Base-catalyzed intramolecular heterocyclization of o-alkynylbenzhydrazides

Article abstract of DOI:10.1007/s11172-010-0133-0

The reaction of methyl o-(2-R-ethynyl)benzoates with hydrazine affords either fused 4-R-methylphthalazin-1-ones or 2-amino-3-R-methylideneisoindolin-1- ones. The latter are on treatment with KOH undergo recyclization into the corresponding 4-R-methylphthalazin- 1-ones.

Full text of DOI:10.1007/s11172-010-0133-0

Russian Chemical Bulletin, International Edition, Vol. 59, No. 3, pp. 632—636, March, 2010
632
Baseꢀcatalyzed intramolecular heterocyclization
of oꢀalkynylbenzhydrazides
T. F. Mikhailovskaya and S. F. Vasilevsky
Institute of Chemical Kinetics and Combustion, Siberian Branch of the Russian Academy of Science,
3 ul. Institutskaya, 630090 Novosibirsk, Russian Federation.
Fax: +7 (383) 330 7350. Eꢀmail: vasilev@kinetics.nsc.ru
The reaction of methyl oꢀ(2ꢀRꢀethynyl)benzoates with hydrazine affords either fused
4ꢀRꢀmethylphthalazinꢀ1ꢀones or 2ꢀaminoꢀ3ꢀRꢀmethylideneisoindolinꢀ1ꢀones. The latter are
on treatment with KOH undergo recyclization into the corresponding 4ꢀRꢀmethylphthalazinꢀ
1ꢀones.
Key words: oꢀalkynylbenzhydrazides, crossꢀcoupling, heterocyclization, recyclization, isoinꢀ
dolinones, phthalazinones.
Accessibility and high synthetic potential of aromatic
philic centers (αꢀ and βꢀcarbon atoms of the triple bond)
and two nucleophilic centers (amine and amide nitrogen
atoms of the hydrazide groups), which provide multichanꢀ
nel transformations.
In fact, the study of the reactivity of vicinal alkynylpyrꢀ
azolecarboxhydrazides showed that the intramolecular adꢀ
dition of the functional group follows several directions
and depends on the nature of the substituent at the carbon
atom of the triple bond.7,8
We have recently published the data on the unusual
intramolecular heterocyclization of оꢀalkynylbenzhydrꢀ
azides5 (Scheme 1).
The formation of 2ꢀaminoꢀ3ꢀ(4ꢀmethoxybenzylidene)ꢀ
isoindolinꢀ1ꢀone (see Scheme 1, route a) is quite predictꢀ
able: it is the product of the nucleophilic attack of the
acetylenes determine increasing interest of chemists in this
class of compounds.1 Vicinal functionally substituted arylꢀ
acetylenes play a special role. They are highly reactive
building blocks in the synthesis of annelated heterocycles,
which are promising structures in the search for biologiꢀ
cally active compounds.1,2 From the fundamental point
of view, they are convenient models for studying the cyꢀ
clization rules: the dependence of the heterocyclization
direction on internal and external factors (nature of subꢀ
stituents, substrate structure, electronic and steric effects).
We are carrying out systematic studied of the reactivity
of vicinal hydrazides of alkynylbenzoic3—6 and alkyꢀ
nylpyrazolecarboxylic acids.7,8 Among advantages of the
chosen substrates, we consider the presence of two electroꢀ
Scheme 1
R = 4ꢀMeOC6H4 (a), 1,5ꢀdimethylpyrazolꢀ4ꢀyl (b)
i. NH2NH2, EtOH.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 618—622, March, 2010.
1066ꢀ5285/10/5903ꢀ0632 © 2010 Springer Science+Business Media, Inc.

Cyclization of 2ꢀalkynylbenzhydrazides
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 3, March, 2010
633
αꢀcarbon atom of the triple bond by the Nꢀanion generatꢀ
ed from the amide moiety under basic conditions. In the
case of the pyrazole analog (see Scheme 1, route b), the
pyridazinone cycle was formed unexpectedly and formally
represented the result of the attack of the αꢀcarbon atom
of the triple bond by the amine nitrogen atom followed by
prototropic isomerization. Similar cyclization to benzopyꢀ
ridazinones has earlier been observed only under neutral
conditions,3—8 where the amine nitrogen atom was a stronꢀ
ger nucleophile than the amide nitrogen atom. We asꢀ
sumed that 4ꢀ[(1,5ꢀdimethylꢀ1Нꢀpyrazolꢀ4ꢀyl)methyl]ꢀ
phthalazinꢀ1(2Н)ꢀone5 is formed due to the rearrangement
of intermediate Nꢀaminolactam (see Scheme 1, route b).
To confirm or reject this assumption, we decided to study
this recyclization in more detail, extending the set of acetꢀ
ylene substituents in the series of oꢀalkynylbenzhydrazides.
The starting compounds, viz., esters of оꢀalkynylbenꢀ
zoic acids 1a—c, were synthesized by the reaction of meꢀ
thyl оꢀiodobenzoate with the corresponding alkꢀ1ꢀynes
under the Sonogashira reaction conditions9 (using the sysꢀ
tem Pd(PPh3)2Cl2—CuI—NEt3), and the yields of prodꢀ
ucts 1a—с were 68—77% (Scheme 2).
Depending on the substrate structure, the reaction of
ethynylbenzoates 1a—с with hydrazine hydrate in boiling
ethanol affords either the corresponding Nꢀaminoꢀγꢀlacꢀ
tams 2b—c, or benzopyridazinones 3a (Scheme 3).
The choice of the structure of the products formed
between fiveꢀ (2b,c) and sixꢀmembered (2b´,c´) Nꢀaminoꢀ
lactams cannot be done on the basis of the 1H NMR specꢀ
tra, since the chemical shifts for the exoꢀ and endoꢀmeꢀ
thine protons are similar.
The structures of lactams were determined from the
difference in stretching vibration frequencies of the carboꢀ
nyl groups (ν(СО)) for the isomeric fiveꢀ and sixꢀmemꢀ
bered rings in the IR spectra. It is known10,11 that an
increase in the strain on going from the sixꢀ to fiveꢀmemꢀ
bered ring increases ν(СО) by 30—35 cm–1. In the known
δꢀlactams the stretching vibration frequency of the С=О
group is 1660—1680 cm–1, whereas in γꢀlactams it is at
least 1695—1700 cm–1. For the products synthesized, the
ν(СО) values in the IR spectra are 1706—1716 cm–1
,
which indicates unambiguously the Nꢀaminoꢀγꢀlactam
structure of 2b,c. The substantiality of this approach is
confirmed by our preliminary report6 on the structure for
the methoxy derivative determined from the 2D NMR
data, which established its structure as γꢀlactam.
Scheme 2
Another additional confirmation of the correct strucꢀ
ture determination is the fact that the synthesized Nꢀamiꢀ
nolactams 2b,c on heating with KOH yield phthalazinoꢀ
nes 3b,c (43—67%). Note that the sixꢀmembered Nꢀamiꢀ
nolactams 2b´,c´ do not interact with alkalis. This simulꢀ
taneously confirm our assumption about the recyclization
of fiveꢀmembered isoindolinones to phthalazinones.
The result of the reaction of the 2ꢀpyridylꢀsubstituted
ester derivative 1a with hydrazine was unexpected: the
R = 2ꢀpyridyl (а), 4ꢀMe2NC6H4 (b), C(OH)Me2 (c)
i. HC≡CR, [Pd(PPh)3]2Cl2, CuI, Et3N.
Scheme 3
R = 2ꢀpyridyl (а), 4ꢀMe2NC6H4 (b), C(OH)Me2 (c)

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Russ.Chem.Bull., Int.Ed., Vol. 59, No. 3, March, 2010
Mikhailovskaya and Vasilevsky
Scheme 5
major reaction product was the corresponding benzopyꢀ
ridazinone 3а (70%), which is the net result of the attack
of the αꢀcarbon atom of the triple bond by the amine
nitrogen atom, which is a weaker nucleophile than the
Nꢀanion formed by the action of KOH.
We believe that in this case the mechanism of the prodꢀ
uct formation is different and is not due to the rearrangeꢀ
ment of a possible intermediate aminolactam, because it
has previously been shown5 that fiveꢀmembered lactam
bearing the electronꢀwithdrawing substituent (NO2 group)
cannot be transformed into sixꢀmembered diazinone even
on heating with KOH.
It can be assumed that the formation of the "anoꢀ
malous" product from compound 1а is due to the specific
conformation of intermediate hydrazide in which the hydrꢀ
ogen atom of the terminal amino group of the hydrazide
moiety is bound to the nitrogen atom of the pyridine moiꢀ
ety by the hydrogen bond. This approaches the terminal
nitrogen atom to the αꢀcarbon atom of the triple bond and
thus favors sixꢀmembered ring (diazinone) (see Scheme 3,
intermediate В). It should be noted that available pubꢀ
lished method for the synthesis of similar compounds reꢀ
quire high temperatures (200 °С)12 or the use of absolute
media and organometallic compounds.13
Since chemists pay great attention to phthalazinones
as promising compounds in the search for biologically acꢀ
tive compounds,12—16 we studied in comparison the above
described method and another approach to these derivaꢀ
tives, namely, through the corresponding phthalides. We
aimed at revealing which of these methods is preferable
from the preparative point of view. It is known that the
reaction of hydrazine with 3ꢀbenzylidenephthalides affords
phthalazinones.17
R = Ph (5a, 3d), 4ꢀMe2NC6H4 (5b, 3b), CH2OPh (5c, 3e),
4ꢀBrC6H4 (5d, 3f), Bu (5e)
i. NH2NH2, EtOH
The starting phthalides 5a—e were synthesized by the
known method using the Castro reaction18 (Scheme 4).
the case of the butyl derivative 5e, diazepinone 7 was
formed (72%).
A comparison of the methods for synthesis of phthalaziꢀ
nones from acid esters and phthalides as the starting comꢀ
pounds shows that they are approximately equivalent for
the aromatic derivatives. At the same time, the "phthaꢀ
lide" method gives diazepinones in the case of the aliphatꢀ
ic derivatives.
Scheme 4
Thus, the reaction of methyl оꢀalkynylbenzoates with
hydrazine hydrate in ethanol affords either the correspondꢀ
ing pyridazinones, or the intramolecular cyclization prodꢀ
ucts, viz., Nꢀaminoꢀγꢀlactams. The latter are treated with
a stronger bas (KOH) and rearranged into benzodiazinoꢀ
nes (except for substrates with the withdrawing groups).
The recyclization found can serve as an alternative methꢀ
od for the synthesis of phthalazinones of a wide range of
pharmacological effect.
R = Ph (a), 4ꢀMe2NC4H6 (b), CH2OPh (c), 4ꢀBrC6H4 (d), Bu (e)
i. CuC≡CR, DMF.
Phthalides 5a—e reacted with hydrazine hydrate in
ethanol following two routes (Scheme 5). In the case
of derivatives 5a—d, as should be expected, phthalaziꢀ
nones 3 were obtained in 67—87% yields. Note that
the cyclodimer of benzylidenephthalide 6 is probaꢀ
bly formed due to cyclization upon the storage of
the mother liquor of compound 3d (cf. Ref. 19). In
Experimental
The IR spectra of the new compounds were recorded on
a Vectorꢀ22 spectrometer in KBr pellets. NMR spectra were

Cyclization of 2ꢀalkynylbenzhydrazides
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 3, March, 2010
635
measured on Bruker AVꢀ300 (300.13 MHz) and Bruker AVꢀ400
(400.13 MHz) spectrometers in CDCl3. Highꢀresolution mass
spectra were obtained on a DFS spectrometer (Thermo Electron
Corporation) using direct inlet (ionization temperature of the
chamber was 220—270 °C, ionization voltage 70 eV). Silica gel
60 (70—230 μm, Merck) was used for column chromatography.
The reaction was monitored by TLC on Silufol UVꢀ254 plates
(Merck).
(70%), m.p. 136—137 °C. IR (KBr), ν/cm–1: 1700 (С=О).
1Н NMR, δ: 2.96 (s, 6 H, N(CH3)2); 4.38 (s, 2 H, NH2); 6.67 (s, 1 H,
=CH); 6.73 (d, 2 Н, oꢀН, J = 8.9 Hz); 7.39—7.42 (m, 1 Н,
Н(6)); 7.49 (d, 2 Н, mꢀН, J = 8.9 Hz); 7.52—7.55 (m, 1 Н,
Н(5)); 7.68 (d, 1 Н, Н(4), J = 6.9 Hz); 7.82 (d, 1 Н, Н(7),
J = 7.5 Hz). 13С NMR, δ: 40.18; 108.79; 111.40; 118.91; 121.76;
122.93; 126.08; 128.08; 131.35; 1.65; 136.61; 149.77; 166.88.
MS, m/z: [M+], found 279.1366, calculated 279.1374, C17H17N3O.
2ꢀAminoꢀ3ꢀ(2ꢀhydroxyꢀ2ꢀmethylpropylidene)isoindolinꢀ1ꢀone
(2c) was synthesized similarly to 2b. The yield of product 2c was
0.54 g (60%), m.p. 146—147 °С. IR (KBr), ν/cm–1: 1700 (С=О).
1Н NMR, δ: 1.57 (s, 6 H, (CH3)2); 1.73 (s, 1 Н, ОН); 5.2 (br.s,
NH2); 5.91 (s, 1 H, =CH); 7.44—7.45 (m, 1 H, H(6)); 7.57—7.58
(m, 2 Н, Н(4), H(5)); 7.80 (d, 1 Н, Н(7), J = 8.4 Hz). 13С NMR,
δ: 32.04; 68.48; 116.39; 118.85; 122.74; 125.81; 128.67; 132.16;
132.62; 136.05; 167.16. MS, m/z: [M+], found 218.1048, calcuꢀ
lated 218.1050, C12H14 N2O2.
4ꢀ(4ꢀDimethylaminobenzyl)phthalazinꢀ1(2Н)ꢀone (3b).
А. KOH (8 mg, 0.14 mmol) was added to a solution of hydrazide
2b (40 mg, 0.14 mmol) in ethanol (8 mg, 0.14 mmol), and the
mixture was refluxed for 8 h (TLC monitoring, eluent AcOEt).
The mixture was cooled to 25 °С, and the precipitate that formed
was filtered off and recrystallized from ethanol. Product 3b was
obtained in a yield of 27 mg (67%), m.p. 254—255 °С. IR (KBr),
ν/cm–1: 1657 (С=О). 1Н NMR, δ: 2.88 (s, 6 H, N(CH3)2); 4.18
(s, 2 H, СH2); 6.66 (d, 2 H, oꢀН, J = 8.64 Hz); 7.11 (d, 2 Н,
mꢀН, J = 8.64 Hz); 7.68—7.71 (m, 3 Н, Н(5), Н(6), Н(7));
8.42—8.43 (m, 1 Н, Н(8)); 10.2 (br.s, 1 Н, NН). 13С NMR, δ:
41.26; 115.21 118.62; 124.62; 125.71; 126.31; 127.63; 128.12;
130.25; 133.87; 138.43; 143.26; 148.81; 166.57. MS, m/z: [M+],
found 279.1366, calculated 279.1363, C17H17N3O.
Methyl 2ꢀ(2ꢀpyridylethynyl)benzoate (1a). A solution of
2ꢀbromopyridine (1.58 g, 10 mmol), CuI (0.02 g), Pd(PPh3)2Cl2
(0.04 g), РРh3 (0.02 g), Et3N (3 mL), and methyl 2ꢀethynylbenꢀ
zoate (1.76 g, 11 mmol) in toluene (40 mL) was stirred at 70 °С
for 8 h under argon until the starting bromide disappeared (TLC
monitoring, eluent CH2Cl2). After the end of the reaction, the
mixture was filtered through a small Al2O3 layer, and the filtrate
was concentrated in vacuo. The residue was chromatographed
on a column with Al2O3 (80×20 mm) and SiO2 (20×20 mm,
eluent benzene). Product 1a was obtained in a yield of 1.64 g
(70%), nD =1.5125. IR (KBr), ν/cm–1: 2223 (С=О), 1728
20
(С≡С). 1Н NMR, δ: 3.94 (s, 3 H, OCH3,); 7.32—7.35 (m, 1 H,
γꢀH(Py)); 7.37—7.52 (m, 2 H, H(4), H(5)); 7.56—7.59 (m, 1 Н,
βꢀH(Py)); 7.56 (m, 1 Н, Н(10)); 7.64—7.66 (m, 1 Н, Н(3));
7.69—7.72 (m, 1 Н, βꢀН(Py)); 7.97 (d, 1 Н, Н(6), J = 7.9 Hz);
8.60—8.62 (m, 1 Н, αꢀН(Py)). 13С NMR, δ: 51.83; 87.46; 92.80;
122.45; 124.80; 127.08; 128.14; 130.08; 130.37; 131.37; 134.02;
135.66; 143.10; 149.67; 165.89. MS, m/z: [M+], found 237.0784,
calculated 237.0786, C15H11NO2.
Compounds 1b,c were obtained similarly.
Methyl 2ꢀ[(4ꢀdimethylaminophenyl)ethynyl]benzoate (1b),
76% yield, m.p. 88—89 °С. IR (KBr), ν/cm–1: 2220 (С=О),
1715 (С≡С). 1Н NMR (CDCl3), δ: 2.98 (s, 6 H, N(CH3)2); 3.94
(s, 3 H, OCH3); 6.67 (d, 2 H, оꢀH, J = 8.9 Hz); 7.29 (d, 1 Н,
Н(5)); 7.44—7.57 (m, 3 Н, Н(4), mꢀН); 7.57—7.60 (m, 1 Н,
Н(3)); 7.91 (d, 1 Н, Н(6), J = 7.6 Hz). 13С NMR, δ: 39.75;
51.66; 86.16; 95.63; 111.01; 111.31; 124.21; 126.49; 129.95;
131.11; 132.19; 132.53; 133.13; 149.84; 166.59. MS, m/z: [M+],
found 279.1366, calculated 279.1363, C15H11NO2.
Methyl 2ꢀ(3ꢀhydroxyꢀ3ꢀmethylbutynyl)benzoate (1c). The
yield of 1с was 77%, nD20 = 1.5512 (cf. Ref. 20: nD20 = 1.5505).
4ꢀ(2ꢀPyridylmethyl)phthalazinꢀ1(2Н)ꢀone (3a). NH2NH2•H2O
(84 mg, 1.68 mmol) was added to a solution of ester 1a (200 mg,
0.84 mmol) in ethanol (5 mL), and the mixture was refluxed for
8 h (TLC monitoring, eluent CH2Cl2—AcOEt). The mixture
was cooled to 25 °С, the precipitate that formed was filtered off
through an Al2O3 layer (10×10 mm), and the filtrate was evapoꢀ
rated and recrystallized from ethyl acetate. Product 3a was obꢀ
tained in a yield of 70 mg (70%), m.p. 236—238 °С. IR (KBr),
ν/cm–1: 1668 (С=О). 1Н NMR, δ: 4.48 (s, 2 H, CH2); 7.10—7.11
(m, 1 H, H(7)); 7.22 (d, 1 Н, Н(5), J = 7.7 Hz); 7.53—7.55 (m, 1 H,
H(6)); 7.69—7.92 (m, 3 Н, βꢀН, γ(Py)); 8.52 (m, 1 Н, Н(8));
8.53—8.54 (m, 1 Н, αꢀН); 11.3 (br.s, 1 Н, NH). 13С NMR, δ:
41.78; 121.74; 123.05; 125.67; 126.71; 128.07; 129.81; 131.23;
133.36; 136.60; 145.66; 149.30; 157.72; 160.73. MS, m/z: [M+],
found 237.0820, calculated 237.0897, C14H11N3O.
B. Compound 3b was obtained in 87% yield from compound
5е (see the synthesis of compound 7).
4ꢀ(2ꢀHydroxyꢀ2ꢀmethylpropyl)phthalazinꢀ1(2Н)ꢀone (3c)
was obtained similarly to 3b in a yield of 60 mg (43%), m.p.
178—179 °С. IR (KBr), ν/cm–1: 1649 (С=О). 1Н NMR, δ: 1.35
(s, 6 H, С(CH3)2); 3.10 (s, 2 H, СH2); 3.43 (s, 1 H, ОH);
7.77—7.87 (m, 3 Н, Н(5), Н(6), Н(7)); 8.46—8.48 (m, 1 Н,
Н(8)); 10.4 (br.s, 1 Н, NН). 13С NMR, δ: 29.92; 42.36; 70.84;
125.52; 127.08; 128.03; 130.55; 131.62; 133.54; 145.98; 136.61;
149.77; 159.98. MS, m/z: [M+], found 218.1048, calculated
218.1038, C12H14 N2O2.
Compounds 3d—f were synthesized similarly to compound 7
(see below).
4ꢀBenzylphthalazinꢀ1(2H)ꢀone (3d) in 83% yield, m.p.
203—204 °С (see Ref. 3: m.p. 197—198 °С). The benzylideneꢀ
phthalide, viz., 2,2´ꢀ(1,3ꢀdihydroxyꢀ2,4ꢀdiphenylcyclobutaneꢀ
1,3ꢀdiyl)dibenzoic acid diꢀγꢀlactone 6, was isolated from the
mother liquor. The yield was 12%, m.p. 280—282 °С (cf. Ref. 19:
m.p. 294—296 °С).
4ꢀ(2ꢀPhenoxyethyl)phthalazinꢀ1(2H)ꢀone (3e), 67% yield,
m.p. 149—150 °С (cf. Ref. 4: m.p. 156—157 °С).
4ꢀ(4ꢀBromobenzyl)phthalazinꢀ1(2Н)ꢀone (3f), 67% yield,
m.p. 230—231 °С (cf. Ref. 6: m.p. 229—230 °С).
2ꢀAminoꢀ3ꢀ(4ꢀdimethylaminobenzylidene)isoindolinꢀ1ꢀone
(2b). 80% NH2NH2•H2O (36 mg, 0.72 mmol) was added to
a solution of ester 1b (100 mg, 0.36 mmol) in ethanol (5 mL),
and the mixture was refluxed for 8 h (TLC monitoring, eluent
CH2Cl2—AcOEt). The mixture was cooled to 25 °С, and the
precipitate that formed was filtered off and recrystallized from
ethanol (5 mL). Product 2b was obtained in a yield of 70 mg
3ꢀ(2ꢀPhenoxyethylidene)isobenzofuranꢀ1(3Н)ꢀone (5b). A soluꢀ
tion of 2ꢀiodobenzoic acid (1.24 g, 5 mmol) and copper pheꢀ
noxymethylacetylenide (1.17 g, 6 mmol) in DMF (20 mL) was
refluxed for 40 min under argon (TLC monitoring, eluent
СН2Сl2). The cooled reaction mixture was diluted with dichloroꢀ
methane (25 mL), washed with 25% aqueous NH3 (5×20 mL) to
remove copper(I) salts, and water (50 mL), and dried with anꢀ

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Russ.Chem.Bull., Int.Ed., Vol. 59, No. 3, March, 2010
Mikhailovskaya and Vasilevsky
hydrous Na2SO4. The solution was passed through an Al2O3
layer (80×25 mm, eluent CH2Cl2). The solvent was removed
in vacuo, and the residue was recrystallized from hexane. The
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Compounds 5a,c—е were synthesized similarly.
3ꢀPentylideneisobenzofuranꢀ1(3Н)ꢀone (5c), 72% yield, m.p.
40—40.5 °С. IR (KBr), ν/cm–1: 1725 (С=О). 1Н NMR, δ: 0.94
(t, 3 H, CH3, J = 7.3 Hz); 1.36—1.42 (m, 2 H, δꢀСН2); 1.68—1.70
(m, 2 H, βꢀСН2); 2.52 (t, 2 Н, αꢀСН2, J = 7.8 Hz); 6.24 (s, 1 Н,
=СН); 7.34 (d, 1 Н, Н(4), J = 7.8 Hz); 7.43—7.45 (m, 1 Н,
Н(6)); 7.63—7.66 (m, 1 Н, Н(5)); 8.23 (d, 1 Н, Н(7), J = 9.2 Hz).
13С NMR, δ: 13.63; 21.97; 28.83; 33.08; 102.71; 119.94; 124.84;
127.38; 129.37; 134.54; 137.45; 158.16; 163.03. MS, m/z: [M+],
found 202.0988, calculated 202.0991, C13H14O2.
3ꢀ(4ꢀDimethylaminobenzylidene)isobenzofuranꢀ1(3Н)ꢀone
(5e), 67% yield, m.p. 195—196 °С. IR (KBr), ν/cm–1: 1765
(С=О). 1Н NMR, δ: 3.01 (s, 6 H, N(CH3)2); 6.35 (s, 1 H,
=СH); 6.71 (d, 2 H, oꢀН, J = 8.9 Hz); 7.40—7.70 (m, 5 Н,
Нarom); 7.87—7.88 (m, 1 Н, Н(7)). 13С NMR, δ: 40.03; 90.38;
108.20; 111.68; 119.67; 126.42; 129.49; 131.54; 134.61; 138.30;
151.20; 154.68; 162.66; 167.37. MS, m/z: [M+], found 265.1097,
calculated 265.1099, C17H15NO2.
3ꢀBenzylideneisobenzofuranꢀ1ꢀ(3Н)ꢀone (5a). The yield of
5a was 73%, m.p. 101—102 °С (cf. Ref. 17: m.p. 90—92 °С).
3ꢀ(4ꢀBromobenzylidene)isobenzofuranꢀ1ꢀ(3Н)ꢀone (5d). The
yield of product 5d was 78%, m.p. 151—152 °С (cf. Ref. 21: m.p.
154—155 °С).
4ꢀButylꢀ2Нꢀbenzo[d][1,2]diazepinꢀ1(5Н)ꢀone (7). 80%
NH2NH2•H2O (25 mg, 0.5 mmol) was added to a solution
of phthalide 5e (50 mg, 0.25 mmol) in ethanol (6 mL), and
the mixture was refluxed for 2 h (TLC monitoring, eluent
CH2Cl2—AcOEt). The mixture was cooled to 25 °С and filtered
through an Al2O3 layer (15×10 mm), the solvent was evaporatꢀ
ed, and the precipitate was recrystallized from hexane. The yield
was 38 mg (72%), m.p. 71—72 °С. IR (KBr), ν/cm–1: 1652
(С=О). 1Н NMR, δ: 0.85 (t, 3 H, CH3, J = 7.2 Hz); 1.21—1.23
(m, 2 H, γꢀСН2); 1.52—1.55 (m, 2 H, βꢀСН2); 2.40 (t, 2 Н,
αꢀСН2, J = 7.4 Hz); 3.57 (s, 2 Н, СН2); 7.19—7.39 (m, 2 Н,
Н(6), H(7)); 7.51—7.52 (m, 1 Н, Н(8)); 7.98 (d, 1 Н, Н(9),
J = 6.9 Hz); 8.4 (br.s, 1 Н, NH). 13С NMR, δ: 13.57; 22.04;
27.92; 36.98; 37.89; 24.67; 126.96; 127.51; 130.67; 131.15;
133.06; 136.95; 165.97. MS, m/z: [M+], found 216.1257, calcuꢀ
lated 216.1256, C13H16N2O.
19. I. B. Hannout, A. M. Islam, A. A. ElꢀMaghraby, S. A.
Ahmed, Indian J. Chem., 1977, 15, 11.
20. M S. Shvartsberg, A. A. Moroz, Izv. Akad. Nauk SSSR,
Ser. Khim., 1971, 1582 [Bull. Acad. Sci. USSR, Div. Chem.
Sci. (Engl. Transl.), 1971, 20, 1488].
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 07ꢀ03ꢀ
00048a), the Russian Academy of Sciences (Program of
International Integration Projects of the Siberian Branch
of the Russian Academy of Sciences, Grant 93, Program
of International Integration Projects of the Russian Acadꢀ
emy of Sciences, Grant 5.9.3), and the Chemical Service
Center of Program of International Integration Projects of
the Siberian Branch of the Russian Academy of Sciences.
21. C. F. H. Allen, J. W. Gates, J.Org. Chem., 1943, 65, 419.
Received July 13, 2009;
in revised form December 15, 2009