2,4,6-Trichloro-1,3,5-triazine and N,N′-dimethylformamide as an effective Vilsmeier-Haack reagent for the synthesis of 2-chloro-3-formyl quinolines from acetanilides

Article abstract of DOI:10.1016/j.tetlet.2015.07.056

TCTA-DMF (2,4,6-trichloro-1,3,5-triazine/N,N′-dimethylformamide) adduct has been used as a Vilsmeier-Haack type reagent for effective synthesis of 2-chloro-3-formyl quinolines from acetanilides under conventional and ultrasonically assisted conditions. The reaction times under sonication are quite significantly shorter than conventional methods even though the yields obtained under sonication are comparable with those obtained under reflux conditions.

Full text of DOI:10.1016/j.tetlet.2015.07.056

Accepted Manuscript
2, 4, 6-trichloro-1, 3, 5-triazine and N, N’-dimethylformamide as an effective
Vilsmeier - Haack reagent for the synthesis of 2-chloro-3-formyl quinolines
from acetanilides
P. Venkanna, K.C. Rajanna, M. Satish Kumar, Mohd. Bismillah Ansari, M.
Moazzam Ali
PII:
S0040-4039(15)01209-5
DOI:
http://dx.doi.org/10.1016/j.tetlet.2015.07.056
TETL 46545
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
13 April 2015
16 July 2015
17 July 2015
Please cite this article as: Venkanna, P., Rajanna, K.C., Satish Kumar, M., Bismillah Ansari, Mohd., Moazzam Ali,
M., 2, 4, 6-trichloro-1, 3, 5-triazine and N, N’-dimethylformamide as an effective Vilsmeier - Haack reagent for the
synthesis of 2-chloro-3-formyl quinolines from acetanilides, Tetrahedron Letters (2015), doi: http://dx.doi.org/
1
0.1016/j.tetlet.2015.07.056
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Tetrahedron Letters
2, 4, 6-trichloro-1, 3, 5-triazine and N, N’-dimethylformamide as an effective
Vilsmeier - Haack reagent for the synthesis of 2-chloro-3-formyl quinolines from
acetanilides
c
a
b
b
d
P. Venkanna , K. C. Rajanna *, M. Satish Kumar , Mohd. Bismillah Ansari , M. Moazzam Ali
b
Department of Chemistry, Osmania University, Hyderabad-500 007, T. S. India
a
Department of Chemistry, Jawaharlal Nehru Technological University, Hyderabad- T. S. India
C
Department of Chemistry, Aizza College of Engineering & Technology, Hyderabad- T. S. India
SABIC Technology & Innovation Centre, Riyadh -11551, Saudi Arabia
d
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
TCTA-DMF (2, 4, 6-trichloro-1, 3, 5-triazine / N, N’-dimethylformamide) adduct has been used
as a Vilsmeier - Haack type reagent for effective synthesis of 2-chloro-3-formyl quinolines from
acetanilides under conventional and ultrasonically assisted conditions. The reaction times under
sonication are quite significantly shorter than conventional method even though the yields
obtained under sonication are comparable with those obtained under reflux conditions.
Available online
2
009 Elsevier Ltd. All rights reserved.
Keywords:
2
, 4, 6-trichloro-1, 3, 5-triazine / N, N’-
dimethylformamide; Vilsmeier – Haack type reagent;
acetanilides; 2-chloro-3-formyl quinolines;
sonication; rate acceleration
Introduction
Symmetric 1, 3, 5-triazine derivatives have been known for a long
period of time for their widespread pharmaceutical, textile,
plastic, and industrial applications. Besides they are also used as
pesticides, dyestuffs, optical bleaches, explosives, and surface
silsesquioxane
(POSS)/polyimide
(PI)
nanocomposites
comprising quinoline backbone. Prepared polymer composites
exhibited thermal and mechanical properties. Few of these
composites exhibited good antimicrobial activity. Shelar et.al
developed a novel route for the synthesis of ortho amino formyl
quinoline (heterocyclic ortho amino aldehyde) which in turn was
utilized for the synthesis of series of benzonaphthyridines which
exhibited excellent fluorescent properties .Over the years, the
Vilsmeier-Haack (VH) reagent is used as an efficient, economical
and mild reagent for the formylation of aromatic and
heteroaromatic substrates. Basically, DMF and oxychloride under
1-6
active agents . Quinoline is one of the most important
heterocyclic compounds, which is used as a feedstock for the
preparation of hydroxy quinoline sulfate, niacin; for manufacture
of dyes and as a solvent for resins and terpenes. Hydroxy
quinolines derived from quinoline are used as versatile chelating
agents and precursors; its 2- and 4-methyl derivatives are
precursors to cyanine dyes, while 8- hydroxy derivative is a
32
7
33
precursor to pesticides . Besides, quinoline derivatives are some
chilled conditions in situ forms a chloromethyleniminium salt,
of the oldest compounds that are used for the treatment of a
variety of diseases . Quite a good number of quinoline derivatives
which is used as a powerful synthetic tool to achieve several
aromatic and heterocyclic compounds including quinoline
8
3
4-40
are important constituents of pharmacologically active synthetic
compounds, which exhibited a broad spectrum of biological
derivatives . But the oxychlorides such as phosphoryl chloride,
thionyl chloride, or phosgene that are used in the preparation of
9
-14
41
activities
.
Interesting pharmacological properties such as
VH reagents are toxic in nature. Recently Dune-Ren Hour et al
antimicrobial, antimalarial, anti-inflammatory, antitumor, and
anti-parasitic activities have been associated with 2-
used trichlorotriazine (TCTA) or Cyanuric Chloride is used in
place of oxychloride for the preparation of VH type reagent
during the preparation of α,β-unsaturated enol aldehydes such as
3-Ethoxymethacrolein and 5-formyl-3,4-dihydro-2H-pyran from
enol ethers. Trichlorotriazine (TCTA) is also earlier used for the
synthesis of alcohols, diazo carbonyl, acyl azides, and
hydroxamic acids as well as acyl chlorides from carboxylic
15-23
chloroquinoline-3-carbaldehydes and their derivatives . Many
-chloro-3-formyl-quinolines, 3-formyl-2- mercaptoquinolines
2
and transition metal complexes derived from Schiff bases of these
compounds have been reported as potential antifungal and
biodynamic agents. Zn (II) complex Schiff bases of 3-formyl-2-
mercaptoquinolines has also been found to be a fluorescent
42
acids . In addition, it has been shown that TCTA could
24
42-45(a)
compound . Quinoline derivatives such as 2-Chloroquinoline-3-
carbaldehyde and their thioanalogues have become back bone for
efficiently promote several reaction protocols
such as
carboxylic acid activation, Swern oxidation, Friedel–Crafts
2
5-30
44
45
the synthesis of several bioactive agents
.
Govindaraj et al
acylation, Beckman rearrangement and Lossen rearrangement .
Encouraged by these features, we have embarked on exploring
prepared series of functional polyhedral oligomeric
a

2
(
TCTA/DMF) adduct for the cyclization of acetanilides under
NMR peak corresponding to aldehydic proton observed at
31
conventional and ultrasonically assisted conditions . Present
work is an effort in which TCTA-DMF (2, 4, 6-trichloro-1, 3, 5-
triazine / N, N’-dimethylformamide) adduct has been used as a
Vilsmeier - Haack type reagent for effective synthesis of 2-
chloro-3-formyl quinolines from acetanilides under conventional
and ultrasonically assisted conditions.
δ7.952 almost disappeared. Interestingly, two methyl singlets
(observed in DMF spectra) underwent dramatic shifts (δ2.88,
2.72). The signals around δ 2.5 (in both DMF and TCTA-DMF
the spectra Fig S4 and S5 of Supplementary data) could be
assigned to residual protons of deuterated DMSO. The broad
signal at 4.069 may come from water. These observations
together with IR spectral results envisage the formation of
4
6
Cl
[
TCTA-DMF] adduct and thereby chloro methyleniminum
O
Me
N
N
45(b)
species
.
N
CHO
Cl
N
Cl
Cl
Me
H
H
N
Cl
N
CH Cl
,
refleux
Cl
O
O
N
2
2
O
R
NHCOMe
N
N
N
N
N
N
N
R
H
N
Cl
Cl
Cl
Cl
Cl
N
Cl
Scheme 1: Synthesis of 2-chloro-3-formyl quinolines from
acetanilides using TCTA/DMF as Vilsmeier-Haack Reagent
H
N
Cl
47
The [TCTA/DMF] reactions with acetanilides underwent
smoothly at reflux temperatures. The reaction times for most of
the studied reactions are in the range of 3 to 18 hrs, depending on
the structure (Table 1). Mechanism of the reaction could be
explained through the formation of [TCTA-DMF] adduct
comprising “chloromethyleniminum” moiety. Formation of
Chloro methyleniminum cation intermediate can be supported on
the basis of spectroscopic results obtained under different
conditions. IR spectrum of DMF (neat), recorded in this study
Scheme-2: Formation of chloro methyleniminum cation
Chloromethyleniminum cation thus formed in turn reacted with
acetanilide to afforded chloro acetyl derivatives as shown in
Scheme -3. (Spectroscopic data of (isolated products) chloro
formyl quinolines are given in supplementary data).
H
N
Cl
Cl
O
O
O
H
N
N
N
N
N
H
N
N
N
-1
N
Cl
Cl
Cl
N
Cl
depicted different bands. The bands appeared in 450-1550 cm
Cl
Cl
N
Cl
−1
range are attributed to C-N, band at 1675 cm corresponds to
C=O stretching frequency, which is lower than an unsubstituted
C=O bond. The observed reduction in the bond order of the
carbonyl C=O bond followed by an increase in the carbon-
nitrogen bond order could be explained probably because of the
two possible resonance structures of amide. The bands observed
beyond 2500 (i.e., 2500- 4000) cm are attributed to methyl (C-
H) groups respectively. The infrared spectrum of TCTA (KBr
disc) indicated three important bands respectively at 536, 764,
Me
N
H
O
R
-1
NMe2 NMe2
OH
CHO
Cl
N
N
N
Cl
N
Cl
N
Cl
1
399 cm-1 are explained due to C-Cl, and the four band
R
-1
aggregations in the range 1679-1780 cm (1679, 1719,1752 and
-1
Scheme 3: Mechanism of 2-chloro-3-formyl quinoline
formation from acetanilide using TCTA/DMF as Vilsmeier-
Haack Reagent
1776 cm ) could be due to C=N stretching. These observations
are by and large in agreement with SDBS information for organic
compounds. However, the infrared spectrum recorded for the
mixture of TCTA/DMF exhibited three overlapping band
Data presented in table -1shows that some of the conventional
4
8
-1
reactions are too sluggish. However, under sonication “Reaction
Times” reduced amazingly from 3 to 18 hrs under conventional
methods to 35 to 90 minutes at room temperature. Observed
dramatic sonocatalysis could be attributed to cavitation
phenomenon as explained in earlier literature reports by Mason,
aggregations in the range 1718-1780 (1718, 1753 and 1779) cm ,
+
attributed to C=N stretching vibrations. This observation
probably strengthens the interaction of TCTA with DMF to result
in [TCTA-DMF] adduct, in the lines of Vilsmeier –Haack (DMF-
POCl ) adduct.
3
4
9, 50
Suslick and many other pioneers
Conclusions
.
H
N
Cl
O
In summary, in the present work we have developed TCTA-DMF
2, 4, 6-trichloro-1, 3, 5-triazine / N, N’-dimethylformamide)
N
N
(
Cl
N
Cl
adduct as an efficient and modified form VH reagent for effective
synthesis of 2-chloro-3-formyl quinolines from acetanilides.
TCTA (2, 4, 6-trichloro-1, 3, 5-triazine) used for the preparation
of VH reagent is eco-friendly, readily available and inexpensive
compound. The reactions afforded very good yields of under
stirred conditions at room temperature. Depending on the
structure of acetanilide, reaction times recorded under
conventional conditions reduced from (3 to 18) hours to (35 to
[
TCTA-DMF] Adduct
Proton NMR spectrum of DMF(in DMSO-d
6
) indicated three
peaks on δ –scale, one singlet at δ7.952, attributed to aldehydic
proton, and two singlets of 3 protons each at δ 2.891 and 2.731,
instead of one singlet of 6 protons. This observation could be
explained due to the partial double bond character of C-N, which
made the rotation about the C-N axis in DMF slow at room
temperature and also the two methyl groups inequivalent on the
NMR time scale. In the presence of TCTA, HNMR spectrum of
DMF underwent several changes and became more complex.
9
0) minutes under sonication. Even the most sluggish reaction (2-
nitroacetanilide) underwent rate acceleration from 18 to 1.5 hours
90 min). Product yields are also increased from 6 to 10% under
(

sonication as compared to conventional procedures. All
synthesized compounds were characterized by H NMR and mass
spectral studies.
Table 1: Synthesis of 2-chloro-3-formyl quinolines from acetanilides using TCTA/DMF as VH Reagent
Cl
O
Me
N
N
N
CHO
Cl
Cl
N
Cl
Me
H
CH2Cl2
NHCOMe
,
refleux
R
N
R
S.N.
Acetanilide
2-chloro-3-formyl quinolines
Conventional
Sonication
R.T
Yield
(%)
89
R.T
(min)
35
Yield
(%)
85
(hr)
1
2
3
4
5
6
7
8
9
4-Cl
acetanilide
4-NO
acetanilide
2-Cl
acetanilide
4-Me
acetanilide
2-ethyl
acetanilide
4-OMe
2, 6-dichloroquinoline
3-carbaldehyde
2-chloro-6-nitro quinoline-
3-carbaldehyde
2, 8- dichloro quinoline-3-
carbaldehyde
2-chloro-6-methyl quinoline-3-
carbaldehyde
2-chloro-8-ethyl quinoline-
3-carbaldehyde
2-chloro-6-methoxy quinoline-
3-carbaldehyde
2-chloro-8-nitro quinoline-
3-carbaldehyde
2-chloro-7-nitro quinoline-
3-carbaldehyde
3
2
5
7
85
92
87
85
88
82
87
86
40
50
75
90
80
95
45
85
87
90
85
87
85
90
90
89
10
13
9
acetanilide
2-NO
acetanilide
3-NO
2
18
5
2
acetanilide
4-Br
acetanilide
acetanilide
2-CH
acetanilide
2-chloro-6-bromo quinoline-
3-carbaldehyde
2-chloroquinoline-3-carbaldehyde
2-chloro-8-methyl quinoline-
3-carbaldehyde
9
1
1
0
1
11
11
88
85
90
85
90
90
3
VCH 2005.;
b) Jaromin,
(
A.; Kozubek, A.; Suchoszek-Lukaniuk,K.; Malicka-Blaszkiewicz, M.;
Peczynska-Czoch, W.; Kaczmarek,W. Drug Delivery. 2008, 15, 49.
Supplementary Material
9
. (a) Meth-Cohn, O.; Narine, B. Tetrahedron 1978, 19, 2045 (b) Meth-
All the chemicals were purchased from Aldrich or Arcos
Organics and used without further purification. Analytical TLC
was carried out using Merck aluminum-backed 0.2 mm silica gel
Cohn,O.; Tarnowski, B.; Hayear, R.; Keyzad, A.; Rhousati, S. J. Chem.
Soc., Perkin Trans.1981, 1, 2509.
10. S Levy; SJ Azoulay, Cardiovas. Electrophysiol. 1994, 5, 635-636
11. El-Subbagh HI.; Abu-Zaid SM.; Mahran MA.; Badria FA.; Alofaid
AM. J. Med. Chem.2000, 43:2915
60 F-254 plates. Column chromatography was conducted using
Merck silica gel 60 (230-400mesh). Ultrasonically assisted
reactions were performed in a Sonicator bath (KQ-250B, China).
A flat transducer with a frequency of 40 kHz and voltage of 220
V (with an output of 100 W electric power rating) was mounted
at the bottom of the Sonicator. The reaction vessel placed inside
the ultrasonic bath containing water. See also separate file for
further details.
1
1
2. Gupta R, Gupta AK, Paul S. Ind. J. Chem .2000, 39B:847
3. Selvi, S. T.; Nadaraj, V.; Mohan, S.; Sasi, R. Hema, M. Bioorg.
Med. Chem. 2006, 14, 3896
4. (a) Pokalwar, R. U.; Hangarge, R. V.; Maske, P.V.; Shingare, M. S.
1
Arkivoc 2006, (xi) 96 (b) Mehdi Ghandi.; Nahid Zarezadeh.
Tetrahedron. 2013, 69, 8668 (c) Zhang, Y.; Fang, Y.; Liang, H.; Wang,
H.;Hu, K.;Liu, X.;Yi, X.;Peng, Y. Bioorg. Med. Chem. Lett. 2013, 23,
1
1
07 and references cited therein
5.(a) Khidre, R. E.; Abu-Hashem, A. A.; El-Shazly, M. Eur. J.Med.
References and notes:
1
.Smolin,E.M.; Rapoport, L.s-Triazine and Derivatives in The Chemistry
Chem. 2011, 46, 5057. (b) Kidwai, M.; Saxena, S.; Khalilur Rahman
Khan, M.; Thukral, S. S. Eur. J. Med. Chem. 2005, 40, 816.
1
Dominguez,J. N.; Gamboa, N.; Rodrigues, J. R.; Angel, J. E. Lett. Drug
Design. Discov. 2007, 4, 49.
of Heterocyclic Compounds; Interscience: New York, NY, 1959.
2
3
. Mur, V. I. Russ. Chem. Rev. 1964, 33, 92–103 and references therein.
Quirke, M. E. 1,3,5-Triazines. Comprehensive Heterocyclic
6 Charris, J. E.; Lobo, G. M.; Camacho, J.; Ferrer,R.; Barazarte, A.;
.
Chemistry; Katritzky, A. R., Rees, C. W., Eds.; Pergamon: New York,
NY, 1984; Vol. 3, pp 457–530.
1
7. Kaur, K.; Jain, M.; Reddy, R. P.; Jain, R.
Eur. J. Med. Chem. 2010, 45, 3245
8. Khidre, R. E.; Abdel-Wahab, B. F.; Badria, F. A.-R.
Lett. Drug Design Discov. 2011, 8,640.
4
. Bartholomew, D.1,3,5-Triazines. In Comprehensive Heterocyclic
Chemistry II; Boulton, A. J., Ed.; Pergamon: Oxford, 1996; Vol. 6, pp
1
5
75.
5
. Comins, D. L.; O´ ’Connor. Advances in Heterocyclic Chemistry;
1
9. Chen, Y.-L.; Chen, I.-L.; Lu, C.-M.; Tzeng, C.-C.; Tsao, L.-T.;
Katritzky, A. R., Ed.; Academic: New York, NY, 1988; Vol. 44, pp 243.
Wang, J.-P. Bioorg. Med.Chem. 2004, 12, 387.
2
2
Arch. Pharm. Chem. Life Sci. 2012, 345, 123
2
6
1
7
8
. Giacomelli, G.; Porcheddu, A.; De Luca, L. Curr. Org. Chem.2004, 8,
497– 519.
. Elderfield, R. Heterocycl.Compd. 1952, 4, 1.
. (a) Gird Collin.; Hartmut Höke. Quinoline and Isoquinoline",
0 . Bawa, S.; Kumar, S. Indian J. Chem. 2009, 48B, 142.
1. Abdou, W. M.; Khidre, R.; E. Kamel, A. A.
2. (a) P. G. Goekjian, PCT Int. Appl. WO 2009090623, 2009; EP.; (b)
Ullmann's Encyclopedia of Industrial Chemistry, Weinheim: Wiley-
Patin,A.;Belmont,P .Synthesis. 2005, 14, 2400.

4
Tetrahedron Letters
2
3. Kouznetsov, V. V.; Méndez, L. Y. V.; Leal, S. M.; Cruz, U. M.;
43. Kangani, C. O.; Day, B. W. Org. Lett. 2008, 10, 2645–2648.
44. (a) De Luca, L.; Giacomelli, G.; Porcheddu, A. J. Org. Chem. 2002,
67, 272–6274; (b) Furuya, Y.; Ishihara, K.; Yamamoto, H. J. Am. Chem.
Soc. 2005,127, 11240–11241; (c) Betti, C.; Landini, D.; Maia, A.; Pasi,
M. Synlett. 2008, 908–910
Coronado, C. A.; mez, C. M. M.; Bohórquez, A. R. R. Rivero, P. E. Lett.
Drug Design Discov. 2007, 4, 293.
2
4 Phaniband , M. A.; Dhumwad, S. D.
J. Coord. Chem. 2009, 62, 2399.
5. Parab, R.H. ; Chudasama, C.J. ; Patel, H.N. ; Dixit, B.C. ; Desai, D.J.
Asian J. Chem. 2010, 22, 7641.
2
45.(a) Hamon, F..; Prié, G..; Lecornué, F..;Papot, S. .Tetrahedron. Lett.
2009,50,p 6800–6802(b) De Luca, L.; Giacomelli, G.; Porche, A. Org.
Lett.2002, 553-555
46. Preparation of TCTA-DMF reagent: All the chemicals were
purchased from Aldrich or Arcos Organics and used without further
purification. TCTA-DMF reagent was always prepared fresh prior to the
reaction. About 0.110mol of TCTA and 0.13mol of DMF were added
to 50ml CH Cl solvent in a round bottomed flask and stirred for about 3
2 2
h at room temperature white colored precipitate formed as [TCTA-DMF]
reagent.
2
4
2
2
6. Kalita, P. K.; Baruah, B.; Bhuyan, P. J. Tetrahedron. Lett. 2006,
7(44), 7779.
7. Mistry,B. M.; Jauhari, S. Med. Chem. Res.. 2013, 22(2), 647-658.
8. Herbert, M. R.; Siegel, D. L.; Staszewski, L.; Cayanan, C.;
Banerjee, U.; Dhamija, S.; Anderson, J.; Wang, A. Fan, Li.; Rix, P.
Shiau. A. K.; Rao, T. S.; Noble, S. A.; Heyman, R. A.; Bischoff, E.;
Guha, M.; Kabakibi, A.; Pinkerton, A .B. Bioorg. Med. Chem. Lett.,
;
2
010, 20, 5718.
2
9. (a) Mogilaiah, K.; Reddy, N.; Vasudeva, Rao,; Babu, R.; Indian J.
47. Cyclization reaction using TCTA-DMF reagent: To the prepared
TCTA-DMF reagent, 9.8 mmol of the Acetanilide was added and stirred
under reflux conditions. Progress of the reaction was checked by TLC
till the completion of the reaction. Analytical TLC was carried out using
Merck aluminum-backed 0.2 mm silica gel 60 F-254 plates. Column
chromatography was conducted using Merck silica gel 60 (230-
400mesh). After completion of the reaction, water was added to the
reaction mixture and stirred for few more minutes to extract inorganic
component in to water. Organic layer was separated and the crude
product thus obtained was further purified with column chromatography
Hetero. Chem.. 2002, 11(3), 253 (b) Srivastava, A.; Singh, M. K.;
Singh, R. M. Indian J. Chem. 2006, 45B, 292. (c) Biswajita Baruah,
Pulak J.; Bhuyan.Tetrahedron. 2009, 65(34), 7099-7104. (d) Devi, I.;
Baruah, B.; Bhuyan, P. J. Synlett. 2006, 2593. (e) Shashikumar, N. D.;
Krishnamurthy, G,; . Bhojyanaik, H. S.; Lokesh, M. R.; Jithendra
Kumara, K. S. J. Chem. Science. 2014, 126, 205.
3
0. Venkata Reddy, L.; Suresh Babu, N.; Beevi, S.S.; Mangamoori, L.
N.; Mukkanti, K.; Pal, S. J. Braz. Chem.Society. 2011, 22, 1742;
1. Govindaraj, B .; Sundararajan, P .; Sarojadevi, M. Polymer
International. 2012, 61, 1344
2. Shelar, D. P.; Birari, D. R.; Rote, R . V.; Patil, S . R.; Toche, R .
B.; Jachak, M . N. J. Phys. Org. Chem. 2011, 24, 203.
3. (a) Anton Vilsmeier, A.; Haack, A. Chem. Ber. 1927, 60, 119-122.;
b) Arnold, Z. Coll. Czech. Chem. Com. 1959, 24, 4048-4049.; (c)
3
(silica gel, ethyl
acetate/n-hexane).
3
48. Cyclization reaction using TCTA-DMF reagent under
Sonication: Methodology for the ultrasonically assisted cyclization of
substituted Acetanilide by TCTA-DMF under sonication is largely
similar to the classical method. After preparing the reaction mixture, as
3
(
47
Meth-Cohn, O.; Stanforth, S. P.Comp. Org. Syn. 1991, 2,777– 794.; (d)
Marson, C. M. Tetrahedron. 1992, 48, 3659–3726.
3
3
detailed above , the reaction flask is clamped in a Sonicator bath (KQ-
250B, China). The reaction vessel was placed inside the ultrasonic bath
containing water, which was supported at the corner of the ultrasonic
cleaning bath 2 cm above from the position of the transducer to get the
maximum ultrasound energy. Progress of the reaction was checked by
TLC till the completion of the reaction. After completion of the reaction
as ascertained by TLC, similar work up procedure mentioned in the
above section
4. Amaresh,R. R.; perumal, P.T. Synth. Commun.1997, 27,337
6. (a) Meth-Cohn, O.; Narine, A. B.Tetrahedron Lett. 1978, 23, 2045.;
(
b) Khan, A. K.; Shoeb, A. Indian J. Chem. Sect. B. 1985, 24, 62
3
2
7. (a) Sreenivasulu, M.; Rao, K. G. S. Indian J. Chem. Sect. B. 1989,
8, 584.; (b) Mahata, P. K.; Venkatesh, C.; Syam Kumar, U.K.; Ila,
H.; Junjappa, H. J. Org.Chem. 2003, 68, 3966. (c) Chupp, J. P.; Metz,
S. J. Heterocycl. Chem.1979, 16, 65 (d) Katrtizky, A.R.; Arend, M. J.
Org. Chem. 1998, 63, 9989
49. (a) Mason. T.J.; Lorimer, J.P. "Sonochemistry, Theory, Applications
and Uses of Ultrasound in Chemistry", John Wiley and Sons, New York,
1
988; (b) Suslick, K.S. Science. 1990,249, 1439. (c) Mason, T.J. Chem.
3
8.(a) Moazzam Ali, M. ; Tasneem.; Rajanna, K. C.; Saiprakash, P. K.
Soc. Rev. 1997,26, 443; (d) Weissler, A.; Coofer, H.W. ; Snyder, S. J.
Am. Chem. Soc.1950, 72, 1976 (e) V. Singh, K.P.; Kaur, A.; Khurana
and G.L. Kad, Resonance. 1998, 56(f) Mason, T.J. "Chemistry with
Ultrasound", Elsevier Science Publishers Ltd., England 1990; (g)
Suslick, K.S. "Ultrasound, its chemical, Physical and biological effects",
VCH Publishers, Inc., 1988; (h) Margulis,M.A. "Advances in
Sonochemistry", ed. by Mason,T.J. Greenweich Connection. JA.,
London, 1, (1990), 49; (i) Einhorn, C.; Einhorn,J.; Luche, J.L. Synthesis.
Synlett. 2001, 2, 251; (b) Moazzam Ali, M.; Sana, S.; Tasneem.;
Rajanna, K .C.; Saiprakash, P. K. Synth. Com.. 2002, 32, 1351.
3
4
9. (a) Falorni, M.; Porcheddu, A.; Tadei, M. Tetrahedron Lett. 1999,40,
395–4396.; (b) Forbes, D. C.; Barrett, E. J.; Lewis, D. L.; Smith, M.
C.Tetrahedron Lett. 2000, 41,943–9947.; (c) Bandgar, B. P.; Pandit, S.
S.Tetrahedron Lett. 2002, 43, 3413–3414.; (d) Giacomelli, G.;
Porcheddu,A.; Salaris, M. Org. Lett. 2003, 5, 2715–2717.
0. Ranise, A.; Cesarini, S.; Spallarossa, A.; Sancassan, F.; Bondavalli,
F.; Bruno, O.; Schenone, S.; Menozzi, G.; Fossa, P.; Mosti, L. Synthesis
1
989, 787 (j) Ley, S.V.; Low, C.M.R. "Ultrasound in Synthesis",
4
Springer, Berlin, 1989
5
1
0.(a) Srivastava, A.; Singh, R. M. Indian J. Chem. 2055,44B, p 1868-
875 (b) Blasko, G.; Dancso, A.. Synth. Com.2006, 36, p 3581–3589
2
4
007, 2495-2502
1. Hou,D.R.; Sun,C.S.; Sie,W.S.;Jian, J.Y.; Hsu,Y. J. Chinese Chem.
Soc. 2004, 51, 671-674
4
4
2.(a) Luo, G.; Xu, L.; Poindexter, G. S. Tetrahedron Lett. 2002,
3,8909–8912.; (b) Venkataraman, K.; Wagle, D. R. Tetrahedron.
Lett. 1979, 20, 3037–3040.; (c) De Luca, L.; Giacomelli, G.; Porcheddu,
A. J. Org. Chem. 2001, 66, 7907–7909.

Graphical Abstract
, 4, 6-trichloro-1, 3, 5-triazine and
Leave this area blank for abstract info.
2
N, N’-dimethylformamide as an effective
Vilsmeier - Haack reagent for the synthesis of
2-chloro-3-formyl quinolines from acetanilides
*
P. Venkanna, K. C. Rajanna ,M. Satish Kumar, Mohd. Bismillah Ansari, M. Moazzam Ali
Cl
O
Me
N
N
N
CHO
Cl
N
Cl
Cl
Me
H
CH Cl
refleux
2
2
,
R
NHCOMe
N
R