Features of reactions of 10-methyl-9,10-dihydroacridine heteroanalogs with imines

Article abstract of DOI:10.1134/S1070428009050157

Relying on the values of the energy of the highest occupied molecular orbitals calculated ab initio a series of reactivity was established for ylides isomeric to 10-methyl-9,10-dihydroacridine, dibenzopyran, dibenzothiopyran, 1,3-benzodithiol, and the ten

Full text of DOI:10.1134/S1070428009050157

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 5, pp. 735−739. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © L.P. Yunnikova, T.V. Makhova, A.L. Yunnikov, V.Yu. Gorokhov, 2009, published in Zhurnal Organicheskoi Khimii, 2009,
Vol. 45, No. 5, pp. 749−753.
Features of Reactions of 10-Methyl-9,10-dihydroacridine
Heteroanalogs with Imines
L. P.Yunnikova, T. V. Makhova,A. L. Yunnikov, and V. Yu. Gorokhov
Pryanishnikov Perm State Agricultural Academy, Perm, 614000 Russia
e-mail: yunnikova@yahoo.com
Received July 4, 2008
Abstract—Relying on the values of the energy of the highest occupied molecular orbitals calculated ab initio a
series of reactivity was established for ylides isomeric to 10-methyl-9,10-dihydroacridine, dibenzopyran,
dibenzothiopyran, 1,3-benzodithiol, and the tentative threshold value was determined for imines reaction with the
mentioned heterocycles. One- or two-stage imines interaction with 10-methyl-9,10-dihydroacridine or dibenzopyran
was confirmed by two reactions of ionic hydroheterylation of N-benzylideneaniline in the presence of sodium
tetrahydroborate by the cation of 10-methyl-9,10-dihydroacridinium or the cation of dibenzopyrylium.
DOI: 10.1134/S1070428009050157
Among the heterocyclic compounds the 10-methyl-
9,10-dihydroacridine and its heteroanalogs attract atten-
tion as compounds simulating the behavior of coenzyme
NADH [1]. The investigation of dehydrogenation
mechanisms of these H-nucleophiles extends the under-
standing of the hydride transfer reactions and supplements
synthetic procedures [2–5].
methyleneanilines (imines) provided dissimilar results. For
instance, N-methylacridane in the presence of trifluoro-
acetic acid reduced the C=N bond of imines V [6]
(Scheme 1). Xanthene and thioxanthene under the same
conditions formed products of reductive heterylation
[7, 8]. 1,3-Benzodithiol in these conditions did not react
with imines [9]; it was unexpected since compound IV
in the known series of reactivity of these heterocycles
[N-methylacridane > thioxanthene > 1,3-benzodithiol >
xanthene (series 1)] took the third place. As hydride-ion
acceptor here served tritylium cation and solvents pyridine
We formerly demonstrated that the dehydrogeneration
of 10-methyl-9,10-dihydroacridine (N-methylacridane)
(I), dibenzopyran (xanthene) (II), dibenzothiopyran (thio-
xanthene) (III), and 1,3-benzodithiol (IV) with N-aryl-
Scheme 1.
I
+
ArCH2NHPh+
VII
N
CH3
VIII
R
R
CF3COOH II (III)
CF3COOH
ArCH2NHPh+
+
ArCH2NH
X
X
IX, X
VII
CH
NH
Ph
CH
NH+
Ph
XI, XII
IV
S
ArCH2NH
VIa_VIe
Va_Ve
S
R = H (a), Cl (b), Br (c), OCH3 (d), NO2 (e); X = O (IX, XI), S (X, XII).
735

YUNNIKOVA et al.
736
[10] or tetrahydrofuran [11]. Thus the reactivity order of
the above heterocycles is strongly affected by the
acceptor and the medium.
xanthene B, thioxanthene C, 1,3-benzodithiola D cal-
culated by nonempirical quantum-chemical method RHF/
6-31G(d). We regard ylides as intermediate species in
the reaction in question. The properties of such inter-
mediates were considered by Kharchenko and Chalaya
[12]. Describing the substituted thiabenzenes as very
reactive and short-lived species they concluded that
thiabenzenes were cyclic sulfonium ylides, e.g., ylide E.
Our assumption on ylides involvement is also based on
the important role of the trifluoroacetic acid for in its
absence the reaction of the N-methylacridane hetero-
analogs with the protonated imines does not occur.
Another feature of these compounds dehydrogenetion
by imines consists in the fact of greater reactivity of
xanthene than thioxanthene. For instance, the thio-
xanthene unlike the xanthene did not react with N-benzyl-
ideneaniline and reacted only with imines containing
electron-acceptor substituents (Cl, Br, NO2) in the para-
position of the benzene ring of the imine aldehyde frag-
ment. The rate constants of reactions between 4-nitro-
benzylideneaniline and xanthene or thioxanthene were
equal to 4 × 10–4 and 1.3 × 10–4 l mol–1s–1 respectively
[6]. These data show the difference in the dehydrogena-
tion mechanism of heterocyclic H-nucleophiles I–IV by
a tritylium cation and by protonated imines.
We believe that in acid medium heterocycles I–IV
are protonated to give salt F (for structures I–III) that
can transform into the ylides A–C isomeric to the
heterocycles (Scheme 2).
In extension of this research we set a goal to establish
the reason of the inconsistency between the reactivity of
the N-methylacridane heteroanalogs and the known series
(1), and to find the criteria governing the direction of the
reaction, either imines reduction or their reductive
heterylation.
The calculated data (see the table) demonstrated
a considerable increase in values of EHOMO, in dipole
moments and the negative charges on atoms C9 or C2 in
ylides A–D compared with the same characteristics of
heterocycles I–IV indicating the higher reactivity of the
ylide structures.
To elucidate the mechanism of hydrogen transfer to
imines from the C–H group of N-methylacridane and its
heteroanalogs we analyzed the energies of the frontier
orbitals ΔELUMO of the protonated N-phenylmethylene-
aniline (VIa), N-(4-chlorophenyl)methyleneaniline (VIb),
N-(4-bromophenyl)methyleneaniline (VIc), N-(4-
methoxyphenyl)methyleneaniline (VId), N-(4-nitro-
phenyl)methyleneaniline (VIe), ΔEHOMO of heterocycles
I–IV and their isomeric ylides of methylacridane A,
Analysis of calculated values of the energy gaps
between the protonated imines VIa–VIe and structures
I–IV, A–D shows a considerable approach to each other
of HOMO and LUMO energies of compounds VIa–VIe
and ylides A–D compared to the energy difference of
the fromtier orbitals of the same imines and heterocycles
I–IV. For instance, the energy differences ΔΕ of reagent
VId with N-methylacridane and N-methylacridane ylide
Scheme 2.
H
H
H
_
H
H
_CF3COOH
CF3COOH
+
X
+
X
X
_
CF3COO
H
A_C
H
F
I_III
H
H
_
_
S
S+ H
+
SH
R
E
D
X = NCH3 (I, A), O (II, B), S (III, C).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 5 2009

FEATURES OF REACTIONS OF 10-METHYL-9,10-DIHYDROACRIDINE HETEROANALOGS
737
Energies of the highest occupied molecular orbitals (ΔEHOMO), charges on atoms C9 of structures I–III, A–C, or C2 (IV, D)(q),
dipole moments (μ), and energy gaps ΔEHOMO(I–IV, A–D) – ΔELUMO(VIa–VIe) (|ΔE|)
a
ΔELUMO (VId) –2.559 eV. bΔELUMO (VIa) –2.929 eV. cΔELUMO (VIc) –3.118 eV. dΔELUMO (VIb) –3.119 eV. eΔELUMO (VIe) –3.381 eV
energy gaps between ΕLUMO of protonated imine imine
VIa and ΕHOMO of xanthene ylide is significantly smaller
(ΔΕ 2.526 eV) than the analogous difference with the
were 5.222 and 2.594 eV respectively. The comparison
of the energy gaps values between the same protonated
imine and ylides A–D shows that the minimum ΔΕ value
always corresponds to the pair protonated imine–N-
methylacridane ylide, and the maximum value, to the pair
with the 1,3-benzodithiol ylide. Thus the ΔΕ2 values
calculated for the protonated N-phenylmethyleneaniline
and ylides of N-methylacridane or 1,3-benzodithiol
amount to 2.224 and 4.020 eV repectively. Besides the
Ε
HOMO of thioxanthene ylide (ΔΕ 2.737 eV) in agreement
with the experimentally established fact of the partial
transformation of the series (1): xanthene in the reaction
of reductive heterylation is more active than thioxanthene.
Consequently, by the reactivity the ylides of heterocycles
I–IV form a series (2):
H
_
H
H
H
_
_
_
S
S H
+
>
>
>
N
O
S
H
C
+
+
+
H CH3
H
D
À
B
in the trifluoroacetic acid that leads to the formation of
product traces can be tentatively regarded as the threshold
value: Below this value the imine reactions with N-
methylacridane heteroanalogs are possible, at higher
values the reaction is impossible. It is important for the
prediction of new reactions.
In series (2) 1,3-benzodithiol ylide D is on the last
place and thus possesses the lowest reactivity. This is
the reason why 1,3-benzodithiol (IV) does not react with
imines under the studied conditions.
The calculated values of energy gaps ΔΕ for the
reactions of ylides A–D with protonated imines containing
electron-acceptor substituents (NO2) are considerably
lesser than for imines with the electron-donor substituents
(OCH3) in agreement with the experimental data on the
reaction kinetics for imines and xanthene [6].
Hence the assumption of the oxidation with the
protonated imines of ylides isomeric to the heterocycles
is in agreement with the experimental data and the
quantum-chemical calculations; therewith the ab initio
procedure better fits to the experiment (in the case of
1,3-benzodithiol) than the preliminary analysis of the
The value ΔΕ 2.737 eV characterizing the reaction of
the protonated N-benzylideneaniline with the thioxanthene
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 5 2009

YUNNIKOVA et al.
738
Scheme 3.
+
Ph
CH
N
ClO4_
(1) NaBH4
(2)H2O
Ph CH N Ph
THF
+
+
PhCH2NH
O
ClO4_
O
Ph
Va
O
IXa
XI
O
+
Ph
Ph
ClO4_
(1) NaBH4
(2) H2O
Ph CH N Ph
CH
N
THF
CH2
NH
Ph
+
+
+
N
ClO4_
N
Ph
CH3
XIII
H3C
VIIIa
N
Va
VIIa
CH3
reaction between imines and N-methylacridane hetero-
analogs performed by the AΜ1 procedure [6].
reduction of imine Va to N-benzylaniline (VIIa) and to
the formation of acridone XIII. In the latter case the
role of cation VIIIa consisted only in the imine activation.
The control experiment showed that in the absence of
N-methylacridinium cation the N-benzylideneaniline was
not reduced by sodium tetrahydroborate within 1 h. Thus
the experiment confirms the dependence of the process
described in Scheme 1 on the electron affinity of cations
VIII and IX.
In order to elucidate the reasons governing the
direction of imine reactions with heterocycles I–III it
was presumed that the reaction of N-arylmethylene-
anilines V with H-nucleophiles (Scheme 1) proceeded in
one or two stages. The first one-stage mechanism involves
the ionic hydrogenation of imines in the system H-nucleo-
phile–trifluoroacetic acid leading to the formation of
N-arylmethylaniline VII and aromatic cation [N-methyl-
acridinium (VIII), xanthylium (IX), thioxanthylium (X)].
Further cations IX or X react with amine VII to give
N-arylmethyl-4-[(thio)xanthen-9-yl]-anilines XI and XII.
EXPERIMENTAL
N-Benzyl-4-(xanthen-9-yl)]aniline (XI). To a mix-
ture of 0.36 g (2 mmol) of imine Va and 0.56 g (2 mmol)
of perchlorate IXa in 30 ml of THF was added 0.08
g (2.1 mmol) of NaBH4 while stiring at 20°C, reaction
time 30 min. The reaction mixture was poured into water,
the separated precipitate was recrystallized from ethanol.
Yield 0.51 g (70%), colorless crystals, mp 145–146°C
[7].
We compared the calculated values of electron affinity
(A = –ΕLUMO) of cations N-methylacridinium (3.287 eV),
xanthylium (3.955 eV), 1,3-benzodithiolium (4.007 eV),
and thioxanthylium (4.089 eV.As seen, N-methylacridin-
ium cation is a weaker electron acceptor than thio-
xanthylium cation. That is why the N-methylacridane only
reduces the imines and the xanthylium and thioxanthylium
cations formed in the course of the reaction effect the
heterylation of secondary amines. To confirm experi-
mentally the dependence of the reaction direction on the
electron affinity of cation we studied the hydrogenation
of N-benzylideneaniline (Va) in two systems: xanthylium
perchlorate (IXa)–NaΒH4 and N-methylacridinium
perchlorate (VIIIa)–NaΒH4 (Scheme 3) under the condi-
tions we had described before [9].
N-Benzylaniline (VIIa). To a mixture of 0.18 g
(1 mmol) of imine Va and 0.29 g (1 mmol) of perchlorate
VIIIa in 10 ml of THF while stiring at 20°C was added
0.08 g (2 mmol) of NaBH4, reaction time 1 h. The
precipitate was filtered off. The precipitate and the filtrate
were diluted with water. From the filtrate a precipitate
settled, N-benzylaniline (VIIa), colorless crystals, mp
38°C (37–38°C [13]). The hydrolysis of the precipitate
provided 10-methyl-9H-acridone (XIII), yellow crystals,
mp 201°C [14].
We established that the first reaction proceeded as
ionic hydroheterylation and afforded N-benzyl-4-
(xanthen-9-yl)aniline (XIa) identical to the sample obtained
by procedure [7]. The second reaction led only to
The quantum-chemical calculations were performed
using software GAUSSIAN 03 W [15].
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 5 2009

FEATURES OF REACTIONS OF 10-METHYL-9,10-DIHYDROACRIDINE HETEROANALOGS
739
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tiopiriliya i rodstvennye soedineniya (Thiopyrans,
Thiopirillium Salts and Related Compounds), Saratov: Izd.
Saratov. Univ., 1987, p. 134.
The authors express their gratitude to Doctor of
Chemical Sciences V.P. Feshin for carrying out the
calculations.
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14. Charbit, J.J., Galy,A.M., Galy, J.P., and Barbe, J., J. Chem.
Eng. Data, 1989, vol. 34, p. 136.
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