꢀone (8) (R¹= Cl, R²= R³= H, R⁴= R⁵= Me).

Synthesis of βꢀtropolones

Russ.Chem.Bull., Int.Ed., Vol. 55, No. 11, November, 2006 2041

Scheme 2

Scheme 3

which prevents the formation of isomeric adduct 8´ and

blocks the alternative reaction channel giving rise to isoꢀ

meric 4,6ꢀdi(tertꢀbutyl)ꢀ2ꢀ(quinolinꢀ2ꢀyl)ꢀβꢀtropoꢀ

lones 6´ and 7´. The steric hindrances caused by the

tertꢀbutyl group adjacent to the carbonyl group of quinone

are responsible for very low (lower than 4%) yields of

2ꢀ(quinolinꢀ2ꢀyl)ꢀβꢀtropolones 11 in condensation of

2ꢀmethylquinolines with symmetrical 3,6ꢀdi(tertꢀbutyl)ꢀ

1,2ꢀbenzoquinone (12) (Scheme 3).

The formation of isomers 6´ and 7´ by isomerization

6→6´ or 7→7´, which occurs by a mechanism presented

in Scheme 4, is also highly unlikely because of the high

energy barrier (27.6 kcal mol^–1, including 26.6 kcal mol^–1

in the step of rotation about the C_quin—C_tropbond, acꢀ

cording to B3LYP/6ꢀ31G** calculations). Calculaꢀ

tions by the B3LYP/6ꢀ31G** method demonstrated that

βꢀtropolones 6e and 7a are 2—4 kcal mol^–1energetically

more favorable than their positional isomers 6´ and 7´.

Therefore, the formation of 2ꢀ(quinolinꢀ2ꢀyl)ꢀβꢀtropoꢀ

lones 6 and 7 (see Scheme 2) is thermodynamically and

kinetically controlled.

The detailed mechanism of formation of 2ꢀ(quinolinꢀ

2ꢀyl)ꢀβꢀtropolones 6 and 7 was studied by simulation of

the critical regions of the potential energy surfaces (PES)

for individual steps of the transformation described by

Scheme 2. It was found that the preliminary proton transꢀ

fer from the methylene group of intermediate adduct 8 to

the nitrogen atom of the heterocycle is a necessary condiꢀ

tion for the closure of the norcaradiene ring (8→9). Since

the geometry of the H₂C—C=N triad in adduct 8 is steriꢀ

cally unfavorable for the intramolecular proton transfer,

this reaction, like some other reactions involving the

1,3ꢀproton transfer,^18—20proceeds in a complex with an

2042

Russ.Chem.Bull., Int.Ed., Vol. 55, No. 11, November, 2006

Minkin et al.

Scheme 4

appropriate carrier molecule, which provides a rather low

barrier to the concerted double proton transfer. In the

transformation under consideration, the solvent molꢀ

ecule (acetic acid) or the catalyst molecule (pꢀtolueneꢀ

sulfonic acid) serves as the proton carrier. The calculated

pathway of the model reaction of oꢀbenzoquinone with

4ꢀmethylquinoline, starting from the formation of a stable

1 : 1 adduct of intermediate 8 with an acetic acid molꢀ

ecule, is shown in Fig. 5. The structures of the intermediꢀ

ates and transitions states are presented in Figs 6 and 7,

respectively. The corresponding energies are given in

Table 8.

The proton transfer CH→N leading to the isomerizaꢀ

tion M8•AcOH → M13•AcOH is the rateꢀdetermining

step of the transformation. The energy barrier for the

concerted double proton transfer calculated by the

B3LYP/6ꢀ31G** method is 25.4 kcal mol^–1. In the next

step of the transformation, the solvated intermediate

M13•AcOH is rearranged into the conformer

M´13•AcOH, which undergoes further isomerization to

form the zwitterionic intermediate M13⁺•AcO^–characꢀ

terized by the energy barrier of 10.9 kcal mol^–1. The calꢀ

culations demonstrated that the transformation of the

zwitterion M13⁺•AcO^–into 1,6ꢀdihydroxynorcaradiene

can occur through two different pathways. One of these

pathways is associated with the transfer of the proton of

the N—H...O=C fragment (see Fig. 5, dashed line),

whereas another pathway corresponds to the concerted

double proton transfer through the transition state TS4(2)

(see Fig. 7). The first pathway gives rise to the conformer

of solvated 1,6ꢀdihydroxynorcaradiene M´9•AcOH,

whereas the second pathway (which is 5.3 kcal mol^–1

energetically more favorable) produces the conformer

M9•AcOH and is, consequently, the main minimumꢀ

energy reaction path to dihydroꢀβꢀtropolone 10. It should

be noted that the potential energy surface of the transforꢀ

mation M13´•AcOH → M9•AcOH is strongly flattened,

and the inclusion of the ZPE correction into the total

energy leads to a change in the order of the relative enerꢀ

gies of the structures involved in the reaction. For exꢀ

ample, the local minimum corresponding to the intermeꢀ

diate M13⁺•AcO^–calculated with the zeroꢀpoint energy

∆E/kcal mol^–1

30

TS4(1)

TS1

25

TS4(2)

TS3

20

TS5(1)

M13⁺•AcO^–

15

10

M8+AcOH

M´9•AcOH

TS2

TS5(2)

M9•AcOH

M´13•AcOH

M´10•AcOH

M10•AcOH

M13•AcOH

5

0

M8•AcOH

Fig. 5. Reaction energy profile of the multistep rearrangement of the solvated intermediate (M8) into solvated dihydroꢀβꢀtropolone

(M10) calculated by the B3LYP/6ꢀ31G** method.

Synthesis of βꢀtropolones

Russ.Chem.Bull., Int.Ed., Vol. 55, No. 11, November, 2006 2043

1.389

1.324

2.451

1.369

1.349

1.506

1.769

1.447

1.520

1.973

1.589

1.360

1.550

1.761

1.549

1.448

1.354

1.465

1.677

M8•AcOH

M13•AcOH

1.370

1.526

1.383

1.434

1.348

1.352

1.567

1.344

1.533

1.470

1.448

1.352

1.542

1.855

1.635

1.458

1.354

1.655

1.465

1.795

1.003

1.507

M´13•AcOH

M13⁺•AcO^–

1.326

1.483

1.540

1.355

1.480

1.534

1.587

1.327

1.707

1.520

1.587

1.355

1.446

1.447

1.355

1.817

1.946

1.668

1.002

1.465

0.984

1.465

1.355

1.767

1.806

M´9•AcOH

M9•AcOH

1.320

1.515

1.518

1.702

2.357

1.377

1.433

1.787

0.991

1.363

0.981

1.743

1.909

1.438

1.525

2.420

1.374

1.791

1.364

1.786

1.435

M´10•AcOH

M10•AcOH

Fig. 6. The geometry of the structures (calculated by the B3LYP/6ꢀ31G** method) corresponding to the local minima shown in Fig. 5.

The bond lengths are given in Å.

2044

Russ.Chem.Bull., Int.Ed., Vol. 55, No. 11, November, 2006

Minkin et al.

1.386

1.943

1.368

1.532

1.538

1.467

1.356

1.433

1.343

1.459

1.354

1.345

1.419

1.218

1.580

1.916

1.457

1.751

1.549

1.691

1.354

1.466

TS1

TS2

1.358

1.408

1.541

1.349

1.513

1.533

1.450

1.355

1.450

1.460

1.052

TS3

1.348

1.427

1.588

1.339

1.467

1.750

1.217

1.369

1.163

1.563

1.625

1.466

1.352

1.546

1.530

1.449

1.348

1.448

1.351

1.193

1.842

1.474

1.695

1.643

TS4(1)

TS4(2)

1.323

1.495

1.713

1.498

1.767

1.371

1.514

1.491

1.513

1.761

1.325

1.427

1.692

1.371

1.808

1.947

1.434

1.371

1.427

1.370

1.436

1.747

1.811

TS5(1)

TS5(2)

Fig. 7. The geometry of the structures (calculated by the B3LYP/6ꢀ31G** method) of the transitions states shown in Fig. 5. The bond

lengths are given in Å.

Synthesis of βꢀtropolones

Russ.Chem.Bull., Int.Ed., Vol. 55, No. 11, November, 2006 2045

Table 8. Total energies (E_tot), the zero point energies (ZPE), and

the relative energies of the structures corresponding to the staꢀ

tionary points on the potential energy surface for the formation

of 2ꢀ(quinolinꢀ2ꢀyl)ꢀβꢀtropolones

Table 9. Total energies (E_tot), the zero point energies (ZPE),

and the relative energies (with the ZPE correction) of the strucꢀ

tures corresponding to the stationary points on the potential

energy surface for the reaction shown in Fig. 8

Strucꢀ

ture

–E_tot

*

ZPE

∆E

Strucꢀ

ture

–E_tot

*

ZPE

∆E

/kcal mol^–1

au

M13

TS6

1282.297686

1282.274865

(i911.9)

1282.292376

1282.289275

(i327.5)

0.242690

0.238337

8.4

20.0

M8•AcOH

TS1

1511.429465

1511.388908

(i1192.5)

1511.416592

1511.410618

(i29.1)

0.306917

0.301741

0

25.4

M´8

TS7

0.243034

0.241967

12.0

13.2

M13•AcOH

TS2

0.307066

0.306139

8.1

11.8

M´9

1282.312358

0.243966

0

M´13•AcOH 1511.415293

TS3

0.306917

0.304663

8.9

19.8

* The imaginary vibrational frequencies (cm^–1) for the transiꢀ

tion states are given in parentheses.

1511.397894

(i206.7)

1511.399071

1511.387803

(i817.3)

1511.404279

1511.402998

(i339.9)

M13⁺•AcO^–

TS4(1)

0.306141

0.302192

19.1

26.1

acetic acid molecule was taken into account (see Fig. 5).

The calculated barrier for the reverse norcaradiene rearꢀ

rangement of the 1,3,5ꢀcycloheptatriene derivative M´10

into M´9 is 13.2 kcal mol^–1. This value is rather close to

the experimental energy barrier for thermal isomerizaꢀ

tion of unsubstituted 1,3,5ꢀcycloheptatriene into norcaraꢀ

M´9•AcOH

TS5(1)

0.307171

0.306484

15.8

16.6

M´10•AcOH 1511.424287

TS4(2)

0.308096

0.301843

3.2

20.8

1511.396311

(i375.6)

1511.411150

1511.409716

(i335.4)

diene (11 kcal mol^{–1 22}

and the barrier for the latter reꢀ

)

M9•AcOH

TS5(2)

0.306896

0.306220

11.5

12.4

action calculated by the B3LYP/6ꢀ31G* method

(10.0 kcal mol^–1).²³Therefore, it can be concluded that

the reaction mechanism shown in Scheme 2 agrees well

with the calculated data.

10•AcOH

1511.425152

0.307183

2.7

* The imaginary vibrational frequencies (cm^–1) for the transiꢀ

tion states are given in parentheses.

Synthesis of 5,7ꢀdi(tertꢀbutyl)ꢀ4ꢀnitroꢀ2ꢀ(quinolinꢀ2ꢀ

yl)ꢀβꢀtropolones 15 and 4,6ꢀdioxoꢀ2ꢀazabicyclo[3.3.0]ꢀ

octaꢀ2,7ꢀdiene Nꢀoxides 16. 5,7ꢀDi(tertꢀbutyl)ꢀ4ꢀnitroꢀ

2ꢀ(quinolinꢀ2ꢀyl)ꢀβꢀtropolones 15 (Table 10) and

5,7ꢀdi(tertꢀbutyl)ꢀ2ꢀ(quinolinꢀ2ꢀyl)ꢀβꢀtropolones 6 and 7

containing no nitro groups in the tropolone moiety

were prepared in low yields by refluxing a solution of

2ꢀmethylquinoline 4 (R¹= H or Cl) and 4,6ꢀdi(tertꢀbuꢀ

tyl)ꢀ3ꢀnitroꢀ1,2ꢀbenzoquinone (14)²⁴in oꢀxylene for 1 h

(the conditions corresponding to the method B used for

the synthesis of 2ꢀ(quinolinꢀ2ꢀyl)ꢀβꢀtropolones 6 and 7).

Under the same conditions, the reactions of quinolines 4

(R¹= NO₂or morpholino) with quinone 14 proꢀ

duced easily isolable yellow crystals of 4,6ꢀdioxoꢀ2ꢀazaꢀ

bicyclo[3.3.0]octaꢀ2,7ꢀdiene Nꢀoxides 16 (Scheme 5,

Table 11). The structures of these crystalline products

were established by Xꢀray diffraction. The physicochemiꢀ

cal characteristics of compounds 15 and 16 are given in

Tables 10—14. The probable reaction mechanism for the

formation of bicyclic compounds 16 is presented in

Scheme 6.

correction is higher than the energy levels of the two

adjacent transitions states TS3 and TS4(2). In such cases

described in the literature (see, for example, the study²¹

and references therein), it is necessary to apply a more

rigorous approach to studies of the corresponding regions

of the potential energy surface using an anharmonic apꢀ

proximation. Since this detailed investigation is beyond

the scope of the present study, the ZPE correction was

ignored in estimating the relative energies shown in Fig. 5.

The intermediates M9•AcOH and M´9•AcOH readily

undergo the rearrangement (the energy barriers are as low

as 0.9 and 0.8 kcal mol^–1, respectively) accompanied by

expansion of the sixꢀmembered ring to form dihydroꢀβꢀ

tropolones M10•AcOH and M´10•AcOH. Subsequent

oxidation of compounds 10 with quinone 3 affords

2ꢀ(quinolinꢀ2ꢀyl)ꢀβꢀtropolones of types 6 and 7 as the

final products.

We also performed B3LYP/6ꢀ31G** calculations for

the rearrangement of the unsolvated intermediate M13

with the proton transferred from the methylene group to

the nitrogen atom of the quinoline ring. The results of

calculations presented in Fig. 8 and Table 9 agree well

with the results of calculations, in which solvation by one

The molecular structures of two compounds, which

are representatives of the previously unknown heterocyclic

system 16, are shown in Figs 9 and 10. Selected bond

lengths and bond angles are given in Table 15. The inꢀ

tramolecular electrophilic addition of the nitrogen atom

2046

Russ.Chem.Bull., Int.Ed., Vol. 55, No. 11, November, 2006

Minkin et al.

∆E/kcal mol^–1

1.352

1.422

1.767

1.549

1.178

1.305

25

20

15

10

5

1.509

1.320

1.495 1.322

1.513

1.753

1.369

TS6

1.791

0.986

TS7

M´9

1.358

1.319

1.514

1.520

1.526

M13

1.438

1.373

2.429

1.739

0.991

1.346

1.327

1.477

1.556

1.559

1.391

1.779

0.989

M´10

0

Fig. 8. Theoretical simulation of the reaction mechanism of the gasꢀphase rearrangement of the intermediate (M13) into

dihydronorcaradiene (M´9) followed by the transformation into dihydroꢀβꢀtropolone (M´10). The bond lengths are given in Å.

of the nitro group to the methine carbon atom in the

initially formed intermediate product 17 of aldol condenꢀ

sation of quinoline 4 with quinone 14 is the critical step of

the transformation. Intramolecular cyclization of the prodꢀ

uct of aldol condensation of oꢀnitrobenzaldehyde with

acetone, which is the rateꢀdetermining step of the classiꢀ

cal Baeyer—Drewson indigo synthesis,²⁵is the direct

analog of the above reaction. The reaction producing

4,6ꢀdioxoꢀ2ꢀazabicyclo[3.3.0]octaꢀ2,7ꢀdiene Nꢀoxides 16

can, presumably, further proceed as a sequence of the

transformations 17 → 18 → 19 → 16.

Byꢀproducts of the reaction. The transformations preꢀ

sented in Schemes 1 and 5 occur under rather severe

conditions and, consequently, they are accompanied by

Scheme 5

Synthesis of βꢀtropolones

Russ.Chem.Bull., Int.Ed., Vol. 55, No. 11, November, 2006 2047

Table 10. Yields, the melting points, and elemental analysis data for 5,7ꢀdi(tertꢀbutyl)ꢀ3ꢀhydroxyꢀ4ꢀnitroꢀ2ꢀ(quinolinꢀ2ꢀyl)tropones 15

Comꢀ

pound

R¹

R²

R³

R⁴

R⁵Yield (%)

(Method)

M.p.

/°С

Found

Calculated

Molecular

formula

(%)

C

H

Cl

—

N

15a

15b

15c

H

Cl

H

7(B)

6(B)

233—235

259—261

228—230

70.83 6.38

70.92 6.45

68.41 5.50

68.50 5.54

66.12 5.73

66.00 5.98

66.47 6.01

66.59 6.23

66.48 6.15

66.59 6.23

60.02 5.11

60.06 5.24

66.64 6.21

66.59 6.23

60.66 5.45

60.76 5.49

6.79 C₂₄H₂₆N₂O₄

6.89

7,8ꢀBenzo

7.13

7.22

7.62

7.79

7.45

7.56

7.49

7.56

7.13

7.09

7.4

5.64 C₂₈H₂₇ClN₂O₄

5.71

H

Me

6.04 C₂₅H₂₇ClN₂O₄

6.16

15d

15e

15f

Cl

H

Me

H

Me

H

Me

6(B)

8(B)

7(B)

6(B)

7(B)

214—216

200—202

250—252

240—242

6.02 C₂₆H₂₉ClN₂O₄

5.97

6.01 C₂₆H₂₉ClN₂O₄

5.97

8.29 C₂₅H₂₆ClN₃O₆

8.40

5.92 C₂₆H₂₈ClN₃O₆

5.97

H

NO₂

H

15g

15h

Me

H

7.56

6.96

6.90

Me

8.09 C₂₆H₂₈ClN₃O₆

8.18

15i

15j

15k

15l

H

Me

H

Me

H

89(D)

88(D)

91(D)

90(D)

220—222

195—197

238—240

200—202

68.62 6.73

68.89 6.98

69.22 6.93

69.34 7.18

69.26 7.04

69.34 7.18

66.56 6.74

66.78 6.76

—

8.14 C₂₉H₃₅N₃O₅

8.31

8.18 C₃₀H₃₇N₃O₅

8.09

7.88 C₃₀H₃₇N₃O₅

8.09

7.98 C₂₉H₃₅N₃O₆

8.06

Me

H

OMe

15m

15n

15o

H

Me

H

Me

90(D)

84(D)

89(D)

199—201

204—206

221—223

71.62 7.43

71.54 7.40

71.82 7.48

71.93 7.59

73.32 6.80

73.44 6.91

—

8.12 C₃₀H₃₇N₃O₄

8.34

7.92 C₃₁H₃₉N₃O₄

8.12

7.64 C₃₃H₃₇N₃O₄

7.79

7,8ꢀBenzo

C(34)

O(37)

C(6)

C(26)

C(16)

O(36)

C(17)

C(15)

C(18)

C(12)

C(4)

C(3)

C(33)

N(9)

C(5)

C(25)

C(23)

C(14)

C(13)

C(10)

C(7)

C(8)

N(27)

C(32)

C(1)

C(11)

C(28)

N(2)

O(35)

C(24)

C(29)

O(30)

C(31)

C(20)

C(19)

C(21)

C(22)

Fig. 9. Molecular structure of 1,7ꢀdi(tertꢀbutyl)ꢀ3ꢀ(6,8ꢀdimethylꢀ4ꢀmorpholinoquinolinꢀ2ꢀyl)ꢀ4.6ꢀdioxoꢀ2ꢀazabicyclo[3.3.0]octaꢀ

2,7ꢀdiene Nꢀoxide (16b). Displacement ellipsoids are drawn at the 50% probability level. The angle between the C(1)N(2)C(3)C(4)C(5)

and C(1)C(8)C(7)C(6)C(5) planes is 120.4°. The C(4)C(3)C(10)C(11) dihedral angle is 140.1(2)°.

2048

Russ.Chem.Bull., Int.Ed., Vol. 55, No. 11, November, 2006

Minkin et al.

Table 11. Yields, the melting points, and elemental analysis data for 4,6ꢀdioxoꢀ2ꢀazabicyclo[3.3.0]octaꢀ2,7ꢀdiene Nꢀoxides (16)

Comꢀ

pound

R¹

R²

R³

R⁴

R⁵

Yield

(%)

M.p.

/°С

Found

Calculated

Molecular

formula

(%)

C

H

N

16a

16b

16c

H

Me

H

Me

28

26

22

210—212

220—222

237—239

71.08

71.14

71.48

71.54

71.38

71.54

7.02

7.21

7.36

7.40

7.32

7.40

8.46

8.58

8.18

8.34

8.36

8.34

C₂₉H₃₅N₃O₄

C₂₆H₃₂ClNO₂

C₃₀H₃₇N₃O₄

Me

16d

16e

NO₂

H

Me

22

20

219—221

221—223

67.48

67.65

68.08

68.11

6.72

6.81

6.92

7.01

10.38

10.52

10.14

10.25

C₃₀H₃₆N₄O₅

C₃₁H₃₈N₄O₅

Me

Table 12. ¹H NMR spectroscopic data for 5,7ꢀdi(tertꢀbutyl)ꢀ3ꢀhydroxyꢀ4ꢀnitroꢀ2ꢀ(quinolinꢀ2ꢀyl)tropones (15) and 4,6ꢀdioxoꢀ2ꢀ

azabicyclo[3.3.0]octaꢀ2,7ꢀdiene Nꢀoxides (16)

Comꢀ

pound

δ (J/Hz)

15a

15b

15c

1.30 (s, 9 H, Bu^t(5)); 1.31 (s, 9 H, Bu^t(7)); 6.37 (s, 1 H, H(6)); 7.45—8.25 (m, 6 H, quinoline);

18.00 (br.s, 1 H, C(3)ОH)

1.33 (s, 9 H, Bu^t(5)); 1.35 (s, 9 H, Bu^t(7)); 6.47 (s, 1 H, H(6)); 7.78—8.72 (m, 6 H, arom.);

8.47 (s, 1 H, H(3´)); 19.52 (br.s, 1 H, C(3)ОH)

1.30 (s, 9 H, Bu^t(5)); 1.31 (s, 9 H, Bu^t(7)); 2.72 (s, 3 H, Me(8´)); 6.38 (s, 1 H, H(6));

7.51 (t, 1 H, H(6´), J = 7.7); 7.65 (d, 1 H, H(7´), J = 7.6); 8.03 (d, 1 H, H(5´), J = 7.6);

8.34 (s, 1 H, H(3´)); 18.03 (br.s, 1 H, C(3)ОH)

15d

15e

15f

15g

15h

15i

1.30 (s, 9 H, Bu^t(5)); 1.31 (s, 9 H, Bu^t(7)); 2.65 (s, 3 H, Me(6´)); 2.69 (s, 3 H, Me(8´)); 6.38 (s, 1 H,

H(6)); 7.48 (s, 1 H, H(7´)); 7.80 (s, 1 H, H(5´)); 8.32 (s, 1 H, H(3´)); 18.12 (br.s, 1 H, C(3)ОH)

1.30 (s, 9 H, Bu^t(5)); 1.31 (s, 9 H, Bu^t(7)); 2.54 (s, 3 H, Me(7´)); 2.61 (s, 3 H, Me(8´)); 6.36 (s, 1 H, H(6));

7.43 (d, 1 H, H(6´), J = 8.4); 7.92 (d, 1 H, H(5´), J = 8.4); 8.28 (s, 1 H, H(3´)); 17.93 (br.s, 1 H, C(3)ОH)

1.30 (s, 9 H, Bu^t(5)); 1.31 (s, 9 H, Bu^t(7)); 2.78 (s, 3 H, Me(8´)); 6.52 (s, 1 H, H(6)); 7.58 (d, 1 H, H(7´),

J = 8.5); 7.68 (d, 1 H, H(6´), J = 8.5); 8.40 (s, 1 H, H(3´)); 18.40 (br.s, 1 H, C(3)ОH)

1.25 (s, 9 H, Bu^t(5)); 1.38 (s, 9 H, Bu^t(5)); 2.40 (s, 3 H, Me(6´)); 2.70 (s, 3 H, Me(8´)); 6.68 (d, 1 H, H(4),

J = 1.82); 6.82 (d, 1 H, H(6), J = 1.82); 7.50 (s, 1 H, H(7´)); 8.28 (s, 1 H, H(3´)); 18.02 (s, 1 H, C(3)ОH)

1.30 (s, 9 H, Bu^t(5)); 1.32 (s, 9 H, Bu^t(7)); 2.58 (s, 3 H, Me(7´)); 2.65 (s, 3 H, Me(8´)); 6.44 (s, 1 H, H(6));

7.52 (s, 1 H, H(6´)); 8.32 (s, 1 H, H(3´)); 18.29 (br.s, 1 H, C(3)ОH)

1.30 (s, 18 H, Bu^t(5), Bu^t(7)); 2.69 (s, 3 H, Me(8´)); 3.34 (m, 4 H, morpholine); 3.99 (m, 4 H, morpholine);

6.33 (s, 1 H, H(6)); 7.38 (t, 1 H, H(6´), J = 7.7); 7.53 (d, 1 H, H(7´), J = 7.6); 7.75 (d, 1 H, H(5´), J = 7.6);

7.77 (s, 1 H, H(3´)); 17.15 (br.s, 1 H, C(3)ОH)

15j

1.31 (s, 18 H, Bu^t(5), Bu^t(7)); 2.48 (s, 3 H, Me(6´)); 2.65 (s, 3 H, Me(8´)); 3.30 (m, 4 H, morpholine);

3.99 (m, 4 H, morpholine); 6.32 (s, 1 H, H(6)); 7.34 (s, 1 H, H(7´)); 7.51 (s, 1 H, H(5´)); 7.70 (s, 1 H,

H(3´)); 17.10 (br.s, 1 H, C(3)ОH)

15k

15l

1.30 (s, 18 H, Bu^t(5), Bu^t(7)); 2.49 (s, 3 H, Me(7´)); 2.58 (s, 3 H, Me(8´)); 3.34 (m, 4 H, morpholine);

4.00 (m, 4 H, morpholine); 6.32 (s, 1 H, H(6)); 7.27 (d, 1 H, H(5´), J = 8.5); 7.64 (d, 1 H, H(6´), J = 8.5);

7.72 (s, 1 H, H(3´)); 17.06 (br.s, 1 H, C(3)ОH)

1.30 (s, 18 H, Bu^t(5), Bu^t(7)); 3.30 (t, 4 H, morpholine); 3.92 (s, 3 H, O(6´)Me); 4.00 (t, 4 H, morpholine);

6.37 (s, 1 H, H(6)); 7.21 (d, 1 H, H(5´), J = 2.7); 7.32 (d.d, 1 H, H(7´), J₁= 9.0, J₂= 2.7); 7.63 (d, 1 H,

H(8´), J = 9.0); 7.77 (s, 1 H, H(3´)); 17.52 (br.s, 1 H, C(3)ОH)

15m

1.29 (s, 18 H, Bu^t(5), Bu^t(7)); 1.6—2.0 (m, 6 H, piperidine); 2.67 (s, 3 H, Me(8´)); 3.2—3.4 (m, 4 H, piperidine);

6.31 (s, 1 H, H(6)); 7.32 (t, 1 H, H(6´), J = 7.8); 7.49 (d, 1 H, H(7´), J = 7.8); 7.71 (d, 1 H, H(5´), J = 7.8);

7.74 (s, 1 H, H(3´)); 16.94 (br.s, 1 H, C(3)ОH)

(to be continued)

Synthesis of βꢀtropolones

Table 12 (continued)

Russ.Chem.Bull., Int.Ed., Vol. 55, No. 11, November, 2006 2049

Comꢀ

pound

δ (J/Hz)

15n

1.30 (s, 18 H, Bu^t(5,7)); 1.7—1.9 (m, 6 H, piperidine); 2.47 (s, 3 H, Me(6´)); 2.64 (s, 3 H, Me(8´));

3.2—3.5 (m, 4 H, piperidine); 6.31 (s, 1 H, H(6)); 7.33 (s, 1 H, H(7´)); 7.50 (s, 1 H, H(5´)); 7.72 (s, 1 H,

H(3´)); 16.98 (br.s, 1 H, C(3)ОH)

15o

16a

1.31 (s, 18 H, Bu^t(5), Bu^t(7)); 1.7—1.9 (m, 6 H, piperidine); 3.35 (m, 4 H, piperidine); 6.37 (s, 1 H, H(6));

7.7—8.0 (m, 6 H, arom.); 8.60 (d, 1 H, H(3´)); 18.38 (br.s, 1 H, C(3)ОH)

1.23 (s, 18 H, Bu^t(1), Bu^t(7)); 2.82 (s, 3 H, Me(8´)); 3.25 (t, 4 H, morpholine); 3.78 (s, 1 H, H(5)); 3.98 (t, 4 H,

morpholine); 7.41 (t, 1 H, H(6´), J = 7.5); 7.53 (d, 1 H, H(7´), J = 7.5); 7.61 (s, 1 H, H(8)); 7.73 (s, 1 H,

H(3´)); 7.84 (d, 1 H, H(5´), J = 7.5)

16b

16c

16d

16e

1.23 (s, 18 H, Bu^t(1), Bu^t(7)); 2.50 (s, 3 H, Me(6´)); 2.79 (s, 3 H, Me(8´)); 3.22 (m, 4 H, C(4´)N(СH₂)₂);

3.77 (s, 1 H, H(5)); 3.99 (m, 4 H, О(СH₂)₂C(4´)); 7.37 (s, 1 H, H(7´)); 7.59 (s, 1 H, H(5´)); 7.60 (s, 1 H,

H(8)); 7.75 (s, 1 H, H(3´))

1.23 (s, 18 H, Bu^t(1), Bu^t(7)); 2.48 (s, 3 H, Me(7´)); 2.79 (s, 3 H, Me(8´)); 3.23 (t, 4 H, morpholine); 3.77 (s, 1 H,

H(5)); 3.98 (t, 2 H, morpholine); 7.33 (d, 1 H, H(6´), J = 8.5); 7.61 (s, 1 H, H(8)); 7.73 (s, 1 H, H(3´));

7.75 (d, 1 H, H(5´), J = 8.5)

1.23 (s, 18 H, Bu^t(1,7)); 1.6—1.9 (m, 6 H, piperidine); 2.6—2.8 (m, 2 H, piperidine); 2.84 (s, 3 H, Me(8´));

3.2—3.4 (m, 2 H, piperidine); 3.78 (s, 1 H, H(5)); 7.50 (d, 1 H, H(6´), J = 8.0); 7.59 (s, 1 H, H(8)); 7.64

(d, 1 H, H(7´), J = 8.0); 7.98 (s, 1 H, H(3´))

1.23 (s, 18 H, Bu^t(1,7)); 1.71 (m, 6 H, piperidine); 2.49 (s, 3 H, Me(7´)); 2.73 (m, 2 H, piperidine);

2.80 (s, 3 H, Me(8´)); 3.30 (m, 2 H, piperidine); 3.79 (s, 1 H, H(5)); 7.50 (s, 1 H, H(6´)); 7.59 (s, 1 H,

H(8)); 7.96 (s, 1 H, H(3´))

the formation of byꢀproducts of the reaction. Presently,

polyfused heterocyclic system, viz., 8,9a,11,13ꢀtetra(tertꢀ

butyl)ꢀ16ꢀchloroꢀ3,4ꢀdimethylcyclopentaꢀ[2´,3´]ꢀchroꢀ

meno[4´,3´:3,4]pyrrolo[1,2ꢀa]quinolineꢀ6,7(9aH )ꢀdione

(20), in 6% yield. The structure of molecule 20 was estabꢀ

lished by Xꢀray diffraction.²⁶Apparently, the formation

of compound 20 is preceded by acidꢀcatalyzed dimerizaꢀ

tion of quinone 3. However, an additional investigation is

we preparatively isolated two of these products and

established their structures by Xꢀray diffraction. The reꢀ

actions of 4ꢀchloroꢀ2,7,8ꢀtrimethylquinoline (4, R¹= Cl,

R²= R³= H, R⁴= R⁵= Me) and 3,5ꢀdi(tertꢀbutyl)ꢀ1,2ꢀ

benzoquinone (3) under the conditions described for the

methods A and B produced a derivative of the new

Scheme 6

2050

Russ.Chem.Bull., Int.Ed., Vol. 55, No. 11, November, 2006

Minkin et al.

Table 13. Massꢀspectrometric data (EI, 70 eV) for 5,7ꢀdi(tertꢀ

butyl)ꢀ3ꢀhydroxyꢀ4ꢀnitroꢀ2ꢀ(quinolinꢀ2ꢀyl)tropones (15)

Table 14. IR spectroscopic data for 2ꢀazabicyclo[3.3.0]octaꢀ2,7ꢀ

dieneꢀ4,6ꢀdione Nꢀoxides (16)

Comꢀ

pound

m/z (I_rel(%))

Comꢀ

pound

ν/cm^–1

15a

15b

15c

15d

15g

15m

406 (15) [М]⁺, 378 (40), 360 (95), 128 (100),

91 (34), 57 (65), 41 (95)

16a

1740, 1700, 1567, 1513, 1500, 1447, 1400,

1367, 1340, 1246, 1233, 1220, 1180, 1140,

1100

1740, 1700, 1620, 1580, 1527, 1460, 1367

1740, 1700, 1580, 1527, 1500, 1460, 1447,

1433, 1400, 1313, 1273, 1246, 1233, 1220,

1180, 1150, 1100

1740, 1700, 1580, 1527, 1500, 1460, 1447,

1400, 1313, 1273, 1246, 1233, 1220, 1180,

1150, 1100

1740, 1700, 1620, 1580, 1527, 1500, 1460,

1447, 1400, 1313, 1273, 1246, 1233, 1220,

1180, 1150, 1100

490 (15) [М]⁺, 462 (30), 444 (70), 190 (60),

91 (28), 57 (80), 41 (100)

16b

16c

454 (10) [М]⁺, 426 (25), 408 (50), 384 (10), 352 (25),

322 (20), 176 (30), 154 (30), 91 (35), 57 (70), 41(100)

468 (15) [М]⁺, 440 (45), 422 (100), 398 (15),

366 (15), 154 (10), 91 (15), 57 (30), 41(35)

468 (5) [М]⁺, 440 (75), 425 (75), 397 (20),

379 (18), 91 (33), 57 (90), 41 (100)

16d

16e

1633, 1607, 1590, 1527, 1460, 1420, 1367,

1340, 1273, 1233

required for an understanding of the detailed reaction

mechanism.

we performed model (alkyl groups were ignored)

B3LYP/6ꢀ31G** calculations, which revealed the seꢀ

quence of transformations giving rise to ketone 21

(Scheme 7, Fig. 12). The data on the energy characterisꢀ

tics of the structures involved in the reaction are given in

Table 17. Dehydration of the initially formed adduct 8

affords stable methylenequinone hydrate 5, which is

transformed into carbinol 22 with a low energy barrier

The presence of considerable amounts (~10%) of

2ꢀ(2ꢀhydroxybenzoyl)quinoline derivative 21 was parꢀ

ticularly unexpected for us. The structure of this deꢀ

rivative was established by Xꢀray diffraction (Fig. 11,

Table 16).

To elucidate the mechanism of formation of quinoline

21 as a product of the side reaction shown in Scheme 1,

Table 15. Selected bond lengths (d) and bond angles (ω) for compounds 16b and 16d

Bond

d/Å

Angle

ω/deg

Angle

ω/deg

Compound 16b

C(1)—C(8)

C(1)—C(5)

C(1)—N(2)

N(2)—O(35)

N(2)—C(3)

C(3)—C(4)

C(3)—C(10)

C(4)—O(36)

C(4)—C(5)

C(6)—O(37)

1.512(5)

1.522(4)

1.532(4)

1.252(3)

1.322(4)

1.473(5)

1.474(5)

1.198(4)

1.516(5)

1.204(4)

C(8)—C(1)—C(5)

C(8)—C(1)—N(2)

C(5)—C(1)—N(2)

N(2)—C(1)—C(19)

O(35)—N(2)—C(3)

O(35)—N(2)—C(1)

C(3)—N(2)—C(1)

N(2)—C(3)—C(4)

N(2)—C(3)—C(10)

104.1(3)

109.0(3)

102.1(2)

109.7(3)

126.7(3)

118.5(3)

114.7(3)

108.2(3)

123.3(3)

O(36)—C(4)—C(3)

O(36)—C(4)—C(5)

C(3)—C(4)—C(5)

C(10)—N(9)—C(18)

N(9)—C(10)—C(11)

N(9)—C(10)—C(3)

C(11)—C(10)—C(3)

C(4)—C(3)—C(10)

126.6(3)

125.1(3)

108.3(3)

117.6(3)

124.5(3)

115.1(3)

120.3(3)

128.5(3)

Compound 16d

C(1)—C(8)

C(1)—C(5)

C(1)—N(2)

N(2)—O(35)

N(2)—C(3)

C(3)—C(4)

C(3)—C(10)

C(4)—O(36)

С(4)—C(5)

C(6)—O(37)

1.503(2)

1.522(2)

1.524(2)

1.259(2)

1.324(2)

1.453(2)

1.471(2)

1.210(2)

1.523(2)

1.205(2)

C(8)—C(1)—C(5)

C(8)—C(1)—N(2)

C(5)—C(1)—N(2)

C(5)—C(1)—C(19)

N(2)—C(1)—C(19)

O(35)—N(2)—C(3)

O(35)—N(2)—C(1)

C(3)—N(2)—C(1)

N(2)—C(3)—C(4)

103.8(1)

106.6(1)

102.7(2)

116.3(1)

111.2(2)

126.6(2)

119.6(2)

113.7(2)

109.8(2)

N(2)—C(3)—C(10)

C(4)—C(3)—C(10)

O(36)—C(4)—C(3)

O(36)—C(4)—C(5)

C(3)—C(4)—C(5)

C(10)—N(9)—C(18)

N(9)—C(10)—C(11)

N(9)—C(10)—C(3)

C(11)—C(10)—C(3)

123.1(2)

127.1(2)

126.9(2)

125.1(2)

107.9(2)

117.3(2)

124.4(3)

115.1(2)

120.4(2)

N(33)—O(38) 1.215(3)

N(33)—O(39) 1.221(3)

Synthesis of βꢀtropolones

Russ.Chem.Bull., Int.Ed., Vol. 55, No. 11, November, 2006 2051

C(26)

C(25)

C(34)

O(37)

C(23)

O(36)

C(6)

C(5)

C(16)

C(15)

C(17)

C(18)

N(9)

C(4)

C(24)

C(7)

C(10)

C(8)

C(14)

N(33)

C(3)

N(2)

C(1)

C(13)

C(20)

C(11)

O(38)

C(19)

C(12)

O(35)

O(39)

N(27)

C(32)

C(22)

C(21)

C(28)

C(29)

C(30)

C(31)

Fig. 10. Molecular structure of 1,7ꢀdi(tertꢀbutyl)ꢀ3ꢀ(8ꢀmethylꢀ

5ꢀnitroꢀ4ꢀpiperidinoquinolinꢀ2ꢀyl)ꢀ4,6ꢀdioxoꢀ2ꢀazabicycloꢀ

[3.3.0]octaꢀ2,7ꢀdiene Nꢀoxide (16d). Displacement ellipsoids

are drawn at the 50% probability level. The angle between the

C(1)N(2)C(3)C(4)C(5) and C(1)C(8)C(7)C(6)C(5) planes

is 114.2°. The C(4)C(3)C(10)C(11) dihedral angle is 137.7(2)°.

O(2)

O(1)

Cl

Scheme 7

C(9)

C(7)

C(1)

C(6)

C(24)

C(2)

C(8)

C(10)

C(11)

C(25)

C(26)

C(20)

N

C(12)

C(13)

C(3)

C(4)

C(16)

C(15)

C(5)

C(22´)

C(19)

C(22)

C(14)

C(17)

C(18)

C(21´)

C(23)

C(23´)

C(21)

Fig. 11. Molecular structure of 4ꢀchloroꢀ2ꢀ(3,5ꢀdiꢀtertꢀbutylꢀ2ꢀ

hydroxybenzoyl)ꢀ7,8ꢀdimethylquinoline (21). The O(1)...O(2)

distance is 2.55 Å. The deviations of the O(1), C(7), O(2),

and H(1) atoms from the plane through the C(1), C(2), C(3),

C(4), C(5), and C(6) atoms are smaller than 0.05 Å. Two

fragments are rotated about the C(7)—C(8) bond by the

NC(8)—C(7)—C(1) angle of 39.2(2)°.

Table 16. Selected bond lengths (d) и bond angles (ω) for comꢀ

pound 21

Bond

d/Å

Angle

ω/deg

O(1)—C(2)

O(1)—H(1)

O(2)—C(7)

N—C(8)

1.342(3)

0.830(4)

1.236(3)

1.318(3)

1.365(3)

1.403(4)

1.404(4)

1.464(4)

1.500(3)

C(2)—O(1)—H(1)

C(8)—N—C(16)

C(2)—C(1)—C(6)

C(2)—C(1)—C(7)

C(6)—C(1)—C(7)

O(1)—C(2)—C(1)

O(2)—C(7)—C(1)

O(2)—C(7)—C(8)

C(1)—C(7)—C(8)

N—C(8)—C(9)

108.0(2)

118.4(2)

118.8(2)

120.3(2)

120.8(2)

120.4(2)

121.4(2)

115.7(2)

122.9(2)

123.7(2)

117.9(2)

(12.6 kcal mol^–1for structure M5 deprived of all methyl

and tertꢀbutyl groups). Subsequent oxidation of 22 gives

rise to ketone 21.

N—C(16)

C(1)—C(2)

C(1)—C(6)

C(1)—C(7)

C(7)—C(8)

Experimental

The ¹H and ¹³C NMR spectra were recorded on Varian

Unity 300 spectrometers. The ¹⁵N NMR spectra were measured

on a Bruker AMꢀ500 spectrometer (500 MHz). The mass specꢀ

N—C(8)—C(7)

2052

Russ.Chem.Bull., Int.Ed., Vol. 55, No. 11, November, 2006

Minkin et al.

∆E/kcal mol^–1

1.452

1.424

1.476 1.086

2.238

1.287

1.398

1.086

1.516

25

1.464

1.088

TS8

1.364

1.231

2.331

20

15

M5 + H₂O

M5•H₂O

10

5

1.414

1.360

0.977

1.522

1.452

1.509

1.367

1.520

1.468

1.090

1.794

1.238

2.272

0

1.909

0.974

M22

Fig. 12. Energy profile of the rearrangement of hydrated methylenequinone (M5) into carbinol (M22) calculated by the B3LYP/6ꢀ31G**

method. The bond lengths are given in Å. The dihedral angles, deg: 30.8 (M5), 37.2 (M5•H₂O), 43.4 (TS8), and 71.9 (M22).

Table 17. Total energies (E_tot), the zero point energies (ZPE),

and the relative energies (with the ZPE correction) of the strucꢀ

tures corresponding to the stationary points on the potential

energy surface for the reaction shown in Fig. 12

5 mmol), and pꢀtoluenesulfonic acid (0.20 g) was kept at

160—170 °C for 20 min. After cooling, the melt was dissolved in

a 2 : 1 hexane—CHCl₃mixture. The solution was passed through

an alumina column (hexane—CHCl₃, 2 : 1, as the eluent), and

a brightꢀyellow fraction was collected. Compound 6 was obꢀ

tained in a yield of 0.22 g (11%) as yellow crystals, m.p.

189—191 °C (propanꢀ2ꢀol).

Structure

–E_tot

*

ZPE

∆E

/kcal mol^–1

au

Method B. 5,7ꢀDi(tertꢀbutyl)ꢀ2ꢀ(4ꢀchloroꢀ6,8ꢀdimethylquinoꢀ

linꢀ2ꢀyl)ꢀ3ꢀhydroxytropone (6f). A solution of 3,5ꢀdi(tertꢀbutyl)ꢀ

1,2ꢀbenzoquinone (3) (2.20 g, 10 mmol), 4ꢀchloroꢀ2,6,8ꢀ

trimethylquinoline (1.03 g, 5 mmol), and pꢀtoluenesulfonic acid

(0.20 g) in oꢀxylene (10 mL) was refluxed for 6 h. After cooling,

the solution was passed through an alumina column (hexꢀ

ane—CHCl₃, 2 : 1, as the eluent) and a brightꢀyellow fraction

was collected. Compound 6f was obtained in a yield of 0.55 g

(26%) (6f) as yellow crystals, m.p. 198—201 °C (propanꢀ2ꢀol).

5,7ꢀDi(tertꢀbutyl)ꢀ2ꢀ(4ꢀchloroꢀ6,8ꢀdimethylꢀ5ꢀnitroquinolinꢀ

2ꢀyl)ꢀ3ꢀhydroxyꢀ4ꢀnitrotropone (15g) and 5,7ꢀdi(tertꢀbutyl)ꢀ2ꢀ

(4ꢀchloroꢀ6,8ꢀdimethylꢀ5ꢀnitroquinolinꢀ2ꢀyl)ꢀ3ꢀhydroxytropone

(6j). A solution of 4,6ꢀdi(tertꢀbutyl)ꢀ3ꢀnitroꢀ1,2ꢀbenzoquinone

(14)²⁴(2.65 g, 10 mmol), 4ꢀchloroꢀ2,6,8ꢀtrimethylꢀ5ꢀnitroꢀ

quinoline²⁸(4) (1.03 g, 5 mmol), and pꢀtoluenesulfonic acid

(0.20 g) in oꢀxylene (10 mL) was refluxed for 1 h. After cooling,

the solution was passed through an alumina chromatographic

column (hexane—CHCl₃, 1 : 1, as the eluent) and two brightꢀ

yellow fractions were collected. Fraction I contained comꢀ

pound 6j; fraction II, compound 15g.

M5 + H₂O

M5•H₂O

TS8

1282.307526

1282.321137

1282.300359(i582.6)

1282.35101

0.237440

0.240628

0.239877

0.244960

22.7

16.1

28.7

0

M21

* The imaginary vibrational frequency (cm^–1) for the structure

of the transition state is given in parentheses.

tra were obtained on a Finnigan MAT INOS 50 mass spectromꢀ

eter. The IR spectra were recorded on an IRꢀ75 spectrometer as

Nujol mulls. Chromatography was carried out on columns

packed with Al₂O₃(Brockmann activity II—III). The melting

points were measured in glass capillaries on a PTP apparatus

and are uncorrected. The starting 2ꢀmethylquinolines were synꢀ

thesized according to procedures described earlier.^27,28

Synthesis of 5,7ꢀdi(tertꢀbutyl)ꢀ3ꢀhydroxyꢀ2ꢀ(quinolinꢀ2ꢀ

yl)tropones 6 and 7 (general procedures). Method A. 5,7ꢀDi(tertꢀ

butyl)ꢀ2ꢀ(4ꢀchloroꢀ8ꢀmethylquinolinꢀ2ꢀyl)ꢀ3ꢀhydroxytropone

(6e). A mixture of 3,5ꢀdi(tertꢀbutyl)ꢀ1,2ꢀbenzoquinone (3)

(2.20 g, 10 mmol), 4ꢀchloroꢀ2,8ꢀdimethylquinoline²⁷(0.96 g,

Compound 6j, the yield was 0.07 g (3%), yellow crysꢀ

tals, m.p. 223—225 °C (propanꢀ2ꢀol). Compound 15g, the

Synthesis of βꢀtropolones

Russ.Chem.Bull., Int.Ed., Vol. 55, No. 11, November, 2006 2053

yield was 0.154 g (6%), yellow crystals, m.p. 250—252 °C

(propanꢀ2ꢀol).

4ꢀChloroꢀ2ꢀ(3,5ꢀdiꢀtertꢀbutylꢀ2ꢀhydroxybenzoyl)ꢀ7,8ꢀdiꢀ

methylquinoline (21) and 8,9a,11,13ꢀtetra(tertꢀbutyl)ꢀ16ꢀchloroꢀ

3,4ꢀdimethylcyclopentaꢀ[2´,3´]chromeno[4´,3´,3,4]pyrroꢀ

lo[1,2ꢀa]quinolineꢀ6,7(9aH)dione (20). A solution of 3,5ꢀdi(tertꢀ

butyl)ꢀ1,2ꢀbenzoquinone (3) (2.20 g, 10 mmol), 4ꢀchloroꢀ2,7,8ꢀ

trimethylquinoline (1.03 g, 5 mmol), and pꢀtoluenesulfonic acid

(0.20 g) in oꢀxylene (10 mL) was refluxed as described in the

method B. After cooling, the solution was passed through an

alumina chromatographic column (hexane—CHCl₃, 10 : 1, as

the eluent), and the first two fractions eluted prior to the brightꢀ

yellow fraction of tropolone (6g) were collected. The first paleꢀ

yellow fraction contained compound 21; the second orange fracꢀ

tion, compound 20. Compound 21, the yield was 0.22 g (10%).

Method C. 5,7ꢀDi(tertꢀbutyl)ꢀ2ꢀ(4ꢀchloroꢀ7,8ꢀdimethylquinoꢀ

linꢀ2ꢀyl)ꢀ3ꢀhydroxytropone (6g). A solution of 3,5ꢀdi(tertꢀbuꢀ

tyl)ꢀ1,2ꢀbenzoquinone (3) (4.40 g, 20 mmol) and 4ꢀchloroꢀ2,7,8ꢀ

trimethylquinoline (2.05 g, 10 mmol) in AcOH (10 mL) was

heated at 50 °C for 20 h and then kept at room temperature for

1 day. The precipitate of tropolone (6g) that formed was filtered

off and washed with AcOH (10 mL) and water (100 mL). The

yield of the precipitate was 1.8 g. The mother liquor was diluted

with water, and the oily residue was extracted with chloroform

(30 mL). The extract was washed with a sodium carbonate soluꢀ

tion (3×50 mL) and water (3×50 mL) in a separating funnel and

dried with anhydrous Na₂SO₄for 3—4 h. The dry extract was

passed through an alumina chromatographic column (hexꢀ

ane—CHCl₃, 1 : 1, as the eluent), and a brightꢀyellow fracꢀ

tion was collected. Compound 6g was obtained in a yield of

0.87 g. The total yield was 2.67 g (63%), yellow crystals, m.p.

174—176 °C (propanꢀ2ꢀol).

Method D. 5,7ꢀDi(tertꢀbutyl)ꢀ3ꢀhydroxyꢀ2ꢀ(8ꢀmethylꢀ4ꢀ

morpholinoquinolinꢀ2ꢀyl)tropone (7a). A solution of 5,7ꢀdi(tertꢀ

butyl)ꢀ2ꢀ(4ꢀchloroꢀ8ꢀmethylquinolinꢀ2ꢀyl)ꢀ3ꢀhydroxytropone

(6e) (0.3 g, 0.73 mmol) in a freshly distilled morpholine (3 mL)

was refluxed for 1 h. The cooled solution was diluted with cold

water. The precipitate that formed was filtered off, washed with

warm water (200 mL), and dried. Compound 7a was obtained in

a yield of 0.3 g (89%) as yellow crystals, m.p. 200—202 °C

(propanꢀ2ꢀol).

Yellow crystals, m.p. 144—145 °C (propanꢀ2ꢀol). IR, ν/cm^–1

:

1607, 1580, 1540, 1500, 1473, 1406, 1367, 1353, 1340, 1287,

1260, 1233. ¹H NMR (CDCl₃), δ: 1.29 (s, 9 H, Bu^t(5)); 1.50 (s,

9 H, Bu^t(3)); 2.56 (s, 3 H, Me(7´)); 2.77 (s, 3 H, Me(8´)); 7.59

(d, 1 H, H(6´), J = 8.5 Hz); 7.64 (d, 1 H, H(4), J = 2.4 Hz); 8.00

(s, 1 H, H(3´)); 8.09 (d, 1 H, H(5´), J = 8.5); 8.20 (d, 1 H, H(6),

J = 2.4 Hz); 12.92 (s, 1 H, OH(2)). Found (%): C, 73.57;

H, 6.98; Cl, 8.18; N, 3.22. C₂₆H₃₀ClNO₂. Calculated (%):

C, 73.66; H, 7.13; Cl, 8.36; N, 3.30. Compound 20, the yield

was 0.18 g (6%). Orange crystals, m.p. 216—218 °C (propanꢀ

1

2ꢀol). H NMR (CDCl₃), δ: 1.00 (s, 9 H, Bu^t(9)); 1.29 (s, 9 H,

Bu^t(7)); 1.32 (s, 9 H, Bu^t(5a)); 1.43 (s, 9 H, Bu^t(4)); 2.31 (s,

3 H, Me(15)); 2.35 (s, 3 H, Me(16)); 6.70 (s, 1 H); 7.03 (m, 3 H);

7.23—7.24 (m, 2 H). Found (%): C, 76.54; H, 7.53; Cl, 5.32;

N, 2.12. C₄₀H₄₈ClNO₃. Calculated (%): C, 76.71; H, 7.73;

Cl, 5.66; N, 2.24.

4,7ꢀDi(tertꢀbutyl)ꢀ2ꢀ(4ꢀchloroꢀ8ꢀmethylquinolinꢀ2ꢀyl)ꢀ

3ꢀhydroxytropone (11) was synthesized by the reaction of

3,6ꢀdi(tertꢀbutyl)ꢀ1,2ꢀbenzoquinone (12) (20 mmol) with

4ꢀchloroꢀ2,8ꢀdimethylquinoline (4) (5 mmol) analogously to

βꢀtropolone (6f) (method B). The yield was 4%. Yellow crystals,

Xꢀray diffraction study. Xꢀray diffraction data sets were

collected on an automated KUMAꢀDIFFRACTION KMꢀ4

diffractometer at room temperature (MoꢀKα radiation,

ω/2 scanning technique, graphite monochromator). All strucꢀ

tures were solved by direct methods with the use of the

SHELXSꢀ97 program package²⁹and refined by the fullꢀmatrix

leastꢀsquared method with anisotropic displacement paramꢀ

eters for nonhydrogen atoms. All hydrogen atoms, except for

the hydrogen atoms of the tertꢀbutyl group of compound 7a

(high temperature vibration) and the tertꢀbutyl group of comꢀ

pound 21 (disorder in a ratio of 1 : 1), were located in differꢀ

ence electron density maps. The atomic coordinates, comꢀ

plete tables of the bond lengths, bond angles, and atomic disꢀ

placement parameters for compounds 6e, 7a, 8, 16b, 16d,

and 21 were deposited with the Cambridge Structural Database

(CCDC 607742 (6e), 299736 (7a), 299737 (8), 299738 (16b),

299739 (16d), and 299740 (21)). Principal crystallographic paꢀ

rameters of compounds 6e, 7a, 8, 16b, 16d, and 21 are given in

Table 18.

1

m.p. 180—182 °C (propanꢀ2ꢀol). H NMR (CDCl₃), δ: 1.30 (s,

9 H, Bu^t(4)); 1.35 (s, 9 H, Bu^t(7)); 2.75 (s, 3 H, Me(8´)); 6.38

(d, 1 H, H(5), J = 8.0 Hz); 6.58 (d, 1 H, H(6), J = 8.0 Hz); 7.44

(t, 1 H, H(6´)); 7.6 (d, 1 H, H(7´)); 8.0 (d, 1 H, H(5´)); 8.26

(s, 1 H, H(3´)); 19.05 (s, 1 H, OH(3)). MS (EI, 70 eV),

m/z (I_rel(%)): 409 [М]⁺(100), 394 (15), 381 (30), 366 (70), 338

(75), 57 (40), 41 (44). Found (%): C, 73.13; H, 6.80; Cl, 8.68;

N, 3.42. C₂₅H₂₈ClNO₂. Calculated (%): C, 73.25; H, 6.88;

Cl, 8.65; N, 3.42.

5,7ꢀDi(tertꢀbutyl)ꢀ3ꢀhydroxyꢀ4ꢀnitroꢀ2ꢀ(quinolinꢀ2ꢀyl)troꢀ

pone (15a) and 5,7ꢀdi(tertꢀbutyl)ꢀ2ꢀ(4ꢀchlorobenzo[h]quinolinꢀ

2ꢀyl)ꢀ3ꢀhydroxyꢀ4ꢀnitrotropone (15b) were synthesized by the

reaction of 4,6ꢀdi(tertꢀbutyl)ꢀ3ꢀnitroꢀ1,2ꢀbenzoquinone (14)

(10 mmol) with the corresponding 2ꢀmethylquinoline (4)

(5 mmol) analogously to βꢀtropolone 15g (method B).

1,7ꢀDi(tertꢀbutyl)ꢀ3ꢀ(6,8ꢀdimethylꢀ4ꢀmorpholinoquinolinꢀ2ꢀ

yl)ꢀ4,6ꢀdioxoꢀ2ꢀazabicyclo[3.3.0]octaꢀ2,7ꢀdiene Nꢀoxide (16b).

A solution of 4,6ꢀdi(tertꢀbutyl)ꢀ3ꢀnitroꢀ1,2ꢀbenzoquinone (14)

(3.18 g, 12 mmol), 2,6,8ꢀtrimethylꢀ4ꢀmorpholinoquinoline

(2.56 g, 10 mmol), and pꢀtoluenesulfonic acid (0.50 g) in oꢀxylene

(10 mL) was refluxed for 1 h. After cooling, the solution was

passed through an alumina chromatographic column (CHCl₃as

the eluent) and a yellow fraction was collected. Compound 16b

was obtained in a yield of 1.31 g (26%) as yellow crystals, m.p.

220—222 °C (propanꢀ2ꢀol). ¹³C NMR (CDCl₃), δ: 18.0, 22.1,

25.9, 28.1, 32.7, 36.6, 52.6, 60.8, 66.8, 87.3, 108.7, 119.8, 123.1,

131.7, 136.5, 137.8, 138.8, 143.5, 147.0, 149.4, 156.2, 158.0,

185.3, 196.6. ¹⁵N NMR (CDCl₃), δ: 42.05, 277.53, 324.60.

Calculation methods. All calculations were carried out with

the use of the B3LYP hybrid functional, including Becke’s threeꢀ

parameter exchange functional^30,31and the Lee—Yang—Parr

correlation functional,³²and the 6ꢀ31G** basis set with the

use of the GAUSSIAN 03 program package.³³The nature of

the stationary points on the potential energy surface was characꢀ

terized based on analysis of the force constant matrix (Hesse

matrix). The zeroꢀpoint corrections were calculated from anaꢀ

lytical vibrational frequencies without additional scaling. The

energies of monomer dimerization were calculated as the difꢀ

ference between the energy of the dimer and the sum of

the energies of the monomers without basis set superposition

error (BSSE).³⁴

2054

Russ.Chem.Bull., Int.Ed., Vol. 55, No. 11, November, 2006

Minkin et al.

Table 18. Crystallographic data for compounds 6e, 7a, 8, 16b, 16d, and 21

Compound

6e

7a

8

16b

16d

21

Molecular formula

C

₂₅H₂₈NOCl

409.93

C₂₉H₃₆N₂O₃

460.60

C₂₆H₃₂NO₂Cl

425.98

C₃₀H₃₇N₃O₄C₃₀H₃₆N₄O₅C₂₆H₃₀NO₂Cl

Molecular weight

Crystal system

Space group

a/Å

b/Å

c/Å

503.63

532.63

423.96

Monoclinic

P2₁/с

Triclinic

–

P1

14.057(8)

13.199(9)

11.923(7)

90

90.95(5)

90

2212(2)

4

1.231

11.602(6)

17.326(8)

14.355(6)

99.66(4)

105.73(5)

102.82(5)

2627(2)

4

10.907(3

13.014(4

10.808(6)

109.85(4)

112.65(4)

103.14(3)

1213.1(8)

2

9.946(2)

12.260(2)

13.042(3)

110.72(3)

90.06(4)

109.14(3)

1393.1(5)

2

10.055(2)

11.376(1)

14.489(3)

67.38(2)

74.17(2)

74.41(2)

1446.6(4)

2

10.699(5)

18.686(9)

6.800(6)

81.80(7)

68.50(7)

71.61(5)

1199.7(13)

2

α/deg

β/deg

γ/deg

V/Å³

Z

D/g cm^–3

1.165

0.075

1.166

0.178

1.201

1.223

1.174

–1

µ/mm

0.193

0.080

0.084

0.180

Scan range

Number of measured

reflections

1.45—26.09

3459

1.24—25.07

6681

1.83—25.06

3178

1.68—25.17

4930

1.55—22.47

3768

2.12—23.05

3335

Number of reflections

with I > 2σ(I )

Number of parameters

in refinement

R

2446

265

3867

601

1300

275

2466

350

3169

368

2109

317

0.045

0.072

0.057

0.128

0.079

0.221

0.058

0.164

0.044

0.052

0.048

0.099

R_w

Radiation

GOOF

MoꢀKα

1.107

MoꢀKα

1.068

MoꢀKα

0.946

MoꢀKα

1.119

MoꢀKα

1.045

MoꢀKα

0.958

6. A. W. Johnson, J. Chem. Soc., 1954, 1954.

7. H. Zinser, S. Henkel, and B. Föhlish, Eur. J. Org. Chem.,

2004, 1344.

8. M. M. Rahman, Y. Matano, and H. Suzuki, J. Chem. Soc.,

Perkin Trans. 1, 1999, 1533.

9. H. Kogler, H.ꢀW. Fehlhaber, K. Leube, and

W. Durckheimer, Chem. Ber., 1989, 122, 2205.

10. G. O. Schenck, B. Brahler, and M. Cziesla, Angew. Chem.,

1956, 7, 248.

11. G. W. G. Fishwick and D. W. Jones, in The Chemistry of the

Quinonoid Compounds. Chemistry of Functional Groups,

Eds. S. Patai and Z. Rappoport, Ch. 9. Vol. 2. Part 1. J. Wiley,

Chichester, 1988.

12. V. N. Komissarov, D. N. Bang, V. I. Minkin, S. M. Aldoshin,

V. V. Tkachev, and G. V. Shilov, Mendeleev Commun.,

2003, 219.

13. P. M. Dominiak, E. Grech, G. Barr, S. Teat, P. R.

Mallinson, and K. Wozniak, Chem. Eur. J., 2003, 9, 963.

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Rev., 2005, 105, 3513.

This study was financially supported by the Russian

Academy of Sciences (Project "New Reaction of Sixꢀ

membered Aromatic Ring Expansion: Synthesis and

Structures of Difficultly Accessible Derivatives of the

Tropolone System», the Subprogram "Development of

the Methodology of Organic Synthesis and Design of

Compounds with Valuable Applied Properties," and Proꢀ

gram No. 8 of the Presidium of the Russian Academy of

Sciences "Development of Methods for the Synthesis of

Chemical Compounds and Design of New Materials"),

the Russian Foundation for Basic Research (Project

No. 05ꢀ03ꢀ32081ꢀa), and the Council on Grants of the

President of the Russian Federation (Program for State

Support of Leading Scientific Schools of the Russian Fedꢀ

eration, Grant NShꢀ4849.2006.3).

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Received July 26, 2006;

in revised form September 25, 2006

Article Doi

New method for the synthesis of β-tropolones: Structures of condensation products of o-quinones with 2-methylquinolines and the mechanism of their formation

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