Reactions of nitrogenous derivatives of substituted salicylaldehydes with cyclic ketones and enamines

Article abstract of DOI:10.1023/A:1020956614588

The reactions of aminals, the Mannich bases, and azomethines derived from substituted salicylaldehydes were studied. Derivatives of tetrahydrocyclopenta[b]- and hexahydrocyclohepta[b]chromenes and substituted 2,2′-spirobichromenes were prepared from aminals, and substituted hexahydroxanthenes were synthesized from the Mannich bases. Azomethine derivatives of 5-nitrosalicylaldehyde and aliphatic amines react with cyclohexanone to form 4a-amino-7-nitro-2,3,4,4a-tetrahydro-1H-xanthenes. 4a-Morpholino-7-nitro-9-phenylethynyl-1,2,3,4,9,9a-hexahydroxanthene was studied by X-ray diffraction analysis.

Full text of DOI:10.1023/A:1020956614588

1262
Russian Chemical Bulletin, International Edition, Vol. 51, No. 7, pp. 1262—1269, July, 2002
Reactions of nitrogenous derivatives of substituted salicylaldehydes
with cyclic ketones and enamines
a
a
b
b
L. Yu. Ukhin,a L. V. Belousova, Zh. I. Orlova, S. V. Shishkina, and O. V. Shishkin
ꢀ
аInstitute of Physical and Organic Chemistry at the Rostov State University,
194/2 ul. Stachki, 344090 RostovꢀonꢀDon, Russian Federation.
Fax: +7 (863 2) 43 4776. Eꢀmail: may@ipoc.rsu.ru
bInstitute for Single Crystals, National Academy of Sciences of the Ukraine,
60 ul. Lenina, 310001 Kharkov, Ukraine.
Fax: +7 (057 2) 320273
The reactions of aminals, the Mannich bases, and azomethines derived from substituted
salicylaldehydes were studied. Derivatives of tetrahydrocyclopenta[b]ꢀ and hexahydroꢀ
cyclohepta[b]chromenes and substituted 2,2´ꢀspirobichromenes were prepared from aminals,
and substituted hexahydroxanthenes were synthesized from the Mannich bases. Azomethine
derivatives of 5ꢀnitrosalicylaldehyde and aliphatic amines react with cyclohexanone to form
4aꢀaminoꢀ7ꢀnitroꢀ2,3,4,4aꢀtetrahydroꢀ1Hꢀxanthenes. 4aꢀMorpholinoꢀ7ꢀnitroꢀ9ꢀphenylꢀ
ethynylꢀ1,2,3,4,9,9aꢀhexahydroxanthene was studied by Xꢀray diffraction analysis.
Key words: aminals, azomethines, Mannich bases, substituted salicylaldehydes, quinoꢀ
methides, cyclic ketones, enamines, cycloaddition, 2Hꢀchromenes, 2,2´ꢀspirobichromenes,
tetrahydroxanthenes, hexahydroxanthenes.
We have recently1 reported that aminals of substiꢀ
tuted salicylaldehydes react readily with cyclohexanone
to form tetrahydroxanthene derivatives. It turned out
that other cyclic ketones can react similarly. For exꢀ
ample, 3,5ꢀdichlorosalicylaldehyde aminal 1a and cycloꢀ
pentanone (2a) produced 3aꢀmorpholinoꢀ5,7ꢀdichloroꢀ
1,2,3,3aꢀtetrahydrocyclopenta[b]chromene (3).
Scheme 1
The mechanism of these reactions assumes the conꢀ
certed formation of оꢀquinomethide from aminal 1а and
of enamine from ketone 2а and their [4+2]ꢀcycloaddiꢀ
tion.1 In fact, heating of the presynthesized 1ꢀmorphoꢀ
linocyclopentene (4а) and aminal 1а affords chromene 3
(Scheme 1).
3,5ꢀDichloroꢀ and 3,5ꢀdibromosalicylaldehyde
aminals 1a,b react with cycloheptanone (2b) to form
hexahydrocyclohepta[b]chromenes 5a,b (Scheme 2).
Chromene 5а exhibited an unexpected abnormality,
which distinguishes it from both chromene 5b and all
tetrahydroxanthenes prepared previously1 and in this
work. According to the 1H NMR spectroscopic data
(Table 1), it exists in a CDCl3 solution as at least two
geometric isomers.
Each signal from the С(8)H, С(10)H, and С(11)H
protons is duplicated by the signal from the isomer (С(8)H
and С(10)H protons are duplicated by downfield douꢀ
blets, and С(11)H is duplicated by an upfield singlet).
The ratio of these isomers is approximately 2 : 1 (see
Table 1). We specially used the expression "at least" beꢀ
cause the 1H NMR spectrum of chromene 5а exhibits
another set of signals from admixtures, viz., from three
aromatic protons, two of which are doublets with virtuꢀ
ally the same spinꢀspin coupling constants as those of
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1167—1174, July, 2002.
1066ꢀ5285/02/5107ꢀ1262 $27.00 © 2002 Plenum Publishing Corporation

Synthesis of chromenes and xanthenes
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
1263
Scheme 2
cycle. The existence of hindered conformers with differꢀ
ent geometries of the sevenꢀmembered saturated cycle,
i.e., conformational isomerism, seems most probable.2
The reaction of cycloheptanone (2b) and cycloꢀ
octanone (2c) with 5ꢀnitrosalicylaldehyde aminal 1с 3
leads to quite different results. The assumed mechanism
of this reaction is presented in Scheme 3, and its prodꢀ
ucts are 2,2´ꢀspirobichromenes 10a,b.
The initial steps in this scheme (up to compounds 8)
are the same as in the mechanism proposed previously1
for the reaction of aminal 1с with cyclohexanone, viz.,
concerted formation of quinomethide 6 and enamines 4,
their cycloaddition, and elimination of two morpholine
molecules from tricyclic compounds 7 (the lowest hoꢀ
molog 8 with l = 3 was isolated and characterized in the
same study1). Compounds 8a,b can be considered as
anhydrobases of the corresponding 2,3ꢀcycloalkabenzoꢀ
pyrilium salts. The condensation of such salts with
salicylaldehydes followed by treatment with a base is the
known method for the synthesis of 3,3´ꢀpolymethyleneꢀ
2,2´ꢀspirobipyrans.4 In our case, anhydrobases 8 add a
R = Cl (a), Br (b)
two main isomers. Diastereomers or cis—transꢀisomers
cannot form because compound 5а contains only one
asymmetrical C atom and a rigid double bond in the
Table 1. Spectral characteristics of compounds 3, 5, 10, 11, 12, and 15
Comꢀ
pound
IR,
ν/cm–1
1H (CDCl3),
δ (J/Hz)
Comꢀ
pound
IR,
ν/cm–1
1H (CDCl3),
δ (J/Hz)
3
1707 w, 1554 w,
1.70—2.00 (m, 3 H, (CH2)3); 2.50 (m, 11b 3366, 3313
2.47 (m, 7 H, Me, 2 CH2N); 3.64 (t,
4 H, 2 CH2O, J = 4.4); 5.11 (s, 1 H,
CH); 6.90 (m, 3 H, CH arom.); 7.20
(d, 1 H, CH arom., J = 7.85); 7.56
(d, 1 H, CH arom., J = 7.7); 7.88
(dd, 1 H, CH arom., 3J = 8.95,
4J = 2.85); 8.22 (br.s, 1 H,
1114 (С—О—С), 3 H, (CH2)3); 2.55 (m, 2 H, CH2N);
941 (cyclopent.) 2.78 (m, 2 H, CH2N); 3.55 (m, 4 H,
2 CH2O); 6.33 (m, 1 H, C(9)H);
(OH, NH),
1607, 1581,
1548 (arom.),
1514,
6.85 (d, 1 H, C(8)H, J = 2.3); 7.12
(d, 1 H, C(6)H, J = 2.3)
1.20—4.00 (m, 18 H, 9 CH2); 6.32
1341 (NO2),
1107 (C—O—C)
5а 1560 w (arom.),
1107 (С—О—С) (s, C(11)H); 6.97 (d, C(10)H,
J = 2.4); 7.19 (d, C(8)H, J = 2.4)
(isomer 1) and 6.36 (s, C(11)H); 6.81
(d, C(10)H, J = 2.5); 7.10 (d, C(8)H,
J = 2.5) (isomer 2)*
CH arom.); 10.86 (s, 1 H, OH);
12.58 (s, 1 H, NH)
12a 2220 w (C≡C),
1614, 1394,
1.00—1.80 (m, 6 H, 3 CH2); 2.10 (m,
2 H, CH2); 2.33 (m, 1 H, C(9a)H);
2.65 (t, 4 H, 2 CH2N, J = 4.5); 3.58
(m, 4 H, 2 CH2O); 4.54 (d, 1 H,
C(9)H, J = 5.0); 6.87 (d, 1 H, C(5)H,
J = 9.0); 7.32 (m, 3 H, CH arom.);
7.48 (m, 2 H, CH arom.); 8.05 (dd,
1581 (arom.),
1507,
1341 (NO2),
1114 (C—O—C)
5b 3060 w
1.35—1.95 (m, 10 H, 5 CH2); 2.61 (m,
2 H, CH2N); 2.81 (m, 2 H, CH2N);
3.57 (m, 4 H, 2 CH2O); 6.34 (s, 1 H,
(CH arom.),
1554 w (arom.),
1114 (C—O—C) C(11)H); 6.98 (d, 1 H, C(10)H,
J = 2.3); 7.39 (d, 1 H, C(8)H,
J = 2.3)
3
1 H, C(6)H, J = 9.0, 4J = 2.75); 8.50
(dd, 1 H, C(8)H, 4J = 2.75, 4J = 1.20)
10а 1654, 1607,
1.55 (m, 2 H, CH2); 2.10 (m, 2 H,
CH2); 2.35 (m, 2 H, CH2); 2.65 (m,
2 H, CH2); 6.75 (s, 2 H, C(4)H);
6.85 (d, 2 H, C(8)H, J = 8.8); 8.10
(d, 2 H, C(5)H, J = 2.6); 8.05 (dd,
2 H, C(7)H, 3J = 8.8, 4J = 2.6)
1.60 (m, 4 H, 2 CH2); 1.78 (m, 2 H,
CH2); 2.43 (m, 4 H, 2 CH2); 6.68 (s,
2 H, 2 C(4)H); 6.89 (d, 2 H, 2 C(8)H,
J = 10.0); 8.05 (d, 2 H, 2 C(5)H,
J = 2.6); 8.06 (dd, 2 H, 2 C(7)H,
3J = 10.0, 4J = 2.6)
12b 3260 (NH), 1710 w 1.10—2.10 (m, 9 H, CH2, CH); 2.54
1574 (arom.),
1514,
1347 (NO2)
(cyclohex.),
1614, 1581
(s, 3 H, Me); 2.91 (m, 4 H, 2 CH2N);
3.69 (m, 4 H, 2 CH2O); 4.41 (d, 1 H,
C(9)H, J = 11); 6.72—7.33 (m, 4 H,
CH arom.); 6.88 (d, 1 H, C(5)H,
J = 9.0)
(arom.), 1514,
1334 (NO2),
1107 (С—O—C)
1674 w (C=C),
1614, 1581
10b 1667 w, 1647,
1607, 1580
15
1.10—2.60 (m, 12 H, 6 CH2); 2.70 (m,
2 H, CH2N); 2.90 (m, 2 H, CH2N);
6.17 (d, 1 H, C(9)H, J = 1.5); 6.68 (d,
1 H, C(5)H, J = 9.0); 7.77 (d, 1 H,
C(8)H, J = 3.0); 7.90 (dd, 1 H,
(arom.), 1521,
1347 (NO2)
(arom.), 1514,
1341 (NO2)
3
C(6)H, J = 9.0, 4J = 3.0)
* Ratio of isomers ∼1 : 2.

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Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
Ukhin et al.
Scheme 3
2: n = 6 (b), 7 (c); 4: m = 5 (b), 6 (c); 7: m = 5 (a), 6 (b); 8, 9, 10: l = 4 (a), 5 (b)
molecule of quinomethide 6 at the double bond conjuꢀ
The dihydropyran fragment has a distorted sofa conꢀ
gated with the 2Hꢀchromene structure, after which
morpholine is eliminated from intermediate compounds 9.
It is known1 that the elimination of morpholine from
4аꢀmorpholinoꢀ7ꢀnitroꢀ2,3,4,4aꢀtetrahydroꢀ1Hꢀxanthene
is very difficult. It is most likely that analogs with sevenꢀ
and eightꢀmembered rings eliminate morpholine much
more easily, and this explains such a strong difference in
the final products.
formation. The exit of the С(11) and С(6) atoms from
the rootꢀmeanꢀsquare plane passing through other atꢀ
oms of the ring (O(1), C(5), C(13), and C(12)) are
–0.63 and 0.14 Å, respectively. The cyclohexane and
morpholine rings have chair conformations. The exit of
the С(10) and С(7), N(2) and O(4) atoms from the rootꢀ
O(2)
The Mannich bases derived from salicylaldehyde can
reversibly dissociate to оꢀquinomethide and an amine.5,6
This property allows their use in syntheses of hexaꢀ
hydroxanthene derivatives. The preparation of 2ꢀaminoꢀ
chromones from the Mannich bases (derivatives of
phenols and enamines) has been described.7 We found3
that brief heating of the Mannich bases 11a,b with
1ꢀmorpholinocyclohexene (4b) affords hexahydroxanꢀ
thenes 12a,b (Scheme 4). As in the case of aminals,
these reactions occur with cyclohexanone (2d), i.e., with
the formation of enamine 4b in situ (the yields of comꢀ
pounds 12a,b are 66 and 51%, respectively).
O(3)
N(1)
C(2)
C(3)
C(1)
C(24)
C(25)
C(4)
C(5)
C(13)
C(12)
C(19)
C(20)
O(1)
N(2)
C(23)
C(16)
O(4)
C(18)
C(17)
C(6)
C(11)
C(10)
C(9)
C(22) C(21)
C(15)
C(14)
C(8)
C(7)
The structure of molecule 12а was confirmed by Xꢀray
diffraction analysis (Fig. 1, Tables 2 and 3).
Fig. 1. Structure of molecule 12a.

Synthesis of chromenes and xanthenes
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
1265
Scheme 4
Table 3. Bond angles (ω) in molecule 12a
Angle
ω/deg
Angle
ω/deg
O(3)—N(1)—O(2) 123.8(2) O(3)—N(1)—C(2)
118.4(2)
O(2)—N(1)—C(2) 117.7(2) C(14)—N(2)—C(17) 108.2(1)
C(14)—N(2)—C(6) 115.6(1) C(17)—N(2)—C(6) 114.3(1)
C(5)—O(1)—C(6)
119.4(1) C(16)—O(4)—C(15) 109.6(2)
C(2)—C(1)—C(13) 120.6(2) C(1)—C(2)—C(3)
C(1)—C(2)—N(1) 118.9(2) C(3)—C(2)—N(1)
121.9(2)
119.2(2)
120.5(2)
C(4)—C(3)—C(2)
O(1)—C(5)—C(4)
118.4(2) C(3)—C(4)—C(5)
115.7(2) O(1)—C(5)—C(13) 123.5(2)
C(4)—C(5)—C(13) 120.8(2) O(1)—C(6)—N(2)
O(1)—C(6)—C(7) 104.5(1) N(2)—C(6)—C(7)
105.5(1)
115.3(1)
O(1)—C(6)—C(11) 108.5(1) N(2)—C(6)—C(11) 111.3(1)
C(7)—C(6)—C(11) 111.1(1) C(8)—C(7)—C(6) 113.5(2)
C(7)—C(8)—C(9) 111.8(2) C(8)—C(9)—C(10) 110.7(2)
C(9)—C(10)—C(11) 112.0(2) C(10)—C(11)—C(12) 113.1(1)
C(10)—C(11)—C(6) 111.6(2) C(2)—C(11)—C(6) 108.6(1)
C(18)—C(12)—C(13)113.5(1) C(18)—C(12)—C(11) 113.9(1)
C(13)—C(12)—C(11)108.4(1) C(1)—C(13)—C(5) 117.7(2)
C(1)—C(13)—C(12) 123.5(2) C(5)—C(13)—C(12) 118.8(2)
N(2)—C(14)—C(15) 110.0(2) O(4)—C(15)—C(14) 112.5(2)
O(4)—C(16)—C(17) 111.9(2) N(2)—C(17)—C(16) 109.6(2)
C(19)—C(18)—C(12)174.9(2) C(18)—C(19)—C(20) 176.9(2)
C(21)—C(20)—C(25)117.9(2) C(21)—C(20)—C(19) 120.1(2)
C(25)—C(20)—C(19)122.0(2) C(22)—C(21)—C(20) 121.0(2)
C(23)—C(22)—C(21)120.4(2) C(24)—C(23)—C(22) 119.3(2)
C(23)—C(24)—C(25)120.7(2) C(20)—C(25)—C(24) 120.7(2)
Reagents and conditions: i. 150—170 °C, 2 min.
ii. 130—140 °C, 2 min.
meanꢀsquare planes passing through other atoms of the
rings are –0.66 and 0.63 Å, –0.69 and 0.64 Å, respecꢀ
tively. The dihydropyran and cyclohexane rings are
cisꢀfused (torsion angle H(11)—С(11)—С(6)—N(2)
63.6°). The morpholine ring is axially oriented
toward the dihydropyran ring (torsion angle
С(5)—О(1)—С(6)—N(2) 80.1(2)°), and the substituent
at the С(12) atom is in the equatorial position (torsion
angle С(5)—С(13)—С(12)—С(18) 156.4(2)°). The plane
of the NO2 group deviates from the plane of the benzene
ring by 11.3(3)°.
Unfavorable nonbonded interactions (shortened
intramolecular contacts H(7А)...С(17) 2.75 Å,
H(10А)...С(18) 2.79 Å, and H(1)...С(18) 2.65 Å at a
sum of van der Waals radii of 2.87 Å)8 elongate the
С(12)—С(13) (1.536(2) Å), С(11)—С(12) (1.558(2) Å),
С(12)—С(18) (1.492(2) Å), and N(2)—C(6) (1.489(2) Å)
bonds compared to average values of 1.503, 1.513, 1.466,
and 1.469 Å, respectively.9 It can be assumed that the
nonequivalent shortened intramolecular H(10А)...С(18)
and H(1)...С(18) contacts bend the triple bond
(С(12)—С(18)—С(19) and С(18)—С(19)—С(20) angles
are 174.9(2) and 176.9(2)°, respectively).
It is known that 5ꢀnitrosalicylaldehyde forms aminal
only with morpholine (pKa = 8.33).10 Its reaction with
strongly basic (pKa ∼11) secondary aliphatic amines afꢀ
fords ion associates.11 Their anions, like aminals, react
with enamines in cycloaddition reactions to form the
corresponding tetrahydroxanthenes.1 Scheme 5 repreꢀ
sents the first example of the oneꢀpot synthesis of previꢀ
ously undescribed 7ꢀnitroꢀ4аꢀpyrrolidinoꢀ2,3,4,4aꢀtetraꢀ
hydroꢀ1Hꢀxanthene (15) in which the ion associate and
enamine are formed in situ. Tetrahydroxanthene 15 was
also prepared in the independent synthesis from ion asꢀ
Table 2. Bond lengths (d) in molecule 12а
Bond
d/Å
Bond
d/Å
N(1)—O(3)
N(1)—C(2)
N(2)—C(17)
O(1)—C(5)
O(4)—C(16)
C(1)—C(2)
C(2)—C(3)
C(4)—C(5)
C(6)—C(7)
C(7)—C(8)
C(9)—C(10)
C(11)—C(12)
C(12)—C(13)
C(16)—C(17)
C(19)—C(20)
C(20)—C(25)
C(22)—C(23)
C(24)—C(25)
1.243(2)
1.486(3)
1.487(2)
1.381(2)
1.434(2)
1.389(3)
1.398(3)
1.404(3)
1.543(3)
1.536(3)
1.543(3)
1.558(2)
1.536(2)
1.527(3)
1.464(3)
1.394(3)
1.381(3)
1.395(3)
N(1)—O(2)
N(2)—C(14)
N(2)—C(6)
O(1)—C(6)
O(4)—C(15)
C(1)—C(13)
C(3)—C(4)
C(5)—C(13)
C(6)—C(11)
C(8)—C(9)
C(10)—C(11)
C(12)—C(18)
C(14)—C(15)
C(18)—C(19)
C(20)—C(21)
C(21)—C(22)
C(23)—C(24)
1.245(2)
1.486(2)
1.489(2)
1.472(2)
1.438(2)
1.402(2)
1.396(3)
1.427(3)
1.562(2)
1.539(3)
1.548(2)
1.492(2)
1.526(3)
1.201(2)
1.394(3)
1.392(3)
1.377(3)

1266
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
Ukhin et al.
sociate 16 and enamine 4с using a procedure described
hydroxanthenes 20, which are dehydrated to give tetraꢀ
hydroxanthene derivatives 18 (Scheme 7). The formaꢀ
tion of analogs of compound 20 by the condensation of
salicylaldehydes with enamines has previously been deꢀ
scribed.13
earlier1 (see Scheme 5).
Scheme 5
Scheme 7
All presented reactions of cyclic ketones can easily
be explained by the concerted formation of enamine and
оꢀquinomethide and their cycloaddition. The formal
scheme assumes the dissociation of aminal or the
Mannich base to quinomethide and amine and condenꢀ
sation of the latter with cyclic ketone to form an enamꢀ
ine. The possibility of this dissociation is confirmed by
spectroscopic data.1,5,6 However, it is known that synꢀ
thesis of enamines takes a long time. This requires boilꢀ
ing of components in toluene for many hours in the
presence of acid catalysts and with continuous removal
of water that formed.14
Secondary amines were used in all reactions discussed
above. The use of azomethines instead of aminals proꢀ
vides the formation of analogous structures with primary
amines as substituents. It has been found12 that heating
of azomethines 17 derived from 5ꢀnitrosalicylaldehyde
and aliphatic amines with cyclohexanone (2d) produces
4аꢀaminoꢀ7ꢀnitroꢀ2,3,4,4aꢀtetrahydroꢀ1Hꢀxanthenes 18
(Scheme 6).
In our cases, the reactions take dozens of seconds,
and the yields of final products suggest high degrees of
conversion of cyclic ketones and amines to enamines
over such short time intervals. These facts suggest that
enamine formation and cycloaddition occur, in fact, in
the intermediate (or activated) complex formed by the
nitrogenous base of the salicylaldehyde derivative and
cyclic ketone. The available data on the structure of
nitrogen bases15,16 suggest that complex formation inꢀ
volves cyclic structures with intramolecular hydrogen
bonding, which can be considered as an intermediate
step of proton transfer.17 The reaction scheme including
such intramolecular acid catalysis is presented below
(Scheme 8).
Scheme 6
If R2 = NR1 , then compound 21 is an aminal comꢀ
2
plex; if R2 is an organic radical, then compound 21 is a
complex of the Mannich base. We assume that the forꢀ
mation of tetrahydroxanthenes 18 involves the proton
transfer to the carbonyl oxygen atom and cycloaddition
in a similar complex 22 formed by the cyclic aldehyde
structure with the intramolecular hydrogen bond and
enamine (Scheme 9).
We believe that the first step of this reaction is tranꢀ
samination with the formation of 5ꢀnitrosalicylaldehyde
(13) and the corresponding cyclohexanone azomeꢀ
thine 19. The reaction of these compounds (cyclohexꢀ
anone azomethines in the enamine form) affords hexaꢀ

Synthesis of chromenes and xanthenes
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
1267
Scheme 8
Table 4. Spectral parameters of tetrahydroxanthenes 18a—e
Comꢀ IR,
pound ν/cm–1
1H (CDCl3),
δ (J/Hz)
18а 3313 (NH),
0.99 (t, 3 H, Me, J = 7.1); 1.30—2.50
1614,
(m, 8 H, 4 CH2); 2.59 (q, 2 H, CH2,
1574 (arom.), J = 7.1); 6.25 (s, 1 H, C(9)H); 6.73
1514,
1341 (NO2)
(d, 1 H, C(5)H, J = 8.9); 7.88 (d, 1 H,
C(8)H, J = 2.7); 7.91 (dd, 1 H,
3
C(6)H, J = 8.9, 4J = 2.7)
18b 3333 (NH),
0.82 (t, 3 H, Me, J = 7.35); 1.20—2.60
1607, 1581
(m, 12 H, 6 CH2); 6.25 (s, 1 H,
(arom.), 1514, C(9)H); 6.73 (d, 1 H, C(5)H, J = 8.9);
1334 (NO2)
7.82 (d, 1 H, C(8)H, J = 2.75); 7.95
(dd, 1 H, C(6)H, 3J = 8.9, 4J = 2.75)
0.90—2.70 (m, 19 H, CH2, СH); 6.21
(s, 1 H, C(9)H); 6.72 (d, 1 H, C(5)H,
18c 3340 (NH),
1607,
1581 (arom.), J = 8.9); 7.84 (d, 1 H, C(8)H,
1514,
1334 (NO2)
18d 3360 (NH),
1607,
J = 2.75); 7.96 (dd, 1 H, C(6)H,
3J = 8.9, 4J = 2.75)
1.40—2.65 (m, 8 H, 4 CH2); 3.73 (d,
2 H, CH2N, J = 9.0); 6.31 (d, 1 H,
1574 (arom.), C(9)H, J = 1.9); 6.76 (d, 1 H, C(5)H,
1514,
1334 (NO2)
J = 8.9); 7.24 (m, 5 H, Ph); 7.85 (d,
1 H, C(8)H, J = 2.75); 7.97 (dd, 1 H,
3
C(6)H, J = 8.9, 4J = 2.75)
18e 3350 (NH),
1.40—2.65 (m, 8 H, 4 CH2); 3.74
(s, 2 H, CH2N); 5.99 (d, 1 H, furan
1607,
1574 (arom.), С(3)H, J = 3.15); 6.21 (m, 1 H,
Scheme 9
1507,
furan C(4)H); 6.30 (d, 1 H, C(9)H,
J = 1.85); 6.69 (d, 1 H, C(5)H,
J = 8.9); 7.27 (d, 1 H, furan C(5)H,
J = 1.85); 7.84 (d, 1 H, C(8)H,
J = 2.75); 7.94 (dd, 1 H, C(6)H,
3J = 8.9, 4J = 2.75)
1334 (NO2)
troleum, dried in air, and used in syntheses without additional
purification. The yields were 90—100%, m.p.: 147—156 °С
(17а), 114—115 °С (17b), 142—143 °С (17с), 88—89 °С (17d),
120 °C (17е).
5,7ꢀDichloroꢀ3aꢀmorpholinoꢀ1,2,3,3aꢀtetrahydrocycloꢀ
penta[b]chromene (3). A. 3,5ꢀDichlorosalicylaldehyde aminal
1а (0.35 g, 1 mmol) and cyclopentanone 2а (0.2 mL, 2 mmol)
were boiled for 2 min at 110—120 °С. The mixture was cooled,
MeOH (3 mL) was added, and the resulting solution crystalꢀ
lized upon cooling with ice. The precipitate was filtered off,
washed with cold МеОН, and dried. Chromene 3 (0.24 g,
58%) was obtained as colorless crystals with m.p. 135—137 °С
(from МеОН).
B. A mixture of aminal 1a (0.35 g, 1 mmol) and 1ꢀmorphoꢀ
linocyclopentene 4а (0.3 mL, 2 mmol) was heated to 145 °С
and cooled. MeOH (3 mL) was added to the mixture, which
was then processed as described above. Chromene 3 (0.23 g,
70%) was obtained as colorless crystals with m.p. 135—137 °С
(from МеОН). Found (%): С, 58.98; H, 5.16; Cl, 21.22;
N, 4.35. C16H17Cl2NO2. Calculated (%): C, 58.91; H, 5.25;
Cl, 21.74; N, 4.29.
Experimental
IR spectra were recorded on a Specord IRꢀ75 instrument in
Nujol. 1H NMR spectra were obtained on a Varian UNITYꢀ300
spectrometer. Aminal 1с was synthesized according to a previꢀ
ously described procedure.16 Cycloalkanone enamines were synꢀ
thesized by known procedures.14 The spectral parameters of
the compounds obtained are presented in Tables 1 and 4.
Synthesis of azomethines 17 (general procedure). 5ꢀNitroꢀ
salicylaldehyde (1.7 g, 0.01 mol) was dissolved in boiling PriOH
(10 mL), and aliphatic amine (0.11 mol) was added to the hot
solution (in the case of azomethine 17а, gaseous ethylamine
was passed through a hot solution). The mixture was cooled,
and light petroleum (5 mL) was added. The yellow crystalline
precipitate that formed was filtered off, washed with light peꢀ
7,9ꢀDichloroꢀ5аꢀmorpholinoꢀ1,2,3,4,5,5aꢀhexahydrocycloꢀ
hepta[b]chromene (5а). A mixture of aminal 1a (1.05 g, 3 mmol)

1268
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
Ukhin et al.
and cycloheptanone 2b (0.6 mL, 5 mmol) was heated for 2 min
at 140—145 °С. After cooling MeOH (5 mL) was added, and
the mixture was cooled with ice and scratched with a glass rod.
After storing on ice for 1 h, the crystals that formed were
filtered off, washed with cold MeCN and hexane, and dried.
Chromene 5a (0.5 g, 47%) was obtained as colorless crystals
with m.p. 125 °С (from MeCN). Found (%): С, 60.52; H, 5.64;
Cl, 20.69; N, 3.71. C18H21Cl2NO2. Calculated (%): C, 61.03;
H, 5.97; Cl, 20.01; N, 3.95.
7,9ꢀDibromoꢀ5аꢀmorpholinoꢀ1,2,3,4,5,5aꢀhexahydrocycloꢀ
hepta[b]chromene (5b). A mixture of aminal 1b (2.6 g, 6 mmol)
and cycloheptanone 2b (1 mL, 8 mmol) was boiled for 2 min at
135 °С, and MeOH (15 mL) was added after cooling. The
mixture was cooled with ice and scratched with a glass rod to
complete solidification. The precipitate was filtered off, washed
repeatedly with cold MeOH, and dried. The yield of the crude
product was 1.8 g. Recrystallization from PriOH (40 mL) gave
1 g (39%) of chromene 5b as colorless crystals with m.p.
132—135 °С. Found (%): С, 49.15; H, 4.65; Br, 36.72;
N, 3.27. C18H21Br2NO2. Calculated (%): C, 48.78; H, 4.78;
Br, 36.06; N, 3.16.
130—140 °С, and MeOH (16 mL) was added after cooling. The
mixture was cooled with ice and scratched with a glass rod. The
light yellow crystalline precipitate was filtered off, washed with
cold MeOH, and dried. The yield of the crude product was
66% (0.82 g). After recrystallization from MeOH (25 mL), a
colorless substance with m.p. 190—193 °С was obtained.
Found (%): С, 71.67; H, 6.89; N, 6.95. C25H26N2O4. Calcuꢀ
lated (%): C, 71.75; H, 6.26; N, 6.69.
9ꢀ(2ꢀMethylindolꢀ3ꢀyl)ꢀ4aꢀmorpholinoꢀ7ꢀnitroꢀ
1,2,3,4,4a,9аꢀhexahydroxanthene (12b). А. A mixture of the
Mannich base 11b (0.45 g, 1.2 mmol) and 1ꢀmorpholinoꢀ
cyclohexene (4b) (0.9 mL, 5 mmol) was heated for 2 min at
165—170 °С and cooled to ∼50 °С, and 4 mL of CCl4 were
added. The mixture was scratched with a glass rod, and hexane
(4 mL) was added. The precipitate was filtered off, washed with
hexane, and dried. Compound 12b (0.45 g, 82%) was obtained
as colorless crystals with m.p. 227—230 °С.
B. A mixture of compound 11b (1 g, 2.7 mmol) and cycloꢀ
hexanone (2d) (0.8 mL, 8 mmol) was heated at 130—135 °С to
complete homogenization and cooled to 70—80 °С. MeOH
(5 mL) was added, and the mixture was boiled until a crystalꢀ
line precipitate formed (2—3 min). The mixture was cooled
and filtered. The precipitate was cooled with cold MeOH and
dried. Compound 12b (0.62 g, 51%) was obtained as colorless
crystals with m.p. 227—230 °С (from MeOH). Found (%):
С, 69.48; H, 6.00; N, 9.73. C26H29N3O4. Calculated (%):
C, 69.78; H, 6.53; N, 9.39.
7ꢀNitroꢀ4аꢀpyrrolidinoꢀ2,3,4,4aꢀtetrahydroꢀ1Hꢀxanthene
(15). A. A mixture of 5ꢀnitrosalicyladehyde (13) (1.67 g,
10 mmol) and pyrrolidine (14) (1 mL, 12 mmol) was heated to
dissolution, cyclohexanone (2d) (1.5 mL, 14 mmol) was added,
and the mixture was boiled for 2 min. The reaction mixture was
dissolved in CHCl3 and passed through a column with Al2O3.
The solvent was evaporated, and a light yellow oil was crystalꢀ
lized on cooling with ice and trituration with hexane. The
precipitate was filtered off, washed with hexane, and dried.
Compound 15 was obtained in 33% yield (0.7 g) with m.p.
106—108 °С (from a PriOH—hexane (1 : 1) mixture).
3,3´ꢀTetramethyleneꢀ6,6´ꢀdinitroꢀ2,2´ꢀspirobichromene
(10а). A mixture of aminal 1c (0.65 g, 2 mmol) and cycloꢀ
heptanone 2b (0.4 mL, 3.4 mmol) was heated for 2 min at
125—130 °С. After cooling 3 mL of МеОН were added, and
the mixture was worked up as described for compound 3. The
yield was 0.16 g (41%). After recrystallization from MeCN
(20 mL), spirobichromene 10a was obtained as colorless crystals
with m.p. 292—295 °С. Found (%): С, 64.11; Н, 3.95; N, 7.48.
C
21H16N2O6. Calculated (%): C, 64.28; H, 4.11; N, 7.14.
3,3´ꢀPentamethyleneꢀ6,6´ꢀdinitroꢀ2,2´ꢀspirobichromene
(10b). Aminal 1c (0.65 g, 2 mol) was added to the melt of
cyclooctanone (2c) (0.35 g, 2 mmol), and the resulting mixture
was heated for 2 min at 120 °С. After cooling, 5 mL of MeOH
were added, and the mixture was cooled with ice and scratched
with a glass rod. The precipitate was filtered off, washed with
МеОН, and dried. Spirobichromene 10b was obtained in 34%
yield (0.14 g) as colorless crystals with m.p. 295—305 °С (from
МеCN). Found (%): С, 64.70; H, 4.60; N, 7.20. C22H18N2O6.
Calculated (%): C, 65.02; H, 4.46; N, 6.85.
2ꢀMethylꢀ3ꢀ[morpholino(2ꢀhydroxyꢀ5ꢀnitrophenyl)meꢀ
thyl]indole (11b). A mixture of aminal 1c (0.65 g, 2 mmol) and
2ꢀmethylindole (0.52 g, 4 mmol) was ground in a mortar and
melted at 110 °С whereupon a new crystalline precipitate rapꢀ
idly formed. After cooling, 3 mL of MeCN were added, and the
mixture was cooled with ice and washed with cold MeCN and
hexane. Compound 11b was obtained in 84% yield (0.62 g) as
light yellow crystals with m.p. 220—225 °С (from MeCN).
Found (%): С, 65.50; H, 5.45; N, 11.32. C20H21N3O4. Calcuꢀ
lated (%): C, 65.38; H, 5.76; N, 11.44.
4аꢀMorpholinoꢀ7ꢀnitroꢀ9ꢀphenylethynylꢀ1,2,3,4,4a,9аꢀhexaꢀ
hydroxanthene (12а). A. A mixture of amine 11а 16 (0.67 g,
2 mmol) and 1ꢀmorpholinocyclohexene (4b) (0.8 mL, 5 mmol)
was heated for 2 min at 150—155 °С, and PriOH (8 mL) was
added after cooling. The mixture was cooled with ice and
scratched with a glass rod, and the precipitate that formed was
filtered off and washed with cold PriOH and light petroleum.
Compound 12a (0.29 g, 36%) was obtained as light yellow
crystals with m.p. 190—192 °С (from MeCN).
B. A mixture of ion associate 16 11 (0.66 g, 2 mmol) and
1ꢀpyrrolidinocyclohexene (4c) (0.8 mL, 4 mmol) was heated
for 1 min at 135 °С and cooled. MeOH (10 mL) was added,
and the mixture was poured into 50 mL of cold water. The
precipitate was filtered off, washed with 50% EtOH, and dried.
The yield of the crude product was 0.3 g. Recrystallization
from PriOH gave compound 15 (0.18 g, 30%) as yellow crystals
with m.p. 106—108 °С. Found (%): С, 67.50; H, 6.45; N, 9.62.
C
17H20N2O3. Calculated (%): C, 67.98; H, 6.71; N, 9.33.
4аꢀEthylaminoꢀ7ꢀnitroꢀ2,3,4,4aꢀtetrahydroꢀ1Hꢀxanthene
(18а). A mixture of azomethine 17a (0.4 g, 2 mmol) and cycloꢀ
hexanone (2d) (0.4 mL, 4 mmol) was heated for 2 min at
110—120 °С and cooled, and water (0.5 mL) was added. The
oil that formed crystallized after cooling with ice and trituraꢀ
tion. The precipitate was filtered off and recrystallized from
hexane. The yield was 0.35 g (63%).* Double recrystallization
from MeOH gave colorless crystals with m.p. 104—105 °С.
Found (%): С, 65.31; H, 6.24; N, 10.57. C15H18N2O3. Calcuꢀ
lated (%): C, 65.68; H, 6.61; N, 10.21.
B. A mixture of amine 11a (1 g, 3 mmol) and cyclohexꢀ
anone (2d) (0.8 mL, 7 mmol) was heated for 2 min to
* The substance contains an insignificant amount of a colored
admixture, which confers a reddish color to the substance.

Synthesis of chromenes and xanthenes
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
1269
4аꢀPropylaminoꢀ7ꢀnitroꢀ2,3,4,4aꢀtetrahydroꢀ1Hꢀxanthene
(18b). A mixture of azomethine 17b (0.21 g, 1 mmol) and
cyclohexanone (2d) (0.2 mL, 2 mmol) was boiled for 1 min at
∼140 °С, cooled, and passed through a column with Al2O3
(eluent CHCl3), The solvent was evaporated and the oily resiꢀ
due crystallized upon trituration. Compound 18b was obtained
in 79% yield (0.23 g) with m.p. 95 °С (from hexane). Found (%):
С, 66.19; H, 6.75; N, 9.37. C16H20N2O3. Calculated (%):
C, 66.65; H, 6.99; N, 9.72.
4аꢀCyclohexylaminoꢀ7ꢀnitroꢀ2,3,4,4aꢀtetrahydroꢀ1Hꢀ
xanthene (18с). A mixture of azomethine (17c) (0.5 g, 2 mmol)
and cyclohexanone (2d) (0.4 mL, 4 mmol) was boiled for 2 min
at 145—155 °С. After cooling, 2 mL of MeOH were added, and
the mixture was cooled with ice and scratched with a glass rod.
The precipitate that formed was filtered off and recrystallized
from hexane (10 mL) and MeOH (in ice). The precipitated was
filtered off, washed with cold MeOH, and dried. Comꢀ
pound 18c was obtained in 30% yield (0.2 g) as colorꢀ
less crystals with m.p. 113—115 °С. Found (%): С, 69.12;
H, 7.60; N, 8.32. C19H24N2O3. Calculated (%): C, 69.49;
H, 7.37; N, 8.53.
4аꢀBenzylaminoꢀ7ꢀnitroꢀ2,3,4,4aꢀtetrahydroꢀ1Hꢀxanthene
(18d). A mixture of azomethine 17d (0.52 g, 2 mmol) and
cyclohexanone (2d) (0.4 mL, 4 mmol) was heated for 2 min at
110—120 °С. After cooling 2 mL of MeOH were added, and
the mixture was triturated. The precipitate that formed was
filtered off, washed with cold MeOH, and dried. The yield of
the crude product was 0.5 g. Recrystallization from MeOH
(25 mL) gave compound 18d (0.35 g, 51%) as paleꢀyelꢀ
low crystals with m.p. 113—115 °С. Found (%): С, 71.94;
H, 6.24; N, 8.21. C20H20N2O3. Calculated (%): C, 71.41;
H, 5.99; N, 8.33.
4аꢀFurylaminoꢀ7ꢀnitroꢀ2,3,4,4aꢀtetrahydroꢀ1Hꢀxanthene
(18е). A mixture of azomethine 17e (2.46 g, 10 mmol) and
cyclohexanone (2d) (2 mL, 19 mmol) was heated to boiling
(∼135 °С) and boiled for 1 min. After cooling MeOH (10 mL)
was added, and the mixture was heated to homogenization,
cooled with ice, and triturated. The light crystalline precipitate
that formed was filtered off, washed with cold MeOH, and
dried. The yield was 2.32 g (71%). Recrystallization from 15 mL
of EtOH gave 2.1 g of light yellow crystals with m.p. 90—95 °С.
Repeated crystallization from 20 mL of MeOH gave 1.8 g of
compound 18e as light yellow crystals with m.p. 95—97 °С.
Found (%): С, 66.53; H, 5.48; N, 8.71. C18H18N2O4. Calcuꢀ
lated (%): C, 66.25; H, 5.56; N, 8.58.
References
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Lokshin, E. Yu. Bulgarevich, V. I. Minkin, O. S. Filipenko,
M. A. Novozhilova, S. M. Aldoshin, and L. O. Atovmyan,
Izv. Akad. Nauk, Ser. Khim., 1992, 2389 [Bull. Russ. Acad.
Sci., Div. Chem. Sci., 1992, 41, 1875 (Engl. Transl.)].
7. M. Von Strandtman, M. P. Cohen, and J. Shavel,
J. Heterocycl. Chem., 1970, 7, 1311.
8. Yu. V. Zefirov and P. M. Zorkii, Usp. Khim., 1989, 58, 713
[Russ. Chem. Rev., 1989, 58 (Engl. Transl.)].
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Weinheim, 1994, 2, 741.
10. A. T. Gordon and R. A. Ford, The Chemist´s Companion.
A Handbook of Practical Data, Techniques and References,
Wiley Interscience, New York—London—Sydney—Toronꢀ
to, 1972.
11. L. Yu. Ukhin, Zh. I. Orlova, S. V. Lindeman, V. N.
Khrustalev, and Yu. T. Struchkov, Izv. Akad. Nauk, Ser.
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Transl.)].
12. L. Yu. Ukhin and Zh. I. Orlova, Tez. dokl. IV Vseros. seminara
po magnitnomu rezonansu [Abstrs. IV AllꢀRussian Seminar on
Magnetic Resonance], RostovꢀnaꢀDonu, 1998, 58 (in Russian).
13. L. A. Paquette and H. Stucki, J. Org. Chem., 1966, 31, 1232.
14. Organikum, VEB Deutscher Verlag der Wissenschaften, Berꢀ
lin, 1976.
15. V. I. Minkin, Yu. A. Zhdanov, I. D. Sadekov, and A. D.
Garnovskii, in Azometiny — stroenie, svoistva, primenenie
[Azomethines: Structure, Properties, and Application], Izdꢀvo
Rostov. Gos. Univ., RostovꢀnaꢀDonu, 1967, 155 (in Russian).
16. L. Yu. Ukhin, V. N. Komissarov, S. V. Lindeman, V. N.
Khrustalev, and Yu. T. Struchkov, Izv. Akad. Nauk, Ser.
Khim., 1994, 455 [Russ. Chem. Bull., 1994, 43, 413 (Engl.
Transl.)].
17. R. P. Bell, The Prоton in Chemistry, Chapman and Hall,
London, 1972.
18. G. M. Sheldrick, SHELXTL PLUS. PC Version. A System of
Computer Programs for the Determination of Crystal Structure
from Xꢀray Diffraction Data, Rev. 5.02, Siemens Analytical
Xꢀray Instruments Inc., Göttingen (Germany), 1994.
Xꢀray diffraction analysis of compound 12а. Crystals 12а are
monoclinic (С25H26N2O4), at 20 °С a = 12.387(4) Å, b =
11.549(3) Å, c = 16.296(5) Å, β = 102.65°, V = 2274.7(12) Å3,
M = 418.48, Z = 4, space group Р21/n, dcalc = 1.222 g cm–3
,
µ(MoꢀKα) = 0.083 mm–1, F(000) = 888. Unit cell parameters
and intensities of 4199 reflections were measured on a Siemens
P3/PC automated fourꢀcircle diffractometer (MoꢀKα radiaꢀ
tion, graphite monochromator, θ/2θ scan mode, 2θ
= 50°).
max
The structure was solved by the direct method using the
SHELXTL PLUS program package.18 Positions of H atoms
were calculated geometrically and refined using the riding model
(Ui = 1.2Ueq of the atom bound to the specific hydrogen atom).
The structure was refined by F 2 using the fullꢀmatrix leastꢀ
squares method in the anisotropic approximation to wR2 = 0.098
from 4002 reflections (R1 = 0.044 from 2018 reflections with
F > 4σ(F ), S = 0.953).
Received April 26, 2001;
in revised form September 9, 2001