Mass-spectral behavior and thermal stability of hetaryl analogs of unsymmetrical benzoins

Article abstract of DOI:10.1007/s10593-006-0110-6

The main path in the mass-spectral dissociation of the hetaryl analogs of unsymmetrical benzoins is β-fragmentation with cleavage of the central C-C bond. Here, the strongest peak in the mass spectra of α-benzoins is the peak of the hydroxymethylhetaryl cation, and in β-benzoins it is the peak of the hetaroyl cation. The thermal α → β isomerization of the hetaryl analogs of benzoin was studied. In the case of indole and pyrrole derivatives the formation of polyheterocyclic systems is observed. 2006 Springer Science+Business Media, Inc.

Full text of DOI:10.1007/s10593-006-0110-6

Chemistry of Heterocyclic Compounds, Vol. 42, No. 4, 2006
MASS-SPECTRAL BEHAVIOR AND
THERMAL STABILITY OF HETARYL
ANALOGS OF UNSYMMETRICAL BENZOINS
S. P. Ivonin1, A. V. Mazepa2, and A. V. Lapandin1
The main path in the mass-spectral dissociation of the hetaryl analogs of unsymmetrical benzoins is
β-fragmentation with cleavage of the central C–C bond. Here, the strongest peak in the mass spectra of
α-benzoins is the peak of the hydroxymethylhetaryl cation, and in β-benzoins it is the peak of the
hetaroyl cation. The thermal α → β isomerization of the hetaryl analogs of benzoin was studied. In the
case of indole and pyrrole derivatives the formation of polyheterocyclic systems is observed.
Keywords: benzoins, polyheterocycles, isomerization, mass spectrometry.
Benzoins have found widespread use as synthons in organic synthesis (e.g., see [1-8]). Of particular
interest in the chemistry of benzoins in recent times has been their use as model biochemical substrates (e.g., see
[9-11]). However, many problems concerning the structure and characteristics of unsymmetrical benzoins have
not so far been resolved. Thus, during investigation of the spectral characteristics of unsymmetrical benzoins in
order to establish their structure and their affiliation to an isomeric series (the α- or β-isomer) it was shown that
electron-impact mass spectrometry is not very suitable for this purpose [12]. It was observed that the main
fragmentation path was β-fragmentation with cleavage of the central C–C bond, and peaks for both aroyl and
both hydroxybenzyl cations were observed in the mass spectra. It is interesting to note that such bond cleavage
provides a source of radicals during polymerization, where benzoins and their alkyl ethers are used as a
photosensitive material [13]. In [14] during the preparation of unsymmetrical benzoins the mass spectra were
used to confirm the structure of the obtained compounds, and the main fragmentation path was also cleavage of
the central C–C bond. However, it is difficult to establish any general relationship in the fragmentation and
formation of the ions giving the base peaks by analyzing the mass spectral data.
Earlier during investigation of the isomerization of α-benzoins obtained by electrophilic
1
hydroxymethylation of π-excessive heterocycles [15] we demonstrated differences in the H NMR spectral
characteristics of the α- and β-isomers [16]. In the present work we studied the differences in the mass spectral
characteristics of the obtained isomeric benzoins. The spectra were recorded with direct injection of the sample
into the ionization zone.
We established that the main path is β-fragmentation. Here, the charge is mainly located on the fragment
in which greatest stabilization of positive charge is realized; for hetarylphenylbenzoins it is the cation containing
the group from the π-excessive heterocycle. Each of the investigated series of isomers has a characteristic base
peak, and this makes it possible to distinguish clearly between them: The peak of the
__________________________________________________________________________________________
1
Dnepropetrovsk National University, Dnepropetrovsk 49050, Ukraine; e-mail: ivonin@dp.ukrtel.net.
2 A. V. Bogatsky Physico-Chemical Institute, National Academy of Sciences of Ukraine, Odessa 65080; e-mail:
chemtor@paco.net. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 515-521, April, 2006.
Original article submitted June 7, 2004.
0009-3122/06/4204-0451©2006 Springer Science+Business Media, Inc.
451

hydroxybenzoyl cation for the α-isomers; the peak of the hetaroyl cation for the β-isomer. In the case of the
β-benzoin 10, in which the fragments have approximately identical ability to delocalize the positive charge and
identical mass, both types of cation are formed with approximately identical intensity.
.
+
OH
OH
Ph
+
RH2
+
R
– CO
R
O
100 %
1, 3, 5, 7, 9, 11, 13
.
+
O
O
+
Ph
+
R
R
R
– CO
OH
2, 4, 6, 8, 10, 12, 14
100 %
In most cases (with the exception of the hydrazones 11-14) in the mass spectra the second in intensity is
the peak of the fragments formed during subsequent elimination of CO molecules by the ions presented above.
In the case of the α-isomers this is a σ-complex. Here the intensity of the peak is probably related to the stability
of this complex for the given heterocycle. Thus, the highest intensity is observed in the case of the derivatives of
1,2,5-trimethylpyrrole and indole; in the case of the furan derivatives such signals are absent altogether. In the
case of the β-isomers the intensity of the hetaryl cations formed similarly by elimination of CO is lower on
account of their low stability.
It should be noted that the series of isomers differ in their stability to electron impact. The α-isomers
give more stable molecular ions than the β-isomers. In the case of the furans 7 and 8 the molecular ions have
identical intensity, due to the small difference in the electron-donating characteristics of the phenyl and furan
residues. This relationship only breaks down for the hydrazones 11-14, in which the conjugation between the
dimethylamino and carbonyl groups leads to higher stability for the molecular peaks of the β-isomers.
However, as seen from the data in Table 1, in each mass spectrum of one isomer there signals that are to
a large degree characteristic for the other isomer. In our opinion this is due to the fact that some of the molecules
of the substance in the ionization chamber before ionization manage to undergo thermal isomerization when
heated under vacuum [17] to the enediol form, which is always present in benzoin [18]. Although measured at
higher ionization chamber temperatures (up to 240°C) the patterns of the mass spectra remain practically
unchanged.
The absence of a relationship in the mass-spectral data in [14] can probably be explained by chemical
transformations that take place under the conditions used to record the mass spectra, i.e., the obtained mass
spectra did not correspond to the data of the individual compound.
For confirmation we studied the thermal stability of unsymmetrical benzoins. Thus, α-benzoins 1, 3, 5,
and 9 are capable of isomerizing to the β-isomers with quantitative yields (10% for the pyrrole 3) when heated
for 10 min at 200°C (at 150°C for the pyrrole 3) (Table 2). The yield is not reduced by increasing the heating
time to 30 min. This indicates that whether thermal isomerization occurs does not depend on the structure of the
benzoin, unlike α→β isomerization in a basic medium, where the transformation time depends strongly on the
electronic effect of the hetaryl group [16]. Consequently, the thermal transformation takes place through the
enediol form as a result of keto–enol tautomerism. In the case of the pyrrole 3 the tetramerization product the
porphyrin 15 was isolated during thermal isomerization. Its structure was confirmed by spectral data. Thus, its
1
mass spectrum contained a molecular ion peak at m/z 784. In the H NMR spectrum there were singlets in the
region of 5.41 and 6.25 ppm corresponding to the olefinic and pyrrole protons respectively.
452

453

O
OH
200 oC
Ph
Ph
R
R
OH
2, 6, 10, 17
O
1, 5, 9, 16
16, 17
Me
R =
N
Bz
Bz
Bz
Bz
Me
NMe
MeN
.
+
OH
NMe
150 oC
4
Ph
+
R
NMe
O
3
15
The behavior of the indole derivatives under these conditions is more complicated. Thus,
1,2-dimethylindole 16 isomerizes with a high yield to the β-isomer 17. At the same time the indoles 7 and 18,
not containing substituents at position 2, form the dimerization products indolo[3,2-b]carbazoles 19 and 20.
Here, in the case of the indole 7 strong resin formation is observed, and the dimer 20 is isolated with a small
yield, whereas the N-methylindole 18 gives a high yield of the dimer 20. The structure of the dimeric products is
confirmed by the mass-spectral data, which contain the corresponding molecular ion peaks, whereas the position
1
of the signals in the H NMR spectra differs little from the signals of the corresponding protons in the initial
α-benzoins [15].
HO
Bz
Bz
R
200 oC
N
N
N
R
R
Bz
7, 18
19, 20
7, 19
R = H , 18, 20 R = Me
The polyheterocyclic products are probably formed by electrophilic alkylation at the ortho position of
the heterocyclic by the benzylic hydroxyl group followed by oxidation, leading to the formation of an aromatic
structure. The dimerization of α-benzoins found here is one of the new methods for the synthesis of
indolocarbazoles [19].
The β-benzoins 2, 4, 6, 8, and 10 remain stable when heated, although resinification occurs after very
prolonged heating (more than 2 h).
The hydrazones 11 and 13 form the β-isomers 12 and 14 respectively even in boiling benzene. However,
α→β isomerization probably occurs in this case [16] under the influence of the basic dimethylamino group.
80 oC
11, 13
12, 14
C6H6
Thus, we have demonstrated that the main dissociation path in the mass spectrum of unsymmetrical
benzoins is β-fragmentation with retention of the charge on the fragment with the possibility of greatest
delocalization of the positive charge. The α-benzoins are capable of isomerizing thermally to the β-isomers.
454

TABLE 2. The Yields of the Products from Thermal Isomerization of
α-Benzoins
Initial compound
Product
mp of product, °C (solvent)
167-168 (ethanol) [12]
Yield, %
95
1
3
2
4
15
107-108 (hexane) [16]
217-218 (methanol)
10
20
5
7
9
6
137-138 (ethanol) [16]
299-301 (benzene)
150-151 (ethanol) [16]
185 (ethanol) [16]
96
10
97
89
91
19
10
17
20
16
18
213-215 (methanol)
EXPERIMENTAL
1
The H NMR spectra were recorded in DMSO-d6 on a Varian VXR-300 instrument (300 MHz) with
TMS as internal standard. The IR spectra were obtained in tablets with potassium bromide on a UR-20
instrument. The UV spectra were obtained in DMFA on a Specord M-40 instrument with an absorbing layer
1 cm thick. The mass spectra were recorded on an MX-1321 instrument under electron impact at 70 eV with
direct injection of the sample and an ionization chamber temperature of 160°C (for data on the benzoins, see
Table 1). The reaction and the purity of the obtained compounds were monitored by TLC on Silufol UV-254
plates in 1:5 benzene–acetone. The benzoins 1, 3, 5, 7, 9, 16, 18 [15], 4, 6, 8, and 10 [16] were obtained by
familiar procedures. The physicochemical characteristics of the β-benzoins 2 [12], 4, 6, 10, and 17 [16] agreed
fully with published data.
Preparation of α-Benzoins 11 and 12 (General Procedure). To a solution of phenylglyoxal hydrate
(0.76 g, 5.00 mmol) in dichloromethane (5 ml) we added a solution of furfural N,N-dimethylhydrazone or
N-methylpyrrole-2-carbaldehyde (5.00 mmol) in dichloromethane (5 ml). The solution was kept at room
temperature for three days, dried over sodium sulfate, filtered, and evaporated under vacuum. The residue was
crystallized from hexane.
2-[5-(Dimethylhydrazinomethyl)furan-2-yl]-2-hydroxy-1-phenylethanone (11). Yield 86%, yellow
powder; mp 136.5-137°C. IR spectrum, ν, cm-1: 3430, 3140, 3000, 2940, 2875, 2805, 1690, 1600, 1575, 1290,
1230. UV spectrum, λmax, nm (log ε): 244.9 (3.94), 308.3 (4.23). 1H NMR spectrum, δ, ppm (J, Hz): 2.87 (6H, s,
N(CH3)2); 5.00 (1H, d, J = 6.5, CHOH); 6.19 (1H, d, J = 6.5, CHOH); 6.32 (1H, d, J = 3.4, Fur H-3); 6.45 (1H,
d, J = 3.4, Fur H-4); 7.05 (1H, s, CH=N); 7.49 (2H, t, J = 7.8, Ph H-3,5); 8.05 (2H, d, J = 7.8, Ph H-2,6).
Found, %: C 66.32; H 5.81. C15H16N2O3. Calculated, %: C 66.16; H 5.92.
2-[5-(Dimethylhydrazonomethyl)-1-methyl-1H-pyrrol-2-yl]-2-hydroxy-1-phenylethanone
(12).
Yield 88%, yellow powder; mp 136-137°C. IR spectrum, cm-1: 3175, 2970, 2868, 1682, 1597, 1261, 1234, 1200,
1
1155, 1070, 1042, 1013, 990, 952, 920. UV spectrum, λmax, nm (log ε): 243.9 (4.06), 305.3 (4.20). H NMR
spectrum, δ, ppm (J, Hz): 3.30 (3H, s, Pyr CH3); 3.81 (1H, s, N(CH3)2); 5.63 (1H, d, J = 7.6, CHOH); 5.70 (1H,
d, J = 4.0, Pyr H-3); 6.03 (1H, d, J = 4.0, Pyr H-4); 6.17 (1H, d, J = 7.6, CHOH); 7.25 (1H, s, CH=N); 7.43 (2H,
t, J = 8.6, Ph H-3,5); 7.57 (1H, d, J = 8.6, Ph H-4); 7.90 (2H, d, J = 8.06, Ph H-2,6). Found, %: C 67.36; H 6.71.
C16H19N3O2. Calculated, %: C 67.36; H 6.71.
Thermal Isomerization (General Procedure). A 1.5-mmole sample of the α-benzoin was kept at
200°C (150°C in the case of the pyrrole 3) for 10 min. The residue was cooled to room temperature and
crystallized (Table 2). The characteristics of the polyheterocyclic products formed under the conditions of
thermal isomerization and some details of the experiments are given.
455

Phenyl(10,15,20-tribenzoyl-21,22,23,24-tetrahydroporphyrin-5-yl)methanone (15). The compound
was obtained by crystallization of the residue insoluble in acetone. IR spectrum, ν, cm-1: 3085, 2965, 1705,
1
1610, 1470, 1425, 1320, 1225, 1015. UV spectrum, λmax, nm (log ε): 284.1 (4.47). H NMR spectrum, δ, ppm
(J, Hz): 3.31 (12H, s, NCH3); 5.41 (4H, s, Het H-7,8,17,18); 6.25 (4H, s, Het H-2,3,12,13); 7.46 (8H, t, J = 7.8,
Ph H-3,5); 7.56 (4H, t, J = 7.8, Ph H-4); 7.95 (8H, d, J = 7.8, Ph H-2,6). Mass spectrum, m/z (Irel, %): 784 [M]+
(3), 488 (14), 409 (11), 291 (37), 212 (21), 173 (18), 122 (14), 105 (100), 94 (94), 77 (65). Found, %: C 79.39;
H 5.10. C52H40N4O4. Calculated, %: C 79.57; H 5.14.
(11-Benzoyl-6,12-dihydro-6,12-diazaindeno[1,2-b]fluoren-5-yl)phenylmethanone (19). IR spectrum,
ν, cm-1: 3420, 3080, 1695, 1610, 1470, 1333, 1239, 1012. UV spectrum, λmax, nm (log ε): 284.8 (4.40). 1H NMR
spectrum, δ, ppm (J, Hz): 6.90 (2H, t, J = 7.8, Het H-3,9); 7.30 (2H, t, J = 7.8, Het H-4,10); 7.31 (2H, d, J = 7.8,
Het H-2,8); 7.45 (2H, d, J = 7.8, Het H-5,11); 7.57 (4H, d, J = 7.8, Ph H-3,5); 7.73 (2H, t, J = 7.8, Ph, H-4); 7.99
(4H, d, J = 7.8, Ph H-2,6); 11.32 (2H, s, NH). Mass spectrum, m/z (Irel, %): 464 [M]+ (100), 359 (5), 245 (19),
179 (10), 105 (46), 77 (24). Found, %: C 82.70; H 4.25. C32H20N2O2. Calculated, %: C 82.74; H 4.34.
(11-Benzoyl-6,12-dimethyl-6,12-dihydro-6,12-diazaindeno[1,2-b]fluoren-5-yl)phenylmethanone (20).
IR spectrum, ν, cm-1: 3070, 2958, 1704, 1610, 1490, 1382, 1345, 1219, 1010. UV spectrum, λmax, nm (log ε):
286.7 (4.45). 1H NMR spectrum, δ, ppm (J, Hz): 3.53 (6H, s, NCH3); 6.48 (2H, t, J = 7.8, Het H-3,9); 6.98 (2H,
t, J = 7.8, Het H-4,10); 7.31 (2H, d, J = 7.8, Het H-2,8); 7.38 (2H, d, J = 7.8, Het H-5,11); 7.45 (4H, d, J = 7.8,
Ph H-3,5); 7.73 (2H, t, J = 7.8, Ph H-4); 8.06 (4H, d, J = 7.8, Ph H-2,6). Mass spectrum, m/z (Irel, %): 492 [M]+
(7), 388 (11), 273 (12), 249 (14), 144 (100), 105 (21), 77 (20). Found, %: C 82.84; H 4.79. C34H24N2O2.
Calculated, %: C 82.91; H 4.91.
Isomerization of Benzoins 11 and 12 (General Procedure). A solution of the α-benzoin (1.50 mmol)
was boiled in benzene (6 ml) for 1 h 30 min. The mixture was cooled, and the precipitate was filtered off and
crystallized from benzene.
1-[5-(Dimethylhydrazonomethyl)furan-2-yl]-2-hydroxy-2-phenylethanone (13). Yield 53%, yellow
powder; mp 160-162°C. IR spectrum, ν, cm-1: 3425, 3115, 2955, 2880, 1650, 1560, 1510, 1350, 1275.
1
UV spectrum, λmax, nm (log ε): 293.8 (3.88), 375.4 (4.14). H NMR spectrum, δ, ppm (J, Hz): 2.99 (6H, s,
N(CH3)2); 5.70 (1H, d, J = 5.1, CHOH); 6.06 (1H, d, J = 5.1, CHOH); 6.54 (1H, d, J = 3.6, Fur H-4); 7.09 (1H,
s, CH=N); 7.28 (1H, d, J = 7.5, Ph H-4); 7.32 (2H, t, J = 7.5, Ph H-3,5); 7.47 (2H, d, J = 7.5, Ph H-2,6); 7.65
(1H, d, J = 3.6, Fur H-3). Found, %: C 66.15; H 5.89. C15H16N2O2. Calculated %: C 66.16; H 5.92.
1-[5-(Dimethylhydrazonomethyl)-1-methyl-1H-pyrrol-2-yl]-2-hydroxy-2-phenylethanone (14).
Yield 45%, yellow powder; mp 140-141°C. IR spectrum, ν, cm-1: 3390, 3136, 2940, 2885, 2800, 1616, 1568,
1494, 1446, 1400, 1360, 1340, 1297, 1207, 1180, 1056, 1000, 931, 909. UV spectrum, λmax, nm (log ε): 254.1
(3.74), 367.1 (4.42). 1H NMR spectrum, δ, ppm (J, Hz): 3.33 (6H, s, N(CH3)2); 3.69 (3H, s, Pyr CH3); 5.66 (1H,
d, J = 6.9, CHOH); 5.77 (1H, d, J = 6.9, CHOH); 6.31 (1H, d, J = 4.5, Pyr H-4); 7.17 (1H, s, CH=N); 7.23 (1H,
d, J = 4.5, Pyr H-3); 7.30 (1H, d, J = 9.0, Ph H-4); 7.37 (2H, t, J = 9.0, Ph H-3,5); 7.46 (2H, d, J = 9.0, Ph
H-2,6). Found %: C 67.28; H 6.59. C16H19N3O2. Calculated %: C 67.35; H 6.71.
The work was carried out with financial support from the Ministry of Education and Science of Ukraine
(State Registration No. 0104U000476).
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