Chapter-1 Recent synthetic developments of Povarov...
Transcript of Chapter-1 Recent synthetic developments of Povarov...
Chapter-1
Recent synthetic developments of Povarov
Reaction and 2,3-dihydroquinazolinone
derivatives: A short review
Chapter-1
1
1.1 Introduction
Heterocyclic chemistry is a very important branch of organic chemistry accounting
for about one-third of contemporary publications. Indeed, two thirds of organic
compounds are heterocyclic compounds. Nitrogen, oxygen and sulfur are the most
common heteroatoms but heterocyclic rings containing other hetero atoms are too
widely recognized. An enormous number of heterocyclic compounds are known and
this number is increasing rapidly day to day. In addition, these compounds also
comply with the general rule proposed by Huckel. They are highly distributed in
natural products and present as a major components in biological molecules.
The rich activity of heterocyclic compounds in biological systems is important for
pharmaceuticals, and they provide a platform for the rapid exchange of research in the
areas of pharmaceutical, medicinal, and organic chemistry. Over 75% of the top two
hundred branded drugs in the pharmaceutical industry have heterocyclic fragments in
their structures. N-containing family of more than 12,000 natural products includes
molecules of a wide ranging (Figure 1) expanse of structural diversity,[1] among the
heterocycles found in nature, nitrogen containing heterocycles are the most abundant
due to their wide distribution in nucleic acids. This illustrate their involvement in
almost every physiological process of plants and creatures.
Figure-1 Natural alkaloids
Chapter-1
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1.2. Short literature review on Povarov reaction
Quinolines rings are present in a number of natural products and synthetic
pharmaceuticals. Because of its wide spread biological activities, many methods have
been developed for the synthesis of quinolines, the classic methods includes Doebner-
Miller reaction, Combes synthesis, Conrad Limpach synthesis, Bischler-Napieralski
synthesis, Friedlander synthesis and Povarov reaction etc.
The [4+2] cycloaddition reaction of N-aryl imines with nucleophilic olefins is one of
the most desirable methods of quinoline preparation, quinolines can be easily held by
using Lewis acids. BF3-OEt2 has been mainly applied for this purpose since the
revolutionary works of Povarov.[2] Acid-mediated cycloaddition between the
azadiene moieties of N-aryl imines and dienophiles also has turn an established route
to various tetrahydroquinolines and consequently, quinolines, the major class of
heterocycles. Hence, this interaction between N-aryl imines and electron-rich
dienophiles (Scheme 1) should be placed as the Povarov reaction.
Today, these types of Diels−Alder reactions are valuable synthetic routes in organic
synthesis, generating heterocyclic rings where the size of the second ring depends on
chain broadening. Indeed, multi-component inter and intramolecular Povarov
reactions have gained popularity in both diversity-oriented synthesis and target
oriented synthesis.
Scheme-1
Chapter-1
3
The reaction mechanism for the Povarov reaction to the quinoline is represented in
Scheme 2, initially aniline and benzaldehyde react to form imine. The Povarov
reaction requires a lewis acid such as boron trifluoride to activate the imine for an
electrophilic addition of the activated alkene. This reaction step forms an oxonium ion
which then reacts with the aromatic ring in a electrophilic aromatic substitution, two
steps of additional elimination reactions forms the quinoline ring.
Scheme-2 Mechanism of povarov reaction.
This short review covers the literature, but does not intend to be strictly complete,
although its goal is to highlight the improvements in the synthesis of quinoline
derivatives via the Povarov reaction.
1.2.1 Lewis acid catalyzed multicomponent povarov reaction
Numerous approaches have been reported in the literature using Lewis acid catalyst
for the synthesis of 2-aryl quinoline derivatives. BF3-OEt2 is well known acid catalyst,
by using this catalyst many protocols are reported. It has many advantages like mild
reaction conditions, easy work-up, a wide range of substrate applicability, and
products in good yields.
Chapter-1
4
D. J. Dibble and co workers[3] reported poly quinolines by using schiff base with
acetylene by using lewis acid catalyst with phenylacetylene in the presence of a
Lewis acid mediator and the sacrificial oxidant chloranil (Scheme 3).
Scheme-3
C. D. Smith and group[4] reported tetrahydroquinoline by using anilines and
benzaldehydes, with different norbornenes with high diversity in a multicomponent
fashion and are obtained in good yield with high diastereoselectivity (Scheme 4).
NH2 R2
HO
BF3.OEt220 mol%
R1
R3
CH2Cl245 0C
NH
H
H
R2
R3
R1
Scheme-4
Carmindo Ribeiro Borel et al.[5] reported 2-(2-pyridyl)quinolines was achieved via a
multi component Povarov reaction of aromatic aldehydes, anilines, and ethyl vinyl
ether under boron trifluoride methyl etherate, it shows several advantages over
previous reported methods (Scheme 5).
Scheme-5
Diego R. Merchan and co workers[6] reported 6,7-methylendioxy-
tetrahydroquinolines, by using iso eugenol as a alkene with aromatic aldehydes and
Chapter-1
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anilines in presence of Lewis acid catalyst, racemic products are formed in moderate
to good yields (Scheme 6).
Scheme-6
Alexey V. Tarantin et al.[7] developed synthesis of 3-ethoxy-carbonyl-5-isopropyl-9-
methoxy carbonyl-9,12a-dimethyl-7,8,8a,9,10,11,12,12a-octahydronaphtho [1,2 f]
quinoline by using iminoglyoxylate with ethyl vinyl ether in the presence of 15 mol%
BF3·OEt2 with moderate diastereoselectively (Scheme 7).
Scheme-7
Vladimir V. Kouznetsov et al. developed a synthesis of tetrahydro quinolines[8] by
using aniline, benzaldehyde and in presence of trans anithole as a alkene source by
using lewis acid catalyst BF3·OEt2. New different substituted tetrahydroquinolines are
reported from the trans anithole under supercritical fluid (CO2) conditions has been
reported (Scheme 8).
Chapter-1
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Scheme-8
1.2.2 Chiral phosphoric acid catalysed povarov reaction
Chiral phosphoric acid (Figure 1) is one among the best catalyst which is using in
synthesis of quinolines and it is having so many advantages like stereo selectivity,
catalytic amount is enough to carry out reaction effectively.
Figure-2 R= C6H4Cl, tri-isopropyl phenyl, 1-napthyl,
G. Dagousset and co workers[9] reported, chiral phosphoric acid catalyzed three-
component Povarov reactions using enethioureas as dienophile. Different functional
bearing aromatic and aliphatic aldehydes, as well as anilines, were tolerated in this
catalytic multicomponent reaction, leading to hexahydropyrrolo [3,2-c] quinolines in
high yields with excellent diastereo and enantioselectivities (Scheme 9).
Scheme-9
Chapter-1
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G. Dagousset et al. developed[10] three-component Povarov reaction of aldehydes,
anilines, and enecarbamates by using chiral phosphoric acid as a catalyst, this
reaction afforded cis-4-amino-2-aryl(alkyl)-1,2,3,4-tetrahydroquinolines in high
yields with excellent diastereo selectivities and absolute enantioselectivities (Scheme
10).
Scheme-10
Hua Liu et al. developed an approach[11] which combines the advantages of both
MCRs and organocatalysis, most important is the highly efficient synthesis of
enantiomerically pure (2,4-cis)-4-amino2-aryl(alkyl)-tetrahydroquinolines. Its
application has led to the development of a short, efficient synthesis of torcetrapib
(Scheme 11).
NH2 R1
HO
R CH2Cl2, 0 0C NH
0.1 equivalentchiral phosphoric acid
R1
R
CbzHN NHCbz
Scheme-11
Giulia Bergonzini and coworkers developed[12] an asymmetric Povarov reaction of N-
arylimines with 2- and 3-vinylindoles has been developed using a chiral phosphoric
acid ((S)-TRIP) as a catalyst. This method makes a versatile synthetic platform for the
construction of enantio enriched compounds containing an indole moiety, a very
common structure in natural and bioactive molecules (Scheme 12).
Chapter-1
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Scheme-12
Hong-Hao Zhang et al. developed a first catalytic asymmetric Povarov[13] reaction of
isatin containing 2-azadienes with 3-vinylindoles was reported in the presence of
chiral phosphoric acid, which tolerates a wide range of substrates with generally
excellent diastereoselectivity and good enantioselectivity (Scheme 13).
NN
O
R2
R1
NH
NH
NH
1-napthyl Chirolphosphoric acid 35 mol %
NO
R2
R1
R
R
O-xylene, 45 0C,
Scheme-13
1.2.3 Transition and inner transition metal triflates catalysed povarov reaction.
Ala Bunescu and co workers developed[14] a two-step synthesis of 2-acyl-
tetrahydroquinoline, through three-component reaction of α-oxo aldehydes, anilines
and dienes, by using yetribium triflate as catalyst yields tetrahydro quinolines in good
yield (Scheme 14).
Scheme-14
Chapter-1
9
Courtney E. Meyet and co workers[15] reported a alkyl substituted quinolines from
anilines, aldehydes, and alkynes. Copper (II) triflate catalyzes this three-component
coupling reaction without cocatalyst. Both electron-rich and electron-poor anilines
react efficiently in these three-component reaction (Scheme 15).
Scheme-15
Heather Twin et al. synthesized pyrrolo[3,4]quinolines[16] through the coupling of
anilines with propargylic substituted heterocyclic aldehydes in the presence of metal
triflates (Dy(OTf)3). This reaction proceeds through formation of imine and a formal
intramolecular aza Diels−Alder reaction. This approach was utilized in a total
synthesis of quinoline alkaloids (Scheme 16).
Scheme-16
Mingsheng Xie et al. reported[17] asymmetric Povarov reaction catalyzed by an N,N’-
dioxide L4–Sc(OTf)3 complex, wide variety of N-aryl aldimines and α-alkyl styrenes
were tolerated in this reaction, and the products are in good yields with excellent
diastereo and enantioselectivities (Scheme 17).
Chapter-1
10
Scheme-17
1.2.4 Iodine catalysed povarov reaction
Qinghe Gao and group[18] reported highly efficient iodine-mediated formal [3+2+1]
cycloaddition for the direct synthesis of substituted quinolines using acetophenones,
arylamines, and styrenes has been developed. This synthetic pathway represents an
interesting new form of reactivity for the Povarov reaction. This autotandem catalytic
process promote three mechanistically distinct reactions in a one pot using molecular
iodine (Scheme 18).
Scheme-18
Xiang-Shan Wang et al.[19] have showed that a facile method to synthesize exo-
tetrahydroindolo[3,2-c]quinoline derivatives in a three component reaction between
an aromatic aldehyde, a reactive amine, and an indole, with iodine as catalyst. The
advantages of this method include mild reaction conditions, moderate yields, high
stereoselectivity, metal-free catalyst, and operational simplicity (Scheme 19).
Chapter-1
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Scheme-19 1.2.5 Acid catalysed povarov reaction
Yu-Long Zhao et al. described[20] a proficient synthetic method for 4-((1,3-dithian-2-
ylidene)methyl)quinolines, mediated by trifluoromethanesulfonic acid, ethynyl
ketene-S,S-acetals can react with various arylamines and aldehydes gives
corresponding quinoline derivatives in high yields through arylimine formation, and
the products are regiospecific (Scheme 20).
Scheme-20
Jing Sun and co workers have showed,[21] three-component reaction of aromatic
aldehydes, arylamines and methyl propiolates, mediated by p-toluenesulfonic acid.
This acid catalyst efficiently established the imino Diels–Alder reaction with β-
enamino ester as dienophile. This reaction provides a suitable and stereoselective
procedure for the preparation of 2-aryl-4-arylamino-1,2,3,4-tetrahydroquinoline-3-
carboxylates in satisfactory yields (Scheme 21).
Chapter-1
12
Scheme-21
1.2.6 Radical cation catalysed povarov reaction.
Xiaodong Jia and group[22] reported a domino process between iminoethyl glyoxylate
and N-vinylamides was achieved by using catalytic radical cation salt induced
conditions producing a series of quinoline-2-carboxylates. N-Vinylamides were
involved as an acetylene equivalent (Scheme 22).
Scheme-22
Yaxin Wang et al. describd[23] an efficient synthesis of quinoline-fused lactones and
lactams using a radical cation salt-prompted sp3 C−H aerobic oxidation. The catalytic
aerobic oxidation of glycine esters and amides was screened for a broad range of
substrates. This approach provides one-step access to these biologically and
synthetically relevant core structures from simple starting materials (Scheme 23).
Scheme-23
Chapter-1
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1.2.7 Microwave assisted povarov reaction
Abhijit R. Kulkarni have showed that[24] efficient and speedy microwave-assisted
synthesis of cyclopentadiene ring-fused tetrahydroquinolines using multi-component
Povarov reaction catalyzed by indium(III)chloride. This protocol has so many
advantages like shorter reaction time with high yields (Scheme 24).
Scheme-24
1.2.8 Montmorillonite as a catalyst
Hans-Georg Imrich et al. asssembled[25] a three-component reaction between a nitro-
benzene, different substituted aldehyde, and a dienophile in the presence of iron
powder as a reductant and montmorillonite K10 as a catalyst in aqueous citric acid
condition undergo Povarov reaction with high stereo-selectivity (Scheme 25).
Scheme-25
Sankar K. Guchhait have reported[26] a novel HClO4-modified montmorillonite-
promoted Povarov reaction, then aerobic dehydrogenation to provide the synthesis of
polysubstituted quinolines. HClO4-modified montmorillonite as a privileged catalyst,
advantages of this method are potential use for promoting povarov reactions and
possible successive aerobic dehydrogenation (Scheme 26).
Chapter-1
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Scheme-26
1.2.9 Post transition Metal chlorides as catalyst
Vellaisamy Sridharan et al. developed[27] a new domino reaction that involves the
creation of two C–C bonds and the generation of two stereocenters, one of them
quaternary, with complete diastereoselectivity and in a single synthetic operation.
This transformation can be considered as a novel type of vinylogous aza-Povarov
reaction, and establishes the foremost example of an α, β-unsaturated hydrazone
behaving as the dienophile component in an aza Diels–Alder reaction (Scheme 27).
Scheme-27
Vladimir V. Kouznetsov and group showed[28] that general protocol for the simple and
efficient BiCl3-catalyzed synthesis of 2-alkyl-1,2,3,4-tetrahydroquinolines. Synthetic
protocols described the one-pot preparation of these tetrahydroquinolines using ali-
phatic aldehydes, anilines and N-vinyl acetamide in the multicomponent condensation
reaction (Scheme 28).
Chapter-1
15
Scheme-28
1.2.10 Intramolecular povarov reaction
Ming Chen and coworkers developed[29] a facile indeno [1,2-b] quinolines by using
Povarov reaction through intramolecular cyclisation. Reactions proceeded efficiently
in the absence of oxidants, aromatization was achieved by elimination of a leaving
group. A broad kind of substitutes may well be incorporated, that permits for a
convenient structural modification of straightforward indenoquinolines (Scheme 29).
Scheme-29
1.3. Short literature review on synthetic efferts of 2,3-dihydroquinazolinones
1.3.1 Acid catalysed synthesis
Vilas B. Labade et al. developed[30] an efficient synthetic route for 2,3-
dihydroquinazolin-4(1H)-ones using 2-morpholinoethanesulfonic acid as a new
organocatalyst. The developed synthetic protocol represents a completely unique and
extremely easy route for the preparation of 2,3-dihydroquinazolin-4(1H)-one
derivatives. Additionally, the microwave irradiation technique is with success
enforced for ending the reactions in shorter reaction times (Scheme 30).
Chapter-1
16
Scheme-30
B. V. Subba Reddy and co workers assembled[31] a condensation of 2-
aminobenzamide with aldehydes or ketones has been achieved using cellulosesulfonic
acid under mild reaction conditions to furnish 2,3-dihydroquinazolin-4(1H)-ones in
good yields with a high selectivity. The usage of solid acid catalyst makes this
methodology quite straightforward (Scheme 31).
Scheme-31
1.3.2 Amberlyst-15 mediated synthesis
P. VNS Murthy et al.[32] reported economical and clear technique for the synthesis of
2-aryl 2,3-dihydroquinazolin-4(1H)-ones exploitation amberlyst-15 as a recyclable
catalyst. A variety of dihydroquinazolinones were prepared from 2-aminobenzamide
and aldehydes under beneath gentle conditions in excellent yields (Scheme 32).
Scheme-32
1.3.3 Base mediated synthesis
Xiao-Feng Wu and group[33] developed an remarkable and convenient procedure for
2,3-dihydroquinazolin-4(1H)-ones synthesis. Inexpensive inorganic base was applied
Chapter-1
17
as a promoter and water was used as a green solvent for this transformation (Scheme
33).
NH2
O
Ph HNH
NH
O
Ph
K3PO4,H2O, 100 0C, 8 hCN
Scheme-33
1.3.4 Chiral phosphoric acid catalysed asymmetric synthesis
Figure-3 R= 9-anthracenyl, 2,4,6-(i-Pr)3C6H2
Dao-Juan Cheng showed[34] that for the first time, an efficient catalytic asymmetric
synthesis of aminal containing heterocyclic compounds from imines. In the presence
of 10 mol% of a commercially available (Figure 2) chiral phosphoric acid, a range of
aromatic, α, β-unsaturated, and aliphatic imines react with 2-aminobenzamides to
grant dihydroquinazolinones in excellent yields (Scheme 34).
NH2
O
NH2
N
Ph H NH
NH
O
PhCHCl3, rt, 24 h
Catalyst (10 mol%)X
Scheme-34
Magnus Rueping report on the development[35] of a replacement metal-free, extremely
enantioselective, Bronsted acid catalyzed condensation reaction for the synthesis of
2,3-dihydroquinazolinones starting from readily available starting materials. Thus, a
highly extremely economical and general approach to valuable enantiomerically
Chapter-1
18
enriched 2,3-dihydroquinazolinones with preference for the more active S
enantiomers has been established (Scheme 35).
Scheme-35
Yan Jiang and co workers established[36] the enantioselective synthesis of various
substituted Spiro [indoline-3,20-quinazolines]. More significantly, this protocol not
solely takes into consideration the speedy building of the chiral Spiro [indoline-3,20-
quinazoline] design with potential applications in medicinal chemistry, however
additionally provides enantioselective Spiro [indoline-3,20-quinazoline] derivatives
for more structural modification and bioassay (Scheme 36).
Scheme-36
1.3.5 Click reaction
Ahmad Shaabani and co workers developed[37] an efficient condensation reaction of
2-aminobenzamide with various alkyl, aryl, and alicyclic aldehydes or ketones, that
provides 2,3-dihydroquinazolin-4(1H)-one derivatives in good yields. This reaction
will be classified as a brand new click synthesis as a result this reaction takes place in
short times (Scheme 37).
Chapter-1
19
Scheme-37
1.3.6 Intramolecular Pinner/Dimroth Rearrangement
Jian-Hong Tang et al. [38] reported the synthesis of quinazolin-4(3H)-one derivatives,
these are obtained by the cyclization of o-aminonitriles with carbonyl compounds
using zinc chloride as catalyst by exploitation DMF as a solvent. The reaction scope
is significant, and a number of aryl aldehydes could be successfully applied to react
with O-aminonitriles to provide quinazolinone compounds with excellent yields
(Scheme 38).
NH2
O
R3 HNH
NH
O
R3
CNR2
R1
DMF, ZnCl2
reflux
R2
R1
Scheme-38
1.3.7 Co-CNTs as a green reaction medium and a catalyst
Javad Safari and group assembled[39] the importance of quinazolinone analogues as
synthons in organic synthesis, they have reported the synthesis of a number of these
compounds through the Co-CNT catalyzed heterocyclization of O-aminobenzamide
with different aldehydes. Short reaction times, mildness, easy work-up are the benefits
of this protocol (Scheme 39).
Scheme-39
Chapter-1
20
1.3.8 Ionic liquid mediated synthesis
Jiuxi Chen et al. have been synthesized[40] 2,3-dihydroquinazolin-4(1H)-ones in high
yields through one-pot three-component cyclocondensation of isatoic anhydrides,
ammonia acetate and aldehydes in ionic liquid water solvent system while not the
utilization of any further catalyst (Scheme 40).
Scheme-40
Junke Wang and group[41] reported poly(4-vinylpyridine) supported acidic ionic liquid
catalyst, and employed in the synthesis of 2,3-dihydroquinazolin-4(1H)-ones
underneath supersonic irradiation. Effective convalescent and reusability of the
catalyst square measure the a number of the benefits of this methodology. Most
significantly, the utilization of supersonic irradiation will clearly speed up the reaction
(Scheme 41).
Scheme-41
1.3.9 Using low valent Titanium
Daqing Shi reported a short[42] and facile synthesis of 1,2-dihydroquinazolin-4(3H)-
ones via the novel reductive cyclization of O-nitrobenzamides and aldehydes or
ketones promoted by TiCl4/Zn, benefits of this protocol area unit simply accessible
starting materials, convenient operation and moderate to good yields (Scheme 42).
Chapter-1
21
Scheme-42
1.3.10 Using metal triflates
Muthuraj Prakash et al.[43] developed metal catalysed 2,3-dihydroquinazolinones
enantioselective synthesis through intramolecular amidation of imines in excellent
yields. The scandium(III)-inda-pybox catalyst provided exceptional catalytic
activation of 2-amino N-phenylbenzamide to afford the corresponding 2,3-
dihydroquinazolinone with excellent enantioselectivity (Scheme 43).
Scheme-43
1.3.11 By reductive cyclisation
Yu Hu et al.[44] reported a series of 10-H-spiro[indoline-3,20-quinazoline]-2,40(30H)-
diones were synthesized by the reaction of 2-nitrobenzamides with isatins
respectively, mediate by SnCl2-2H2O system. A kind of substrates can participate in
the process with moderate to good yields (Scheme 44).
Chapter-1
22
Scheme-44
1.3.12 Nanoparticles used as recoverable catalyst
Amin Rostami and cluster[45] reported MNPs-PSA as a eco-friendly, efficient and
magnetically recoverable catalyst was used in synthesis of 2,3-dihydroquinazolin-
4(1H)-ones by direct cyclocondensation of anthranilamide and aryl aldehydes or
ketones with sensible to high yields in water, benefits of this catalyst are speedy,
simple and efficient separation by using an appropriate external magnet (Scheme 45).
Scheme-45
M. Z. Kassaee have assembled[46] Al/Al2O3 NPs as an effective catalyst in the one-
pot multicomponent synthesis of 2,3-dihydroquinazolin-4(1H)-ones. This catalyst is
very economical, simply offered, operationally straightforward, and needs gentle
reaction conditions. Conjointly the product were got in good yields with short reaction
times (Scheme 46).
Scheme-46
Chapter-1
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1.3.13 Supramolecular synthesis
K. Ramesh and group showed an eco-friendly method[47] to synthesize 2,3-
dihydroquinazolin-4(1H)-ones in excellent yields, beneath neutral conditions in one-
pot involving catalysis by β-cyclodextrin in water. Catalyst can be recovered and
reused with a little loss of catalytic activity (Scheme 47).
NH2
O
NH2
CHO
NH
NH
O
R R
-CD/H2O
55-60 0C
Scheme-47
1.3.14 Grinding under Solvent-Free Conditions
Quan-Sheng Ding and group[48] have demonstrated a light and economical eco-
friendly synthesis of 2,3-dihydroquinazolin-4(1H)-ones underneath solvent-free
conditions, using citric acid as a novel organoacid green promoter, which uses neither
harsh conditions nor the use of hazardous catalysts and reagents. Notable benifits of
this protocol are wide substrates scope, short interval, inexpensive, water-solubility
organoacid, and high yields (Scheme 48).
Scheme-48
1.3.15 Ruthenium-catalysed oxidative synthesis.
Andrew J. A.Watson reported Ruthenium-catalysed oxidative synthesis[49] for the
conversion of alcohols into 2,3-dihydroquinazolines. Reaction conditions are 2-
aminobenzamide and alcohol, with crotononitrile, in presence of Ru(PPh3)3(CO)(H2)
Chapter-1
24
permits for the selective formation quinazolinones, and also the product in good
yields (Scheme 49).
Scheme-49
1.3.16 Miscelanious
Moni Sharma et al. developed[50] an efficient cyanuric chloride (2,4,6-trichloro-1,3,5-
triazine, TCT) catalyzed approach for the synthesis of 2,3-dihydroquinazolin-4(1H)-
one, 2-spiroquinazolinone, and glycoconjugates of 2,3-dihydro- quinazolin-4(1H)-one
derivatives. The reaction permits fast cyclization (8−20 min) with 10 mol % cyanuric
chloride to give skeletal complexity in excellent yield (Scheme 50).
Scheme-50
Matthieu Desroses reported[51] an simple easy and efficient protocol for the synthesis
of 2,3-dihydroquinazolinones. This technique, using T3P® as the catalyst, has several
advantages such as a easy operational procedure, a short reaction time, the
employment of very gentle conditions and a simple access to the compounds in good
yields (Scheme 51).
Chapter-1
25
Scheme-51
Someshwar D. Dindulkarwe and group[52] have successfully created a cost-effective
protocol for the synthesis of 2,3-dihydroquinazolin-4 (1H) -ones victimization CAN-
SiO2 as a fast reusable catalyst at room temperature. Compare to the earliest known
methodologies, this method offers several advantages, together with high production
of products, short reaction times, the recyclability of the catalyst (Scheme 52).
Scheme-52
Rong Zhang Qiao et al. reported[53] 2-substituted 2,3 dihydro quinazolinones in high
yields by condensation of anthranyl amides with aldehydes or ketones in the refluxing
2,2,2-trifluroethanol with none catalyst the gentle and neutral reaction conditions
permit the acid or base sensitive substrates to be involved in the reaction timescale
(Scheme 53).
Scheme-53
Chapter-1
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1.4. Scope of the present work:
Recent days heterocyclic compounds have become an important source of discovery
of drug molecules. Particularly nitrogen containing heterocyclic ring play an
important role in bioorganic and medicinal chemistry, especially reports concerning
quinoline containing heterocyclic compounds have gradually increased because of
their potential biological activity and these quinolines are present in plants as
alkaloids best example is quinine and it is used as anti malarial drug by chinese and
indian ancient medicine.
2,3-dihydroquinazolinones containing heterocyclic compounds have got so much
importance because these quinazolinones are integral part of so many alakaloids and
these molecules are used as anticancer agents. Due to the biological significance of
these heterocycles so many synthetic efforts have been reported, during the course of
our research we have developed a new synthetic protocol for the synthesis of 2-aryl
quinoline and 2,3-dihydroquinazolinones derivatives.
Propylphosphonic anhydride (T3P®)-DMSO mediated one pot three component
synthesis of 2-aryl quinolines by modified povarov reaction provides 2-aryl
quinolines in a single step from benzyl alcohols, anilines and ethyl vinyl ether
mediated by T3P®-DMSO as shown in Scheme 83 and evaluated for their anticancer
activity against different human cancer cell lines. The results showed that compound
F16 was found to be most potent against human cancer cell lines at lower
concentrations.
Chapter-1
27
Scheme- 83
One-pot synthesis of 2, 3-dihydroquinazolin-4(1H)-ones from gem-
dibromomethylarenes using 2-aminobenzamide is described. Gem-
dibromomethylarenes used as aldehyde equivalent for the efficient synthesis of 2, 3-
dihydroquinazolin-4(1H)-ones, as shown in Scheme 101 and evaluated for their
anticancer activity against different human leukemic cell lines. The results showed
that compound F27 was found to be most potent against human cancer cell lines at
lower concentrations.
Where R1, R= H/Cl/Br/OMe.
Scheme-101
ZrO2-Al2O3 used as effective nano catalyst for the efficient synthesis of 2, 3-
dihydroquinazolin-4(1H)-ones from 2-aminobenzamide using benzaldehyde is
described, as shown in Scheme 119, we extended our work to synthesize biologically
active piperidine conjugated derivatives, the requisite title compounds F41-44 were
synthesized by the reaction of 6-chloro-2-(piperidin-4-yl)-2,3-dihydroquinazolin-
4(1H)-one with different benzene sulfonyl chlorides, benzoyl chlorides, benzyl
chlorides as shown in Scheme 120 and the product are obtained in good yields. Later
evaluated for their anticancer activity against different human cancer cell lines. The
results showed that compound F44 was found to be most potent against human cancer
cell lines at lower concentrations.
Chapter-1
28
NH
NH
O
R1
NH2
O
NH2
ZrO2-Al2O3 20 mol%
Ethanol, refluxR RR1-CHO
Scheme-119
Scheme-120
Chapter-1
29
References and Notes
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