Bismuth triflate catalyzed solvent-free synthesis of 2,4,6-triaryl pyridines and an unexpected selective acetalization of tetrazolo[1,5-a]- quinoline-4-carbaldehydes

Article abstract of DOI:10.1016/j.tetlet.2012.01.059

Bismuth triflate has been found as a potential catalyst for an efficient and solvent-free synthesis of symmetrical 2,4,6-triarylpyridines in 86-93% yields. Moreover, catalytic reactivity of bismuth triflate toward tetrazolo[1,5-a]quinoline-4-carbaldehydes

Full text of DOI:10.1016/j.tetlet.2012.01.059

Tetrahedron Letters 53 (2012) 1523–1527
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Tetrahedron Letters
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Bismuth triflate catalyzed solvent-free synthesis of 2,4,6-triaryl pyridines and
an unexpected selective acetalization of
tetrazolo[1,5-a]-quinoline-4-carbaldehydes
⇑
Pravin V. Shinde, Vilas B. Labade, Jitendra B. Gujar, Bapurao B. Shingate, Murlidhar S. Shingare
Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431 004, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Bismuth triflate has been found as a potential catalyst for an efficient and solvent-free synthesis of sym-
metrical 2,4,6-triarylpyridines in 86–93% yields. Moreover, catalytic reactivity of bismuth triflate toward
tetrazolo[1,5-a]quinoline-4-carbaldehydes for the unexpected formation of their corresponding acetals
has been exploited.
Received 29 December 2011
Revised 15 January 2012
Accepted 16 January 2012
Available online 26 January 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Bismuth triflate
Triarylpyridines
Acetal formation
Tetrazolo[1,5-a]-quinoline-4-carbaldehydes
Being environment friendly, bismuth compounds have been
used in catalysis and organic synthesis in the past two decades.
However, till now there are only a few reports on the use of bis-
Since, Krohnke’s original report on the synthesis of 2,4,6-triaryl-
9
pyridines, there has been a plethora of research targeting their syn-
1
0
theses. Pyridines with 2,4,6-triaryl substitution pattern (Krohnke
pyridines) have been synthesized using various methods and proce-
muth compounds, for example, Bismuth chloride (BiCl
nitrate (Bi(NO ), Bismuth bromide (BiBr ), Bismuth triflate
Bi(OTf) ), etc., as catalysts in organic synthesis possibly due to
3
), Bismuth
1
1
3
)
3
3
dures. Traditionally, these compounds have been synthesized
1
(
3
through the reaction of N-phenacyl pyridinium salts with
the unstable nature of Bi–C bonds. In view of the ever increasing
importance of green/sustainable chemistry and significance of bis-
muth compounds as catalysts, it was aimed to develop bismuth
catalyzed ecofriendly organic transformations.
a
(NH
,b-unsaturated ketones in the presence of ammonium acetate
1
0,12
4
OAc).
Recently, several new improved methods have been
13–17
developed for the synthesis of these 2,4,6-triaryl pyridines.
Among all these methods, one pot reaction between acetophenones,
aryl aldehydes, and NH OAc is the well established protocol for the
synthesis of triaryl pyridines using NaOH in PEG-400, PEG-300
Pyridine ring system, particularly 2,4,6-triarylpyridine is of
immense interest because of its unique position in medicinal
4
18
2
,3
19
20
chemistry. Moreover, they are prominent synthons in supramo-
4
along with NaOH, catalytic amount of acetic acid, HClO –
2
1
22
lecular chemistry, with their
P
-stacking ability along with direc-
SiO
2,4,6-trichloro-1,3,5-triazine (TCT), 3-methyl-1-(4-sulfonylbutyl)
imidazolium hydrogen sulfate [HO S(CH MIM][HSO ] and a Bron-
2
,
preyssler type heteropolyacid H14[NaP
W
5 30
O110],
wet
tional H-bonding capacity.4 In addition, the excellent thermal
stabilities of these pyridines have instigated a growing interest
for their use as monomeric building blocks in thin films and orga-
23
3
2
)
4
4
2
4
sted acidic ionic liquid. But, most of these protocols are having one
or more drawbacks, thus leaving room for further improvements.
Owing to the aforementioned chemical and pharmacological
significance of the Krohnke pyridines, synthesis of such type of
molecules is becoming interesting area of research and hence,
chemists are diverting their attention to search simple routes for
their syntheses exploring the applications of efficient catalysts by
utilizing the concepts of greener chemistry.
5
nometallic polymers. Recent studies have highlighted the biolog-
ical activity of triarylpyridines, providing impetus for further
6
studies in utilizing this scaffold in new therapeutic drug classes.
These molecules have been found to be useful for the synthesis
of DNA binding ligands, in particular targeting G-quadruplex
DNA which has recently received much attention as a possible tar-
7
,8
get in cancer therapy.
2
5
26
In the pharmaceutical, phyto pharmaceutical, fragrance, and
2
7
lacquer industries, acetals are used both as intermediates and as
end products. Different types of acetals are also applied as plasti-
cizers and vulcanizers, as physiologically active substances, and
⇑
Corresponding author. Tel.: +91 240 2403313; fax: +91 240 2403113.
E-mail address: prof_msshingare@rediffmail.com (M.S. Shingare).
0
040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2012.01.059

1
524
P. V. Shinde et al. / Tetrahedron Letters 53 (2012) 1523–1527
as potential protective groups for aldehydes and ketones. Acetal-
ization is probably the most important protection strategy for car-
bonyl groups and it plays an important role in organic synthesis.
We observed that sulfamic acid and sulfanilic acid cannot afford
more than 32 and 43% yields (Table 1, entries 1–2). In comparison,
(±) CSA is able to deliver only 59% product yield after 4 h (Table 1,
2
8
In general, this aim of formation of acetals and ketals is gener-
ally achieved in the presence of mineral liquid acids or Lewis acids
3
entry 3). As a matter of fact p-TSA and Bi(OTf) furnished the
desired product in good, 77, and 83% yields, respectively, within
2 h (Table 1, entries 4–5). In view of the good catalytic activity of
2
8,29
as catalysts.
Acetal formation is achieved by treating aldehydes
or ketones with an excess (10 equiv or more) of an alcohol or diol
in the presence of a drying reagent and a Lewis or Bronsted acid,
Bi(OTf)
To evaluate the effect of solvent, model reaction was further
performed using Bi(OTf) in ethanol and water as solvent. Water
did not bring the reaction to completion (Table 1, entry 7), but in
contrast ethanol found to furnish the product in a good yield (Table
1, entry 6). Considering the increasing importance of solvent-free
reactions in organic synthesis, our next attempt was to examine
3
it was finalized for subsequent optimization studies.
3
0
or by removing water through the formation of an azeotrope with
3
the solvent and the use of a Dean–Stark trap.2
8
It is worthy to point out here that, most of the catalysts are not
selective toward the substrates, that is, aldehydes and ketones.
Consequently, there is a demand for selective acetalization meth-
ods, which can selectively carry out acetalization of aldehyde in
the presence of ketone and vice-versa. But, this could be rarely
achieved, since requirement of acetalizing reagent, for example,
ethanol for the reaction is 10 equiv, which leaves room for both
the substrates, that is, aldehyde and ketone to form their corre-
sponding acetals and ketals, respectively.
3
the catalytic efficiency of Bi(OTf) in the absence of solvent. Pre-
dictably, it was observed that in the absence of solvent, reaction
rate increased enormously and desired product was obtained in
higher yields (Table 1, entry 8).
To determine the appropriate concentration of the catalyst, that
is, Bi(OTf)
tions of Bi(OTf)
that the product was formed in 56%, 69%, 89%, and 90% yields,
3
, model reaction was investigated at different concentra-
Traditionally acetals and ketals are synthesized by the reaction
of aldehyde and ketones with alcohol in the presence of acid cata-
3
such as 1, 2, 5, and 10 mol %. This study revealed
3
1
lysts. Magnesium perchlorate, p-toluene sulfonic acid, and differ-
respectively. This indicates that 5 mol % of Bi(OTf)
carry out the reaction efficiently.
3
is enough to
ent metal complexes of Pt(II), Pd(II), Rh(II) are also reported to
accomplish this organic transformation.3
2–34
Progress has also
A mechanism for the formation of triaryl pyridines has been
proposed with the help of Figure 1.
been made in the alternative catalysts for the acetalization of car-
35
bonyl compounds, such as organometallic reagents, silyl re-
3
Initially, acetophenone A in the presence of Bi(OTf) is
3
6
37
agents, inorganic compounds, etc.
converted into its enol form, which gives nucleophilic addition
on the aldehyde molecule B to afford aldol condensation product
C. Then second molecule of acetophenone undergoes Michael addi-
tion reaction with C to form the 1,5-diketone intermediate D. This
1,5-diketone on reaction with ammonium acetate followed by
cyclization and dehydration gives compounds E. Finally, air oxida-
tion of E leads to the formation of corresponding triaryl pyridine F.
To establish generality of the optimized reaction conditions,
various aldehydes were allowed to undergo this cyclocondensation
Copper(II) tetrafluoroborate is an effective catalyst for the for-
3
8
À
mation of acetals, but the BF4 counter ion is harmful to the envi-
ronment. Metal triflates have previously been reported to catalyze
3
9,40
acetalization reactions.
3 3
In particular, Bi(OTf) and In(OTf)
effectively catalyze this process. But, literature reveals that, these
triflates, while being efficient, are associated with some draw-
backs. For example, when reactions are carried out using In(OTf)
3
an aqueous work-up cannot be used as the acetal undergoes rapid
hydrolysis back to the corresponding carbonyl,3 making recycling
of the catalyst difficult, whereas, previous protocol involving the
9
41
reaction. Almost all the aromatic aldehydes proved to be amena-
ble to these reaction conditions. However, no significant substitu-
ent effect was found in case of all aryl aldehydes (Table 2).
To sum up, we have investigated a new approach for the
3
use of Bi(OTf) reveals that there is a need of reagent trialkyl ortho-
formate for acetalization of carbonyl compounds. Moreover, the
reactions require to be carried out under reflux condition and suf-
fer from relatively longer reaction times.40
However, all these methods have not been entirely satisfactory,
owing to various side-effects associated with them. Notably,
almost all of the reported procedures do not selectively form
corresponding acetal of only one carbonyl compound either
aldehyde or ketone.
3
synthesis of 2,4,6-triaryl pyridines in the presence of Bi(OTf) as
an efficient catalyst. The remarkable advantages offered by this
method are- (i) solvent-free reaction conditions which do not need
any solvent or reaction medium to achieve the targeted com-
pounds, (ii) short reaction times as compared to other protocols,
(iii) ease of product isolation, purification and avoids the need of
column chromatography technique, and (iv) high yields of the
desired products. We believe that this method is a useful alterna-
tive to the existing methodologies for the synthesis of 2,4,6-triaryl
pyridine derivatives.
In search of the best experimental reaction conditions for the
preparation of 2,4,6-triaryl pyridines, reaction of benzaldehyde
1
a, two molecules of acetophenone 2, and ammonium acetate 3
was selected as a model reaction (Scheme 1). For this study, we
have screened various acid catalysts bearing sulphonated function-
alities owing to their wide spread catalytic applications in organic
synthesis. For this purpose, sulfamic acid, sulfanilic acid, p-TSA, (±)
Table 1
a
Screening of catalysts and solvents
CSA, and Bi(OTf)
3
were screened as catalysts in aq. ethanol.
Entry
Catalyst
Solvent
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
Sulfamic acid
Sulphanilic acid
(±) CSA
Aq. Ethanol
Aq. ethanol
Aq. ethanol
Aq. ethanol
Aq. ethanol
Ethanol
4
2
4
2
2
3
4
2
32
43
59
77
83
78
Trace
89
CHO
p-TSA
Bi(OTf)
Bi(OTf)3
Bi(OTf)
Bi(OTf)3
3
1a
O
3
Water
Neat
N
2
NH OAc
4
Note: Aq. Ethanol used was 30% aqueous.
Reaction and conditions: 1a (0.001 mol), 2 (0.002 mol), 3 (0.0015 mol) and
catalyst (5 mol %).
a
2
3
4a
b
Isolated Yields.
Scheme 1. Standard model reaction.

P. V. Shinde et al. / Tetrahedron Letters 53 (2012) 1523–1527
1525
Bi(OTf)3
O
OH
CH2
Bi(OTf)3
O
Ph
CH3
Ph
Ph
CH3
(A)
Bi(OTf)3
O
O
Bi(OTf)3
Ar
H
Ar
H
(B)
-
H O
2
Ph
OH
CH2
O
Ar
O
Bi(OTf)3
O
Ar
NH
Ph
O
NH OAc
4
Ph
Ph
Ph
-H O
Ph
Ar
2
Cyclization
-H O
2
(D)
(C)
Ar
Ar
N
[O]
Ph
N
Ph
Ph
Ph
(E)
(F)
Figure 1. A plausible mechanism involved in the synthesis of 2,4,6-triaryl pyridines.
In the next attempts, several solvents like water, ethanol, tolu-
ene, and THF were examined to achieve the targeted compounds.
In all these solvents except ethanol no reaction was observed at
their respective reflux temperatures. As noted, reaction carried
out in ethanol as a solvent delivered the product after 3 h, but
spectral analysis study of thus formed product revealed the unex-
pected results. It was observed that the obtained product was not
the desired one, but unexpected acetal of tetrazolo[1,5-a]quino-
line-4-carbaldehyde was formed. This observation reflected that
tetrazolo[1,5-a]quinoline-4-carbaldehyde has greater affinity
toward ethanol as compared to acetophenone.
Table 2
Synthesis of 2,4,6-triaryl pyridines 4(a–j)
O
Ar
H
Ar
Bi(OTf) (5 mol%)
3
1
(a-j)
O
o
Neat, 120 C, 2h
N
NH OAc
2
4
2
3
4(a-j)
Entry
Compd
Ar
Yielda (%)
MP (°C)
Bi(OTf)
in the presence of Bi(OTf)
competes with the methylene carbon
3
is a hard Lewis acid and is oxophilic. So, quite possibly
, the oxygen atom of EtOH solvent
- to carbonyl group of ace-
1
2
3
4
5
6
7
8
9
4a
4b
4c
4d
4e
4f
4g
4h
4i
Ph
89
87
91
89
92
91
93
89
86
88
133–135
124–126
98–99
194–196
195–197
113–114
127–128
102–104
161–163
170–171
3
4-Me-Ph
4-OMe-Ph
4-OH-Ph
a
tophenone for the nucleophilic attack on carbonyl carbon of the
aldehyde and dominate over it, thereby eliminating the possibility
of reaction between aldehyde and acetophenone.
2
4-NO -Ph
2-Cl-Ph
4-Cl-Ph
4-Br-Ph
2-Thienyl
2-Furyl
It was thought that, this putative competition would be largely
removed by omitting the use of ethanol. But, reaction under neat
condition did not led to the formation of the desired product. Inci-
dentally, it should be noted that use of various acid catalysts such
as sulphanilic acid, sulfamic acid, p-TSA and boric acid under neat
conditions as well as in the presence of ethanol as a solvent failed
to deliver the desired product (i.e., triaryl pyridine), but, sulphani-
lic acid and p-TSA furnished the corresponding acetals in moderate
yields. Finally, it was concluded that formation of the desired tri-
1
0
4j
a
Isolated Yields.
Success of bismuth triflate as an air/moisture tolerant and
remarkably efficient catalyst for the synthesis of triaryl pyridines
led us to investigate its efficacy for the formation of tetrazolo
3
aryl pyridine derivative was quite difficult, but, Bi(OTf) efficiently
[
[
1,5-a]quinoline based triaryl pyridines from a variety of tetrazolo
1,5-a]quinoline-4-carbaldehydes, acetophenone, and ammonium
forms the acetals of tetrazolo[1,5-a]quinoline-4-carbaldehyde.
Therefore, we extended our study for the acetalization of series
of tetrazolo[1,5-a]quinoline-4-carbaldehydes.
acetate. Initially, reaction between tetrazolo[1,5-a]quinoline-4-
carbaldehyde 5a, acetophenone 2, and ammonium acetate 3 was
performed in the presence of Bi(OTf) with the hope to obtain tet-
3
razolo[1,5-a]quinoline based 2,4,6-triarylpyridines (Scheme 2).
But, unfortunately no reaction was observed even after longer
reaction time (4 h).
In this endevor, efforts were directed to determine the appro-
priate concentration of the catalyst (Bi(OTf)
reaction. Hence, model reaction was performed at different
concentrations of (Bi(OTf) ) such as 1, 2, 3, 5, and 10 mol %. Forma-
tion of the product was formed in 59%, 93%, 94%, 93%, and 91%
3
) for the acetalization
3

1
526
P. V. Shinde et al. / Tetrahedron Letters 53 (2012) 1523–1527
N
N
N
N
CHO
N
N
N
N
N
5
a
Bi(OTf) (5 mol%)
3
Expected Product
O
Ethanol , Reflux
(Not Formed)
NH OAc
2
4
O
O
2
3
N
N
N
N
Unexpected Product
(
Formed)
6
a
Scheme 2. Unexpected formation of 4-(diethoxymethyl)-tetrazolo[1,5-a]quinoline.
yield, respectively. This indicates that 2 mol % of Bi(OTf)
cient to carry out the reaction effectively.
3
is suffi-
3
The taming effect of ethanol and Bi(OTf) on the reaction was
confirmed by performing the acetalization reactions of various
substituted tetrazolo[1,5-a]quinoline-4-carbaldehydes. In all the
cases, similar results were observed for different substituents like
Me, OMe, Et, and OEt affording the corresponding acetal in good
Results of our earlier work on the synthesis of triaryl pyridines
4
0
involving simple aromatic aldehydes and literature report
involving the use of Bi(OTf) reveals that there is a need of reagent
3
trialkyl orthoformate for acetalization of aldehydes and ketones. In
the absence of trialkyl orthoformate, acetalization of aldehydes,
and ketones do not take place. To confirm this, reaction of aceto-
to excellent yields. Complete results are summarized in Table 3.
1
Formation of the product was confirmed with the help of
H
1
3
42
NMR, C NMR, and mass spectroscopic data.
phenone with ethanol in the presence of Bi(OTf)
performed (Scheme 3), but no reaction was observed even after
h. This study revealed that, selective acetalization of tetrazol-
o[1,5-a]quinoline-4-carbaldehyde takes place even in the presence
of acetophenone.
3
was also
In summary, the procedure described here provides the oppor-
tunity to perform the selective acetal protection reaction of various
substituted tetrazolo[1,5-a]quinoline-4-carbaldehydes in the pres-
ence of other carbonyl compounds. This protocol may be useful
while carrying out diverse organic transformations on tetrazol-
o[1,5-a]quinoline-4-carbaldehydes.
4
Acknowledgments
Bi(OTf)3 (5 mol%)
O
O
O
Authors are thankful to the Head, Department of Chemistry, Dr.
Babasaheb Ambedkar Marathwada University, Aurangabad, for
providing the laboratory facilities. PVS acknowledge financial
support from Dr. Babasaheb Ambedkar Marathwada University,
Aurangabad in the form of Golden Jubilee Junior Research
Fellowship.
Ethanol
, Reflux
Scheme 3. Reaction between acetophenone and ethanol.
Table 3
References and notes
Acetalization of a series of tetrazolo[1,5-a]quinoline-4-carbaldehydes (6a–h)
1.
(a) Postel, M.; Dunach, E. Coord. Chem. 1996, 155, 127; (b) Hisashi, Y. Lewis Acids
in Organic Synthesis In Vols. 1 and 2; Wiley-VCH, 2000; (c) Suzuki, H.; Matano, Y.
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J. Synlett 2002, 181; (e) Leonard, N. M.; Wieland, L. C.; Mohan, R. S. Tetrahedron
O
Bi(OTf) (2 mol%)
R1
R2
CHO
N
3
R1
R2
O
CH CH OH
3
2
2002, 58, 8373; (f) Iloughmane, G.; Le Roux, H. C. Eur. J. Org. Chem. 2004, 12,
N
Reflux, 3h
N
N
N
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Chem. 2004, 39, 433.
5
(a-h)
6(a-h)
Yielda (%)
Entry
Compd
R
1
R
2
R
3
MP (°C)
1
2
3
4
5
6
7
8
6a
6b
6c
6d
6e
6f
H
H
H
H
H
OMe
H
H
H
Me
H
OMe
H
H
Me
H
OMe
H
H
93
91
89
83
81
78
89
81
95–97
117–119
110–111
212–214(d)
203–205(d)
230–232(d)
148–150
97–98
4
.
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Dunphy, E. L.; Housecroft, C. E.; Kylberg, W.; Neuberger, M.; Schaffner, S.;
6g
6h
H
H
Et
H
OEt
a
Isolated yields; d = decompose.

P. V. Shinde et al. / Tetrahedron Letters 53 (2012) 1523–1527
1527
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3
12, 1782.
41. General experimental procedure for the synthesis of compounds 4(a–j): A
mixture of aldehyde 1 (0.001 mol), acetophenone 2 (0.002 mol), ammonium
acetate 3 (0.0015 mol) and bismuth triflate (5 mol %) was heated at 120 (C for
2 h. Reaction progress was monitored by TLC (ethyl acetate/n-hexane, 1:9).
After 2 h, reaction mass was allowed to cool down to room temperature. To the
solid reaction mass thus obtained, was added aq. ethanol (water/ethanol, 7:3)
(10 mL), reaction mixture was shaken well and then product was collected by
simple filtration. This crude product 4 was purified by crystallization using aq.
ethanol (water/ethanol, 3:7).
5
.
.
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Schubert, U. S. Angew. Chem. Int. Ed. 2002, 41, 3825; (c) Lohmeijer, B. G. G.;
Schubert, U. S. J. Polym. Sci. Part A: Poly. Chem. 2003, 41, 1413; (d) Andres, P. R.;
Schubert, U. S. Adv. Mater. 2004, 1043, 16.
(a) Lowe, G.; Droz, A. S.; Vilaivan, T.; Weaver, G. W.; Tweedale, L.; Pratt, J. M.;
Rock, P.; Yardley, V.; Croft, S. L. J. Med. Chem. 1999, 42, 999; (b) Bonse, S.;
Richards, J. M.; Ross, S. A.; Lowe, G.; Krauth-Siegel, R. L. J. Med. Chem. 2000, 43,
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4
812; (c) Zhao, L.-X.; Kim, T. S.; Ahn, S.-H.; Kim, T.-H.; Kim, E.; Cho, W.-J.; Choi,
H.; Lee, C.-S.; Kim, J.-A.; Jeong, T. C.; Chang, C.; Lee, E.-S. Bioorg. Med. Chem. Lett.
001, 11, 2659; (d) Zhao, L.-X.; Moon, Y.-S.; Basnet, A.; Kim, E.; Jahng, Y.; Park, J.
42. General experimental procedure for the synthesis of compounds 6(a–h): To the
solution of tetrazolo[1,5-a]quinoline-4-carbaldehyde 5 (0.001 mol) in ethanol
(5 mL), bismuth triflate (2 mol %) was added and this reaction mass was
subjected to reflux condition for 3 h. Progress of the reaction was monitored by
TLC (ethyl acetate/n-hexane, 3:7). After 3 h, reaction mass was allowed to cool
at room temperature and excess of ethanol was then removed on rotary
evaporator to afford the crude product. Thus obtained solid product was
purified by crystallization with 10% aq. ethanol to afford the pure product 6.
Experimental
2
G.; Jeong, T. C.; Cho, W.-J.; Choi, S.-U.; Lee, C. O.; Lee, S.-Y.; Lee, C.-S.; Lee, E.-S.
Bioorg. Med. Chem. Lett. 2004, 14, 1333.
(a) Han, H.; Hurley, L. H. Trends Pharmacol. Sci. 2000, 21, 136; (b) Borman, S.
Chem. Eng. News 2002, 80, 9.
(a) Li, J. L.; Harrison, R. J.; Reszka, A. P.; Brosh, R. M.; Bohr, V. A.; Neidle, S.;
Hickson, I. D. Biochemistry 2001, 40, 15194; (b) Siddiqui-Jain, A.; Grand, C. L.;
Bearss, D. J.; Hurley, L. H. Proc. Nat. Acad. Sci. 2002, 99, 11593; (c) Kelland, L. R.
Eur. J. Cancer 2005, 41, 971; (d) Chang, C. C.; Chu, J. F.; Kaol, F. J.; Chiu, Y. C.; Lou,
P. J.; Chen, H. C.; Chang, T. C. Anal. Chem. 2006, 78, 2810; (e) Dexheimer, T. S.;
Sun, D.; Hurley, L. H. J. Am. Chem. Soc. 2006, 128, 5404.
7
.
.
8
All chemicals were purchased and used without any further purification. 1H
NMR and 13C NMR spectra were recorded on Varian AS 400 MHz spectrometer
6 3
and NMR spectrometer AC 200 in either DMSO-d or CDCl . Chemical shifts (d)
9
.
Krohnke, F. Synthesis 1976, 1.
are in (parts per million) ppm relative to TMS. Mass spectra were recorded on a
macro mass spectrometer (waters) by electro-spray (ES) method.
1
0. (a) Potts, K. T.; Cipullo, M. J.; Ralli, P.; Theodoridis, G. J. J. Org. Chem. 1982, 47,
027; (b) Cave, G. W. V.; Raston, C. L. J. Chem. Soc. Perkin Trans 1 2001, 3258; (c)
Rothenberg, G.; Downie, A. P.; Raston, C. L.; Scott, J. L. J. Am. Chem. Soc. 2001,
23, 8701.
3
Spectroscopic data for representative compound 2,4,6-triphenylpyridine (4a): 1
H
NMR (400 MHz, DMSO-d
2H), 8.31 (d, 4H, J = 7.6 Hz); C NMR (50 MHz, CDCl
6
): d 7.46–7.58 (m, 9H), 8.03 (d, 2H, J = 7.2 Hz), 8.18 (s,
13
1
3
): d 117.1, 127.1, 127.2,
1
1. (a) Jones, G. In Comprehensive Heterocyclic Chemistry II; Katritzky, A. R., Rees, C.
W., Scriven, E. V. F., Eds.; Pergamon Press: London, 1996; Vol. 5, p 168. and
references cited therein; (b) Katritzky, A. R.; Abdel-Fattah, A. A. A.;
Tymoshenko, D. O.; Essawy, S. A. Synthesis 1999, 2114.
128.7, 128.9, 129.0, 129.1, 139.1, 139.6, 150.2, 157.5; Mass (ES-MS): m/z 308.1
(M ).
+
Spectroscopic data for compounds 6(a–h). (Diethoxymethyl)tetrazolo[1,5-
a]quinoline (6a): 1H NMR (400 MHz, DMSO-d
6
): d 1.19 (t, 6H, J = 6.8 Hz), 3.70
1
1
2. Krohnke, F.; Zecher, W. Angew. Chem. Int. Ed. 1962, 1, 626.
3. (a) Potts, K. T.; Cipullo, M. J.; Ralli, P.; Theodoridis, G. J. Am. Chem. Soc. 1981,
(q, 4H, J = 6.8 Hz), 6.04 (s, 1H), 7.81 (t, 1H, J = 7.6 Hz), 7.97 (t, 1H, J = 7.6 Hz),
8.29 (s, 1H), 8.32 (d, 1H, J = 7.6 Hz), 8.60 (d, 1H, J = 8.4 Hz); 13C NMR (100 MHz,
1
03, 3584; (b) Potts, K. T.; Cipullo, M. J.; Ralli, P.; Theodoridis, G. J. Am. Chem.
DMSO-d ): d 15.8, 62.8, 97.8, 116.8, 124.1, 124.6, 128.9, 130.6, 130.7, 132.2,
6
+
Soc. 1981, 103, 3585.
146.9; Mass (ES-MS) m/z 273.2 (M ).
1
1
1
1
1
4. Kobayashi, T.; Kakiuchi, H.; Kato, H. Bull. Chem. Soc. Jpn. 1991, 64, 392.
5. Palacios, F.; de Retana, A. M. O.; Oyarzabal, J. Tetrahedron Lett. 1996, 37, 4577.
6. Cave, G. W. V.; Raston, C. L. Chem. Commun. 2000, 2199.
7. Tu, S.; Li, T.; Shi, F.; Fang, F.; Zhu, S.; Wei, X.; Zong, Z. Chem. Lett. 2005, 34, 732.
8. (a) Smith, C. B.; Raston, C. L.; Sobolev, A. N. Green Chem. 2005, 7, 650; (b) Smith,
N. M.; Raston, C. L.; Smith, C. B.; Sobolev, A. N. Green Chem. 2007, 9, 1185.
9. Winter, A.; van den Berg, A. M. J.; Hoogenboom, R.; Kickelbick, G.; Schubert, U.
S. Synthesis 2006, 2873.
0. Adib, M.; Tahermansouri, H.; Koloogani, S. A.; Mohammadi, B.; Bijanzadeh, H.
R. Tetrahedron Lett. 2006, 47, 5957.
1. Nagarapu, L.; Aneesa; Peddiraju, R.; Apuri, S. Catal. Commun. 1973, 2007, 8.
2. Heravi, M. M.; Bakhtiari, K.; Daroogheha, Z.; Bamoha, F. F. Catal. Commun. 1991,
4-(Diethoxymethyl)-9-methyltetrazolo[1,5-a]quinoline (6b): 1H NMR (200 MHz,
DMSO-d
1H), 7.78 (dd, 1H, J = 8.4 Hz), 7.91 (d, 1H, J = 8.4 Hz), 8.22 (s, 1H), 8.31 (d, 1H,
J = 8.4 Hz); 13C NMR (50 MHz, DMSO-d
): d 15.5, 18.1, 61.9, 99.0, 115.5, 124.8,
6
): d 1.18 (t, 6H, J = 7.2 Hz), 2.64 (s, 3H,), 3.71 (q, 4H, J = 7.2 Hz), 6.02 (s,
6
+
125.3, 128.5, 131.2, 131.7, 134.0, 147.5; Mass (ES-MS) m/z 287.3 (M ).
4-(Diethoxymethyl)-8-methyltetrazolo[1,5-a]quinoline (6c): 1H NMR (200 MHz,
1
2
DMSO-d
1H), 7.74 (d, 1H, J = 8.4 Hz), 8.17 (d, 1H, J = 8.4 Hz) 8.27 (s, 1H), 8.53 (s, 1H);
NMR (50 MHz, DMSO-d ): d 15.5, 21.7, 62.0, 99.8, 116.0, 125.2, 125.9, 128.9,
6
): d 1.18 (t, 6H, J = 7.2 Hz), 2.64 (s, 3H,), 3.70 (q, 4H, J = 7.2 Hz), 6.01 (s,
13
C
6
+
131.2, 131.8, 134.4, 147.1; Mass (ES-MS) m/z 287.3 (M ).
2
2
4-(Diethoxymethyl)-9-methoxytetrazolo[1,5-a]quinoline
(6d):
1H
NMR
6 3
(200 MHz, DMSO-d + CDCl ): d 1.21 (t, 6H, J = 7.6 Hz), 3.75 (q, 4H, J = 7.6 Hz),
2
007, 8.
3.88 (s, 3H,), 6.05 (s, 1H), 7.83 (dd, 1H, J = 7.6 Hz and 8.4 Hz), 7.91 (d, 1H,
2
3. Maleki, B.; Azarifar, D.; Veisi, H.; Hojati, S. F.; Salehabadi, H.; Yami, R. N. Chin.
Chem. Lett. 2010, 21, 1346.
4. Davoodnia, A.; Bakavoli, M.; Moloudi, R.; Tavakoli-Hoseini, N.; Khashi, M.
Monatsh Chem. 2010, 141, 867.
J = 7.6 Hz), 8.27 (s, 1H), 8.39 (d, 1H, J = 8.4 Hz); 13C NMR (50 MHz, DMSO-
6 3
d + CDCl ): d 16.1, 59.6, 63.2, 101.0, 112.3, 116.6, 126.0, 128.7, 131.1, 133.1,
+
2
144.7, 152.5; Mass (ES-MS) m/z 303.3 (M ).
4-(Diethoxymethyl)-8-methoxytetrazolo[1,5-a]quinoline (6e): 1H NMR (200 MHz,
2
2
2
2
5. Godefroi, E. F.; Heeres, J. US Patent 3 575 999, 1971.
6. Bruns, K.; Conrad, J.; Steigel, A. Tetrahedron 1979, 35, 2523.
7. Kasper, E. Plaste Kautschuk 1966, 13, 45.
8. (a) Kocienski, P. J. Protecting Groups 1994, 156. Thieme; (b) Cooks, R. G.; Chen,
H.; Eberlin, M. N.; Zheng, X.; Tao, W. A. Chem. Rev. 2006, 106, 188; (c) Greene, T.
W.; Wuts, P. G. M. Green’s Protective Groups in Organic Synthesis, 4th ed.; Wiley:
New Jersey, 2007.
9. (a) Clerici, A.; Pastori, N.; Porta, O. Tetrahedron Lett. 2001, 57, 217; (b) Lee, S. H.;
Lee, J. H.; Yoon, C. M. Tetrahedron Lett. 2002, 43, 2699; (c) Mondal, E.; Sahu, P.
R.; Bose, G.; Khan, A. T. Tetrahedron Lett. 2002, 43, 2843.
0. Torok, D. S.; Figueroa, J. J. J. Org. Chem. 1993, 58, 7274.
1. Adams, E. W.; Adeins, H. J. Am. Chem. Soc. 1925, 47, 1358.
2. Strukul, G. Top. Catal. 2002, 19, 33.
DMSO-d
6.01 (s, 1H), 7.84 (d, 1H, J = 8.0 Hz), 7.97 (d, 1H, J = 8.0 Hz) 8.37 (s, 1H), 8.62 (s,
1H); 13C NMR (50 MHz, DMSO-d
+ CDCl ): d 16.0, 59.6, 63.0, 100.8, 111.9,
6 3
+ CDCl ): d 1.19 (t, 6H, J = 7.2 Hz), 3.71 (q, 4H, J = 7.2 Hz), 3.84 (s, 3H,),
6
3
+
117.1, 125.9, 129.2, 130.8, 132.3, 147.7, 151.2; Mass (ES-MS) m/z 303.4 (M ).
4-(Diethoxymethyl)-7-methoxytetrazolo[1,5-a]quinoline (6f): 1H NMR (200 MHz,
DMSO-d
6.11 (s, 1H), 7.57 (s, 1H), 7.89 (d, 1H, J = 8.4 Hz) 8.32 (s, 1H), 8.61 (d, 1H,
J = 8.4 Hz); 13C NMR (50 MHz, DMSO-d
+CDCl3): d 15.9, 59.0, 62.6, 100.8,
6 3
+ CDCl ): d 1.21 (t, 6H, J = 7.6 Hz), 3.69 (q, 4H, J = 7.6 Hz), 3.88 (s, 3H,),
2
6
109.8, 117.5, 126.0, 129.7, 131.7, 133.4, 148.1, 151.5; Mass (ES-MS) m/z 303.3
+
(M ).
3
3
3
3
3
4-(Diethoxymethyl)-9-ethyltetrazolo[1,5-a]quinoline (6g): 1
H
NMR (200 MHz,
DMSO-d
6
): d 1.15 (t, 6H, J = 7.6 Hz), 1.56 (t, 3H, J = 7.2 Hz), 3.56 (q, 4H,
J = 7.6 Hz), 4.01 (q, 2H, J = 7.2 Hz), 5.98 (s, 1H), 7.67 (dd, 1H, J = 6.8 Hz and
3. MacKinzie, C. A.; Stocker, J. H. J. Org. Chem. 1955, 20, 1695.
4. Cataldo, M.; Neiddu, F.; Gavagnin, R.; Pinna, F.; Strukul, G. J. Mol. Catal. A: Chem.
7.6 Hz), 7.85 (d, 1H, J = 7.6 Hz), 8.18 (s, 1H), 8.41 (d, 1H, J = 6.8 Hz); 13C NMR
6
(50 MHz, DMSO-d ): d 14.9, 15.3, 26.4, 62.0, 98.7, 116.1, 125.9, 126.6, 129.0,
+
1
999, 142, 305.
131.2, 131.9, 133.7, 146.1; Mass (ES-MS) m/z 301.2 (M ).
3
5. (a) Luche, J. L.; Gemal, A. L. Chem. Commun. 1978, 976; (b) Ott, J.; Ramos Tombo,
G. M.; Schmid, B.; Venanzi, L. M.; Wang, G.; Ward, T. R. Tetrahedron Lett. 1989,
4-(Diethoxymethyl)-7-ethoxytetrazolo[1,5-a]quinoline (6h): 1H NMR (200 MHz,
DMSO-d
J = 7.2 Hz), 4.08 (q, 2H, J = 7.6 Hz), 6.08 (s, 1H), 7.55 (s, 1H), 7.91 (d, 1H,
J = 8.0 Hz) 8.28 (s, 1H), 8.56 (d, 1H, J = 8.0 Hz); 13C NMR (50 MHz, DMSO-d
): d
6
): d 1.17 (t, 6H, J = 7.2 Hz), 1.51 (t, 3H, J = 7.6 Hz), 3.61 (q, 4H,
30, 6151.
3
6. Lillie, B. M.; Avery, M. A. Tetrahedron Lett. 1994, 35, 969.
6
3
7. (a) Lu, T.; Yang, J.; Sheu, L. J. Org. Chem. 1995, 60, 2931; (b) Srivastava, N.;
Dasgupta, S. K.; Banik, B. K. Tetrahedron Lett. 2003, 44, 1191.
15.1, 15.7, 60.6, 63.8, 101.1, 110.7, 118.2, 126.9, 130.1, 132.7, 134.0, 149.0,
152.1; Mass (ES-MS) m/z 317.4 (M ).
+
3
8. Kumar, R.; Chakraborti, A. K. Tetrahedron Lett. 2005, 46, 8319.