Mutual influence of (dimethylhydrazono)methyl groups and α-hydroxy ketone moieties in hetaryl analogues of unsymmetric benzoins

Article abstract of DOI:10.1002/ejoc.200400293

Reactions between phenylglyoxal hydrate and the N,N-dimethylhydrazones of furfural and pyrrole-2-carbaldehyde run regioselectively at the 5-position of the heterocycle. The resulting hetaryl analogues of α-benzoins quantitatively isomerize to β-compounds,

Full text of DOI:10.1002/ejoc.200400293

FULL PAPER
Mutual Influence of (Dimethylhydrazono)methyl Groups and α-Hydroxy
Ketone Moieties in Hetaryl Analogues of Unsymmetric Benzoins
Sergey P. Ivonin,*[a] Andrey V. Lapandin,[a] Andrey A. Anishchenko,[a] and
Vasilii G. Shtamburg[a]
Keywords: Benzoins / Electrophilic substitution / Heterocycles / Hydrazones / Isomerization
Reactions between phenylglyoxal hydrate and the N,N-di-
methylhydrazones of furfural and pyrrole-2-carbaldehyde
run regioselectively at the 5-position of the heterocycle. The
resulting hetaryl analogues of α-benzoins quantitatively iso-
merize to β-compounds, the (dimethylhydrazono)methyl
group activating the hetaryl residue and thus affording faster
isomerization than in their unfunctionalized counterparts.
The (dimethylhydrazono)methyl group is easily convertible
into the aldehyde or nitrile group and can also be involved
in rehydrazonation.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
Introduction
Results and Discussion
The chemical properties of benzoins and their hetaryl
analogues studied so far are mainly associated with trans-
formations of the α-hydroxy ketone moiety and the effect
of the het(aryl) residues on its reactivity. The effect of the
α-hydroxy ketone moiety on the reactivity of substituents
in the het(aryl) residues of isomeric benzoins still remains
to be investigated.
Hydroxyalkylation of N,N-dimethylhydrazones 1 with
phenylglyoxal proceeds regioselectively at the 5-position of
the heterocycle to give the corresponding hetaryl analogues
of α-benzoins 2 (less stable than β-isomers) in high yields,
as shown in Scheme 1. Because of the activation of the het-
erocyclic ring by the hydrazonomethyl group, the reaction
can be performed smoothly with less active phenylglyoxal
hydrate at room temp., which was found to be impossible
for the unsubstituted heterocycles.[1] As a result of the
higher electron-donor ability of pyrrole, the corresponding
benzoin 2a forms more rapidly.
We have previously examined the synthesis[1] and iso-
merization in basic media[2] of α-benzoins. Our interest is
in the study of hetaryl analogues of benzoins in which the
het(aryl) residues contain functionalities modifiable over a
wide range. A (dimethylhydrazono)methyl group appears to
be very promising in this respect, as it is readily convertible
into an aldehyde group.[3] At the same time, a (dimethylhy-
drazono)methyl group itself has been extensively applied in
asymmetric synthesis[4] and represents an active nucleo-
philic substrate, like enamines,[5] in electrophilic substi-
tution reactions.
Scheme 1
Hydrazones of aldehydes derived from the most active π-
excessive five-membered heterocycles (pyrrole, furan, thio-
The α-benzoins 2 thus obtained quantitatively isomerize
phene), however, enter into trifluoroacetylation,[6] amino- to the corresponding β-isomers 3 in the presence of a base
methylation,[7] and reactions with electron-deficient unsatu- (Et3N), small amounts of benzoin oxidation products Ϫ the
rated compounds[8] preferably at the 5-position of the ring. hetaryl benzil analogues 4 Ϫ forming in parallel through
We attribute a certain degree of regioselectivity to the fact the action of atmospheric oxygen (Table 1, Entries 1 and 2;
that the highly electron-donating (dialkylhydrazono)methyl Scheme 2). Structural determination of the isomers was
group is efficiently conjugated with the ring, thus activating based on the previously revealed regularities[2] relating to
1
it to a sufficient degree to enable phosphorylation[9] and the positions and shapes of H NMR signals from the pro-
trinitrophenylation[10] (i.e., electrophilic substitutions with tons of the unsubstituted phenyl rings in the benzoins: these
low-reactivity electrophiles).
resonances of β-benzoins 3 are shifted upfield relative to
those in the α-isomers 2.
As demonstrated previously with derivatives of π-excess-
ive heterocycles, an increased electron donor ability of a
hetaryl residue favours αǞβ isomerization of unsymmetric
[a]
Department of Organic Chemistry, Dnepropetrovsk National
University,
13 Nauchnaya Street, Dnepropetrovsk, 49050, Ukraine
E-mail: ivonin@dp.ukrtel.net
4688
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200400293
Eur. J. Org. Chem. 2004, 4688Ϫ4693

Hetaryl Analogues of Unsymmetric Benzoins
FULL PAPER
Table 1. Yields of β-benzoins 3 and benzils 4 under varied conditions
Entry
Reaction
Yield (%)
Benzoins 3
Benzils 4
1
2
3
4
5
6
isomerization of α-benzoin in the presence of Et3N
autoisomerization of α-benzoin
a (92)
b (91)
a (53)
b (45)
a (22)
b (10)
a (5)
b (5)
a (33)
b (38)
a (45)
b (50)
hydroxyalkylation of aldehyde N,N-dimethylhydrazone at 80 °C
Scheme 3
Scheme 2
dimethylamino group in α-benzoins, giving rise to the auto-
catalytic αǞβ isomerization (conducted separately or in-
benzoins.[2] Activation of the heterocyclic rings in α-benzo- stantaneously after the electrophilic substitution in the in-
ins 2 by the (dimethylhydrazono)methyl substituents re- itial N,N-dimethylhydrazones), is drastically weakened in β-
duces the isomerization time relative to those of their un- benzoins, due to the conjugation between the dimethylam-
functionalized counterparts 5.
ino and the carbonyl group. This effect is corroborated by
The activating influence of the (dimethylhydrazono)me- the spectroscopic data: the IR absorption bands of the
thyl group proves to be more pronounced for the furan ring ϾCϭO and ϾCϭN groups of β-benzoins are shifted 40Ϫ70
than for the pyrrole, which is likely to be the result of the cmϪ1 towards lower frequencies relative to their α-benzoin
transmission effect.[11] Thus, furfural N,N-dimethylhydra- counterparts, which is indicative of the fact that the mutual
zone 2a has the same reactivity in the isomerization as non- conjugation of the two groups through the heterocyclic
activated pyrrole 5b (Table 2, Entries 1 and 3; Scheme 2).
ring, as in β-benzoins, is much more efficient and thus
Activation of the hetaryl residue allows the hydrazone loosens the double bonds significantly more than the nonin-
isomerization to be efficiently conducted in a nonpolar sol- teracting carbonylϪphenyl and azomethineϪhetaryl conju-
vent (benzene), whereas unfunctionalized α-benzoins 5 need gations, as in α-benzoins.
a more polar environment (EtOH) to be isomerized.[2] In
At the same time, the long-wavelength absorption bands
EtOH, α-benzoins 2 are completely oxidized by atmos- in the UV spectra of the β-benzoins are shifted bathoch-
pheric oxygen to the corresponding benzil analogues 4; at romically in relation to those of the α-isomers, suggesting a
the same time, the more stable β-benzoins 3 are resistant to more extended π-chromophore in the former case.
oxidation in boiling EtOH.
The involvement of electron density in the conjugation,
α-Benzoins 2 can isomerize without addition of base, and its consequent reduction on the terminal nitrogen atom
merely on heating of their benzene solutions, but in lower of the N,N-dimethylhydrazono group, results in a reduced
yields even under argon (Table 1, Entries 3 and 4). Interest- reactivity of β-benzoins 3 towards alkylating agents: the re-
ingly, hydroxyalkylation of aldehyde hydrazones performed action with methyl iodide proceeds only on long heating,
at elevated temperature yielded mainly β-benzoins 3 and the whereas α-benzoins 2 are readily alkylated even on heating
corresponding oxidation products 4 (Table 1, Entries 5 and for a short time. The salts obtained are easily convertible
6; Scheme 3).
into nitriles or aldehydes if their aqueous solutions are
The formation of β-benzoins 3 probably proceeds as a heated slightly in a neutral or acid medium, respectively
consequence of the basic nature of the terminal dimeth- (Scheme 4). In most cases, α-benzoin salts 7 form benzil
ylamino moiety contained in the N,N-dimethylhydrazono derivatives 9 and 11b (since α-benzoins themselves have a
group. It is evident that the basic nature of the terminal pronounced tendency towards oxidation), whereas β-
Table 2. Isomerization time for α-benzoins 2 and 5 in the presence of Et3N
Entry
Starting compound
Product
X
R
Solvent
Time [h][a]
Yields (%)
1
2a
2b
5b
5a
3a
3b
6b
6a
O
CHϭNNMe2
CHϭNNMe2
H
Me
benzene
benzene
EtOH
1.5
1.5
1.5
9
92
91
51
90
2
NMe
NMe
O
3[2]
4[2]
EtOH
[a]
The time for full conversion of starting compound is monitored by TLC (every 30 min).
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4689

S. P. Ivonin, A. V. Lapandin, A. A. Anishchenko, V. G. Shtamburg
FULL PAPER
benzoin salts 8 smoothly furnish the α-hydroxy ketone or acid medium; as a consequence, only rehydrazonation
derivative 10 and 12.
products are obtained (Scheme 5).
Scheme 5. Reagents and conditions: iv: H2NNHCOAr, EtOH,
78°C; v: H2NNHCOAr, Hϩ, EtOH, 78°C (only for benzoins 2
and 3)
As can be seen from Table 3, the reactivity of β-benzoins,
aldehydes or hydrazones towards para-bromobenzohydra-
zide is higher than that of α-benzoins and does not depend
on the reaction conditions. This effect is attributable to the
acceptor influence exerted by the carbonyl group of the α-
hydroxy ketone moiety, which in β-isomers is transmitted
through the heterocyclic ring. It is noteworthy that furan
derivatives are more reactive than their analogues contain-
ing the pyrrole ring both for α- and β-isomers, which is due
to the lower electron-donor capability of the furan nucleus.
Scheme 4. Reagents and conditions: i: MeI, MeCN, 82°C; ii: HCl
(1:10), 50°C; iii: H2O, 50°C
The dicarbonyl compounds obtained, 11a and 12, have
two reaction centres capable of reacting with N-nucleo-
philes: namely, the aldehyde group and the α-hydroxy ke-
tone moiety. The latter reacts with N-nucleophiles, so the
oxygen atom of the carbonyl group or the hydroxy group
can be substituted to afford α-hydroxy imines[12] or α-amino
ketones, respectively. This twofold course of the reaction
is associated with the isomerization of the intermediately
forming α-hydroxy enamines.[13]
Conclusion
Reactions between phenylglyoxal hydrate and the N,N-
dimethylhydrazones of furfural and pyrrole-2-carbaldehyde
run regioselectively at the 5-positions of the heterocycles.
The (dimethylhydrazono)methyl group activates the hetero-
cyclic ring, thus reducing the αǞβ isomerization time for
substituted benzoins in relation to those of their unfunc-
Compounds 11a and 12 always react regioselectively at tionalized counterparts. In β-benzoins, the acceptor car-
the more active aldehyde carbonyl group with para-bromo- bonyl group of the α-hydroxy ketone moiety is conjugated
benzohydrazide in boiling EtOH. The reactivity of the car- with the donor (dimethylhydrazono)methyl group, which is
bonyl group contained in the α-hydroxy ketone moiety is therefore characterized by reduced electronic density on the
lowered to such a degree that it is not involved in the reac- terminal nitrogen atom and enhanced reactivity of the car-
tion between hydrazones 2 or 3 and a hydrazide in a neutral bon atom towards nucleophiles.
Table 3. Formation times and yields of hydrazones 23Ϫ26 under varied conditions
Entry
Starting compound
Product
Method (Scheme 5)
Time [h]
Yield (%)
1
2
3
4
5
6
7
8
9
11a
12a
12b
2a
13a
14a
14b
13a
13a
13b
13b
14a
14a
14b
14b
i
i
i
i
ii
i
ii
i
ii
i
ii
1.5
0.75
2
2
1.5
5
70
75
62
63
89
55
62
80
99
91
85
2a
2b
2b
3
3a
0.75
0.75
2
3a
10
11
3b
3b
2
4690
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2004, 4688Ϫ4693

Hetaryl Analogues of Unsymmetric Benzoins
FULL PAPER
1-{5-[(Dimethylhydrazono)methyl]-1-methyl-1H-pyrrol-2-yl}-2-
hydroxy-2-phenylethanone (3b): Yellow powder (hexane). M.p.
140Ϫ141 °C. IR: ν˜ ϭ 3390, 3136, 2940, 2885, 2800, 1616, 1568,
1494, 1446, 1400, 1360, 1340, 1297, 1207, 1180, 1056, 1000, 931,
Experimental Section
1
General Remarks: H NMR spectra were recorded in [D6]DMSO
with a Varian VXR-300 instrument at 300 MHz with TMS as in-
ternal standard. IR spectra were measured with a UR-20 spec-
trometer in KBr tablets. UV spectra were scanned in 95% EtOH
with a Specord M-40 apparatus with 1-cm cuvettes. MS spectra
were run at an electronic ionization at 70 eV with an MX-1321
spectrometer. The course of the reaction and product purities were
monitored by TLC on Silufol-UV-254 plates in a benzene/acetone
(5:1) system.
1
909 cmϪ1. UV: λ (lg ε) ϭ 254.1 (3.74), 367.1 (4.42) nm. H NMR:
δ ϭ 3.33 (s, 6 H), 3.69 (s, 3 H), 5.66 (d, J ϭ 6.9, 1 H), 5.77 (d, J ϭ
6.9 Hz, 1 H), 6.31 (d, J ϭ 4.5 Hz, 1 H), 7.17 (s, 1 H), 7.23 (d, J ϭ
4.5 Hz, 1 H), 7.30 (d, J ϭ 9.0 Hz, 1 H), 7.37 (t, J ϭ 9.0 Hz, 2 H),
7.46 (d, J ϭ 9.0 Hz, 2 H) ppm. MS: m/z (%) ϭ 285 (25) [Mϩ], 178
(100), 109 (20). C16H19N3O2 (285.15): calcd. C 67.35; H 6.71; found
C 67.28, H 6.59.
1-{5-[(Dimethylhydrazono)methyl]furan-2-yl}-2-phenylethane-1,2-
dione (4a): Red, viscous liquid. H NMR: δ ϭ 3.04 (s, 6 H), 6.67
(d, J ϭ 3.9 Hz, 1 H), 7.14 (s, 1 H), 7.53 (d, J ϭ 3.9 Hz, 1 H), 7.61
(t, J ϭ 7.5 Hz, 2 H), 7.68 (d, J ϭ 7.5 Hz, 1 H), 7.94 (d, J ϭ 7.5
Hz, 2 H) ppm. C15H14N2O3 (270.10): calcd. C 66.66, H 5.22; found
C 67.01, H 5.51.
General Procedure for Preparation of α-Benzoins 2: A solution of
the aldehyde N,N-dimethylhydrazone (5.00 mmol) in CH2Cl2
(5 mL) was poured into a solution of phenylglyoxal hydrate (0.76 g,
5.00 mmol) in CH2Cl2 (5 mL). The resulting solution was allowed
to stand at room temp. for 3 d and was then concentrated under
reduced pressure. The residue crystallized.
1
1-{5-[(Dimethylhydrazono)methyl]-1-methyl-1H-pyrrol-2-yl}-2-
phenylethane-1,2-dione (4b): Red powder (hexane). M.p. 82Ϫ83 °C.
1H NMR: δ ϭ 3.32 (s, 6 H), 4.15 (s, 3 H), 6.39 (d, J ϭ 4.9 Hz, 1
H), 6.74 (d, J ϭ 4.9 Hz, 1 H), 7.22 (s, 1 H), 7.59 (t, J ϭ 8.1 Hz, 2
H), 7.74 (d, J ϭ 8.1 Hz, 1 H), 7.93 (d, J ϭ 8.1 Hz, 2 H) ppm.
C16H17N3O2 (283.13): calcd. C 67.83, H 6.05; found C 67.82, H
6.04.
2-{5-[(Dimethylhydrazono)methyl]furan-2-yl}-2-hydroxy-1-phenyl-
ethanone (2a): Yield 86%. Yellow powder (hexane). M.p. 136.5Ϫ137
°C. IR: ν˜ ϭ 3430, 3140, 3000, 2940, 2875, 2805, 1690, 1600, 1575,
1
1290, 1230 cmϪ1. UV: λ (lg ε) ϭ 244.9 (3.94), 308.3 (4.23) nm. H
NMR: δ ϭ 2.87 (s, 6 H), 5.00 (d, J ϭ 6.5, 1 H), 6.19 (d, J ϭ 6.5
Hz, 1 H), 6.32 (d, J ϭ 3.4 Hz Hz, 1 H), 6.45 (d, J ϭ 3.4 Hz, 1 H),
7.05 (s, ), 7.49 (t, J ϭ 7.8 Hz, 2 H), 7.62 (d, J ϭ 7.8 Hz Hz, 1 H),
8.05 (d, J ϭ 7.8, 2 H) ppm. MS: m/z (%) ϭ 272 (15) [Mϩ], 67 (100),
124 (10), 105 (14), 77 (13), 44 (32). C15H16N2O3 (272.12): calcd. C
66.16, H 5.92; found C 66.32, 5.81.
General Procedure for Alkylation of Benzoins 2 and 3: A solution
of the benzoin (0.82 g, 3.00 mmol) in a mixture of MeCN (5 mL)
and MeI (3 mL) was heated to reflux for 1 h for α-isomers 7 (pre-
cipitated during boiling) or 24 h for β-isomers 8. On cooling, the
resulting precipitate was filtered off or the solution was concen-
trated under reduced pressure, according to whether α- or β-iso-
mers were involved.
2-{5-[(Dimethylhydrazono)methyl]-1-methyl-1H-pyrrol-2-yl}-2-
hydroxy-1-phenylethanone (2b): Yield 88%. Yellow powder (hex-
ane). M.p. 136Ϫ137 °C. IR: ν˜ ϭ 3175, 2970, 2868, 1682, 1597,
1261, 1234, 1200, 1155, 1070, 1042, 1013, 990, 952, 920 cmϪ1. UV:
1
λ (lg ε) ϭ 243.9 (4.06), 305.3 (4.20) nm. H NMR: δ ϭ 3.30 (s, 3
NЈ-[5-(1-Hydroxy-2-oxo-2-phenylethyl)furan-2-ylmethylene]-N,N,N-
trimethylhydrazinium Iodide (7a): Yield 100%. White powder. M.p.
H), 3.81 (s, 1 H), 5.63 (d, J ϭ 7.6 Hz, 1 H), 5.70 (d, J ϭ 4.0 Hz, 1
H), 6.03 (d, J ϭ 4.0 Hz, 1 H), 6.17 (d, J ϭ 7.6 Hz, 1 H), 7.25 (s, 1
H), 7.43 (t, J ϭ 8.6 Hz, 2 H), 7.57 (d, J ϭ 8.6 Hz, 1 H), 7.90 (d,
J ϭ 8.6 Hz, 2 H) ppm. MS: m/z (%) ϭ 285 (15) [Mϩ], 180 (100),
135 (9), 77 (8), 44 (10). C16H19N3O2 (285.15): calcd. C 67.35, H
6.71; found C 67.36, H 6.71.
1
160Ϫ162 °C. H NMR: δ ϭ 2.08 (s, 9 H), 6.31 (d, J ϭ 6.3 Hz, 1
H), 6.47 (d, J ϭ 6.3 Hz, 1 H), 6.82 (d, J ϭ 4.0 Hz, 1 H), 7.33 (d,
J ϭ 4.0 Hz, 1 H), 7.52 (t, J ϭ 8.1 Hz, 2 H), 7.65 (d, J ϭ 8.1 Hz,
1 H), 8.03 (d, J ϭ 8.1 Hz, 2 H), 8.89 (s, 1 H) ppm. C16H19IN2O3
(412.03): calcd. C 46.39, H 4.62; found C 46.38, H 4.63.
Preparation of β-Benzoins 3 (Table 1). A) Isomerization of α-Benzo-
ins 2: A solution of the α-benzoin (1.50 mmol) in benzene (6 mL),
with or without added Et3N (0.25 mL, 1.80 mmol), was heated to
reflux for 1.5 h. The β-benzoin precipitating on cooling was filtered
off and recrystallized. The filtrate was concentrated under reduced
pressure, and the residue was treated with CCl4 (5 mL). On concen-
tration of the solution under reduced pressure, heterocyclic benzil
analogues were obtained. B) Treatment of Phenylglyoxal Hydrate
with N,N-Dimethylhydrazones 1: A solution of phenylglyoxal hy-
drate (0.76 g, 5.00 mmol) and the aldehyde N,N-dimethylhydrazone
(5.00 mmol) in benzene (8 mL) was heated to reflux for 1.5 h. The
further workup was performed as in method A.
NЈ-[5-(1-Hydroxy-2-oxo-2-phenylethyl)-1-methyl-1H-pyrrol-2-yl-
methylene]-N,N,N-trimethylhydrazinium Iodide (7b): Yield 100%.
White powder. M.p. 199Ϫ201 °C. 1H NMR: δ ϭ 3.46 (s, 9 H), 3.92
(s, 3 H), 6.09 (d, J ϭ 4.2 Hz, 1 H), 6.14 (d, J ϭ 6.9 Hz, 1 H), 6.35
(d, J ϭ 6.9, 1 H), 6.77 d, J ϭ 4.2 Hz, 1 H), 7.49 (t, J ϭ 8.1 Hz, 2
H), 7.62 (d, J ϭ 8.1 Hz, 1 H), 7.97 (d, J ϭ 8.1 Hz, 2 H), 8.85 (s, 1
H) ppm. C17H22IN3O2 (425.06): calcd. C 47.79, H 5.19; found C
47.70, H 5.16.
NЈ-{5-[(Hydroxy)(phenyl)acetyl]furan-2-ylmethylene}-N,N,N-tri-
methylhydrazinium Iodide (8a): Yield 86%. Pale brown powder.
1
M.p. 117Ϫ118 °C. H NMR: δ ϭ 3.33 (s, 9 H), 5.82 (d, J ϭ 5.7, 1
H), 6.37 (d, J ϭ 5.7 Hz, 1 H), 7.26 (d, J ϭ 4.2 Hz, 1 H), 7.36 (d,
J ϭ 8.1 Hz, 1 H), 7.46 (t, J ϭ 8.1 Hz, 2 H), 7.47 (d, J ϭ 8.1 Hz,
2 H), 7.81 (d, J ϭ 4.2 Hz, 1 H), 9.05 (s, 1 H) ppm. C16H19IN2O3
(412.03): calcd. C 46.39, H 4.62; found C 46.29, H 4.60.
1-{5-[(Dimethylhydrazono)methyl]furan-2-yl}-2-hydroxy-2-phenyl-
ethanone (3a): Yellow powder (benzene). M.p. 160Ϫ162 °C. IR: ν˜ ϭ
3425, 3115, 2955, 2880, 1650, 1560, 1510, 1350, 1275 cmϪ1. UV: λ
1
(lg ε) ϭ 293.8 (3.88), 375.4 (4.14) nm. H NMR: δ ϭ 2.99 (s, 6 H),
5.70 (d, J ϭ 5.1, 1 H), .06 d, J ϭ 5.1 Hz, 1 H), 6.54 (d, J ϭ 3.6 NЈ-{5-[(Hydroxy)(phenyl)acetyl]-1-methyl-1H-pyrrol-2-yl-
Hz, 1 H), 7.09 (s, 1 H), 7.28 (d, J ϭ 7.5 Hz, 1 H), 7.32 (t, J ϭ 7.5
methylene}-N,N,N-trimethylhydrazinium Iodide (8b): Yield 87%.
Hz, 2 H), 7.47 (d, J ϭ 7.5 Hz, 2 H), 7.65 (d, J ϭ 3.6 Hz, 1 H) Pale brown powder. M.p. 115Ϫ117 °C. 1H NMR: δ ϭ 3.57 (s, 9
ppm. MS: m/z (%) ϭ 272 (29) [Mϩ], 165 (100), 109 (13), 77 (12), H), 4.04 (s, 3 H), 5.86 (d, J ϭ 5.7 Hz, 1 H), 5.88 (d, J ϭ 5.7 Hz, 1
44 (10). C15H16N2O3 (272.12): calcd. C 66.16, H, 5.92; found C
66.15, H 5.89.
H), 6.89 (d, J ϭ 4.5 Hz, 1 H), 7.26 (d, J ϭ 6.9 Hz, 1 H), 7.33 (t,
J ϭ 6.9 Hz, 2 H), 7.41 (d, J ϭ 4.5 Hz, 1 H), 7.44 (d, J ϭ 6.9 Hz,
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S. P. Ivonin, A. V. Lapandin, A. A. Anishchenko, V. G. Shtamburg
FULL PAPER
2 H), 8.98 (s, 1 H) ppm. C17H22IN3O2 (425.06): calcd. C 47.79, H
5.19; found C, 47.65, H 5.08.
5-[(Hydroxy)(phenyl)acetyl]furan-2-carbaldehyde (12a): Yield 83%.
Straw-coloured needles (hexane). M.p. 165Ϫ166 °C. IR: ν˜ ϭ 3463,
3428, 3152, 3110, 2820, 1680, 1650, 1252, 1214, 1183, 1060, 1025,
General Procedure for Preparation of Nitriles 9 and 10: A solution
of the salt 7 or 8 (0.80 mmol) in H2O (15 mL) was heated in a
water bath at 50 °C (bath temperature) for 1 h. The precipitate
resulting on cooling was filtered off and was then either chromato-
graphed on a column (alumina, CH2Cl2) in the case of α-isomers
or recrystallized in the case of β-isomers.
1
970 cmϪ1. H NMR: δ ϭ 5.82 (d, J ϭ 4.8 Hz, 1 H), 6.34 (d, J ϭ
4.8 Hz, 1 H), 7.29 (d, J ϭ 7.5 Hz, 1 H), 7.35 (t, J ϭ 7.5 Hz, 2 H),
7.47 (d, J ϭ 7.5 Hz, 2 H), 7.58 (d, J ϭ 4.2 Hz, 1 H), 7.74 (d, J ϭ
4.2 Hz, 1 H), 9.75 (s, 1 H) ppm. C13H10O4 (230.06): calcd. C 67.82,
H 4.38; found C 67.79, H 4.38.
5-[(Hydroxy)(phenyl)acetyl]-1-methyl-1H-pyrrole-2-carbaldehyde
(12b): Yield 89%. Pale brown powder (hexane). M.p. 108Ϫ109 °C.
IR: ν˜ ϭ 3500, 3130, 2965, 2830, 2800, 1679, 1655, 1488, 1452, 1413,
5-[Oxo(phenyl)acetyl]furan-2-carbonitrile (9a): Yield 82%. Yellow
powder (hexane). M.p. 107Ϫ108 °C. IR: ν˜ ϭ 3150, 3129, 2248,
1377, 1336, 1280, 1235, 1210, 1174, 1097, 1060, 1007 cmϪ1 1H
.
1663, 1594, 1491, 1445, 1366, 1315, 1237, 1205, 1180, 1041 cmϪ1
.
1H NMR: δ ϭ 7.63 (t, J ϭ 8.1 Hz, 2 H), 7.78 (d, J ϭ 8.1 Hz, 1
H), 7.80 (d, J ϭ 4.2 Hz, 1 H), 7.86 (d, J ϭ 4.2 Hz, 1 H), 8.01 (d,
J ϭ 8.1 Hz, 2 H) ppm. C13H7NO3 (225.04): calcd. C 69.33, H 3.13;
found C 69.27, H 3.10.
NMR: δ ϭ 4.08 (s, 3 H), 5.82 (d, J ϭ 4.9 Hz, 1 H), 5.88 (d, J ϭ
4.9 Hz, 1 H), 7.01 (d, J ϭ 4.8 Hz, 1 H), 7.25 (d, J ϭ 9.00 Hz, 1
H), 7.35 (t, J ϭ 9.0 Hz, 2 H), 7.36 (d, J ϭ 4.8 Hz, 1 H), 7.45 (d,
J ϭ 9.0 Hz, 2 H), 9.77 (s, 1 H) ppm. C14H13NO3 (243.09): calcd.
C 69.12, H 5.39; found C 69.07, H 5.31.
1-Methyl-5-[(oxo)(phenyl)acetyl]-1H-pyrrole-2-carbonitrile
(9b):
General Procedure for the Preparation of Hydrazones 13 and 14
(Table 3): A solution of the corresponding compound (see Scheme
5) (0.90 mmol) and p-bromobenzohydrazide (0.19 g, 0.90 mmol) in
EtOH (8 mL), with or without added concentrated sulfuric acid
(0.05 mL), was boiled for an appropriate time indicated in Table 3.
The precipitate resulting on cooling was filtered off and recrys-
tallized from EtOH.
Yield 75%. Pale brown powder (hexane). M.p. 105Ϫ107 °C. 1H
NMR: δ ϭ 4.13 (s, 3 H), 6.98 (d, J ϭ 5.1 Hz, 1 H), 7.09 (d, J ϭ
5.1, 1 H), 7.62 (t, J ϭ 8.7 Hz, 2 H), 7.79 (d, J ϭ 8.7 Hz, 1 H), 7.98
(d, J ϭ 8.7, 2 H) ppm. C14H10N2O2 (238.07): calcd. C 70.58, H
4.23; found C 70.49, H 4.22.
5-[(Hydroxy)(phenyl)acetyl]furan-2-carbonitrile (10a): Yield 83%.
Yellow powder (hexane). M.p. 140Ϫ141 °C. IR: ν˜ ϭ 3449, 3415,
3151, 3113, 2252, 1674, 1493, 1452, 1395, 1269, 1228, 1210, 1187,
4-Bromo-NЈ-{[5-(1-hydroxy-2-oxo-2-phenylethyl)-2-furyl]meth-
ylene}benzohydrazide (13a): Pale brown powder. M.p. 165Ϫ166 °C.
1H NMR: δ ϭ 6.25 (d, J ϭ 6.3 Hz, 1 H), 6.29 (d, J ϭ 6.3 Hz, 1
H), 6.59 (d, J ϭ 3.0 Hz, 1 H), 6.89 (d, J ϭ 3.0 Hz, 1 H), 7.51 (t,
J ϭ 7.2 Hz, 2 H), 7.63 (d, J ϭ 7.2 Hz, 1 H), 7.75 (d, J ϭ 8.5 Hz,
2 H), 7.84 (d, J ϭ 8.5 Hz, 2 H), 8.02 (d, J ϭ 7.2 Hz, 2 H), 8.23 (s,
1 H), 11.84 (s, 1 H) ppm. C20H15BrN2O4 (426.02): calcd. C 56.22,
H 3.54; found C 56.20, H 3.54.
1
1045, 1024, 972 cmϪ1. H NMR: δ ϭ 5.90 (d, J ϭ 6.0 Hz, 1 H),
6.40 (d, J ϭ 6.0 Hz, 1 H), 7.30 (d, J ϭ 8.1 Hz, 1 H), 7.36 (t, J ϭ
8.1 Hz, 2 H), 7.46 (d, J ϭ 8.1 Hz, 2 H), 7.74 (d, J ϭ 4.2 Hz, 1 H),
7.78 (d, J ϭ 4.2 Hz, 1 H) ppm. C13H9NO3 (227.06): calcd. C 68.72,
H 3.99; found C 68.70, H 3.95.
5-[(Hydroxy)(phenyl)acetyl]-1-methyl-1H-pyrrole-2-carbonitrile
(10b): Yield 74%. Pale brown powder (hexane). M.p. 112Ϫ114 °C.
IR: ν˜ ϭ 3390, 3360, 3120, 2919, 2895, 2238, 1682, 1475, 1444, 1382,
4-Bromo-NЈ-{[5-(1-hydroxy-2-oxo-2-phenylethyl)-1-methyl-1H-
pyrrol-2-yl]methylene}benzohydrazide (13b): Brown powder. M.p.
1
1334, 1273, 1236, 1210, 1189, 1103, 1050, 1004, 919 cmϪ1 1H
.
164Ϫ165 °C. H NMR: δ ϭ 3.01 (s, 3 H), 5.65 (d, J ϭ 3.5 Hz, 1
H), 5.75 (d, J ϭ 5.3 Hz, 1 H), 6.13 (d, J ϭ 5.3 Hz, 1 H), 6.80 (d,
J ϭ 3.5 Hz, 1 H), 7.49 (t, J ϭ 7.7 Hz, 2 H), 7.65 (d, J ϭ 7.7 Hz,
1 H), 7.77 (d, J ϭ 8.1 Hz, 2 H), 7.91 (d, J ϭ 8.1 Hz, 2 H), 8.00 (d,
J ϭ 7.7 Hz, 2 H), 8.37 (s, 1 H), 11.77 (s, 1 H) ppm. C21H18BrN3O3
(429.05): calcd. C 57.29, H 4.12; found C 57.19, H 4.08.
NMR: δ ϭ 3.91 (s, 3 H), 5.84 (d, J ϭ 5.1 Hz, 1 H), 6.07 (d, J ϭ
5.1 Hz, 1 H), 6.99 (d, J ϭ 5.1 Hz, 1 H), 7.25 (d, J ϭ 8.7 Hz, 1 H),
7.33 (t, J ϭ 8.7 Hz, 2 H), 7.37 (d, J ϭ 5.1 Hz, 1 H), 7.45 (d, J ϭ
8.7 Hz, 2 H) ppm. C14H12N2O2 (240.09): calcd. C 69.99, H 5.03;
found C 69.95, H 4.98.
4-Bromo-NЈ-({5-[hydroxy(phenyl)acetyl]-2-furyl}methylene)-
benzohydrazide (14a): Orange powder. M.p. 176Ϫ177 °C. 1H NMR:
δ ϭ 5.78 (d, J ϭ 4.6 Hz, 1 H), 6.25 (d, J ϭ 4.6 Hz, 1 H), 7.10 (d,
J ϭ 3.0 Hz, 1 H), 7.25 (d, J ϭ 3.0 Hz, 1 H), 7.30 (t, J ϭ 7.2 Hz,
2 H), 7.35 (d, J ϭ 7.2 Hz, 1 H), 7.49 (d, J ϭ 7.2 Hz, 2 H), 7.76 (d,
J ϭ 7.6 Hz, 2 H), 7.86 (d, J ϭ 7.6 Hz, 2 H), 8.36 (s, 1 H), 12.13 (s,
1 H) ppm. C20H15BrN2O4 (426.02): calcd. C 56.22, H 3.54; found C
56.19, H 3.50.
General Procedure for the Preparation of Aldehydes 11 and 12: A
solution of the salt 7 or 8 (0.80 mmol) in dilute (1:10) hydrochloric
acid (15 mL) was heated in a water bath at 50 °C (bath tempera-
ture) for 1 h. The precipitate resulting on cooling was filtered off
and recrystallized.
5-(1-Hydroxy-2-oxo-2-phenylethyl)furan-2-carbaldehyde
(11a):
Yield 76%. Straw-coloured needles (hexane). M.p. 87Ϫ88 °C. IR:
ν˜ ϭ 3391, 3378, 3127, 2948, 2820, 1675, 1591, 1516, 1456, 1393,
4-Bromo-NЈ-({5-[hydroxy(phenyl)acetyl]-1-methyl-1H-pyrrol-2-yl}-
methylene)benzohydrazide (14b): Orange powder. M.p. 178Ϫ179 °C.
1H NMR: δ ϭ 3.34 (s, 3 H), 5.83 (d, J ϭ 5.7 Hz, 1 H), 5.87 (d,
J ϭ 5.7 Hz, 1 H), 6.64 (d, J ϭ 3.3 Hz, 1 H), 7.25 (d, J ϭ 7.5 Hz,
1 H), 7.32 (t, J ϭ 7.5 Hz, 2 H), 7.40 (d, J ϭ 3.3 Hz, 1 H), 7.47 (d,
J ϭ 7.5 Hz, 2 H), 7.75 (d, J ϭ 7.8 Hz, 2 H), 7.85 (d, J ϭ 7.8 Hz,
2 H), 8.49 (s, 1 H), 11.93 (s, 1 H) ppm. C21H18BrN3O3 (439.05):
calcd. C 57.29, H 4.12; found C 57.15, H 4.10.
1
1270, 1222, 1200, 1175, 1098, 1025, 980, 959 cmϪ1. H NMR: δ ϭ
6.31 (d, J ϭ 6.3 Hz, 1 H), 6.51 (d, J ϭ 6.3 Hz, 1 H), 6.76 (d, J ϭ
3.9 Hz, 1 H), 7.49 (d, J ϭ 3.9 Hz, 1 H), 7.53 (t, J ϭ 7.8 Hz, 2 H),
7.64 (d, J ϭ 7.8 Hz, 1 H), 8.02 (d, J ϭ 7.8 Hz, 2 H), 9.51 (s, 1 H)
ppm. C13H10O4 (230.06): calcd. C 67.82, H 4.38; found C 67.80,
H 4.37.
1-Methyl-5-[(oxo)(phenyl)acetyl]-1H-pyrrole-2-carbaldehyde (11b):
Yield 61%. Orange powder (hexane). M.p. 74Ϫ75 °C. 1H NMR:
δ ϭ 4.32 (s, 3 H), 6.92 (d, J ϭ 4.5 Hz, 1 H), 7.08 (d, J ϭ 4.5 Hz,
1 H), 7.62 (t, J ϭ 7.5 Hz, 2 H), 7.79 (d, J ϭ 7.5 Hz, 1 H), 7.97 (d,
J ϭ 7.5., 2 H), 9.95 (s, 1 H) ppm. C14H11NO3 (241.07): calcd. C
69.70, H 4.60; found C 6.68, H 4.55.
Acknowledgments
We are pleased to acknowledge financial support provided by the
Ministry of Education and Science of Ukraine (Grant No. 0104
U000476).
4692
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 4688Ϫ4693

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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4693