Synthesis and structures of azine-based crown-containing hetarylphenylethenes

1700

Russian Chemical Bulletin, International Edition, Vol. 54, No. 7, pp. 1700—1709, July, 2005

Synthesis and structures of azineꢀbased

crownꢀcontaining hetarylphenylethenes

a

b

c

a

E. N. Andryukhina,^aM. M. Mashura, O. A. Fedorova, L. G. Kuz´mina, J. A. K. Howard, and S. P. Gromov

ꢀ

^aPhotochemistry Center, Russian Academy of Sciences,

7a ul. Novatorov, 119421 Moscow, Russian Federation.

Fax: +7 (095) 936 1255. Еꢀmail: gromov@photonics.ru

^bN. S. Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences,

31 Leninsky prosp., 119991 Moscow, Russian Federation.

^cDepartment of Chemistry, University of Durham,

South Road, Durham DH1 3LE, UK.

Condensation of methylꢀsubstituted sixꢀmembered heteroaromatics containing one or two

nitrogen atoms with aldehyde derived from benzoꢀ15ꢀcrownꢀ5 ether in DMF in the presence of

Bu^tOK afforded 15ꢀcrownꢀ5ꢀcontaining hetarylphenylethenes. According to the results of

NMR spectroscopy, these compounds exist as mixtures of syn and anti conformers in solution

(MeCNꢀd₃). The structures of two compounds were established by Xꢀray diffraction analysis.

Key words: picoline, quinaldine, lepidine, 4ꢀmethylpyrimidine, 2ꢀmethylpyrazine,

15ꢀcrownꢀ5 ether, complexation.

Scheme 1

Ligands based on substituted pyridines, in which the

cyclic nitrogen atom can form strong coordination bonds

with metal cations and hydrogen bonds with carboxy and

ammonium groups of other organic molecules,¹are widely

used for designing supramolecular assemblies.²It is exꢀ

pected that such ligands and supramolecular assemblies

based on these ligands can be used for molecular recogniꢀ

tion of chiral molecules^3,4and the design of molecular

devices having good luminescence characteristics^5,6and

materials for optoelectronics^7,8and find application in

electrochemical analysis as well.⁹

Hetarylphenylethenes based on pyridine, quinoline,

dipyridyl, 3Hꢀindole, benzothiazole, and benzoxazole can

be prepared by condensation of methylꢀsubstituted hetꢀ

erocyclic bases with substituted benzaldehydes under baꢀ

sic (Py,^10,11piperidine,¹²Bu^tOK,¹³AlkONa (Alk = Me

or Et),^14,15or LDA ¹⁶) or acidic (ZnCl₂,^17,18HCl,¹⁹aceꢀ

tic acid, or acetic anhydride^20,21) conditions. The syntheꢀ

sis of hetarylphenylethenes by the Wittig reaction was also

documented.²²

The synthesis and properties of heterocyclic analogs

of stilbene containing a macrocyclic fragment were conꢀ

sidered in several publications.^23—29It was noted that this

class of compounds holds promise for the design of optiꢀ

cal sensors for metal cations.³⁰

In the present study, we used sixꢀmembered heteroꢀ

aromatic bases containing one or two nitrogen atoms in

the ring (Scheme 1) as the heterocyclic component and

analyzed the influence of the structure of the heterocyclic

component on the formation of the corresponding crownꢀ

containing hetarylphenylethenes.

Reagents and conditions: AlkOM = MeONa or Bu^tOK; DMSO

or DMF as the solvent.

Condensation of azine derivatives 1a—g with

4´-formylbenzoꢀ15ꢀcrownꢀ5 ether (2a) or 3,4ꢀdimethoxyꢀ

benzaldehyde (2b) was carried out at room temperature

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1650—1659, July, 2005.

Crownꢀcontaining hetarylphenylethenes

Russ.Chem.Bull., Int.Ed., Vol. 54, No. 7, July, 2005

1701

Table 1. Influence of the nature of the solvent and alkali metal

alkoxide on the yields of crownꢀcontaining hetarylphenylethenes

(CHPE) 3a,d,e at 20 °C

Analogous results were observed in the presence of an

excess of the heterocyclic component.

The reaction of lepidine (1e) with crownꢀcontaining

benzaldehyde 2a in the presence of Bu^tOK in DMSO at a

ratio of 1 : 1 : 1 afforded target product 3e along with the

known bisheterocyclic derivative 4a,³¹which is apparꢀ

ently produced as a result of the Michael addition of the

second molecule of the heterocyclic base at the double

bond (Scheme 2). The reaction with the use of MeONa

and the reagents in a ratio of 1 : 1 : 0.1 did not afford

product 4a, but 3e was obtained in low yield (15%).

The reaction in DMF allowed us to substantially inꢀ

crease the yield of target product 3e. The formation of 4a

was not observed even in the presence of a fivefold excess

of lepidine.

The reaction conditions and the yields of condensaꢀ

tion products of methylꢀsubstituted heterocyclic bases

1a—g with aromatic aldehydes 2a,b are given in Table 2.

Evidently, the yields of crownꢀcontaining hetarylphenylꢀ

ethenes (CHPE) 3a—e depend substantially on the folꢀ

lowing two factors: the acidity of the methyl group in the

heterocyclic component (pK_a^CH) and the steric effects.

For example, the acidities of the protons of the methyl

groups in quinaldine 1d, lepidine 1e, and γꢀpicoline 1a

are sufficiently high for the reactions to occur, whereas

the acidities of these protons in αꢀ and βꢀpicolines 1f,g

are low,³²which hinders their involvement in condenꢀ

sation.

HetMe AlkOM

Ratio*

Solvent CHPE Yield of

CHPE

(%)

1a

1d

MeONa

Bu^tOK

MeONa

Bu^tOK

MeONa

Bu^tOK

MeONa

Bu^tOK

1 : 1 : 1

5 : 1 : 1.5

1 : 1 : 1

DMSO

DMF

MeOH

DMSO

DMF

3a

3d

0

12

23

78

0

18

25

47

5 : 1 : 1.5

1 : 1 : 1

1 : 1 : 0.1

1 : 1 : 1

DMF

88

0

1e

MeOH

DMSO

DMF

3e

11 + 16**

15

33

38

5 : 1 : 1.5

DMF

* HetMe : AlkOM : 2a.

** The yield of bisheterocyclic byꢀproduct 4a.

because heating of the reaction mixture causes resinifiꢀ

cation. The anhydrous aprotic solvents DMSO and DMF

were used in the reactions. In ethanol, the formation of

condensation products was not observed. We studied the

influence of the nature of alkali metal alkoxide and the

solvent on the yields of the products of the condensation

reactions (Table 1).

The yields in DMF are much higher than those in

DMSO. Among other things, this may be attributed to the

involvement of DMSO in condensation with benzaldeꢀ

hyde. Earlier,¹¹it has been demonstrated that such side

reactions are not associated with the involvement of DMF.

An increase in the basicity of alkoxide leads to an

increase in the yield of the target product (see Table 1).

The protons of the methyl group in lepidine 1e ³²have

the highest acidity (see Table 2). However, the correꢀ

sponding product 3e is formed in lower yield compared to

other crownꢀcontaining derivatives. Presumably, this is

attributable to steric hindrance due to the presence of the

benzene ring in the ortho position with respect to the

methyl group.

The introduction of the second nitrogen atom into the

pyridine ring leads to an increase in the acidity of the

methyl group.³²This is associated with the fact that

Scheme 2

X = N (1b, 3b, 4b), CH (1e, 3e, 4a)

Reaction conditions: i. DMSO or DMF.

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Andryukhina et al.

Scheme 3

Table 2. Yields of hetarylphenylethenes 3a—g in condensation

reactions of 1a—g with 2a,b in DMF; Het—Me : Bu^tOK : 2a =

5 : 1 : 1.5, 20 °C

heteroaromatic bases containing one or two nitrogen

atoms.

As is evident from the spinꢀspin coupling constants

(J = 15.8—16.3 Hz) of the olefinic protons, all the CHPEs

synthesized have a trans configuration. The full assignꢀ

ment of the signals in the NMR spectrum was made using

the COSY technique. The mutual arrangement of the

structural fragments was determined from the NOESY

spectroscopic data.

The aboveꢀdescribed compounds can exist as several

conformers. Thus, two conformers, A and B, can exist

due to rotation of the heterocyclic fragment of the

hetarylphenylethene molecule about the C—C bond

(Scheme 4, heavy line).

СН 32

HetMe

рК_а

Benzaldehyde CHPE

Yield (%)

1a

1b

1c

1d

1e

1f

25

2a

2b

2a

2b

2a

2b

2a

3a

3f

78

28

41*

75

88

—

38

—

25

—

23

22

27

28

3b

3c

3d

—

3е

3g

—

1g

—

* The ratio HetMe : Bu^tOK : 2a = 1 : 1 : 1.

Scheme 4

deprotonation of the methyl group in 4ꢀmethylpyrimidine

1b leads to stabilization of the carbanion through the inꢀ

volvement of two nitrogen atoms. As a results of high

nucleophilicity of the carbanion, the Michael reaction

occurs extensively in the presence of an excess of the

heterocyclic component to yield bisheterocyclic derivaꢀ

tive 4a (see Scheme 2). This side reaction can be avoided

by using reagents in an equimolar ratio (see Table 2).

A comparison of the results of the synthesis of CHPE

by condensation of 1a,d,e with 2a and its analog 2b conꢀ

taining two methoxy groups shows that the presence of

the crown ether fragment facilitates the reaction. Apparꢀ

ently, the latter reactions, like the synthesis of CHPE

from fiveꢀmembered heterocyclic bases,^29,30afford comꢀ

plexes of crown ether with a metal cation (Scheme 3).

This facilitates dissociation of the alkali metal catꢀ

ion—alkoxide anion pair, thus promoting generation of

the anion and its efficient reaction with the heterocyclic

component. The resulting carbanion is sufficiently nuꢀ

cleophilic to add to the carbonyl carbon atom giving rise

to alkoxide. Subsequent water elimination occurs readily

because it gives rise to a conjugated double bond.

Rotation about the second C—C single bond, which is

also indicated by a heavy line in Scheme 4, can lead to the

transformation of the conformers A and B into the conꢀ

formers C and D, respectively.

Therefore, the hetarylphenylethenes under considerꢀ

ation can exist as four conformers, A, B, C, and D, simulꢀ

taneously.

Therefore, the aboveꢀdescribed conditions of condenꢀ

sation can successfully be used for the synthesis of crownꢀ

containing hetarylphenylethenes from sixꢀmembered

There are evident steric restrictions in the arrangeꢀ

ment of the H(5) and H_bprotons of the conformers B

and D of 4ꢀstyrylquinoline derivatives 3e,g, due to which

Crownꢀcontaining hetarylphenylethenes

Russ.Chem.Bull., Int.Ed., Vol. 54, No. 7, July, 2005

1703

Scheme 6

these conformers are unstable (Scheme 5). Actually, as is

evident from the NMR spectroscopic data, compounds

3e and 3g in MeCNꢀd₃exist as mixtures of the conformꢀ

ers A and C, because the NOESY spectra of both comꢀ

pounds have intense crossꢀpeaks from pairs of coupled

protons of these conformers (see Scheme 5).

Scheme 5

direction. The dihedral angle between the planes of these

fragments is as small as 1.4°.

The C(10)—C(11) double bond is substantially localꢀ

ized (1.334(2) Å). The C(3)—C(10) and C(11)—C(12)

single bond lengths in the ethylene fragment are

1.462(2) and 1.471(2) Å, respectively. In the

C(12)—C(13)—C(14)—C(15) fragment of the dimethoxyꢀ

substituted benzene ring, the bonds clearly alternate. The

corresponding bond lengths are 1.401(2), 1.380(2), and

1.407(2) Å. By contrast, the bond lengths in the other

part of this ring, C(15)—C(16)—C(17)—C(12), are equalꢀ

ized within standard deviations (1.385(2), 1.392(2), and

1.390(2) Å). Apparently, these geometric differences are

associated with the conjugation between the lone pairs

(LP) of the oxygen atoms located on the pꢀorbitals and

the π system of the benzene ring. This conjugations is also

evidenced by other characteristic features of the molecuꢀ

lar structure. The bond angles at the oxygen atoms

Analogous results were obtained for 2ꢀstyrylquinoline

3d and CHPE 3b,c. All the above compounds exist in

solution as mixtures of the conformers A and C. The

simultaneous existence of the anti,syn and anti,anti conꢀ

formers is attributed to the fact that the interconversions

of these conformers of all the compounds under considꢀ

eration do not give rise to steric hindrance.

Compound 3a can exist only as two conformers,

A (syn) and C (anti), which were detected in solution by

NMR spectroscopy (Scheme 6).

Molecular structure (Xꢀray diffraction data). The moꢀ

lecular structure of 3g and the atomic numbering

scheme are shown in Fig. 1. There are noticeable torꢀ

sional distortions in molecule 3g. The dihedral angles

formed by the plane of the ethylene fragment

(C(3)—C(10)—C(11)—C(12)) with the planes of the

quinoline bicyclic fragment and the benzene ring

(C(12)...C(17)) are 15.6 and 16.6°, respectively. The

quinoline and benzene systems are twisted in the same

C(19)

C(1)

O(2)

N(1)

C(9)

C(13)

C(2)

C(10)

C(12)

C(11)

C(17)

C(14)

O(1)

C(3)

C(4)

C(5)

C(15)

C(8)

C(7)

C(16)

C(18)

C(6)

Fig. 1. Molecular structure of 3g with displacement ellipsoids

drawn at the 50% probability level.

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Andryukhina et al.

(117.4 and 117.0°) correspond to the sp²ꢀhybridized state

of these atoms. The C_Me—O—C_Ar—C_Artorsion angles at

the O(1) and O(2) atoms (–173.8 and –3.0°, respecꢀ

tively) are indicative of the parallel orientation of these

orbitals.

are twisted in the same direction, because the dihedral

angle between their planes is smaller than each of the

aboveꢀmentioned angle (4.9° in A and 7.3° in B).

The double bond in the ethylene fragment

C(15)—C(16) in 3d is substantially localized (1.328(6) Å

in A and 1.334(6) Å in B). The C(12)—C(15) and

C(16)—C(17) single bond lengths are, respectively,

1.465(6) and 1.485(6) Å in A and 1.472(6) and 1.481(6) Å

in B. In these molecules, a slight alternation of the bond

lengths is observed in the C(9)—C(14)—C(13)—C(12)

fragment of the benzene ring involving the C atoms bound

to the oxygen atoms (1.420(5), 1.388(6), and 1.408(6) Å

in A and 1.416(50, 1.383(6), and 1.416(6) Å in B, respecꢀ

tively). This alternation is analogous to that observed in

the corresponding fragment in molecule 3g. In the second

part of this benzene ring, the bond lengths are equalꢀ

ized within experimental error (1.394(6), 1.397(6),

and 1.387(6) Å in A and 1.390(6), 1.387(6), and

1.399(6) Å in B).

The character of deformation of the benzene ring in

molecule 3d is analogous to that in molecule 3g. Actually,

the endocyclic O—C_Ar—C_Arbond angles in the macroꢀ

cycle decrease to 114.7(3) and 115.3(3)° in A and to

114.7(3) and 115.0(4)° in B, whereas the exocyclic bond

angles at the C(14) and C(9) atoms increase, respectively,

to 125.3(3) and 125.8(4)° in A and to 125.5(3) and

125.0(4)° in B. The distances between the O(1) and

O(5) atoms (2.58 and 2.57 Å in A and B, respectively) are

also shorter than twice the van der Waals radius (~2.8 Å).

This effect cannot be related to the contracting effect of

Two

exocyclic

O—C—C

bond

angles

(O(1)—C(15)—C(16) and O(2)—C(14)—C(13)) inꢀ

crease to 125.3(1) and 125.0(1)°, respectively, whereas

two other bond angles (O(1)—C(15)—C(14) and

O(2)—C(14)—C(15)) decrease to 115.5(1) and 115.3(1)°,

respectively. The character of distortion of these angles is

contradictory to that expected in the case of steric repulꢀ

sion between the oxygen atoms located at a distance

(2.58 Å) shorter than twice the van der Waals radius

(~2.8 Å). Apparently, the geometry of the fragments in

compound 3g is determined by the electronic effects asꢀ

sociated with the conjugation between LP of the oxygen

atoms and the π system of the benzene ring.

The structures of two crystallographically indepenꢀ

dent molecules A and B of crownꢀcontaining 2ꢀstyrylꢀ

quinoline 3d are shown in Fig. 2.

The conjugated fragments in molecules A and B have

similar geometry, which is, to a large extent, similar to

that observed in 3g. Both these fragments are slightly

twisted about the central ethylene bond. The dihedral

angles between the planes of the quinoline system and the

ethylene fragment (C(12)—C(15)—C(16)—C(17)) in

A (B) and between the planes of the latter fragment and

the benzene ring (C(9)...C(14)) are 14.3° (12.8°) and 10.5°

(5.9°), respectively. The quinoline and benzene systems

O(2)

C(3)

C(2)

C(1)

C(4)

C(5)

O(3)

O(5)

O(1)

C(14)

C(24)

N(1)

C(6)

C(13)

C(25)

C(16)

C(15)

C(23)

C(22)

C(7)

C(8)

O(4)

C(9)

C(17)

C(18)

C(10)

C(12)

C(21)

C(11)

C(20)

C(19)

A

C(2´)

O(2´)

C(4´)

O(3´)

C(6´)

C(3´)

C(1´)

O(1´)

C(13´)

C(5´)

O(4´)

O(5´)

C(24´)

N(1´)

C(25´)

C(16´)

C(12´)

C(17´)

C(14´)

C(23´)

C(22´)

C(9´)

C(10´)

C(7´)

C(8´)

C(18´)

C(19´)

C(15´)

C(11´)

C(21´)

C(20´)

B

Fig. 2. Structures of two crystallographically independent molecules A and B of crownꢀcontaining 2ꢀstyrylquinoline 3d.

Crownꢀcontaining hetarylphenylethenes

Russ.Chem.Bull., Int.Ed., Vol. 54, No. 7, July, 2005

1705

and C(8)—O(5)—C(9)—C(10) torsion angles (–8.0°

(–5.4°) and 1.5° (5.9°)) are close to the ideal value.

The crown ether fragments in two independent molꢀ

ecules differ substantially in the geometry, which reflects

the fact of their high conformational mobility.

Crystal packings of compounds 3d and 3g. The crystal

packings of compounds provide an insight into the strucꢀ

tures of supramolecular associates composed of this type

of molecules in solution, although these molecules are

less rigorously and rigidly organized in solution compared

to the crystalline state.

c

0

b

Molecules 3g form parallel centrosymmetric dimers

(sandwiches), which are packed in a herringbone fashion

(Fig. 3). This is one of the typical packings (type c) for

conjugated molecules according to the known classificaꢀ

tion.³⁸The mean planes of the molecules are strictly

parallel to each other, and the distance between the

planes (3.41 Å) is typical of stacked conjugated systems

(from 3.3 to 3.8 Å).³⁹

a

The C(10B)...C(11A) and C(11B)...C(10A) distances

are 3.615 Å, and the ethylene bonds are parallel to each

other. This mutual arrangement of two molecules is faꢀ

vorable for photochemical [2+2] cycloaddition reactions

giving rise only to the centrosymmetric isomer of cycloꢀ

butane. However, this reaction does not occur in the solid

state because of the rigid crystal environment of the dimers.

In the crystal packing of molecules 3g, the hydrophoꢀ

bic and hydrophilic regions are separated, which is always

observed in the crystal packings of crownꢀcontaining styryl

dyes and benzocrown ethers.^33—37

The crystal packing of compound 3d is shown in Fig. 4.

The hydrophilic layers, which are composed of the

crown ether fragments and are perpendicular to the a axis

of the crystal, alternate with the layers of the conjugated

fragments. The latter form a ladder herringbone packing

Fig. 3. Fragment of the crystal packing of compound 3g.

the cyclic system in molecule 3d, because it is also obꢀ

served in molecule 3g, in which the macrocyclic system is

absent. Moreover, this effect is always observed in benzoꢀ

crown ether systems, in which both oxygen atoms have

geometry favorable for conjugation between their LP and

the π system of the benzene ring.^33—37It should be noted

that the angles at the oxygen atoms bound to the benzene

ring in molecules 3d (114.8(3) (115.4(4)) and 116.8(3)

(117.6(3)°) correspond rather closely to the sp²ꢀhybridꢀ

ized state of these atoms. The C(1)—O(1)—C(14)—C(13)

c

b

0

a

Fig. 4. Crystal packing of molecules 3d projected along the c axis.

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Andryukhina et al.

within the layers. The ladders contain molecules A and B

located almost perpendicular to each other. Molecules A,

as well as molecules B, are related by a translation along

the c axis of the crystal. This ladderꢀtype associate is

enclosed by the crown ether fragments. In the supramoꢀ

lecular associate, photochemical [2+2]ꢀcycloaddition

would not be expected to occur.

To summarize, we developed a new procedure for the

synthesis of hetarylphenylethene derivatives containing

sixꢀmembered heterocyclic moieties and a benzoꢀ15ꢀ

crownꢀ5 ether fragment under mild conditions in good

yields. The influence of the structures of the starting hetꢀ

erocyclic compounds and the reaction conditions of conꢀ

densation on the yields of the target products was investiꢀ

gated. The structures of the compounds in solution and in

the crystalline state were established by NMR spectroꢀ

scopy and Xꢀray diffraction analysis.

Experimental

The melting points were measured on a MelꢀTemp II instruꢀ

ment. The ¹H NMR spectra were recorded on a Bruker DRX500

spectrometer (500.13 MHz) in CDCl₃(unless otherwise stated)

with Me₄Si as the internal standard. The chemical shifts and the

spinꢀspin coupling constants were measured with an accuracy of

0.01 ppm and 0.1 Hz, respectively. The signals for the protons

were assigned based on the 2D COSY and NOESY spectra. The

mass spectra were obtained on a Varian MAT 311A instrument

with direct inlet of the sample into the ionization source; the

ionization energy was 70 eV. Elemental analyses were carried

out in the Laboratory of Microanalysis of the A. N. Nesmeyanov

Institute of Organoelement Compounds of the Russian Acadꢀ

emy of Sciences (Moscow). The course of the reactions was

monitored by TLC on DCꢀAlufolien Kieselgel 60 F₂₅₄(Merck)

and DCꢀAlufolien Aluminiumoxid 60 F₂₅₄neutral (Typ E)

(Merck) plates. Column chromatography was carried out on

Table 3. Characteristics of compounds 3a—g and 4b

Comꢀ

pound

M.p./°C

Found

Calculated

Molecular

formula

λ

/nm

ε

max

(%)

/L mol^–1cm^–1

С

H

N

3a

3b

3c

3d

3e

3f

112—114

107—109

101—103

119—121

85—87

68.04

67.91

64.31

64.50

64.19

64.50

71.21

71.24

70.97

71.24

74.64

74.67

78.36

78.33

64.20

64.36

6.76

6.78

6.44

6.50

6.39

6.50

6.30

6.46

6.68

6.46

6.24

6.27

5.77

5.88

6.43

6.48

3.66

3.77

7.48

7.52

7.44

7.52

3.24

3.32

3.12

3.32

5.81

5.80

4.74

4.81

11.49

12.00

C₂₁H₂₅NO₅

C₂₀H₂₄N₂O₅

C₂₅H₂₇NO₅

C₁₅H₁₅NO₂

C₁₉H₁₇NO₂

C₂₅H₃₀N₄O₅

331

346

350

358

354

333

354

—

21340

24176

24036

37951

26736

20156

25032

—

113—115

130—132

58—60

3g

4b

Table 4. Spectroscopic characteristics of compounds 3a—g and 4b

Comꢀ

pound

¹H NMR, δ (³J/Hz), 30 °C*

MS,

m/z (I_rel(%))

3a

3.77 (m, 8 H, 4 ОСH₂); 3.94 (m, 4 H, 2 ОСH₂); 4.20 (m, 4 H, 2 АrОСH₂);

6.88, 7.23 (both d, 2 H, H_a, H_b, J₁= 16.3, J₂= 16.3); 6.90 (d, 1 H, H(6´), J = 8.3);

7.09 (m, 2 H, H(2´), H(5´)); 7.34 (d, 2 H, H(3), H(5), J = 5.7); 8.56 (d, 2 H, H(2),

H(6), J = 5.7)

371 [M]⁺(31), 240 (47),

239 (100), 224 (32), 183 (29),

182 (32), 154 (37), 153 (58),

129 (38), 83 (47)

3b

3.77 (m, 8 H, 4 ОСH₂); 3.94 (m, 4 H, 2 ОСH₂); 4.20 (m, 4 H, 2 АrОСH₂);

6.89 (d, 1 H, H(5´), J = 8.2); 6.97, 7.85 (both d, 2 H, H_a, H_b, J₁= 15.8, J₂= 15.9);

7.17 (s, 1 H, H(2´)); 7.20 (d, 1 H, H(6´), J = 8.2); 7.39, 8.67 (both d, 2 H, H(5),

H(6), J₁= J₂= 5.0); 9.14 (s, 1 H, H(2))

372 [М]⁺(58), 371 (19),

283 (15), 240 (43), 239 (100),

213 (17), 45 (54), 44 (22),

43 (72), 40 (25)

(to be continued)

Crownꢀcontaining hetarylphenylethenes

Russ.Chem.Bull., Int.Ed., Vol. 54, No. 7, July, 2005

1707

Table 4 (continued)

Comꢀ

pound

¹H NMR, δ (³J/Hz), 30 °C*

MS,

m/z (I_rel(%))

3c

3d

3e

3f

3.78 (m, 8 H, 4 ОСH₂); 3.94 (m, 4 H, 2 ОСH₂); 4.18 (m, 2 H, АrОСH₂);

4.21 (m, 2 H, АrОСH₂); 6.88 (d, 1 H, H(5´), J = 8.0); 7.07, 7.76 (both d, 2 H, H_a,

H_b, J₁= J₂= 16.1); 7.18 (d, 1 H, H(6´), J = 8.3); 7.27 (s, 1 H, H(2´));

372 [М]⁺(14), 371 (62),

370 (5), 282 (4), 239 (19),

238 (100), 212 (10), 185 (5),

154 (8), 45 (10)

421 [М]⁺(100), 420 (32),

290 (26), 289 (49), 288 (99),

263 (26), 262 (39), 204 (41),

8.45, 8.54 (both m, 2 H, H(5), H(6)); 8.71 (s, 1 H, H(2))

3.78 (m, 8 H, 4 ОСH₂); 3.95 (m, 4 H, 2 ОСH₂); 4.20 (m, 4 H, 2 АrОCH₂); 6.88 (d, 1 H,

H(5´), J = 8.2); 7.16 (d, 1 H, H(6´), J = 8.2); 7.26, 7.59 (both d, 2 H, H_a, H_b, J₁= 16.2,

J₂= 16.2); 7.37 (s, 1 H, H(2´)); 7.49, 7.69 (both m, 2 H, H(6), H(7)); 7.69, 7.78 (both d,

2 H, H(3), H(4), J₁= 8.0, J₂= 8.0); 8.06, 8.12 (both d, 2 H, H(5), H(8), J₁= 8.4, J₂= 8.6) 178 (25), 108 (42)

3.79 (m, 8 H, 4 ОСH₂); 3.96 (m, 4 H, 2 ОСH₂); 4.20 (m, 4 H, 2 ArОСH₂); 6.92 (d, 1 H,

H(5’), J = 8.0); 7.19 (m, 2 H, H(2´), H(6´)); 7.28, 7.67 (both d, 2 H, H_a, H_b, J₁= 16.0,

J₂= 16.0); 7.59, 7.74 (both m, 2 H, H(6), H(7)); 7.60 (d, 1 H, H(3), J = 4.5);

8.14, 8.23 (both d, 2 H, H(5), H(8), J = 8.3, J = 8.3); 8.89 (d, 1 H, H(2), J = 4.5)

3.92 (m, 3 H, ОMe); 3.97 (m, 3 H, ОMe); 6.89, 7.26 (both d, 2 H, H_a, H_b, J₁= 15.9,

J₂= 15.9); 7.03 (d, 1 H, H(6´), J = 8.1); 7.10 (m, 2 H, H(2´), H(5´));

421 [M]⁺(100), 323 (32),

290 (79), 289 (74), 288 (51),

263 (42), 217 (28), 216 (29),

204 (49), 109 (39)

241 [M]⁺(100), 226 (87),

198 (13), 167 (14), 166 (24),

165 (21), 154 (20), 77 (15),

58 (45), 51 (27)

7.35, 7.37 (both m, 2 H, H(3), H(5)); 8.56, 8.57(both m, 2 H, H(2), H(6))

3g

4b

3.81, 3.87 (both m, 3 H each, ОМе); 7.01 (d, 1 H, H(5´), J = 8.3); 7.30 (d, 1 H,

H(6´), J = 8.3); 7.50 (s, 1 H, H(2´)); 7.54, 7.96 (both d, 2 H, H_a, H_b, J₁= 16.1,

J₂= 16.1); 7.66, 7.78 (both m, 2 H, H(6), H(7)); 7.81 (d, 1 H, H(3), J = 4.6);

8.03, 8.55 (both d, 2 H, H(5), H(8), J₁= 8.4, J₂= 8.4); 8.86 (d, 1 H, H(2), J = 4.6)

3.40 (m, 3 H, 2 CH₂); 3.74 (m, 8 H, 4 CH₂O); 3.87 (m, 4 H, 2 CH₂O);

4.04, 4.08 (both m, 2 H each, АrОСH₂); 4.16 (m, 1 H, CH); 6.55 (d, 1 H, H(5″),

J = 8.0); 6.65 (br.d, 1 H, H(6″), J = 8.0); 6.69 (s, 1 H, H(2″)); 7.24 (d, 2 H, H(5),

H(5´), J = 4.7); 8.68 (d, 2 H, H(6), H(6´), J = 4.9)

291 [M]⁺(100), 290 (27),

276 (28), 261 (26), 260 (60),

233 (21), 217 (21), 216 (31),

205 (21), 204 (45)

—

* The spectra were recorded in CDCl₃, except for compounds 3g and 4b (DMSOꢀd₆).

Table 5. Reagents and conditions of the synthesis of hetarylphenylethenes 3a—g

Azine

Substituted

Base

Solvent

τ*

Method Product Yield

(x/mmol) benzaldehyde

(y/mmol)

(z/mmol)

/days of puriꢀ

fication**

(%)

1а (0.6)

1а (3.0)

1b (3.0)

2а (0.6)

Bu^tOK (0.6)

Bu^tOK (0.9)

DMSO

DMF

1

3

1

I

II

3а

3b

4b

3b

3с

3d

3e

3f

12

23

78

11

13

41

75

18

25

47

88

15

33

38

28

38

DMF

1b (0.6)

1c (3.0)

1d (0.6)

1d (3.0)

1e (3.6)

1e (0.6)

1e (3.0)

1а (3.0)

1e (3.0)

2а (0.6)

2а (3.6)

2а (0.6)

2b (0.6)

Bu^tOK (0.6)

Bu^tOK (0.9)

MeONa (0.6)

Bu^tOK (0.6)

Bu^tOK (0.9)

MeONa (0.36)

Bu^tOK (0.6)

Bu^tOK (0.9)

DMF

DMSO

DMF

DMSO

DMF

3

1

III

IV

V

3g

* The reaction time.

** I, recrystallization from nꢀheptane; II, column chromatography on SiO₂, a 5 : 1 C₆H₆—EtOH

mixture of the eluent; III, recrystallization from MeOH; IV and V, column chromatography on Al₂O₃,

a C₆H₆—EtOH mixture, EtOH (IV), and C₆H₆(V) as the eluents.

1708

Russ.Chem.Bull., Int.Ed., Vol. 54, No. 7, July, 2005

Andryukhina et al.

Table 6. Principal crystallographic data and characteristics of Xꢀ

ray diffraction study

The melting points, elemental analysis data, and the data

from ¹H NMR and UV spectroscopy and mass spectrometry are

given in Tables 3 and 4. (The atomic numbering schemes are

presented in Schemes 5 and 6.)

Compound

3d

3g

Synthesis of hetarylphenylethenes 3a—g and 4b (general proꢀ

cedure). Azine A (х mmol) was mixed with 2a or 2b (у mmol)

and Bu^tOK (z mmol) in dry DMSO or DMF (2—5 mL), and the

mixture was allowed to stand for a certain time at room temꢀ

perature. Then distilled water (20 mL) was added to the reaction

mixture, the mixture was extracted with benzene, chloroform,

or CH₂Cl₂(4×30 mL), and the organic extract was concentrated

in vacuo. The residue was purified by column chromatography

or recrystallization. The reagents and conditions of the synthesis

of compounds 3a—g are given in Table 5. The following comꢀ

pounds were prepared: 4ꢀ[(Е)ꢀ2ꢀ(2,3,5,6,8,9,11,12ꢀoctahydroꢀ

1,4,7,10,13ꢀpentaoxabenzocyclopentadecinꢀ15ꢀyl)ethenꢀ1ꢀ

yl]pyridine (3a), 4ꢀ[(E)ꢀ2ꢀ(2,3,5,6,8,9,11,12ꢀoctahydroꢀ

1,4,7,10,13ꢀpentaoxabenzocyclopentadecinꢀ15ꢀyl)ꢀethenꢀ1ꢀ

Molecular formula

Molar weight

/g mol^–1

Crystal system

Space group

a/Å

C₂₅H₂₇NO₅

421.48

C₁₉H₁₇NO₂

291.34

Monoclinic

P2₁/c

16.396(1)

33.194(3)

7.8165(7)

91.798(5)

4252.1(7)

8

1.317

1792

0.092

10.5854(6)

10.9357(7)

12.6356(6)

99.005(2)

1444.65(14)

4

b/Å

c/Å

β/deg

V/Å³

Z

ρ

_calc/g cm^–3

1.339

616

0.087

F(000)

µ(MoꢀKα)/mm^–1

Crystal dimensions/mm

T/K

yl]pyrimidine

(3b),

4ꢀ[2ꢀ(2,3,5,6,8,9,11,12ꢀoctahydroꢀ

0.36×0.34×0.18 0.28×0.16×0.12

120.0(2)

ω/1.23—28.00

1,4,7,10,13ꢀpentaoxabenzocyclopentadecinꢀ15ꢀyl)ꢀ3ꢀ(4ꢀpyriꢀ

midinyl)propyl]pyrimidine (4b), 2ꢀ[(E)ꢀ2ꢀ(2,3,5,6,8,9,11,12ꢀ

octahydroꢀ1,4,7,10,13ꢀpentaoxabenzocyclopentadecin)ethenꢀ1ꢀ

yl]pyrazine (3c), 2ꢀ[(E)ꢀ2ꢀ(2,3,5,6,8,9,11,12ꢀoctahydroꢀ

1,4,7,10,13ꢀpentaoxabenzocyclopentadecinꢀ15ꢀyl)ethenꢀ1ꢀ

yl]quinoline (3d), 4ꢀ[(E)ꢀ2ꢀ(2,3,5,6,8,9,11,12ꢀoctahydroꢀ

1,4,7,10,13ꢀpentaoxabenzocyclopentadecinꢀ15ꢀyl)ethenꢀ1ꢀ

yl]quinoline (3e), 4ꢀ[(Е)ꢀ2ꢀ(3,4ꢀdimethoxyphenyl)ethenꢀ1ꢀ

yl]pyridine (3f), and 4ꢀ[(Е)ꢀ2ꢀ(3,4ꢀdimethoxyphenyl)ethenꢀ1ꢀ

yl]quinoline (3g).

Xꢀray diffraction study of crystals of 3d,g. Single crystals of

compounds 3d and 3g were grown by crystallization from

an acetonitrile solution, coated with perfluorinated oil, and

mounted on a Bruker SMARTꢀCCD diffractometer under a

stream of cooled nitrogen. The experimental Xꢀray intensity

data were collected from single crystals (MoꢀKα radiation, λ =

0.71073 Å) using ωꢀscanning technique. The crystallographic

parameters and characteristics of Xꢀray diffraction study are

given in Table 6.

120.0(2)

ω/1.95—27.50

Scan mode/scan

range, θ/deg

Ranges of indices of

measured reflections

–21 ≤ h ≤ 21,

–43 ≤ k ≤ 41,

–5 ≤ l ≤ 10

32831

–13 ≤ h ≤ 9,

–13 ≤ k ≤14,

–16 ≤ l ≤ 10

7335

Number of measured

reflections

Number of independent

reflections

10259

3245

R_int

0.1599

4770

0.0278

3245

Number of reflections

with I > 2σ(I )

Number of parameters

in refinement

R factor using reflections

with I > 2σ(I )

R₁

776

267

0.1028

0.2355

0.0448

0.1167

wR₂

The Xꢀray intensity data were processed using the Bruker

SAINT software.⁴¹

R factor using all

reflections

R₁

Both structures were solved by direct methods and reꢀ

fined anisotropically by the fullꢀmatrix leastꢀsquares method

against F ². The hydrogen atoms were located from difference

Fourier syntheses and refined isotropically. All calculations were

carried out using the SHELXTLꢀPlus program package.⁴²

The complete Xꢀray diffraction data were deposited with

the Cambridge Structural Database (CCDC refcodes 275180

and 275181).*

0.2162

0.2764

0.988

0.0666

0.1253

1.076

wR₂

Goodnessꢀofꢀfit on F ²

Residual electron density

(min/max)/e Å^–3

–0.547/0.622

–0.191/0.382

silica gel (Kieselgel 60, 0.063—0.200 mm, Merck) and aluminum

oxide (Aluminiumoxide 150 basic, Typ E, 0.063—0.200 mm,

Merck).

This study was financially supported by the Russian

Foundation for Basic Research (Project Nos 02ꢀ03ꢀ32058,

03ꢀ03ꢀ32178, and 04ꢀ03ꢀ32677), the US Civilian Research

and Development Foundation (CRDF, Grant RC2ꢀ2344ꢀ

MOꢀ02), and the Ministry of Science and Higher Educaꢀ

tion of the Russian Federation (Program "Integration").

4ꢀMethylpyridine (1a), 4ꢀmethylpyrimidine (1b), 2ꢀmethylꢀ

pyrazine (1c), 2ꢀmethylquinoline (1d), 4ꢀmethylquinoline (1e),

and 3,4ꢀdimethoxybenzaldehyde (2b) were purchased from

Aldrich and used without additional purification. 4´ꢀFormylꢀ

benzoꢀ15ꢀcrownꢀ5 ether (2a) was prepared according to a known

procedure.⁴⁰The solvents DMSO (Merck) and DMF (Merck)

were dried by distillation over BaO in vacuo. Alkali metal

alkoxides were prepared by dissolution of metals in the correꢀ

sponding alcohols followed by evaporation of the excess solvent

and drying in vacuo at 60 °C.

* These data can be obtained, free of charge, on application to

Cambridge Crystallographic Data Centre, 12 Union Road, Camꢀ

bridge CB2 1EZ, UK. (fax: +44(0) 1223ꢀ336033, eꢀmail:

deposit@ccdc.cam.ac.uk).

Crownꢀcontaining hetarylphenylethenes

Russ.Chem.Bull., Int.Ed., Vol. 54, No. 7, July, 2005

1709

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Received June 16, 2004;

in revised form October 13, 2004

Article Doi

Synthesis and structures of azine-based crown-containing hetarylphenylethenes

DOI: 10.1007/s11172-006-0025-5

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