Flash vacuum thermolysis of N-(3-and 4-Pyridylmethylidene)-tert- butylamines: Mechanisms of formation of pyrrolopyridines and naphthyridines

Article abstract of DOI:10.1002/ejoc.201400112

Pyrrolopyridines and naphthyridines are formed by flash vacuum thermolysis (FVT) of 3-and 4-pyridylmethylidene-tert-butylimines 8 and 15. Elimination of a methyl radical generates resonance stablized 2-azaallyl radicals a1 and b1. The formation of pyrrolopyridines 9, 16 and 17 is rationalized in terms of cyclization of 1-aziridinyl radicals a2 and b2. Formation of naphthyridine 10 from imine 8, and of 11 and 18 from imine 15, are in accord with cyclization of 1-azaallyl radicals a6 and b9. Formation of naphthyridine 11 from 8, and of 10 and 19 from 15, indicate the operation of the spiro-cyclization pathways forming intermediates a9 and b14. Formation of the 1,8-naphthyridine 20 (3%) indicates a rearrangement through aziridine b22 and biradical b23. DFT calculations at the CAM-B3LYP/6-311G(d,p) level support the proposed reaction mechanisms.

Full text of DOI:10.1002/ejoc.201400112

FULL PAPER
DOI: 10.1002/ejoc.201400112
Flash Vacuum Thermolysis of N-(3- and 4-Pyridylmethylidene)-tert-butylamines:
Mechanisms of Formation of Pyrrolopyridines and Naphthyridines
Katarzyna Justyna,[a] Stanisław Les´niak,*[a] Ryszard B. Nazarski,[b] Michał Rachwalski,[a]
Thien Y. Vu,[c,d] Thi Kieu Xuan Huynh,[d] Saïd Khayar,[c] Alain Dargelos,[c]
Anna Chrostowska,*[c] and Curt Wentrup*[e]
Keywords: High-temperature reactions / Radicals / Rearrangement / Heterocycles / Photoelectron spectroscopy / Density
functional calculations
Pyrrolopyridines and naphthyridines are formed by flash
vacuum thermolysis (FVT) of 3- and 4-pyridylmethylidene-
tert-butylimines 8 and 15. Elimination of a methyl radical
generates resonance stablized 2-azaallyl radicals a1 and b1.
The formation of pyrrolopyridines 9, 16 and 17 is rationalized
radicals a6 and b9. Formation of naphthyridine 11 from 8,
and of 10 and 19 from 15, indicate the operation of the spiro-
cyclization pathways forming intermediates a9 and b14. For-
mation of the 1,8-naphthyridine 20 (3%) indicates a re-
arrangement through aziridine b22 and biradical b23. DFT
in terms of cyclization of 1-aziridinyl radicals a2 and b2. For- calculations at the CAM-B3LYP/6-311G(d,p) level support
mation of naphthyridine 10 from imine 8, and of 11 and 18
from imine 15, are in accord with cyclization of 1-azaallyl
the proposed reaction mechanisms.
idene-tert-butylamine 1a at 800 °C results in the formation
Introduction
of 1,2-dimethylindole
4 and 3-methylisoquinoline 6,
Until recently it was assumed that flash vacuum thermol-
ysis (FVT) of compounds bearing the tert-butyl group at-
tached to sp2- or sp3-hybridized nitrogen atoms leads to the
elimination of isobutene and the formation of the corre-
sponding NH-imine.[1] However, a short while ago, we re-
ported unusual reactions of N-tert-butylimines under FVT
conditions, namely, the elimination of a methyl radical and
subsequent formation of N-heterocycles.[2] Thus, FVT of N-
tert-butyl-E-crotonaldimine at 800 °C leads to the forma-
tion of pyrrole and crotonitrile, whereas 1,4-di(tert-butyl)-
1,4-diazabuta-1,3-diene affords 2-methylimidazole.[2a]
whereas N-(2-pyridylmethylidene)-tert-butylamine 1b gives
rise to 3-methylimidazo[1,5-a]pyridine 7 in high yield
(Scheme 1).[2b]
To explain these results we have proposed a free radical
mechanism, involving initial loss of a methyl group from
the tert-butyl groups to generate a resonance stabilized 2-
azaallyl radical 2. Cyclization of this to an aziridinyl radical
3 or a 1,4-H shift to generate 1-azaallyl radical 5 followed
by cyclization accounted for the observed products.[2b]
Little is known about the chemistry of azaallyl radicals
and aziridinyl radicals, and it is of interest to examine their
behaviour further. Therefore, we investigated the FVT reac-
tions of 3- and 4-pyridyl derivatives 8 and 15. Here, the
pyridine N-atoms can be regarded as ring labels, permitting
a stricter check on the possible reaction pathways. We are
pleased to report the results herein.
Furthermore, aromatic tert-butylimines behave very un-
expectedly under these conditions. Thus, FVT of N-benzyl-
[a] Department of Organic and Applied Chemistry, University of
Łódz´,
Tamka 12, 91-403 Łódz´, Poland
E-mail: slesniak@chemia.uni.lodz.pl
[b] Laboratory of Molecular Spectroscopy, University of Łódz´,
Tamka 12, 91-403 Łódz´, Poland
[c] Université de Pau et des Pays de l’Adour, Institut des Sciences
Analytiques et de Physico-Chimie pour l’Environnement et les
Matériaux UMR CNRS 5254,
Results
64000 Pau, France
E-mail: anna.chrostowska@univ-pau.fr
FVT of N-(4-Pyridylmethylidene)-tert-butylamine (8)
http://iprem-ecp.univ-pau.fr/live/personnel/anna_chrostowska
[d] Université Nationale du Vietnam à Ho Chi Minh Ville,
227 Nguen Van Cu, 5è arr, Ho Chi Minh Ville, Vietnam
[e] School of Chemistry and Molecular Biosciences,
The University of Queensland,
FVT of N-(4-pyridylmethylidene)-tert-butylamine (8)
was carried out at 800 °C and 10–4 hPa (Scheme 2). The re-
action products were examined by means of high-resolution
1H NMR spectroscopy immediately after work-up of the
thermolysates. It was found that FVT of 8 leads to a mix-
ture of 1,2-dimethylpyrrolo[2,3-c]pyridine (9; 34%), 3-
methyl-[2,7]naphthyridine (10; 10%), 3-methyl-[2,6]naphth-
Brisbane, Qld 4072, Australia
E-mail: wentrup@uq.edu.au
http://researchers.uq.edu.au/researcher/3606
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201400112.
3020
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 3020–3027

FVT of N-(3- and 4-Pyridylmethylidene)-tert-butylamines
Scheme 1. Products of FVT of N-benzylidene- and N-(2-pyridylmethylidene)-tert-butylamines 1a and 1b at 800 °C/10–4 hPa.
yridine (11; 11%), and 4-pyridinecarbonitrile (12; 33%).
The starting imine 8 was recovered in 11% yield. In ad-
dition, a small amount of pyridine-4-carbaldehyde (14; ca.
1%) was detected, presumably as the product of hydrolysis
of pyridin-4-ylmethanimine (13), which was not isolated.
The temperature of 800 °C was optimal for the formation
of products 9, 10, and 11, even though a part of starting
material 8 remained unchanged.
Scheme 2. Products of FVT of N-(4-pyridylmethylidene)-tert-
butylamine (8).
The ratio of the products was determined by integration
of the 1H NMR spectra, and their charactrization was con-
firmed after separations and purification. All products were
characterized by spectroscopic analysis and/or by compari-
son with the literature data for known compounds, or the
spectra of authentic, commercially available compounds.
Analysis of the FVT of N-(4-Pyridylmethylidene)-tert-
butylamine (8) by UV-Photoelectron Spectrum (UV-PES)
Figure 1. UV-PES of (a) N-(4-pyridylmethylidene)-tert-butylamine
(8); (b) the products of FVT of 8 at 770 °C; [values in italics corre-
spond to 4-pyridinecarbonitrile (12)].
The UV-PES of N-(4-pyridylmethylidene)-tert-butyl-
amine (8) and the spectrum of the products of FVT at
770 °C are shown in Figure 1a and 1b.
The interpretation of these spectra is corroborated by the followed by a broad massif with two main ionizations at 9.4
theoretical evaluation of the ionization energies (IE; Tables and 9.9 eV as well as several shoulders, namely one on the
S1–S5, Supporting Information). Thus, for 8 the first, very left-hand side at 8.8 eV, and three on the right-hand side at
intense, photoelectron (PE) band at 9.55 eV contains four 10.3, 10.44 and 10.92 eV. In addition, two shoulders are
ionizations corresponding to the four highest occupied mo- clearly distinguished on the second massif at 12.3 and
lecular orbitals. They are mainly the result of an antibond- 12.65 eV.
ing interaction between the aromatic π-system and imine
The interpretation of these spectra is aided by the theo-
C=N π bond, the lone pair of the pyridine nitrogen, the retical evaluation of IEs for 1,2-dimethylpyrrolo[2,3-c]pyr-
lone pair of imine nitrogen, and another antibonding inter- idine (9), 3-methyl-[2,7]naphthyridine (10), and 3-methyl-
action between the pyridine π-system and the imine C=N π [2,6]naphthyridine (11) together with known PES data for
bond, respectively. The second band at 11.3 eV is attributed 4-pyridinecarbonitrile (12).[3] On this basis the spectrum is
to an MO arising from ionization of the imine C=N π bond found to be in large part owing to major product 9, which
itself, whereas the massif above 11.6 eV is assigned to ion- is characterized by the first IE at 8.0 eV corresponding to
izations of sigma bonds.
the HOMO π bond. The band at 8.8 eV corresponds to the
The spectrum obtained upon FVT of 8 at 770 °C (Fig- HOMO-1, which is a result of an antibonding interaction
ure 1, b) is characterized by a low-energy band at 8.0 eV between the two rings. The third IE at 9.4 eV is attributed
Eur. J. Org. Chem. 2014, 3020–3027
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3021

S. Les´niak, A. Chrostowska, C. Wentrup et al.
FULL PAPER
to pyridine nitrogen lone pair ionization, whereas the next FVT of N-(3-Pyridylmethylidene)-tert-butylamine (15)
one at 9.9 eV is ascribed to orbitals arising from π–π inter-
As expected, less symmetric imine 15 afforded more
actions. The bands at 12.3 eV and above contain an anti-
products on FVT (Scheme 3), namely two 1,2-dimethylpyr-
bonding π-interaction and the sigma bond ionizations.
rolo-pyridines (16 and 17), and five methylnaphthyridines
The PES of 4-pyridinecarbonitrile 12 was described pre-
(10, 11 and 18–20) in addition to 3-pyridinecarbonitrile (21)
viously,[3] and its formation upon FVT of 8 is confirmed by
and pyridine-3-carbaldehyde (22; Scheme 4).
the presence of the appropriate bands (Figure 1, b, numbers
The products were separated and purified chromato-
in italics and Table S5). Because 3-methyl[2,7]naphthyridine
graphically. Unambiguous assignment of the NMR spectro-
(10) and 3-methyl[2,6]naphthyridine (11) are formed in
scopic signals was accomplished with the aid of correlation
much lower yields, the assignment of their PE bands is less
spectra (COSY, HMQC, and HMBC and NOESY) as well
clear-cut. Nevertheless, the band at 8.8 eV can be attributed
as calculations of chemical shifts[4] at the DFT-GIAO
to the HOMO of both 10 and 11, those at 9.4 and 9.9 eV
level.[5]
to the antibonding and bonding interactions of nitrogen
lone pairs and, in the case of 10, π–π ionizations. These
ionizations (9.4 and 9.9 eV) can be also attributed to the
antibonding and bonding interaction of nitrogen lone pairs
Discussion
in 11. The bands at 10.3 and 10.6 eV arise from π-ioniza-
The mechanism proposed for the formation of pyrrolo-
tions, whereas that at 12.3 eV from sigma-bond ionizations. pyridine 9 from 4-pyridyl derivative 8 (Scheme 4) follows
The trivial products 12 and 14 are formed by elimination the mechanism put forward earlier[2b] for the formation of
of isobutene as described previously.[2]
indole 4 from imine 1 (Scheme 1). The energy profile calcu-
Scheme 3. Products of FVT of N-(3-pyridylmethylidene)-tert-butylamine (15).
Scheme 4. The “normal” routes to 9 and 10 and the spiro-radical route to naphthyridine 11.
3022
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 3020–3027

FVT of N-(3- and 4-Pyridylmethylidene)-tert-butylamines
lated at the CAM-B3LYP/6-311G(d,p) level is shown in cal a9 (Scheme 4 and Figure 4) is calculated to have an acti-
Figure 2. Similarly to the case of imine 1, the highest acti- vation barrier of only 22 kcal/mol and nicely explains the
vation barrier is calculated for the initial C–C bond cleavage formation of observed product 11.
to form the resonance-stabilized 2-azaallyl radical a1
(76.4 kcal/mol). All subsequent reactions have barriers of
no more than 49 kcal/mol. A crucial role is played by azirid-
inyl radicals like a2 and related radicals b2 and b20 de-
scribed below, which are predicted to be formed with mod-
est activation barriers in the order of 44–48 kcal/mol.
Figure 4. The spiro radical route to naphthyridine 11 from imine 8
through 2-azaallyl radical a1 and spiro radical a9 [CAM-B3LYP/
6-311G(d,p)]. Energies in kcal/mol.
There is excellent precedence for the formation of such
spiro radicals in the literature. Cadogan and McNab[6] as
well as Trahanovsky[7] invoked spiro radical cyclizations ex-
tensively. More recently, Harrowven, McBurney and Wal-
ton[8] describe several examples of this kind. Apart from the
initial C–C bond cleavage with an activation energy of
Figure 2. Energy profile for formation of pyrrolopyridine 9 from
about 76 kcal/mol, the highest activation barriers towards
naphthyridine formation are the 1,4-eliminations of H2 with
a barrier of ≈ 54 kcal/mol. Thermal 1,4-eliminations of H2
from dihydroaromatics is common under FVT conditions,[7]
whereas 1,2-elimination is much less favourable.[9] 1,2-Di-
hydropyridines do not eliminate H2 on gas-phase thermoly-
sis but undergo Cope rearrangement instead.[10]
The calculated energy profiles for naphthyridine forma-
tion according to Scheme 4 are shown in Figures 3 and 4.
The activation barriers for the spiro radical route (Figure 4)
are not higher than those for the “normal” route (Figure 3).
In the case of 3-pyridyl derivative 15, the explanation of
formation of pyrrolopyridines 16 and 17 is straightforward
(Scheme 5). The calculated energy profiles for the formation
of these two products (Figures S1 and S2) are very similar
to the one shown for the formation of 9 in Figure 2. It is
well known that free radicals (e.g. alkyl and phenyl) add
preferentially to the 2-position of pyridine, often given ra-
tios of approximately 2:1 for addition to the 2- and 4-posi-
tions.[8a,11] In agreement with this, 16 (33%) is the main
product, dominating 17 (5%).
4-pyridyl derivative 8 [CAM-B3LYP/6-311G(d,p)]. Energies in kcal/
mol.
The formation of the naphthyridines is more challenging
mechanistically. Compound 10 (Scheme 2) is readily ex-
plained in terms of the “normal” mechanism proposed pre-
viously[2b] as shown in Scheme 4 and Figure 3. Here, the
1,4-H shifts isomerizing the 2-azaallyl radicals to 1-azaallyl
radicals of type a6 is predicted to occur with a relatively
low barrier of about 42 kcal/mol. But this cannot explain
the formation of major naphthyridine 11 (11%) from 8. An
ipso-cyclization reaction to generate the spiro-pyridine radi-
The formation of naphthyridines 11 and 18 is readily ex-
plained in terms of the mechanism developed in Scheme 4
above. This is illustrated in Scheme 5. The formation of 10
requires the spiro radical route through intermediate b14
(Scheme 5 and Figure 5). Compounds 11 and 18 are formed
by the “normal” cyclizations of 1-azaallyl radical b9 to
either the 2- or the 4-position of the pyridine. Again, cycli-
zation to the 2-position is preferred, yielding 18 (4%),
whereas cyclization to the 4-position yields 11 (2%), al-
though the calculated activation barriers are identical
Figure 3. The “normal” naphthyridine-forming route from imine 8
through 2-azaallyl radical a1 [CAM-B3LYP/6-311G(d,p)]. Energies
in kcal/mol.
Eur. J. Org. Chem. 2014, 3020–3027
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3023

S. Les´niak, A. Chrostowska, C. Wentrup et al.
FULL PAPER
Scheme 5. Formation of products from 3-pyridyl derivative 15.
Formation of naphthyridines 10 and 19 from imine 15
requires the spiro radical route through intermediate b14
(Scheme 5 and Figures 5 and 6). Once again, cyclization to
the 2-position of pyridine is preferred, yielding 19 (3%) ver-
Figure 5. The spiro radical route to 10 from 15 through 2-azaallyl
radical b1 and spiro radical b14 [CAM-B3LYP/6-311G(d,p)]. Ener-
gies in kcal/mol.
within 1 kcal/mol. The energy profiles (Figures S3 and S4)
are very similar to the one shown for formation of 10 in
Figure 3.
Figure 6. The route to 19 from 15 through intermdiate b15 [CAM-
B3LYP/6-311G(d,p)]. Energies in kcal/mol.
3024
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 3020–3027

FVT of N-(3- and 4-Pyridylmethylidene)-tert-butylamines
sus 10 (2%). It should be noted that the yields of naphth- signal corresponding to 23 is seen next to the methyl group
yridines, although small, are quite accurate. They were de- signal of 20 in the 1H NMR spectrum of the crude thermo-
1
termined by H NMR spectroscopy of the crude pyrolysis lyzate from 15, but the amount was too small for isolation
products in multiple experiments.
and characterization. Thus, if 23 is formed at all, it is only
To explain the formation of 1,8-naphthyridine 20 a fur- a trace amount. The observed formation of naphthyridine
ther detour starting from spiro-radical b14 is required 20 is once again in line with the common observation men-
(Scheme 6 and Figure 7). ortho-Cyclization to aziridines b21 tioned above that free radical attack at the ortho-position
and b22 followed by ring opening will generate biradical of pyridine is preferred.[8a,11]
b23. Either C–C or C–N bond cleavage is possible in the
Dimethylpyrrolopyridine 16 (the main product in
gas-phase flow pyrolysis of aziridines at 500–600 °C.[12] The Scheme 3) was rethermolyzed at 920 °C. Only the starting
activation barrier for the isomerization of cyclopropane to material was recovered. This control experiment was impor-
propene is 65 kcal/mol; for bicyclo[3.1.0]hexane to cyclo- tant, because there are known cases of ring expansion of
hexene it is 57 kcal/mol; and for bicyclo[3.1.0]hex-2-ene to methylpyrroles and methylindoles to pyridines and quinol-
1,3- and 1,4-cyclohexadiene it is 50 kcal/mol.[13] The latter ines under high-temperature flow-pyrolysis conditions.[14]
reaction is analogous to that proposed for b22Ǟb24 Such isomerizations do not take place under the FVT con-
through biradical b23 below (Scheme 6).
ditions employed here.
Conclusions
FVT of pyridylmethylidene-tert-butylimines proceeds
with predominant fission of a C–C bond in a tert-butyl
group leading to resonance stabilized 2-azaallyl radicals a1
and b1, which in a series of rearrangements and cyclizations
afford pyrrolopyridines and naphthyridines. The formation
of pyrrolopyridines 9, 16 and 17 follows the previously pro-
posed mechanism[2b] with the cyclization of 1-aziridinyl rad-
icals a2 and b2 as key elements. Formations of naphthyrid-
ine 10 from 4-pyridyl derivative 8, and of 11 and 18 from
3-pyridyl derivative 15, are also in line with the previous
proposal.[2b] However, the formation of naphthyridine 11
from 8, and of 10 and 19 from 15, reveal the operation of
a different pathway, which is adequately explained by means
of the spiro-cyclizations forming intermediates a9 and b14
as shown in Scheme 4 and Scheme 5. The formation of 1,8-
naphthyridine 20 (3%) reveals yet another mechanistic de-
tour, which is postulated to take place through biradical
b23. The reaction mechanisms are supported by calcula-
tions of the energies of all proposed intermediates and tran-
sition states at the CAM-B3LYP/6-311G(d,p) level.
Scheme 6. The biradical route to 20.
Several unusual radical reactions have been evidenced in
this work: (1) formation of 2-azaallyl radicals; (2) 1,4-H
shifts interconverting them with 1-azaallyl radicals; and
(3) cyclization to 1-aziridinyl radicals. All the isolated pyr-
rolopyridine and naphthyridines follow from these basic re-
actions. Further research is now aimed at the selective gen-
eration of free radicals of these types from other precursors.
This is expected to provide less-complicated reaction mix-
tures and deeper insight into the reaction mechanisms.
Figure 7. The biradical route to naphthyridine 20 from 3-pyridyl
derivative 15 through radical b15 and biradical b23 [CAM-B3LYP/
6-311G(d,p)]. Energies in kcal/mol.
The formation of 1,4-dihydropyridine derivative b24 is
very advantageous, because it leads to a low barrier towards
H2 elimination to generate 20 (36 kcal/mol; Figure 7).
The formation of 1,8-naphthyridine 20 by the biradical
route suggests that a corresponding para-cyclization of azir-
idinyl radical b20 could lead to isomeric 1,6-naphthyridine
Experimental Section
General: All reagents were purchased from commercial suppliers
and used without further purification. The H and 13C{1H} NMR
1
spectra were recorded with a Bruker Avance III apparatus at 600/
150 (1H/13C) MHz with CDCl3 as a solvent and tetramethylsilane
as an internal standard. Coupling constants J are estimated by
23 (Scheme 6). The methyl group of 23 is expected at δ =
1
2.54 ppm in the H NMR spectrum. In fact a very weak first-order analysis. Splitting patterns are indicated as s, singlet; d,
Eur. J. Org. Chem. 2014, 3020–3027
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3025

S. Les´niak, A. Chrostowska, C. Wentrup et al.
FULL PAPER
doublet; t, triplet; q, quartet; m, multiplet; p, pseudo; br., broad
peak. Melting points were measured in open capillaries with a
MeltTemp apparatus. IR spectra were recorded as KBr pellets with
a Thermo-Nicolet Nexus FTIR spectrometer. High-resolution
mass spectra (HRMS) were recorded by the Central Analysis Labo-
ratory of the Polish Academy of Sciences (Łódz´) with a Finnigan
the column as the last component and further purified with PTLC
(SiO2, AcOEt/methanol, 9:1) and finally by recrystallization, m.p.
122–123 °C (hexane), ref.[17b] 123–124 °C (hexane). The product
had 1H NMR spectroscopic data in good agreement with those
given in ref.,[17b] but its 13C NMR spectroscopic data varied some-
what with the data reported. 13C NMR: δ = 12.66, 29.50, 99.28,
MAT 95 double focusing spectrometer. Accurate mass measure- 104.29, 124.88, 138.36, 139.60, 141.09, 142.05 ppm.
ments were performed by peak matching technique in electron ion-
7-Methyl-[1,6]naphthyridine (18): Separated by column chromatog-
ization (EI) conditions by using perfluorokerosene as an internal
raphy (Al2O3, AcOEt) and purified with PTLC (SiO2, acetonitrile),
standard. Gravitational column chromatography was performed
and recrystallization from petroleum ether, m.p. 85–86 °C (petro-
with Merck silica gel 60 (70–230 mesh). Preparative thin-layer
leum ether), ref.[18] 86–87 °C (petroleum ether). The product has
chromatography (PTLC) was performed with plates coated with
been described in ref.[9] but spectroscopic data were not reported.
Merck silica gel 60 (PF254) and a suitable developing solvent sys-
FTIR (KBr): ν = 3420, 2920, 1615, 1585, 1470, 1335, 1023, 946,
˜
tem. Details of the photoelectron spectrometer and the FVT-PES
1
878, 787, 412 cm–1. H NMR: δ = 2.77 (s, 3 H), 7.46 (dd, J = 8.2
procedure have been reported previously.[2b]
and 4.3 Hz, 1 H), 7.76 (ps, 1 H), 8.25 (ddd, J = 8.2, 1.7 and 0.8 Hz,
1 H), 9.05 (dd, J = 4.3 and 1.7 Hz, 1 H), 9.20 (s, 1 H) ppm. 13C
NMR: δ = 24.46, 120.22, 121.71, 121.73, 135.60, 151.16, 152.25,
154.86, 156.27 ppm. HRMS (EI): m/z calcd. for C9H10N2 [M+]
144.0687; found M 144.0682.
Preparative FVT – General Procedure: The FVT experiments were
performed by using the previously described apparatus and pro-
cedure.[2b] Imines 8 and 15 (2 mmol) were slowly vaporized at room
temperature and thermolyzed at 800 °C/10–4 hPa and the products
were collected in a solid CO2/acetone cold trap. After the end of
the reaction, a part of the thermolyzate was examined by 1H NMR
spectroscopy, whereas the remainder was subjected to chromato-
graphic separation and purification.
6-Methyl-[1,7]naphthyridine (19): Separated by column chromatog-
raphy (Al2O3, AcOEt) and purified with PTLC (SiO2, acetonitrile).
Semisolid. FTIR (KBr): ν = 3420, 2962, 1621, 1597, 1457, 1261,
˜
1
1096, 1032, 803, 417 cm–1. H NMR: δ = 2.74 (s, 3 H), 7.47 (ps, 1
H), 7.54 (dd, J = 8.4 and 4.1 Hz, 1 H), 8.06 (ddd, J = 8.4, 1.5 and
0.8 Hz, 1 H), 8.95 (dd, J = 4.1 and 1.6 Hz, 1 H), 9.45 (br. s, 1
H) ppm. 13C NMR: δ = 24.13, 117.87, 125.01, 131.72, 134.16,
141.90, 151.11, 152.83, 153.64 ppm. HRMS (EI): m/z calcd. for
C9H10N2 [M+] 144.0687; found M 144.0681.
FVT of N-(4-Pyridylmethylidene)-tert-butylamine (8): The products
were separated/purified by column chromatography and/or PTLC,
or by recrystallization or sublimation.
1,2-Dimethylpyrrolo[2,3-c]pyridine (9): Separated by column
chromatography (Al2O3, AcOEt) and purified by recrystallization
3-Methyl-[1,8]naphthyridine (20): Isolated from the reaction mix-
ture by repeated PTLC (SiO2, first AcOEt then AcOEt/methanol,
1:1), m.p. 111–113 °C (hexane), ref.[19] 109–110 °C. The product
had 1H NMR spectroscopic data fully compatible with those given
in ref.[19,20] The following spectroscopic data were in good agree-
ment with those reported.[20] 13C NMR: δ = 18.73, 122.34, 122.74,
132.15, 135.76, 136.71, 152.72, 154.79, 155.73 ppm.
from hexane, m.p. 116–117.5 °C. FTIR (KBr): ν = 3393, 3266,
˜
1
1689, 1605, 1537, 1479, 1399, 1339, 1030, 831 cm–1. H NMR: δ =
2.44 (s, 3 H), 3.725 (s, 3 H), 6.24 (ps, 1 H), 7.38 (dd, J = 5.4 and
1.0 Hz, 1 H), 8.18 (d, J = 5.4 Hz, 1 H), 8.64 (br. s, 1 H) ppm. 13C
NMR: δ = 12.64, 29.61, 99.53, 114.07, 131.65, 132.87, 134.58,
138.68, 141.08 ppm. HRMS (EI): m/z calcd. for C9H10N2 [M+]
146.0844; found 146.0849.
3-Methyl-[2,7]naphthyridine (10): Separated by column chromatog-
raphy (Al2O3, hexane/AcOEt, 8:2) and purified with PTLC (SiO2,
acetonitrile). The product had spectroscopic data identical with
those reported above for 10 prepared from 8.
3-Methyl-[2,7]naphthyridine (10): Separated by column chromatog-
raphy (Al2O3, hexane/AcOEt 8/2) and purified with PTLC (SiO2,
acetonitrile), m.p. 37–38 °C (hexane), ref.[15] 36–37 °C. The product
had 1H NMR spectroscopic data compatible with those reported in
ref.[15] 13C NMR: δ = 24.67, 117.01, 118.66, 122.33, 139.20, 146.86,
152.36, 152.72, 156.54 ppm.
3-Methyl-[2,6]naphthyridine (11): Separated by column chromatog-
raphy (Al2O3, hexane/AcOEt, 8:2) and purified with PTLC (SiO2,
acetonitrile). The product showed spectroscopic data identical with
those for 11 obtained from 8.
3-Methyl-[2,6]naphthyridine (11): Separated by column chromatog-
raphy (Al2O3, hexane/AcOEt 8/2) and purified with PTLC (SiO2,
acetonitrile), m.p. 55–56 °C (subl.), ref.[16] 55.5–56 °C (subl.). The
1H NMR spectroscopic data of the product was in an excellent
agreement with the reported data.[16] 13C NMR: δ = 24.39, 117.15,
119.12, 128.33, 131.04, 143.83, 151.24, 151.44, 153.91 ppm.
Computational Method: Energies of ground- and transition-state
structures were calculated at the CAM-B3LYP/6-311G(d,p)
level.[21] The energy of the open-shell singlet (OSS) diradical b23
was calculated at the unrestricted DFT level with broken spin sym-
metry (50%-50%).[22] The energies of the so-obtained OSS, the
closed-shell singlet (CSS) and the triplet (T) are –458.2417809,
–458.2016791, and –458.2420356 hartrees, respectively. As can be
seen, the OSS and the T are nearly isoergic, and the CSS is about
25 kcal/mol higher in energy. The total spin expectation value
ϽS2Ͼ is 1.0444, indicating little spin contamination. Further com-
putational details are reported in the Supporting Information.
4-Pyridinecarbonitrile (12) and pyridine-4-carbaldehyde (14) were
identified by analysis relative to commercially available compounds.
FVT of N-(3-Pyridylmethylidene)-tert-butylamine (15): The prod-
ucts were separated by column chromatography and/or PTLC, or
by recrystallization.
1,2-Dimethyl-1H-pyrrolo[2,3-b]pyridine (16): Separated by column
chromatography (SiO2, hexane/AcOEt, 9:1). This compound was
eluted from the column as the first component. The oily product
had 1H NMR spectroscopic data compatible with those given in
ref.[8] 13C NMR: δ = 12.98, 27.86, 97.55, 115.53, 120.73, 127.05,
137.65, 141.39, 148.65 ppm.
Supporting Information (see footnote on the first page of this arti-
cle): Details of the UV-PES and FVT/UV-PES methods. Calculated
energy profiles, Figures S1–S4. 1H and 13C NMR spectra of iso-
lated pyrrolopyrroles and naphthyridines. Tables of calculated mo-
lecular orbitals and ionization energies, and Cartesian coordinates,
energies and, where applicable, imaginary frequencies of all calcu-
lated species.
1,2-Dimethyl-1H-pyrrolo[3,2-c]pyridine (17): Separated by column
chromatography (SiO2, AcOEt). This compound was eluted from
3026
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 3020–3027

FVT of N-(3- and 4-Pyridylmethylidene)-tert-butylamines
[10] I. Hasan, F. W. Fowler, J. Am. Chem. Soc. 1978, 100, 6696–
6699.
Acknowledgments
[11] D. H. Hey, E. W. Walker, J. Chem. Soc. 1948, 2213–2220.
[12] J. Meier, F. Akermann, H. H. Günthard, Helv. Chim. Acta
1968, 51, 1686–1691.
R. B. N. thanks the Academic Computer Centre CYFRONET
(AGH University of Science and Technology, Kraków, Poland) for
access to the Gaussian 09 software (computational grant MNiSW/
SGI3700/UŁódzki/057/2010). A. C. and T. Y. V. thank the Agence
Universitaire de la Francophonie Asie-Pacifique for financial sup-
port of the PhD programme. The authors also thank P. Baylère
(Université de Pau et des Pays de l’Adour) for efficient technical
assistance.
[13] J. J. Gajewski, Hydrocarbon Thermal Isomerizations, 2nd ed.,
Elsevier: Amsterdam 2004, and references cited therein.
[14] a) J. M. Patterson, C. F. Mayer, W. T. Smith, J. Org. Chem.
1975, 40, 1511–1514; b) J. M. Patterson, J. W. de Haan, J. Am.
Chem. Soc. 1972, 94, 2487–2494; c) J. M. Patterson, M.
Drenchko, J. Org. Chem. 1962, 27, 1650–1652; d) J. M. Pat-
terson, J. Brasch, M. Drenchko, J. Org. Chem. 1962, 27, 1652–
1659.
[15] E. Barbu, F. Cuiban, Heterocycl. Commun. 2000, 6, 259–264.
[16] D. E. Ames, W. D. Dodds, J. Chem. Soc. Perkin Trans. 1 1972,
705–710.
[17] a) L. Estel, F. Marsais, G. Quéguiner, J. Org. Chem. 1988, 53,
2740–2744; b) C. S. Hong, J. Y. Seo, E. K. Yum, N.-D. Sung,
Heterocycles 2004, 63, 631–640.
[18] N. Ikekawa, Chem. Pharm. Bull. 1958, 6, 263–269.
[19] P. Zhichkin, C. M. C. Beer, W. M. Rennells, D. J. FairFax, Syn-
lett 2006, 379–382.
[20] H. C. van der Plas, A. van Veldhuizen, M. Wozniak, P. Smit, J.
Org. Chem. 1978, 43, 1673–1677.
[21] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B.
Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li,
H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Son-
nenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hase-
gawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai,
T. Vreven, J. A. Montgomery Jr., J. E. Peralta, F. Ogliaro, M.
Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Starov-
erov, T. Keith, R. Kobayashi, J. Normand, K. Raghavachari,
A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N.
Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V.
Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Strat-
mann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W.
Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski,
G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D.
Daniels, O. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski,
D. J. Fox, Gaussian 09, revision C.01, Gaussian, Inc., Wall-
ingford, CT 06492, USA, 2011.
[1]
a) J. D. Perez, G. I. Yranzo, L. M. Phagouape, Bull. Soc. Chim.
Fr. 1986, 1, 129–132; b) V. Metail, S. Joanteguy, A. Chrostow-
ska-Senio, G. Pfister-Guillouzo, A. Systermans, J. L. Ripoll,
Inorg. Chem. 1997, 36, 1482–1487; c) V. Lefèvre, J. L. Ripoll, Y.
Dat, S. Joanteguy, V. Metail, A. Chrostowska-Senio, G. Pfister-
Guillouzo, Organometallics 1997, 16, 1635–1640; d) J. Levil-
lain, G. Pfister-Guillouzo, J. L. Ripoll, Eur. J. Org. Chem. 2000,
3253–3259.
a) S. Les´niak, B. Pasternak, K. Justyna, T. Y. Vu, T. K. X.
Huynh, S. Khayar, A. Dargelos, A. Chrostowska, Tetrahedron
2013, 69, 722–729; b) T. Y. Vu, A. Chrostowska, T. K. X.
Huynh, S. Khayar, A. Dargelos, K. Justyna, B. Pasternak, S.
Les´niak, C. Wentrup, Chem. Eur. J. 2013, 19, 14983–14988.
[2]
[3]
[4]
T. Kobayashi, S. Nagakura, J. Electron Spectrosc. Relat. Phe-
nom. 1974, 4, 207–2012.
a) K. Wolinski, J. F. Hilton, P. Pulay, J. Am. Chem. Soc. 1990,
112, 8251–8260; b) . J. R. Cheeseman, G. W. Trucks, T. A.
Keith, M. J. Frisch, J. Chem. Phys. 1996, 104, 5497–5509.
[5] R. B. Nazarski, K. Justyna, S. Les´niak, A. Chrostowska, paper
in preparation.
[6] a) J. I. G. Cadogan, C. L. Hickson, H. McNab, Tetrahedron
1986, 42, 2135–2165; b) J. I. G. Cadogan, H. S. Hutchison, H.
McNab, J. Chem. Soc. Perkin Trans. 1 1987, 1407–1411; c)
J. I. G. Cadogan, C. L. Hickson, H. S. Hutchison, H. McNab,
J. Chem. Soc. Perkin Trans. 1 1991, 377–384; d) J. I. G. Cado-
gan, H. S. Hutchison, H. McNab, J. Chem. Soc. Perkin Trans.
1 1991, 385–393.
[7] W. S. Trahanovsky, J. L. Tunkel, J. C. Thoen, Y. Wang, J. Org.
Chem. 1995, 60, 8407–8409.
[8] a) Harowven, Org. Biomol. Chem. 2003, 1, 4047–4057; b) R. T.
McBurney, J. C. Walton, Beilstein J. Org. Chem. 2013, 9, 1083–
1092.
[9] R. B. Woodward, R. Hoffmann, Angew. Chem. Int. Ed. Engl.
1969, 8, 781–853; Angew. Chem. 1969, 81, 797–869.
[22] a) C. J. Cramer, J. Am. Chem. Soc. 1998, 120, 6261–6269; b)
P. R. Schreiner, J. Am. Chem. Soc. 1998, 120, 4184–4190; c) J.
Gräfenstein, A. M. Hjerpe, E. Kraka, D. Cremer, J. Phys.
Chem. A 2000, 104, 1748–1763; d) C. J. Cramer, J. Thompson,
J. Phys. Chem. A 2001, 105, 2091–2098.
Received: January 23, 2014
Published Online: March 17, 2014
Eur. J. Org. Chem. 2014, 3020–3027
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3027