2-(Azidomethyl)phenylboronic acid in the synthesis of isoquinoline derivatives

Article abstract of DOI:10.1007/s11172-006-0011-y

2-(Azidomethyl)phenyllead triacetate was obtained by the reaction of 2-(azidomethyl)phenylboronic acid with lead tetraacetate. A strategy for the synthesis of isoquinoline derivatives was proposed that involves a reaction of this organolead reagent with e

Full text of DOI:10.1007/s11172-006-0011-y

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Russian Chemical Bulletin, International Edition, Vol. 54, No. 7, pp. 1606—1611, July, 2005
2ꢀ(Azidomethyl)phenylboronic acid in the synthesis of
isoquinoline derivatives
O. G. Ganina,a,b S. G. Zamotaeva,a M. A. Nosarev,a O. V. Kosenkova,a M. I. Naumov,a
A. S. Shavyrin,c J.ꢀP. Finet,d and A. Yu. Fedorova
ꢀ
aN. I. Lobachevsky Nizhnii Novgorod State University,
23 prosp. Gagarina, 603950 Nizhnii Novgorod, Russian Federation.
Fax: +7 (831 2) 65 8592. Eꢀmail: afnn@rambler.ru
bDepartment of Chemistry, M. V. Lomonosov Moscow State University,
Leninskie Gory, 119992 Moscow, Russian Federation.
Eꢀmail: gognn@rambler.ru
cG. A. Razuvaev Institute of Organometallic Chemistry, Russian Academy of Sciences,
49 ul. Tropinina, 603600 Nizhnii Novgorod, Russian Federation.
Fax: +7 (831 2) 12 7497. Eꢀmail: andrew@imoc.sinn.ru
dUMRꢀCNRS 6517, Universités d´AixꢀMarseille 1 et 3, Faculté des Sciences SaintꢀJérôme,
13397 Marseille, Cedex 20, France.
Fax: + 33 4 91 28 8758. Eꢀmail: jeanꢀpierre.finet@up.univꢀmrs.fr
2ꢀ(Azidomethyl)phenyllead triacetate was obtained by the reaction of 2ꢀ(azidomethyl)pheꢀ
nylboronic acid with lead tetraacetate. A strategy for the synthesis of isoquinoline derivatives
was proposed that involves a reaction of this organolead reagent with enolizable substrates
followed by annelation in the presence of triphenylphosphine. The use of 2ꢀ(azidomethyl)pheꢀ
nylboronic acid allowed αꢀarylation products to be obtained from βꢀdiketones and natural
βꢀoxo lactones in good yields.
Key words: 2ꢀ(azidomethyl)phenylboronic acid, organolead compounds, isoquinolines,
isochromanes, αꢀarylation, reductive coupling, lead tetraacetate.
A century after the Ullmann reactions were discovꢀ
ered,1 lowꢀtoxic arylboronic acids have been recognized
as ecologically attractive2 and convenient reagents for creꢀ
ation of Ar—O, Ar—N, Ar—S, and Ar—C bonds.3,4
Nevertheless, some functional groups are sensitive to both
organocopper and palladiumꢀ or nickelꢀcontaining cataꢀ
lysts. For instance, the azido group belongs to such subꢀ
stituents.5
The goal of the present work was to develop azidoꢀ
containing reagents for Cꢀarylation of enolizable subꢀ
strates. It was suggested that these reagents with 2ꢀ(azidoꢀ
methyl)aryl fragments can be obtained from previously6
synthesized functionalized arylboronic acids. In addition,
the proposed strategy can serve as a basis for construction
of the isoquinoline framework found in many natural comꢀ
pounds that exhibit a broad spectrum of biological acꢀ
tivities.7
responding arylboronic acids.9 It is known that introꢀ
duction of a functional group into the benzyl posiꢀ
tion of oꢀtolyllead triacetate derivatives does not
change significantly their reactivities toward soft nucleoꢀ
philes.10
The synthesis of isoquinoline derivatives from
2ꢀ(azidomethyl)phenylboronic acid includes four succesꢀ
sive reactions without isolation of intermediates at each
step (Scheme 1). Transmetalation between arylboronic
acid 1 and lead tetraacetate in the presence of a catalytic
amount of mercury acetate11 gives 2ꢀ(azidomethyl)pheꢀ
nyllead triacetate 2, which can react in situ with enolizable
substrate 3 in the presence of a base. This reductive couꢀ
pling is characteristic of not only lead derivatives9,12,13
but also aryl compounds of bismuth,12,14 iodine,12,15 and
some other main group elements.12 Supposedly, the proꢀ
cess involves the formation of a covalent intermediate 4,16
which undergoes reductive elimination to give αꢀarylation
product 5. Finally, the subsequent reduction of the azido
group with triphenylphosphane (Staudinger reaction5b) is
followed by spontaneous annelation leading to isoquinoꢀ
line derivatives 6.
As an alternative to Pdꢀcatalyzed arylation using
the Suzuki crossꢀcoupling4 or catalytic αꢀarylation of
enolizable substrates,8 we introduced (azidomethyl)aryl
fragments into a substrate by reductive coupling with
the use of aryllead triacetates prepared from the corꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1560—1565, July, 2005.
1066ꢀ5285/05/5407ꢀ1606 © 2005 Springer Science+Business Media, Inc.

Isoquinoline synthesis via arylboronic acid
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 7, July, 2005
1607
Scheme 1
2ꢀ(bromomethyl)phenylboronic acid with NaN3 was carꢀ
ried out in a THF—H2O emulsion, the resulting free
2ꢀ(azidomethyl)phenylboronic acid 1 became reactive,
giving aryllead triacetate 2 in 52% yield.
The "oneꢀpot" synthesis from dimedone 7 in four steps
afforded isoquinoline derivative 12 in 21% yield. Using
this procedure with unsubstituted 4ꢀhydroxycoumarin 8
and 4ꢀhydroxyꢀ6,7ꢀdimethoxycoumarin 9, we obtained
tetracyclic derivatives 13 and 14 in overall 23 and 15%
yields, respectively.
In the case of coumarins 8 and 9, tetracyclic benzoꢀ
pyrans 15 and 16 were also detected among the reaction
products (10 and 11% yields, respectively). To identify
isoquinoline and benzopyran isostructural analogs, the
latter were synthesized in an independent way (Scheme 2).
For instance, the reactions of 2ꢀ(bromomethyl)phenyllead
triacetate with coumarins 8 and 9 in the presence of
oꢀphenanthroline—potassium tertꢀbutoxide (3 : 1) as a
base for reductive coupling gave compounds 15 and 16 in
76 and 47% yields, respectively.
βꢀDiketone 7, unsubstituted 4ꢀhydroxycoumarin 8,
and its natural diꢀ and trimethoxy derivatives 9—11 17
were used as starting substrates.
Scheme 2
Use of the complex of 2ꢀ(azidomethyl)phenylboronic
acid with DMF previously6 obtained by the reaction of
2ꢀ(bromomethyl)phenylboronic acid with NaN3 in DMF,
did not afford any tetracyclic derivatives of the type 6 or
αꢀarylation products 5. However, when the reaction of

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Russ.Chem.Bull., Int.Ed., Vol. 54, No. 7, July, 2005
Ganina et al.
Thus, the formation of benzopyran analogs 15 and 16
from intermediate azides 5 can be explained by the SN2
process competing with the Staudinger reaction.
It should be noted that
we failed to obtain isoquinoꢀ
line derivatives from 4ꢀhydrꢀ
oxyꢀ5,7ꢀdimethoxycoumaꢀ
rin 10 and 4ꢀhydroxyꢀ5,6,7ꢀ
trimethoxycoumarin 11.
This can be explained by hyꢀ
drogen bonding between the
enol H atom and the O atom of the methoxy group in
position 5 of the coumarin framework. Such interactions
can stabilize the enol form of αꢀarylation product of the
type 5, thus precluding its participation in the Staudinger
reaction (see Scheme 1).18
In connection with this, we decided to isolate
αꢀarylation products 5. Monoꢀαꢀarylation products 18
and 19 were obtained from βꢀdiketones (dimedone 7 and
acetylacetone 17) in 31 and 52% yields, respectively.
Arylation of coumarin derivatives 8—11 gave isoꢀflaꢀ
vonoids 20—23 in 46, 25, 41, and 50% yields, respecꢀ
20
21
22
23
R1
R2
R3
H
H
H
OMe
OMe
H
OMe
H
OMe
OMe
OMe
OMe
Experimental
1
tively. It should be noted that the H NMR spectra of
compounds 20 and 21 show two doublets for the methylꢀ
ene groups, while the CH2N3 fragments in derivatives 22
and 23 appear as singlets. This fact can be explained by
the presence of hydrogen bonding between the enolic
OH group and the nitrene N atom of the azido group in
compounds 20 and 21. It is known19 that the nitrene
N atom of the azido group can serve as a donor of the
electron density in complexes of organic azides with Lewis
acids or a proton. This is confirmed by quantumꢀchemiꢀ
cal calculations that suggest the presence of weak doꢀ
nor—acceptor interactions between the nitrene N atom
of the azido fragment and the H atoms of the hydroxy
groups in 2ꢀ(azidomethyl)phenylboronic acid.6 Such hyꢀ
drogen bonding in compounds 20 and 21 can hinder the
rotation about the C(3)—C(1´) bond formed by the trigoꢀ
nal C atoms, thus making the protons of the methylene
group diastereotopic.20 In derivatives 22 and 23, the
methoxy group in position 5 of the coumarin framework
favors the formation of a competitive O—H—O hydrogen
bond, which is stronger than the O—H—N interaction in
compounds 20 and 21. This allows a relatively free rotaꢀ
tion of the aryl fragment.18
Finally, αꢀarylation product 25 was obtained from βꢀ
oxo ester, namely, ethyl 2ꢀoxocyclohexanecarboxylate 24,
in 28% yield; unfortunately, this product was not sepaꢀ
rated from compound 24 by column chromatography.
Thus, we developed the method for introduction of
benzylazido fragments into enolizable organic substrates
through the use of 2ꢀ(azidomethyl)phenylboronic acid as
a key reagent. This method allows the "oneꢀpot" synthesis
of isoquinoline derivatives in four successive steps. The
reaction conditions will be optimized in the near future.
NMR spectra were recorded on a Bruker AC200 spectromꢀ
eter (200.13 (1H) and 50.32 MHz (13C)). Chemical shifts are
referenced to Me4Si. IR spectra were recorded on a Specord
75IR spectrometer. 4ꢀHydroxycoumarin derivatives 8—11
were prepared according to known procedures.17 Commercial
Pb(OAc)4, Hg(OAc)2, dimedone 7, ethyl 2ꢀoxocyclohexaneꢀ
carboxylate 24, and oꢀphenanthroline (Lancaster) were used as
purchased. Freshly distilled acetylacetone 17 was used.
2ꢀ(Azidomethyl)phenylboronic acid (1). 2ꢀ(Bromomeꢀ
thyl)phenylboronic acid6 (1 g, 4.6 mmol) was dissolved in THF
(7 mL) and distilled water (2 mL) was added. After addition of
NaN3 (0.9 g, 13.8 mmol) to the vigorously stirred mixture, the
reaction mixture was stirred at ~20 °C for 12 h. Then Et2O
(40 mL) was added and the organic layer was washed with water
(3×10 mL) and dried over anhydrous sodium sulfate. The solꢀ
vent was removed under reduced pressure and the residue was
recrystallized from CH2Cl2—light petroleum (1 : 1). Compound
1 (0.5 g, 61%) was isolated as white acicular crystals, m.p. 64 °C.
Found (%): C, 47.32; H, 4.84; N, 23.91. C7H8BN3O2. Calcuꢀ
1
lated (%): C, 47.51; H, 4.56; N, 23.74. H NMR (CDCl3), δ:
4.89 (s, 2 H, CH2); 7.31—7.66 (m, 3 H, C(3), C(4), C(5)); 8.28
(dd, 1 H, C(6), J1 = 7.1 Hz, J2 = 1.2 Hz). 13C NMR (CDCl3), δ:
54.2 (CH2); 128.2, 129.8, 132.9, 137.5 (C(3), C(4), C(5), C(6));
142.3 (C(2)); no signal for the C(1) atom appeared in the
spectrum.6
2ꢀ(Azidomethyl)phenyllead triacetate (2). A solution of
2ꢀ(azidomethyl)phenylboronic acid 1 (0.15 g, 0.84 mmol) in
CHCl3 (5 mL) was added dropwise in an inert atmosphere at
35 °C to a stirred mixture of lead tetraacetate (0.38 g, 0.84 mmol)
and mercury diacetate (0.027 g, 0.084 mmol) in anhydrous
CHCl3 (3 mL). The reaction mixture was kept at this temperaꢀ
ture for 1 h, stirred at ~20 °C for ~20 h, filtered through Celite
(10—15 g) on a sintered glass filter. The Celite layer was washed
with CHCl3 (60 mL) and the solvent was removed under reꢀ
duced pressure. The viscous residue was diluted with penꢀ

Isoquinoline synthesis via arylboronic acid
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 7, July, 2005
1609
tane—ether (1 : 1) (7 mL) and the mixture was vigorously stirred
in an ice bath. The solvent was removed and the product was
recrystallized from CH2Cl2—light petroleum (1 : 1). Product 2
(0.22 g, 52%) was isolated as colorless crystals, m.p. (decomp.)
71 °C. Found (%): C, 30.29; H, 2.97; N, 8.01. C13H15N3O6Pb.
Calculated (%): C, 30.23; H, 2.93; N, 8.14. 1H NMR (CDCl3),
δ: 2.11 (s, 9 H, CH3C(O)); 4.80 (s, 2 H, CH2); 7.27—7.56 (m,
3 H, Harom); 7.94 (d, 1 H, HC(6), J = 7.8 Hz). 13C NMR
(CDCl3), δ: 20.4 (CH3C(O)); 53.0 (CH2); 130.0, 130.9, 131.5,
131.6 (C(3), C(4), C(5), C(6)); 134.4 (C(2)); 162.1 (C(1)),
179.7 (CH3C(O)).
Synthesis of isoquinoline derivatives (general procedure). A soꢀ
lution of boronic acid 1 (0.112 g, 0.63 mmol) in CHCl3 (2 mL)
was added dropwise in an inert atmosphere at 35 °C to a stirred
mixture of lead tetraacetate (0.28 g, 0.63 mmol) and mercury
diacetate (0.020 g, 0.063 mmol) in anhydrous CHCl3 (3 mL).
The reaction mixture was stirred at this temperature for 30 min
and then at room temperature for ~20 h. Dimedone (0.062 g,
0.44 mmol) and pyridine (0.104 g, 1.32 mmol) in anhydrous
CHCl3 (2 mL) were added and the mixture was stirred at 40 °C
for 1 h and at ~20 °C for 12 h. Then Ph3P (0.115 g, 0.44 mmol)
was added and stirring was continued at 40 °C for 12 h. The
solvent was removed under reduced pressure. The product was
purified by column chromatography on SiO2 with Et2O—light
petroleum (1 : 3) as an eluent.
A mixture of compounds 14 and 16 was obtained by applying
the general procedure to 4ꢀhydroxyꢀ6,7ꢀdimethoxycoumarin 9.
Column chromatography on SiO2 with CHCl3—ethanol (44 : 1)
as an eluent followed by preparative TLC on SiO2 with the same
eluent gave derivatives 14 (0.020 g, 15%) and 16 (0.015 g, 11%).
2,3ꢀDimethoxyꢀ5,6ꢀdihydroꢀ11Hꢀ[1]benzopyrano[4,3ꢀc]isoꢀ
1
quinolinꢀ11ꢀone (14), colorless crystals, m.p. 158 °C. H NMR
(CDCl3), δ: 3.97, 4.00 (both s, 3 H each, OMe); 5.47 (s, 2 H,
CH2); 6.84 (s, 1 H, H(5)); 7.09 (d, 1 H, H(3´), J = 6.1 Hz); 7.26
(dt, 1 H, H(4´), J1 = 6.1 Hz, J2 = 1.7 Hz); 7.40 (dt, 1 H, H(5´),
J1 = 6.6 Hz, J2 = 1.8 Hz); 7.64 (s, 1 H, H(8)); 8.83 (d, 1 H,
H(6´), J = 6.6 Hz). 13C NMR (CDCl3), δ: 56.4, 56.3, 71.67,
97.4, 99.2, 105.4, 116.8, 123.6, 125.2, 125.9, 126.9, 128.2,
128.9, 147.6, 147.8, 153.8, 165.4, 175.5. IR (Nujol), ν/cm–1
:
3380 (NH).
2,3ꢀDimethoxyꢀ6H,11Hꢀ[2]benzopyrano[4,3ꢀc][1]benzoꢀ
pyranꢀ11ꢀone (16), light yellow powder, m.p. 132 °C. Found (%):
C, 68.81; H, 4.67. C18H14O5 (310.31). Calculated (%): C, 69.07;
1
H, 4.55. H NMR (CDCl3), δ: 3.96 (s, 6 H, OCH3); 5.38 (s,
2 H, CH2N3); 6.84 (s, 1 H, H(5)); 7.21 (s, 1 H, H(8)); 7.26—7.41
(m, 3 H, Harom); 8.56 (d, 1 H, H(6´), J = 7.6 Hz). 13C NMR
(CDCl3), δ: 56.3, 56.4 (OCH3); 69.7 (CH2); 99.5, 103.1, 123.8,
127.0, 127.7, 129.0 (C—H arom.); 100.4, 107.2, 124.4, 146.4,
149.0, 153.6, 160.6, 160.6; 161.5 (quaternary C).
Compounds 15 and 16 (alternative synthesis). A solution of
2ꢀ(bromomethyl)phenylboronic acid10 (0.054 g, 0.25 mmol) in
CHCl3 (1 mL) was added dropwise in an inert atmosphere
at 40 °C to a stirred mixture of lead tetraacetate (0.111 g,
0.25 mmol) and mercury diacetate (0.008 g, 0.025 mmol) in
anhydrous CHCl3 (1.5 mL). The reaction mixture was kept at
this temperature for 1 h and stirred at ~20 °C for 20 h. Potassium
tertꢀbutoxide (0.02 g, 0.21 mmol) and a solution of the appropriꢀ
ate 4ꢀhydroxycoumarin (0.34 g, 0.21 mmol) and oꢀphenanthroꢀ
line (0.112 g, 0.62 mmol) in anhydrous CHCl3 (1.5 mL) were
added. The reaction mixture was stirred at 45 °C for 4 h and left
at room temperature for 20 h. The solvent was removed under
reduced pressure. Products 15 and 16 were isolated by column
chromatography on SiO2 with Et2O—light petroleum (1 : 1) for
15 and ethyl acetate—pentane (3 : 7) for 16 as eluents. The
yields of compounds 15 and 16 were 76% and 47%, respectively.
Synthesis of compounds 18—23 and 25 (general procedure).
A solution of acid 1 (0.4—0.6 mmol, 1 equiv.) in CHCl3 (2 mL)
was added dropwise in an inert atmosphere at 35 °C to a stirred
mixture of lead tetraacetate (0.4—0.6 mmol, 1 equiv.) and merꢀ
cury diacetate (0.04—0.06 mmol, 0.1 equiv.) in anhydrous
CHCl3 (3 mL). The reaction mixture was kept at this temperaꢀ
ture for 30 min and then stirred at room temperature for 20 h.
An enolizable substrate 7—11, 17, or 24 (0.4—0.55 mmol,
0.83 equiv.) and pyridine (1.2—1.8 mmol, 3.0 equiv.) in anhyꢀ
drous CHCl3 (2 mL) were added and the mixture was stirred at
40 °C for 1 h and at room temperature for 12 h. The solvent was
removed under reduced pressure. The αꢀarylation product was
isolated by column chromatography on SiO2.
3,3ꢀDimethylꢀ3,4,5,6ꢀtetrahydroꢀ2Hꢀphenanthridinꢀ1ꢀone
12 (0.021 g, 21%) was isolated as a transparent oil. Found (%):
C, 79.29; H, 7.78; N, 6.41. C15H17NO. Calculated (%): C, 79.26;
H, 7.54; N, 6.16. 1H NMR (CDCl3), δ: 1.10 (s, 6 H, CH3); 2.41
(s, 2 H, CH2); 2.43 (s, 2 H, CH2); 5.12 (s, 2 H, CH2); 7.02 (d,
1 H, H(7), J = 7.2 Hz); 7.20—7.36 (m, 2 H, H(8), H(9)); 8.38
(d, 1 H, H(10), J = 7.6 Hz). 13C NMR (CDCl3), δ: 28.2 (CH3);
31.4 (CH2, C(3)); 42.5 (CH2, C(4)); 52.1 (C(2)); 69.4 (CH2,
C(6)); 111.7 (C(11)); 123.6, 124.6, 126.8, 128.5 (C(7), C(8),
C(9), C(10)); 126.7, 127.6 (C(13), C(14)); 172.5 (C(12)); 196.3
(C(1)). IR (Nujol), ν/cm–1: 3390 (NH).
A mixture of compounds 13 and 15 was obtained by applying
the general procedure to 4ꢀhydroxycoumarin 8. Column chroꢀ
matography on SiO2 with CHCl3—Et2O—light petroleum
(2 : 2 : 1) as an eluent followed by preparative TLC on SiO2
with the same eluent gave products 13 (0.023 g, 21%) and 15
(0.011 g, 10%).
5,6ꢀDihydroꢀ11Hꢀ[1]benzopyrano[4,3ꢀc]isoquinolinꢀ11ꢀone
(13), colorless crystals, m.p. 138 °C. Found (%): C, 77.23;
H, 4.68; N, 5.67. C16H11NO2. Calculated (%): C, 77.10; H, 4.45;
N, 5.62. 1H NMR (CDCl3), δ: 5.50 (s, 2 H, CH2); 7.10 (d, 1 H,
H(1), J = 7.4 Hz); 7.26 (t, 1 H, H(8), J = 6.8 Hz); 7.35—7.52
(m, 3 H, H(2), H(3), H(4)); 7.68 (dt, 1 H, H(7), J1 = 7.4 Hz,
J2 = 1.3 Hz); 8.29 (d, 1 H, H(9), J = 7.6 Hz); 8.83 (d, 1 H,
H(10), J = 7.8 Hz). 13C NMR (CDCl3), δ: 71.7, 98.0, 117.1,
123.6, 123.7, 125.2, 125.4, 125.8, 126.4, 127.0, 127.9, 129.0,
133.1, 152.3, 165.8, 176.0. IR (Nujol), ν/cm–1: 3375 (NH).
6H,11Hꢀ[2]Benzopyrano[4,3ꢀc][1]benzopyranꢀ11ꢀone (15),
colorless crystals, m.p. 154 °C. Found (%): C, 76.85; H, 4.09.
C16H10O3 (250.25). Calculated (%): C, 76.79; H, 4.03. 1H NMR
(CDCl3), δ: 5.41 (s, 2 H, CH2); 7.13 (d, 1 H, H(1), J = 7.2 Hz);
7.27—7.48 (m, 4 H, Harom); 7.57 (t, 1 H, H(7), J = 7.6 Hz); 7.87
(d, 1 H, H(9), J = 7.8 Hz); 8.55 (d, 1 H, H(10), J = 7.6 Hz).
13C NMR (CDCl3), δ: 69.7 (CH2N3); 116.5, 123.1, 123.9, 124.0,
124.9, 128.2, 129.0, 132.5 (C—H arom.); 102.6, 115.2, 126.6,
127.4, 152.9, 160.1 and 161.2 (quaternary C).
2ꢀ(2ꢀAzidomethylphenyl)ꢀ5,5ꢀdimethylcyclohexaneꢀ1,3ꢀdione
(18) was purified by column chromatography (SiO2, Et2O—light
petroleum, 7 : 3). The yield of compound 18 was 31%, colorꢀ
less crystals, m.p. 130—132 °C (CHCl3—light petroleum).
Found (%): C, 66.12; H, 6.02. C15H17O2N3. Calculated (%):
C, 66.40; H, 6.32. 1H NMR (CDCl3), δ: 1.17, 1.18 (both s, 6 H,
CH3); 2.40 (d, 4 H, CH2C(O), J = 19.4 Hz); 4.16 (d, 2 H,
CH2N3, J = 9.4 Hz); 7.06—7.13 (m, 1 H, Harom); 7.30—7.49

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Russ.Chem.Bull., Int.Ed., Vol. 54, No. 7, July, 2005
Ganina et al.
(m, 3 H, Harom). 13C NMR (CDCl3), δ: 28.3, 28.5 (CH3);
29.7 (C(5)); 31.9 (C(4), C(6)); 53.2 (CH2N3); 115.3 (C(2));
129.2, 129.9, 131.7, 196.8 (C(3´), C(4´), C(5´), C(6´)); 130.5,
of compound 23 was 50%, colorless crystals, m.p. 168 °C
(CHCl3—light petroleum). Found (%): C, 59.31; H, 4.28;
N, 10.68. C19H17O6N3. Calculated (%): C, 59.53; H, 4.47;
1
136.4 (C(1´), C(2´)); 196.8 (C(1), C(3)). IR (Nujol), ν/cm–1
:
N, 10.96. H NMR (CDCl3), δ: 3.88, 3.95, 4.17 (all s, 9 H,
2115 (N3).
OCH3); 4.33 (s, 2 H, CH2N3); 6.72 (s, 1 H, H(8)); 7.30—7.51
(m, 4 H, Harom); 10.10 (br.s, 1 H, OH). 13C NMR (CDCl3), δ:
52.9, 56.4, 61.4 (OCH3); 62.8 (CH2N3); 96.7 (C(8)); 128.2,
128.6, 128.9, 131.6 (C(3´), C(4´), C(5´), C(6´)); 100.7, 102.6,
130.6, 135.4, 137.5, 149.1, 150.4, 157.3, 162.1 (quaternary C).
IR (Nujol), ν/cm–1: 2090 (N3), 3190 (OH).
3ꢀ(2ꢀAzidomethylphenyl)pentaneꢀ2,4ꢀdione (19) was purified
by column chromatography (SiO2, Et2O—light petroleum,
1 : 19). The yield of compound 19 was 52%, colorless oil.
Found (%): C, 62.02; H, 5.37; N, 18.01. C12H13O2N3. Calcuꢀ
1
lated (%): C, 62.33; H, 5.67; N, 18.17. H NMR (CDCl3), δ:
1.81 (s, 6 H, CH3); 4.24 (s, 2 H, CH2N3); 7.10—7.21 (m, 1 H,
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 02ꢀ03ꢀ
33021), the Competitive Center of Basic Natural Sciꢀ
ences (Project No. PD02ꢀ1.3ꢀ443), and the INTAS (Grant
03ꢀ514915).
H
arom); 7.36—7.43 (m, 3 H, Harom); 16.68 (s, 1 H, enol OH).
13C NMR (CDCl3), δ: 29.4, 29.7 (CH3); 52.8 (CH2N3); 112.1
(C(3)); 128.6, 129.2, 129.7, 132.2 (C(3´), C(4´), C(5´), C(6´));
135.2, 136.2 (C(1´), C(2´)); 190.9 (C(2), C(4)). IR (Nujol),
ν/cm–1: 2100 (N3).
3ꢀ(2ꢀAzidomethylphenyl)ꢀ4ꢀhydroxycoumarin (20) was puriꢀ
fied by column chromatography (SiO2, Et2O—light petroleum,
4 : 1). The yield of compound 20 was 45%, colorless crystals,
m.p. 173—174 °C (CHCl3—light petroleum). Found (%):
C, 65.24; H, 3.47; N, 14.16. C16H11O3N3. Calculated (%):
C, 65.53; H, 3.78; N, 14.33. 1H NMR (CDCl3), δ: 4.28 (d, 1 H,
CHaHbN3, J = 14.0 Hz); 4.38 (d, 1 H, CHaHbN3, J = 14.0 Hz);
7.30—7.63 (m, 7 H, Harom); 7.93 (dd, 1 H, Harom, J1 = 7.6 Hz,
J2 = 1.2 Hz). 13C NMR (CDCl3), δ: 52.9 (CH2N3); 104.5,
114.8, 128.5, 137.0, 153.2, 160.8, 161.7 (quaternary C); 117.0,
123.8, 124.2, 129.4, 130.1, 130.2, 131.7, 132.8 (C—Harom).
IR (Nujol), ν/cm–1: 2090 (N3), 3210 (OH).
References
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3ꢀ(2ꢀAzidomethylphenyl)ꢀ4ꢀhydroxyꢀ6,7ꢀdimethoxycoumarin
(21) was purified by column chromatography (SiO2, Et2O—light
petroleum, 1 : 1). The yield of compound 21 was 25%, colorꢀ
less crystals, m.p. 176—177 °C (CHCl3—light petroleum).
Found (%): C, 60.90; H, 3.97; N, 12.01. C18H15O5N3. Calcuꢀ
1
lated (%): C, 61.19; H, 4.28; N, 11.89. H NMR (CDCl3), δ:
3.93, 3.99 (both s, 6 H, OCH3); 4.26 (d, 1 H, CHaHbN3, J =
14.3 Hz); 4.38 (d, 1 H, CHaHbN3, J = 14.3 Hz); 6.83 (s, 1 H,
H(5)); 6.94 (s, 1 H, H(8)); 7.31—7.50 (m, 4 H, Harom).
13C NMR (CDCl3), δ: 56.5, 56.6 (OCH3); 67.9 (CH2N3); 100.1,
103.4 (C(5), C(8)); 108.4, 115.6, 129.8, 135.5, 149.4, 154.1,
156.8, 161.4, 166.6 (quaternary C); 128.1, 128.7, 129.4, 130.5
(C(3´), C(4´), C(5´), C(6´)). IR (Nujol), ν/cm–1: 2095 (N3),
3205 (OH).
3ꢀ(2ꢀAzidomethylphenyl)ꢀ4ꢀhydroxyꢀ5,7ꢀdimethoxycoumarin
(22) was purified by column chromatography (SiO2, Et2O—light
petroleum, 1 : 1) and additionally by preparative TLC with
CHCl3—EtOH (44 : 1) as an eluent. The yield of compound 22
was 41%, colorless crystals, m.p. 185 °C (CHCl3—light petroꢀ
leum). Found (%): C, 60.90; H, 3.99; N, 11.72. C18H15O5N3.
Calculated (%): C, 61.19; H, 4.28; N, 11.89. 1H NMR (CDCl3),
δ: 3.88, 4.02 (both s, 6 H, OCH3); 4.34 (s, 2 H, CH2N3); 6.40 (d,
1 H, H(6), J = 2.1 Hz); 6.55 (d, 1 H, H(8), J = 2.1 Hz);
7.29—7.43 (m, 4 H, Harom); 9.60 (br.s, 1 H, OH). 13C NMR
(CDCl3), δ: 53.0 (CH2N3); 56.1, 57.1 (OCH3); 94.4, 95.8,
98.6, 101.8, 128.3, 128.6, 128.9, 130.9, 131.8, 135.5, 156.1,
157.3, 162.2, 162.5, 163.5. IR (Nujol), ν/cm–1: 3205 (OH),
2095 (N3).
3ꢀ(2ꢀAzidomethylphenyl)ꢀ4ꢀhydroxyꢀ5,6,7ꢀtrimethoxyꢀ
coumarin (23) was purified by column chromatography (SiO2,
Et2O—light petroleum, 1 : 1) and additionally by preparative
TLC with CHCl3—EtOH (44 : 1) as an eluent. The yield
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Received February 11, 2005;
in revised form May 26, 2005