Rhodium(II)-Catalyzed Carbenoid Insertion of N-Tosylhydrazones into Amide N-H Bonds: An Efficient Approach to N3-Benzyl/Alkyl-2-arylquinazolinones

Article abstract of DOI:10.1002/adsc.201500678

Dirhodium(II) acetate-catalyzed reactions of N-tosylhydrazones with dihydroquinazolinones bearing different types of N-H bonds that give N³-benzyl/alkyl-2-arylquinazolin-4(3H)-ones through Csp³-N bond formation by oxidative dehydroge

Full text of DOI:10.1002/adsc.201500678

FULL PAPERS
DOI: 10.1002/adsc.201500678
Rhodium(II)-Catalyzed Carbenoid Insertion of N-Tosylhydra-
3
À
zones into Amide N H Bonds: An Efficient Approach to N -
Benzyl/Alkyl-2-arylquinazolinones
Rajaka Lingayya,a,b Mari Vellakkaran,a Kommu Nagaiah,a,b,*
and Jagadeesh Babu Nanuboluc
a
Organic and Biomolecular Chemistry Division, CSIR – Indian Institute of Chemical Technology, Hyderabad – 500 007,
India
Fax: (+91)-402-719-1659; phone: (+91)-402-719-1659; e-mail: nagaiah.iict@gov.in
Academy of Scientific and Innovative Research (AcSIR), CSIR – Indian Institute of Chemical Technology, Hyderabad –
b
500 007, India
c
Lab of X-ray Crystallography, CSIR – Indian Institute of Chemical Technology, Hyderabad – 500 007, India
Received: July 16, 2015; Revised: October 1, 2015; Published online: January 5, 2016
Dedicated to Dr. A. V. Rama Rao, Former Director, CSIR-IICT (Managing Director, AVRA Research Labo-
ratories Pvt. Ltd., Hyderabad, India), on the occasion of his 80th birthday.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201500678.
Abstract: Dirhodium(II) acetate-catalyzed reactions method features good to excellent yields, good func-
of N-tosylhydrazones with dihydroquinazolinones tional group tolerance, high regioselectivity and
3
À
bearing different types of N H bonds that give N - readily available starting materials.
benzyl/alkyl-2-arylquinazolin-4(3H)-ones
through
3
À
Csp N bond formation by oxidative dehydrogena-
tion and insertion of rhodium-carbenoid into amide Keywords: carbenoids; insertion reactions; nitrogen
N H bond are reported for the first time. This heterocycles; N-tosylhydrazones; rhodium
À
Introduction
tion partners, making this type of insertion reaction
practical in organic synthesis.[5]
The transition metal-catalyzed insertion of metal-car-
benoids into C H or X H (X=N, O, S, etc.) bonds rivatives are certainly a topic of research in very
represents an excellent and powerful method for the recent years because of the presence of an amide N
On the other hand, 2-aryldihydroquinazolinone de-
À
À
À
À
À
formation of carbon-carbon or carbon-heteroatom H group, an amine N H group and active C H bond
bonds.[1] In particular, carbenoid insertion into N H for functionalization. Current studies have shown that
À
bonds is a direct and potentially powerful method of the 2-aryldihydroquinazolinone group can act as a di-
[2]
À
forming C N bonds and this type of reaction has recting group in promoting cross-coupling/annulation
[6]
À
À
been very useful in delivering biologically important by C H/N H activation.
molecules and other N-containing heterocyclic com-
Furthermore, quinazolinone derivatives occur in
pounds. An important practical application of the cat- many natural products, and exhibit a wide range of
À
alyzed N H insertion is the Merck synthesis of the useful biological and pharmacological activities
antibiotic thienamycin.[3a] Moody and co-workers and (Figure 1).[7] Therefore, there is a continued strong
À
other groups, applied the metal carbene N H inser- demand for new and efficient functionalization meth-
tion strategy to obtain heterocycles.[3b–d]
ods of these heterocycles and their amide N H group
À
N-Tosylhydrazones represent a class of stable and functionalization via reductive coupling of N-tosylhy-
reactive nitrogen compounds. They have been exten- drazones to form C N bonds has not been reported
sively used in modern synthetic organic chemistry to in the literature (no hits found on SciFinder and
À
generate unstable diazo compounds in situ by treat- Reaxys).
ment with a base (Bamford–Stevens reaction).[4]
We herein present a novel, simple and practical
Therefore, the N-tosylhydrazones can be used as reac- rhodium(II)-catalyzed regioselective carbenoid inser-
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Rajaka Lingayya et al.
Table 1. Optimization of the reaction conditions.[a]
Entry Catalyst
Base
Solvent Yield [%][b]
Figure 1. Biologically active compounds with a quinazolinone
scaffold.
1
2
3
4
5
6
7
8
CuI
CuI
CuCl
CuBr
K2CO3 toluene
Cs2CO3 dioxane
K2CO3 toluene
K2CO3 toluene
0
0
0
0
0
0
0
0
0
0
[RuCl2(p-cymene)]2 K2CO3 toluene
[RuCl2(p-cymene)]2 Cs2CO3 toluene
[RuCl2(p-cymene)]2 K2CO3 DCE
[RuCl2(p-cymene)]2 K2CO3 DMAc
[RuCl2(p-cymene)]2 K2CO3 CH3CN
[RuCl2(p-cymene)]2 K2CO3 dioxane
[Rh2(OAc)4]
[Rh2(OAc)4]
[Rh2(OAc)4]
[Rh2(OAc)4]
[Rh2(OAc)4]
[Rh2(OAc)4]
[Rh2(OAc)4]
[Rh2(OAc)4]
[Rh2(OAc)4]
no catalyst
À
tion into an amide N H bond for the direct synthesis
of N3-benzyl/alkyl-2-arylquinazolinones from dihydro-
quinazolinones using readily available, non-prefunc-
tionalized, relatively stable, and inexpensive N-tosyl-
hydrazone derivatives as the benzyl/alkyl source and
K2CO3 as the base.
9
10
11
12
13
14
15
16
17
18
19
20
K2CO3 toluene 47
K3PO4 toluene
Na2CO3 toluene 34
Cs2CO3 toluene 41
0
Results and Discussion
K2CO3 DMF
K2CO3 DCE
52
64[c]
At the outset of our study, we investigated the reac-
tion of 2-phenyl-2,3-dihydroquinazolin-4(1H)-one (Ia)
and benzaldehyde-derived N-tosylhydrazone (IIa) as
a model (Table 1). To optimize the reaction condi-
tions, various catalysts, bases, and solvents for the re-
action were investigated. First, CuI was employed as
the catalyst and K2CO3 as base, under air, in toluene
at 908C for 12 h. However, only the oxidized aminal
product 2-phenylquinazolin-4(3H)-one was obtained
K2CO3 dioxane 85[d]
K2CO3 dioxane 84[e]
no base dioxane
K2CO3 dioxane
0
0
[a]
Unless specified, the reaction was carried out with Ia
(0.25 mmol), IIa (0.3 mmol), catalyst (5 mol%), base
(2.0 equiv.), under air, in a solvent (2.0 mL) at 908C for
12 h.
Isolated yield (average of two runs).
Reaction was completed in 6 h.
[b]
[c]
[d]
[e]
À
and no expected amide N H bond functionalized
product 1 was observed (Table 1, entry 1).[8] Change
of base and solvent also resulted in no product forma-
tion (Table 1, entry 2). Switching to other Cu(I) cata-
lysts, such as CuCl and CuBr also resulted in no prod-
Reaction was completed in 4 h.
[Rh2(OAc)4] (1 mol%), 4 h.
uct formation (Table 1, entries 3 and 4). With catalyst [Rh(II)] loading was found to be sufficient to
[RuCl2(p-cymene)]2, under different reaction condi- achieve a satisfactory result (Table 1, entry 18). No re-
tions no desired product was isolated (Table 1, en- action occurred in the absence of each catalyst and
tries 5–10). Dirhodium tetraacetate, the most popular base (Table 1, entries 19 and 20). Thus, the optimized
catalyst for carbenoid formation, was then tested.[1f] reaction conditions were as follows: Ia (0.25 mmol),
To our delight, when [Rh2(OAc)4] was used as cata- IIa (0.3 mmol), K2CO3 (0.5 mmol), [Rh2(OAc)4]
À
lyst, the amide N H insertion occurred smoothly to (1 mol%), under air, in 1,4-dioxane at 908C for 4 h
afford the corresponding benzylated product 1 in (Table 1, entry 18).
47% yield (Table 1, entry 11). Encouraged by this pre-
With the optimized reaction conditions in hand, we
liminary result, we proceeded to further optimize the then investigated the substrate scope of this process.
reaction conditions. First, we investigated the effect of First, a series of substituted dihydroquinazolinone de-
base. As shown in Table 1, a variety of common bases rivatives was explored (Scheme 1). This transforma-
was screened in the reaction (Table 1, entries 12–14), tion displayed excellent functional group tolerance
and the best results were obtained with K2CO3 and proved to be a reasonably general method. The
(2.0 equiv.). Screening of other solvents such as N,N- reactions of dihydroquinazolinones with electron-do-
dimethylformamide (DMF) and 1,2-dichloroethane nating groups, such as methyl and methoxy, gave the
(DCE) further improved the yield of the reaction, corresponding products, 2 and 3 in 86% and 90%
giving 1 in 52% and 64% isolated yield, respectively yields, respectively. Dihydroquinazolinones with elec-
(Table 1, entries 15 and 16). Gratifyingly, an 85% tron-withdrawing groups, such as fluoro, chloro, and
yield of 1 was achieved when 1,4-dioxane was used as bromo, were well tolerated in the reaction and afford-
the solvent (Table 1, entry 17). Notably, 1 mol% of ed the desired products 4–6 in 79–83% yield. These
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Rhodium(II)-Catalyzed Carbenoid Insertion of N-Tosylhydrazones
Figure 2. ORTEP diagram for compound 4.
chloro, dimethoxy, and trimethoxy, gave the desired
products 11–13 in 71–78% yields. Moreover, a hetero-
aryl-bearing dihydroquinazolinone also worked well
in the reaction, and gave the corresponding product
14 in a 72% yield. In addition, 6-chloro- and 6-iodo-
substituted-2-phenyl-2,3-dihydroquinazolin-4(1H)-one
derivatives were also well-tolerated (15 and 16) in
this reaction.
Next, the scope of N-tosylhydrazones was investi-
gated using 2-phenyl-2,3-dihydroquinazolin-4(1H)-one
as the insertion partner (Scheme 2). Benzaldehyde-
derived N-tosylhydrazones with para substituents
such as methyl and methoxy on the aromatic ring re-
À
acted smoothly, to afford the desired amide N H in-
sertion products 17 and 18, in excellent yields. Nota-
bly, the reaction is significantly affected by the posi-
tion of the substituents on the aromatic ring of the N-
tosylhydrazones. Thus, N-tosylhydrazones with ortho
or meta substituents on the aromatic ring reacted with
Scheme 1. Synthesis of N3-benzyl-2-arylquinazolinones from
a variety of dihydroquinazolinone derivatives.
halogen groups provide the opportunity for further 2-phenyl-2,3-dihydroquinazolin-4(1H)-one to give the
transformations through transition metal-catalyzed desired products 19 and 20 in diminished yields.
coupling reactions. The structure of the product 4 was When N-tosylhydrazones bearing halide atoms, such
also confirmed by single crystal X-ray diffraction as fluorine, and chlorine were used as benzylating
(Figure 2).[9] When an electron-neutral group, such as agents, the corresponding products 21 and 22 were
a phenyl-containing dihydroquinazolinone, reacted isolated in 86% and 85% yields, respectively. This cat-
with the N-tosylhydrazone of benzaldehyde, the cor- alytic system was also applied to an N-tosylhydrazone
responding product 7 was obtained in 80% yield. N3- bearing a strong electron-withdrawing substituent,
Benzyl-2-arylquinazolin-4(3H)-one 8, which contains such as trifluoromethyl, affording the desired product
a strong electron-withdrawing cyano substituent, was 23 in 79% yield. Furthermore, insertion of the N-to-
obtained in 70% yield. The reaction is slightly affect- sylhydrazone of pyridine-3-carbaxaldehyde proceeded
ed by the position of substituents on the aromatic smoothly, and the corresponding product 24 was ob-
rings. When 2-(o-tolyl)-2,3-dihydroquinazolin-4(1H)- tained in 76% yield. Additionally, the catalytic system
one and 2-(3-methoxyphenyl)-2,3-dihydroquinazolin- was not limited to the use of aryl N-tosylhydrazones,
4(1H)-one were used as the substrates, the corre- but also allowed good conversion of the more chal-
sponding products 9 and 10 were isolated in some- lenging alkyl N-tosylhydrazones. Propionaldehyde-
what lower yields. Reactions of dihydroquinazoli- and butyraldehyde-derived N-tosylhydrazones were
nones bearing two or three substituents, such as di- reacted smoothly and produced the corresponding
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Scheme 4. Substrate scope.
with TsNHNH2 generated IIa in situ, and then Ia,
base and catalyst were added. Indeed, product
1 could be isolated in 80% yield.
To further demonstrate the efficiency and useful-
ness of this method, alkyl-substituted dihydroquinazo-
linone, sulfonamide group-containing dihydrothiadia-
zine dioxide and disubstituted N-tosylhydrazone were
chosen as the substrates (Scheme 4). First, 2-isopro-
pyl-2,3-dihydroquinazolin-4(1H)-one was readily con-
verted to product 28 in 78% yield. To our delight, 3-
phenyl-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-
dioxide also participated in the reaction to give 29 in
82% yield. Finally, insertion of 3,4-disubstituted N-to-
sylhydrazone proceeded smoothly to form 30 in 81%
yield.
To elucidate the reaction mechanism, we conducted
some control experiments (Scheme 5). First, the
À
amide N H group was blocked by a phenyl ring, the
À
amine N H bond functionalized product was not ob-
served; only oxidative dehydrogenation occurred.
This result indicates the regioselective nature of the
process (Scheme 5a). In the reaction of 2-phenylqui-
nazolinone under standard conditions, 1 was isolated
in 73% yield (Scheme 5b). Then, when the reaction
Scheme 2. Synthesis of N3-benzyl/alkyl-2-aryl quinazolinones
from a variety of N-tosylhydrazones.
products 25 and 26 in 71% and 73% yields, respec- was carried out without adding N-tosylhydrazone, the
tively. Finally, an aliphatic ketone such as cyclohexa- cyclic aminal was oxidized smoothly to give 2-phenyl-
none-derived N-tosylhydrazone was also tested in the quinazolin-4(3H)-one within 1 h. After addition of N-
reaction, affording a good yield of product 27.
tosylhydrazone, 1 was formed in 81% isolated yield
Since N-tosylhydrazone IIa is readily formed by the (Scheme 5c). These results clearly demonstrate that at
À
condensation of benzaldehyde with TsNHNH2 first the amine N H group be would involved in oxi-
(Scheme 3), we thus decided to conduct this reaction dative dehydrogenation, and then insertion of rhodi-
À
in a one-pot manner. Treatment of the benzaldehyde um-carbenoid into the amide N H bond would take
place. A control reaction showed that no oxidation
occurred in the absence of Rh2(OAc)4 (Scheme 5d).
When the reaction was performed under a nitrogen
atmosphere, 32 was isolated in poor yield. This obser-
vation shows that air is necessary for the oxidative de-
hydrogenation (Scheme 5e). In another control ex-
periment it was seen that the presence of a radical-
scavenging reagent such as TEMPO did not influence
the reaction. This result excluded the possibility that
Scheme 3. One-pot insertion of N-tosylhydrazone starting
from aldehyde.
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Rhodium(II)-Catalyzed Carbenoid Insertion of N-Tosylhydrazones
Scheme 6. Proposed mechanism.
À
active carbenoid species B into the amide N H bond
of the quinazolinone, probably via a stepwise inser-
tion mechanism, resulted in the formation of ylide in-
termediates C and V.[11] Then V undergoes a proton
transfer to afford the corresponding benzylated prod-
uct VI.
Conclusions
In summary, we have demonstrated a simple, highly
efficient and general strategy for direct synthesis of
N3-benzyl/alkyl-2-arylquinazolinones via rhodium(II)-
carbenoid involved regioselective insertion of N-tosyl-
À
hydrazones into the amide N H bonds of dihydroqui-
nazolinones. Moreover, the use of easily accessible,
stable and inexpensive N-tosylhydrazones as benzyl/
alkyl source makes the present protocol particularly
attractive and practical. Further studies to fully under-
stand the reaction mechanism and further exploit the
Rh(II)-carbene chemistry are in progress.
Scheme 5. Control experiments.
the reaction occurs by a radical process (Scheme 5f).
We also performed an experiment to check if hydro-
gen gas was released during the reaction by the addi-
tion of a ketone, but no transfer hydrogenation prod-
uct was observed (Scheme 5g).[10i]
Experimental Section
General Procedure
A plausible reaction mechanism is illustrated in
Scheme 6 on the basis of experimental results and
previously reported investigations.[10a–h] The bis(rhodi-
um/acetate) complex oxidizes dihydroquinazolinone I
to afford quinazolinone II. The second step, which in-
A
mixture of dihydroquinazolinone (I, 0.25 mmol,
1.0 equiv.), N-tosylhydrazone (II, 0.3 mmol, 1.2 equiv.),
K2CO3 (0.5 mmol, 2.0 equiv.), [Rh2(OAc)4] (1 mol%), and
1,4-dioxane (2.0 mL) was added to a round-bottomed flask.
The mixture was stirred at 908C and the progress of the re-
action was monitored by TLC. After completion of the reac-
tion, the mixture was cooled to room temperature. The reac-
tion mixture was partitioned between ethyl acetate
(20.0 mL) and water (20.0 mL) in a separatory funnel. The
organic layer was washed with water, and brine, dried over
anhydrous Na2SO4 (s) and concentrated under vacuum. The
À
volves the formation of a Csp3 N bond via reductive
coupling of N-tosylhydrazone III, with quinazolinone
II, starts with the reaction of catalyst A with diazo
compound IV (generated in situ from N-tosylhydra-
zone) to generate Rh(II)-carbenoid intermediate B
with extrusion of nitrogen. Insertion of this highly re- residue was purified by column chromatography using a gra-
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dient of hexane and ethyl acetate as the eluent system to
afford the pure products.
3064, 2923, 1676, 1594, 1490, 1473, 1451, 1378, 1258, 1069,
1
772, 696 cmÀ1; H NMR (500 MHz, CDCl3): d=8.37 (d, J=
3-Benzyl-2-phenylquinazolin-4(3H)-one (1):[12] Yield:
84%; white solid; mp 143–1458C; IR (neat): nmax =3064,
2923, 1682, 1603, 1585, 1474, 1450, 1379, 1230, 1070, 967,
8.0 Hz, 1H), 7.79 (dd, J=6.9, 1.3 Hz, 1H), 7.75 (d, J=
7.4 Hz, 1H), 7.56–7.51 (m, 3H), 7.24–7.20 (m, 5H), 6.94–
6.92 (m, 2H), 5.25 (s, 2H); 13C NMR (100 MHz, CDCl3):
d=162.3, 155.3, 147.0, 136.2, 134.6, 131.7, 129.6, 128.6, 128.3,
127.5, 127.5, 127.4, 127.1, 126.7, 124.4, 120.7, 48.8; MS (ESI):
m/z=393 [M+H]+; HR-MS (ESI): m/z=391.04485, calcd.
for C21H16ON2Br: 391.04405 [M+H]+.
1
771, 694 cmÀ1; H NMR (500 MHz, CDCl3): d=8.38 (d, J=
7.9 Hz, 1H), 8.11 (d, J=7.7 Hz, 1H), 7.79 (d, J=2.8 Hz,
1H), 7.62–7.52 (m, 1H), 7.46 (t, J=7.6 Hz, 1H), 7.41–7.34
(m, 4H), 7.25 (s, 1H), 7.21–7.18 (m, 2H), 6.93–6.91 (m, 2H),
5.28 (s, 2H); 13C NMR (125 MHz, CDCl3): d=162.4, 156.5,
146.9, 136.3, 134.6, 133.5, 130.0, 128.4, 128.3, 127.9, 127.3,
127.2, 127.2, 127.0, 126.8, 120.6, 48.7; MS (ESI): m/z=313
[M+H]+; HR-MS (ESI): m/z=313.13265, calcd. for
C21H17ON2: 313.13354 [M+H]+.
2-([1,1’-Biphenyl]-4-yl)-3-benzylquinazolin-4(3H)-one (7):
Yield: 80%; white solid; mp 120–1218C; IR (neat): nmax
=
3061, 2923, 1677, 1607, 1586, 1567, 1473, 1378, 1240, 1076,
1
969, 770, 696 cmÀ1; H NMR (300 MHz, CDCl3): d=8.39 (d,
J=7.9 Hz, 1H), 7.79 (d, J=3.6 Hz, 2H), 7.70–7.59 (m, 5H),
7.50–7.39 (m, 5H), 7.22 (dd, J=4.9, 1.7 Hz, 3H), 6.98 (dd,
J=6.4, 2.7 Hz, 2H), 5.34 (s, 2H); 13C NMR (125 MHz,
CDCl3): d=162.4, 156.2, 147.2, 142.7, 140.0, 136.5, 134.5,
133.9, 130.5, 128.8, 128.5, 128.4, 127.9, 127.5, 127.4, 127.2,
127.1, 127.0, 126.8, 120.7, 48.9; MS (ESI): m/z=389 [M+
H]+; HR-MS (ESI): m/z=389.16444, calcd. for C27H21ON2:
389.16484 [M+H]+.
3-Benzyl-2-(p-tolyl)quinazolin-4(3H)-one (2):[12] Yield:
86%; white solid; mp 123–1248C; IR (neat): nmax =3063,
2922, 1675, 1608, 1583, 1563, 1471, 1421, 1376, 1238, 1074,
1
966, 774, 694 cmÀ1; H NMR (500 MHz, CDCl3): d=8.35 (d,
J=7.9 Hz, 1H), 7.77–7.73 (m, 2H), 7.51–7.47 (m, 1H), 7.25
(d, J=8.1 Hz, 2H), 7.22–7.18 (m, 5H), 6.96 (dd, J=7.4,
1.9 Hz, 2H), 5.28 (s, 2H), 2.38 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=162.3, 156.4, 147.1, 139.9, 136.5, 134.3, 132.2,
129.8, 129.0, 128.3, 127.8, 127.3, 127.2, 126.8, 126.7, 120.6,
48.7, 21.2; MS (ESI): m/z=327 [M+H]+; HR-MS (ESI):
m/z=327.14817, calcd. for C22H19ON2: 327.14919 [M+H]+.
3-Benzyl-2-(4-methoxyphenyl)quinazolin-4(3H)-one
4-(3-Benzyl-4-oxo-3,4-dihydroquinazolin-2-yl)benzonitrile
(8):[12] Yield: 70%; white solid; mp 68–708C; IR (neat):
nmax =3065, 2924, 1675, 1639, 1608, 1500, 1450, 1380, 1238,
1
746, 693 cmÀ1; H NMR (400 MHz, CDCl3): d=8.38 (dd, J=
8.0, 1.0 Hz, 1H), 7.84–7.79 (m, 1H), 7.74 (d, J=7.3 Hz, 1H),
7.67 (d, J=8.4 Hz, 2H), 7.59–7.54 (m, 1H), 7.43 (d, J=
8.3 Hz, 2H), 7.24–7.18 (m, 3H), 6.87 (dd, J=6.5, 2.9 Hz,
2H), 5.23 (s, 2H); 13C NMR (125 MHz, CDCl3): d=161.9,
154.3, 146.7, 139.0, 135.8, 134.7, 132.1, 128.7, 128.6, 127.7,
127.6, 127.4, 127.1, 126.5, 120.7, 117.8, 113.6, 48.5; MS (ESI):
m/z=338 [M+H]+; HR-MS (ESI): m/z=338.12835, calcd.
for C22H16ON3: 338.12879 [M+H]+.
(3):[12] Yield: 90%; white solid; mp 116–1188C; IR (neat):
nmax =3064, 2922, 1678, 1603, 1512, 1470, 1427, 1376, 1260,
1
1026, 968, 772, 694 cmÀ1; H NMR (500 MHz, CDCl3): d=
8.35 (d, J=6.8 Hz, 1H), 7.84–7.75 (m, 2H), 7.50 (s, 1H),
7.31 (d, J=7.8 Hz, 2H), 7.25–7.20 (m, 3H), 6.97 (d, J=
6.6 Hz, 2H), 6.90 (d, J=7.7 Hz, 2H), 5.30 (s, 2H), 3.82 (s,
3H); 13C NMR (125 MHz, CDCl3): d=162.4, 160.6, 156.3,
147.1, 136.5, 134.4, 129.5, 128.4, 127.5, 127.3, 127.2, 126.9,
126.9, 126.7, 120.6, 113.8, 55.3, 48.9; MS (ESI): m/z=343
[M+H]+; HR-MS (ESI): m/z=343.14327, calcd. for
C22H19O2N2: 343.14410 [M+H]+.
3-Benzyl-2-(o-tolyl)quinazolin-4(3H)-one (9):[12] Yield:
74%; white solid; mp 107–1088C; IR (neat): nmax =3064,
2926, 1673, 1606, 1586, 1567, 1472, 1452, 1376, 1217, 908,
1
774, 693 cmÀ1; H NMR (500 MHz, CDCl3): d=8.41 (dd, J=
3-Benzyl-2-(4-fluorophenyl)quinazolin-4(3H)-one (4):[12]
Yield: 82%; colourless solid; mp 123–1248C; IR (neat):
nmax =3079, 2923, 1678, 1603, 1510, 1429, 1293, 1233, 1094,
8.0, 0.8 Hz, 1H), 7.80–7.75 (m, 2H), 7.56–7.53 (m, 1H),
7.38–7.35 (m, 1H), 7.24–7.12 (m, 6H), 6.86 (dd, J=10.8,
7.4 Hz, 2H), 5.24 (d, J=14.8 Hz, 1H), 5.08 (d, J=14.8 Hz,
1H), 1.95 (s, 3H); 13C NMR (125 MHz, CDCl3): d=162.4,
155.9, 147.1, 136.1, 135.9, 134.5, 134.4, 130.5, 129.8, 128.2,
127.9, 127.6, 127.5, 127.4, 127.1, 127.0, 125.8, 120.9, 48.0,
18.9; MS (ESI): m/z=327 [M+H]+; HR-MS (ESI): m/z=
327.14906, calcd. for C22H19ON2: 327.14919 [M+H]+.
923, 767, 666 cmÀ1 1H NMR (500 MHz, CDCl3): d=8.37
;
(dd, J=8.0, 0.9 Hz, 1H), 7.81–7.74 (m, 2H), 7.55–7.52 (m,
1H), 7.32 (dd, J=8.7, 5.2 Hz, 2H), 7.24–7.21 (m, 3H), 7.07
(t, J=8.6 Hz, 2H), 6.92 (dd, J=6.8, 2.5 Hz, 2H), 5.26 (s,
2H); 13C NMR (125 MHz, CDCl3): d=162.9, 162.3, 156.0,
147.1, 135.0, 134.5, 132.2, 129.9, 128.9, 128.5, 127.9, 127.5,
127.2, 126.9, 120.7, 115.4, 47.9; MS (ESI): m/z=331 [M+
H]+; HR-MS (ESI): m/z=331.12354, calcd. for C21H16ON2F:
331.12412 [M+H]+.
3-Benzyl-2-(3-methoxyphenyl)quinazolin-4(3H)-one
(10):[12] Yield: 79%; white solid; mp 118–1208C; IR (neat):
nmax =3031, 2837, 1671, 1583, 1565, 1470, 1451, 1219, 1042,
1
772, 696 cmÀ1; H NMR (500 MHz, CDCl3): d=8.38 (d, J=
3-Benzyl-2-(4-chlorophenyl)quinazolin-4(3H)-one (5):[12]
8.1 Hz, 1H), 7.81–7.75 (m, 2H), 7.53 (ddd, J=8.2, 6.5,
1.9 Hz, 1H), 7.32 (t, J=7.9 Hz, 1H), 7.24–7.20 (m, 3H),
7.00–6.95 (m, 4H), 6.76 (d, J=1.6 Hz, 1H), 5.26 (s, 2H),
3.61 (s, 3H); 13C NMR (125 MHz, CDCl3): d=162.4, 159.3,
156.1, 147.2, 136.7, 136.2, 134.5, 129.8, 128.5, 127.5, 127.3,
127.1, 127.0, 126.8, 120.8, 120.0, 116.5, 112.7, 55.1, 48.9; MS
(ESI): m/z=343 [M+H]+; HR-MS (ESI): m/z=343.14387,
calcd. for C22H19O2N2: 343.14410 [M+H]+.
Yield: 79%; white solid; mp 158–1598C; IR (neat): nmax
=
;
3064, 2925, 1672, 1600, 1492, 1377, 1233, 1090, 968, 693 cmÀ1
1H NMR (500 MHz, CDCl3): d=8.35 (d, J=7.7 Hz, 1H),
7.81–7.70 (m, 2H), 7.57–7.46 (m, 1H), 7.34 (d, J=7.6 Hz,
2H), 7.26 (d, J=7.9 Hz, 2H), 7.20 (s, 3H), 6.91 (d, J=
4.8 Hz, 2H), 5.23 (s, 2H); 13C NMR (125 MHz, CDCl3): d=
162.1, 155.1, 146.8, 136.1, 135.9, 134.5, 133.3, 129.3, 128.5,
128.4, 127.3, 127.2, 127.2, 126.9, 126.5, 120.5, 48.6; MS (ESI):
m/z=347 [M+H]+; HR-MS (ESI): m/z=347.09394, calcd.
for C21H16ON2Cl: 347.09457 [M+H]+.
3-Benzyl-2-(2,4-dichlorophenyl)quinazolin-4(3H)-one
(11): Yield: 71%; yellow oil; IR (neat): nmax =3066, 2925,
1677, 1595, 1471, 1377, 964, 773, 694 cmÀ1
;
1H NMR
3-Benzyl-2-(4-bromophenyl)quinazolin-4(3H)-one (6):[13]
(500 MHz, CDCl3): d=8.41 (dd, J=8.0, 1.3 Hz, 1H), 7.82–
7.78 (m, 1H), 7.74 (d, J=7.7 Hz, 1H), 7.61–7.55 (m, 2H),
Yield: 83%; white solid; mp 144–1458C; IR (neat): nmax
=
86
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FULL PAPERS
Rhodium(II)-Catalyzed Carbenoid Insertion of N-Tosylhydrazones
7.51 (d, J=2.0 Hz, 1H), 7.23–7.16 (m, 4H), 6.97 (d, J=
8.2 Hz, 1H), 6.87 (dd, J=7.5, 1.8 Hz, 1H), 5.79 (d, J=
15.4 Hz, 1H), 4.58 (d, J=15.4 Hz, 1H); 13C NMR (125 MHz,
CDCl3): d=162.0, 152.6, 147.0, 136.5, 134.6, 133.2, 132.7,
131.1, 129.5, 128.5, 127.7, 127.6, 127.6, 127.2, 127.2, 127.1,
121.1, 119.5, 47.9; MS (ESI): m/z=381 [M+H]+; HR-MS
(ESI): m/z=381.05542, calcd. for C21H15ON2Cl2: 381.05560
[M+H]+.
(125 MHz, CDCl3): d=161.0, 156.9, 146.3, 143.2, 136.0,
135.8, 130.0, 128.5, 128.4, 128.3, 127.8, 127.4, 126.8, 123.2,
122.2, 91.5, 48.9; MS (ESI): m/z=439 [M+H]+; HR-MS
(ESI): m/z=439.02950, calcd. for C21H16ON2I: 439.03018
[M+H]+.
3-(4-Methylbenzyl)-2-phenylquinazolin-4(3H)-one
Yield: 92%; white solid; mp 140–1428C; IR (neat): nmax
3054, 2922, 2855, 1672, 1605, 1585, 1564, 1471, 1375, 771,
694 cmÀ1 1H NMR (500 MHz, CDCl3): d=8.37 (d, J=
(17):
=
3-Benzyl-2-(3,4-dimethoxyphenyl)quinazolin-4(3H)-one
(12):[14] Yield: 78%; white solid; mp 141–1438C; IR (neat):
nmax =3064, 2933, 1676, 1607, 1586, 1564, 1514, 1469, 1374,
;
7.9 Hz, 1H), 7.80–7.75 (m, 2H), 7.54–7.46 (m, 2H), 7.41 (t,
J=7.5 Hz, 2H), 7.37–7.35 (m, 2H), 7.01 (d, J=7.9 Hz, 2H),
6.82 (d, J=8.0 Hz, 2H), 5.23 (s, 2H), 2.28 (s, 3H); 13C NMR
(125 MHz, CDCl3): d=162.3, 156.4, 147.1, 137.0, 135.1,
134.4, 133.4, 129.8, 129.1, 128.5, 128.0, 127.4, 127.0, 126.9,
126.4, 120.8, 48.6, 21.0; MS (ESI): m/z=327 [M+H]+; HR-
MS (ESI): m/z=327.14889, calcd. for C22H19ON2: 327.14919
[M+H]+.
1
1262, 1172, 1141, 1025, 772, 695 cmÀ1; H NMR (500 MHz,
CDCl3): d=8.37 (d, J=7.9 Hz, 1H), 7.82–7.77(m, 2H), 7.53
(t, J=7.3 Hz, 1H), 7.28–7.20 (m, 3H), 7.04 (d, J=8.0 Hz,
1H), 7.00 (d, J=7.2 Hz, 2H), 6.90 (d, J=8.2 Hz, 1H), 6.72
(s, 1H), 5.28 (s, 2H), 3.91 (s, 3H), 3.53 (s, 3H); 13C NMR
(100 MHz, CDCl3): d=162.4, 156.4, 150.3, 148.4, 146.8,
136.8, 134.5, 128.5, 127.6, 127.2, 127.2, 127.1, 127.0, 126.5,
120.8, 120.5, 111.0, 110.8, 55.9, 55.4, 49.2; MS (ESI): m/z=
373 [M+H]+; HR-MS (ESI): m/z=373.15399, calcd. for
C23H21O3N2: 373.15467 [M+H]+.
3-(4-Methoxybenzyl)-2-phenylquinazolin-4(3H)-one
(18):[13] Yield: 98%; white solid; mp 190–1928C; IR (neat):
nmax =3032, 2922, 1673, 1606, 1585, 1564, 1512, 1471, 1031,
772, 699 cmÀ1 1H NMR (400 MHz, CDCl3): d=8.39–8.36
;
3-Benzyl-2-(3,4,5-trimethoxyphenyl)quinazolin-4(3H)-one
(13): Yield: 75%; white solid; mp 129–1308C; IR (neat):
nmax =3063, 2937, 1675, 1583, 1565, 1502, 1468, 1453, 1413,
(m, 1H), 7.79–7.75 (m, 2H), 7.55–7.47 (m, 2H), 7.45–7.41
(m, 2H), 7.36 (dd, J=8.2, 1.4 Hz, 2H), 6.85 (d, J=8.5 Hz,
2H), 6.72 (d, J=8.8 Hz, 2H), 5.22 (s, 2H), 3.75 (s, 3H);
13C NMR (125 MHz, CDCl3): d=162.4, 158.9, 156.3, 147.2,
135.3, 134.4, 129.8, 128.6, 128.5, 128.5, 128.0, 127.5, 127.0,
127.0, 120.9, 113.8, 55.2, 48.1; MS (ESI): m/z=343 [M+H]+;
HR-MS (ESI): m/z=343.14376, calcd. for C22H19O2N2:
343.14410 [M+H]+.
1
1292, 1236, 1123, 1002, 773, 696 cmÀ1; H NMR (500 MHz,
CDCl3): d=8.38 (d, J=8.3 Hz, 1H), 7.82–7.77 (m, 2H),
7.56–7.52 (m, 1H), 7.33–7.20 (m, 3H), 7.01 (d, J=7.4 Hz,
2H), 6.51 (s, 2H), 5.25 (s, 2H), 3.85 (s, 3H), 3.60 (s, 6H);
13C NMR (125 MHz, CDCl3): d=162.4, 156.2, 153.0, 147.0,
139.0, 136.9, 134.5, 130.0, 128.5, 127.4, 127.2, 127.1, 126.9,
126.4, 120.6, 105.0, 60.7, 55.7, 49.2; MS (ESI): m/z=403
[M+H]+; HR-MS (ESI): m/z=403.16512, calcd. for
C24H23O4N2: 403.16523 [M+H]+.
3-(2-Methoxybenzyl)-2-phenylquinazolin-4(3H)-one (19):
Yield: 76%; pale yellow solid; mp 158–1608C; IR (neat):
nmax =3019, 1677, 1605, 1441, 1215, 771, 742, 667 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=8.37 (d, J=7.8 Hz, 1H),
7.88–7.75 (m, 2H), 7.53–7.49 (m, 1H), 7.43–7.31 (m, 4H),
7.25 (d, J=3.1 Hz, 1H), 7.20–7.15 (m, 1H), 6.91 (d, J=
6.2 Hz, 1H), 6.83 (t, J=7.2 Hz, 1H), 6.73 (d, J=8.1 Hz,
1H), 5.26 (s, 2H), 3.59 (s, 3H); 13C NMR (125 MHz,
CDCl3): d=162.4, 156.9, 156.3, 147.1, 134.3, 129.6, 129.6,
128.9, 128.6, 128.2, 127.7, 127.3, 127.0, 126.9, 126.1, 124.6,
120.4, 110.0, 55.0, 44.6; MS (ESI): m/z=343 [M+H]+; HR-
MS (ESI): m/z=343.14392, calcd. for C22H19O2N2: 343.14410
[M+H]+.
3-Benzyl-2-(thiophen-2-yl)quinazolin-4(3H)-one
(14):
Yield: 72%; white solid; mp 141–1438C; IR (neat): nmax
=
1677, 1607, 1552, 1473, 1429, 1219, 1145, 772 cmÀ1; H NMR
(500 MHz, CDCl3): d=8.34–8.31 (m, 1H), 7.79–7.76 (m,
1H), 7.53–7.47 (m, 3H), 7.33–7.25 (m, 4H), 7.17 (dd, J=3.7,
1.1 Hz, 1H), 7.10 (d, J=7.1 Hz, 1H), 7.02–6.99 (m, 1H),
5.50 (s, 2H); 13C NMR (100 MHz, CDCl3): d=162.4, 150.3,
147.1, 136.5, 134.5, 132.5, 129.2, 129.2, 128.8, 127.5, 127.3,
127.2, 127.2, 127.0, 126.1, 120.3, 49.2; MS (ESI): m/z=319
[M+H]+; HR-MS (ESI): m/z=319.08980, calcd. for
C19H15ON2S: 319.08996 [M+H]+.
1
3-(3-Methoxybenzyl)-2-phenylquinazolin-4(3H)-one (20):
Yield: 85%; white solid; mp: 161–1628C; IR (neat): nmax
3032, 2954, 2922, 2851, 1673, 1606, 1585, 1564, 1512, 1443,
1376, 772, 699 cmÀ1 1H NMR (500 MHz, CDCl3): d=8.37
=
3-Benzyl-6-chloro-2-phenylquinazolin-4(3H)-one (15):[12]
Yield: 77%; white solid; mp 126–1278C; IR (neat): nmax
=
;
3062, 3030, 2930, 1682, 1603, 1585, 1560, 1470, 1447, 1072,
(d, J=8.0 Hz, 1H), 7.81–7.76 (m, 2H), 7.52 (m, 1H), 7.46 (t,
J=7.2 Hz, 1H), 7.43–7.35 (m, 2H), 7.33–7.28 (m, 1H), 7.24–
7.19 (m, 1H), 7.12 (t, J=7.9 Hz, 1H), 6.87–6.72 (m, 2H),
6.54–6.45 (m, 1H), 5.24 (s, 2H), 3.69 (s, 3H); 13C NMR
(125 MHz, CDCl3): d=162.3, 159.6, 156.3, 147.1, 145.0,
134.5, 129.8, 129.5, 128.9, 128.5, 127.9, 127.5, 127.1, 126.5,
120.2, 119.1, 112.7, 112.6, 55.1, 48.7; MS (ESI): m/z=343
[M+H]+; HR-MS (ESI): m/z=343.14438, calcd. for
C22H19O2N2: 343.14410 [M+H]+.
1
772, 692 cmÀ1; H NMR (500 MHz, CDCl3): d=8.32 (s, 1H),
7.72–7.67 (m, 2H), 7.50–7.45 (m, 1H), 7.40 (t, J=7.7 Hz,
2H), 7.34–7.32 (m, 2H), 7.22–7.18 (m, 3H), 6.92–6.88 (m,
2H), 5.25 (s, 2H); 13C NMR (100 MHz, CDCl3): d=161.4,
156.5, 145.6, 136.1, 134.9, 134.8, 132.9, 130.0, 129.1, 128.5,
128.4, 127.9, 127.5, 126.9, 126.3, 121.7, 48.9; MS (ESI): m/z=
347 [M+H]+; HR-MS (ESI): m/z=347.09437, calcd. for
C21H16ON2Cl: 347.09457 [M+H]+.
3-Benzyl-6-iodo-2-phenylquinazolin-4(3H)-one
(16):
3-(4-Fluorobenzyl)-2-phenylquinazolin-4(3H)-one (21):[15]
Yield: 86%; white solid; mp 100–1028C; IR (neat): nmax,=
3016, 1677, 1606, 1587, 1566, 1511, 1473, 1219, 1095, 772,
Yield: 71%; white solid; mp 133–1358C; IR (neat): nmax
=
3063, 3031, 2923, 2853, 1717, 1678, 1605, 1554, 1452, 1069,
1
772, 692 cmÀ1; H NMR (400 MHz, CDCl3): d=8.68 (d, J=
698 cmÀ1 1H NMR (500 MHz, CDCl3): d=8.36 (d, J=
;
1.8 Hz, 1H), 8.00 (d, J=8.6 Hz, 1H), 7.47–7.44 (m, 1H),
7.38 (t, J=7.5 Hz, 2H), 7.34–7.23 (m, 4H), 7.20–7.18 (m,
2H), 6.88 (dd, J=6.3, 2.6 Hz, 2H), 5.22 (s, 2H); 13C NMR
7.6 Hz, 1H), 7.80–7.74 (m, 2H), 7.53 (ddd, J=8.2, 6.6,
1.8 Hz, 2H), 7.50–7.47 (m, 2H), 7.42 (t, J=7.5 Hz, 2H), 7.34
(d, J=7.2 Hz, 2H), 6.88 (d, J=7.0 Hz, 2H), 5.24 (s, 2H);
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13C NMR (125 MHz, CDCl3): d=162.3, 161.0, 156.0, 147.1,
134.5, 132.2, 129.9, 128.9, 128.8, 128.5, 127.9, 127.5, 127.2,
126.9, 120.7, 115.4, 47.9; MS (ESI): m/z:=331 [M+H]+;
HR-MS (ESI): m/z=331.12356, calcd. for C21H16ON2F:
331.12412 [M+H]+.
3-Cyclohexyl-2-phenylquinazolin-4(3H)-one (27):[17] Yield:
70%; pale yellow solid; mp 132–1348C; IR (neat): nmax
3033, 2935, 2857, 1672, 1605, 1585, 1565, 1455, 771 cmÀ1
=
;
1H NMR (400 MHz, CDCl3): d=8.30 (d, J=7.9 Hz, 1H),
7.72 (s, 2H), 7.56–7.45 (m, 6H), 3.87 (t, J=11.9 Hz, 1H),
2.74 (q, J=12.3 Hz, 2H), 1.73 (dd, J=25.8, 11.5 Hz, 4H),
1.58 (d, J=21.5 Hz, 1H), 1.23 (d, J=12.2 Hz, 1H), 0.96 (d,
J=11.3 Hz, 2H); 13C NMR (125 MHz, CDCl3): d=162.6,
156.9, 146.6, 136.3, 134.1, 129.7, 128.8, 127.0, 126.9, 126.5,
125.5, 122.1, 62.7, 28.8, 26.2, 24.9; MS (ESI): m/z=305 [M+
H]+; HR-MS (ESI): m/z=305.16451, calcd. for C20H21ON2:
305.16484 [M+H]+.
3-(4-Chlorobenzyl)-2-phenylquinazolin-4(3H)-one (22):[15]
Yield: 85%; white solid; mp 143–1458C; IR (neat): nmax
=
3018, 1675, 1607, 1588, 1567, 1492, 1474, 1215, 1094, 771,
1
742, 666 cmÀ1; H NMR (400 MHz, CDCl3): d=8.37 (d, J=
7.2 Hz, 1H), 7.82–7.75 (m, 2H), 7.54 (ddd, J=8.1, 6.6,
1.7 Hz, 1H), 7.51–7.47 (m, 2H), 7.44–7.40 (m, 1H), 7.34 (dd,
J=8.3, 1.3 Hz, 2H), 7.18 (d, J=8.5 Hz, 2H), 6.86 (d, J=
8.5 Hz, 2H), 5.23 (s, 2H); 13C NMR (125 MHz, CDCl3): d=
162.3, 156.0, 147.1, 135.0, 134.6, 133.3, 130.0, 129.3, 128.6,
128.4, 127.9, 127.5, 127.2, 127.0, 126.7, 120.7, 48.1; MS (ESI):
m/z=347 [M+H]+; HR-MS (ESI): m/z=347.09460, calcd.
for C21H16ON2Cl: 347.09457 [M+H]+.
3-Benzyl-2-isopropylquinazolin-4(3H)-one (28):[18] Yield:
78%; white solid; mp 110–1118C; IR (neat): nm1ax =2958,
2924, 2854, 1676, 1592, 1570, 1455, 773, 695 cmÀ1; H NMR
(500 MHz, CDCl3): d=8.30 (dd, J=8.0, 1.2 Hz, 1H), 7.75–
7.67 (m, 2H), 7.45 (t, J=6.9 Hz, 1H), 7.33–7.24(m, 3H),
7.15 (d, J=7.4 Hz, 2H), 5.47 (s, 2H), 3.10 (septet, J=6.6 Hz,
1H), 1.27 (d, J=6.7 Hz, 6H); 13C NMR (100 MHz, CDCl3):
d=162.7, 161.7, 147.5, 136.5, 134.1, 128.8, 127.4, 127.1, 127.0,
126.3, 126.1, 120.3, 45.8, 32.1, 21.3; MS (ESI): m/z=279
[M+H]+; HR-MS (ESI): m/z=279.14866, calcd. for
C18H19N2O: 279.14919 [M+H]+.
2-Phenyl-3-(4-(trifluoromethyl)benzyl)quinazolin-4(3H)-
one (23): Yield: 79%; white solid; mp 123–1258C; IR (neat):
nmax =3064, 2923, 2852, 1676, 1605, 1588, 1566, 1472, 1375,
1
1323, 1219, 1164, 1120, 1067, 1018, 772, 699 cmÀ1; H NMR
(500 MHz, CDCl3): d=8.37 (d, J=7.6 Hz, 1H), 7.83–7.78
(m, 2H), 7.56–7.53 (m, 2H), 7.48 (d, J=8.5 Hz, 2H), 7.42 (t,
J=7.6 Hz, 2H), 7.36–7.34 (m, 2H), 7.07 (d, J=8.1 Hz, 2H),
5.32 (s, 2H); 13C NMR (125 MHz, CDCl3): d=162.3, 155.9,
147.1, 140.5, 134.7, 133.4, 130.1, 128.9, 128.7, 128.4, 127.9,
127.6, 127.3, 127.2, 127.0, 125.5, 120.6, 48.5; MS (ESI): m/z=
381 [M+H]+; HR-MS (ESI): m/z=381.12103, calcd. for
C22H16ON2F3: 381.12092 [M+H]+.
2-Benzyl-3-phenyl-2H-benzo[e][1,2,4]thiadiazine 1,1-diox-
ide (29): Yield: 82%; pale yellow liquid; IR (neat): nmax
3063, 3030, 2923, 2853, 1558, 1493, 1455, 1342, 1181, 1157,
1128, 1073, 1024, 760, 694 cmÀ1 1H NMR (500 MHz,
=
;
CDCl3): d=7.87 (dd, J=7.8, 1.2 Hz, 1H), 7.77 (d, J=7.3 Hz,
2H), 7.64–7.60 (m, 1H), 7.57–7.51 (m, 2H), 7.49–7.43 (m,
2H), 7.35 (d, J=4.5 Hz, 2H), 7.09–6.98 (m, 2H), 6.71 (d, J=
7.5 Hz, 2H), 4.97 (s, 2H); 13C NMR (100 MHz, CDCl3): d=
155.7, 142.4, 134.9, 133.8, 133.2, 131.7, 129.1, 128.7, 128.4,
128.2, 128.1, 127.8, 127.5, 126.8, 121.1, 51.3; MS (ESI): m/z=
349 [M+H]+; HR-MS (ESI): m/z=349.10168, calcd. for
C20H17O2N2S: 349.10053 [M+H]+.
2-Phenyl-3-(pyridin-3-ylmethyl)quinazolin-4(3H)-one
(24): Yield: 76%; white solid; mp 122–1248C; IR (neat):
nmax =3060, 3033, 2924, 2853, 1671, 1604, 1586, 1565, 1472,
1427, 1219, 1025, 772, 700 cmÀ1
;
1H NMR (500 MHz,
CDCl3): d=8.35 (d, J=8.0 Hz, 1H), 8.09 (d, J=7.4 Hz, 1H),
7.78–7.76 (m, 3H), 7.54–7.49 (m, 3H), 7.45 (d, J=7.2 Hz,
3H), 7.36 (d, J=7.1 Hz, 2H), 5.30 (s, 2H); 13C NMR
(125 MHz, CDCl3): d=162.1, 155.5, 147.6, 146.8, 135.2,
134.6, 134.5, 132.3, 130.0, 129.6, 128.6, 128.0, 127.7, 127.4,
127.1, 126.7, 120.4, 46.3; MS (ESI): m/z=314 [M+H]+; HR-
MS (ESI): m/z=314.12836, calcd. for C20H16ON3: 314.12879
[M+H]+.
3-(3,4-Dichlorobenzyl)-2-phenylquinazolin-4(3H)-one
(30): Yield: 81%; white solid; mp 120–1218C; IR (neat):
nmax,=3063, 2953, 2922, 2852, 1675, 1605, 1587, 1565, 1469,
1030, 754, 697 cmÀ1 1H NMR (500 MHz, CDCl3): d=8.37
;
(dd, J=8.0, 0.8 Hz, 1H), 7.83–7.76 (m, 2H), 7.57–7.49 (m,
2H), 7.45 (t, J=7.5 Hz, 2H), 7.34 (d, J=7.1 Hz, 2H), 7.28
(d, J=8.3 Hz, 1H), 6.96 (d, J=2.0 Hz, 1H), 6.80 (dd, J=8.3,
2.0 Hz, 1H), 5.20 (s, 2H); 13C NMR (100 MHz, CDCl3): d=
162.2, 155.7, 147.0, 136.6, 134.8, 134.7, 132.5, 131.6, 130.4,
130.1, 129.2, 128.7, 127.9, 127.6, 127.3, 127.0, 126.5, 120.6,
47.6; MS (ESI): m/z=381 [M+H]+; HR-MS (ESI): m/z=
381.05799, calcd. for C21H15ON2Cl2: 381.05560 [M+H]+.
2-Phenyl-3-propylquinazolin-4(3H)-one (25):[16] Yield:
71%; white solid; mp 120–1228C; IR (neat): nmax =2942,
2831, 1678, 1604, 1589, 1448, 1219, 1020, 772, 672 cmÀ1
;
1H NMR (500 MHz, CDCl3): d=8.34 (d, J=8.0 Hz, 1H),
7.75 (d, J=3.6 Hz, 2H), 7.55–7.42 (m, 6H), 3.97–3.93 (m,
2H), 1.68–1.60 (m, 2H), 0.76 (t, J=7.4 Hz, 3H); 13C NMR
(125 MHz, CDCl3): d=162.0, 156.2, 146.9, 135.3, 134.2,
129.7, 128.6, 127.7, 127.2, 126.9, 126.6, 120.8, 47.4, 22.0, 11.0;
MS (ESI): m/z=265 [M+H]+; HR-MS (ESI): m/z=
265.13329, calcd. for C17H17ON2: 265.13354 [M+H]+.
Acknowledgements
3-Butyl-2-phenylquinazolin-4(3H)-one
(26):[14]
Yield:
We thank the Director of CSIR – Indian Institute of Chemi-
cal Technology for the generous support and CSIR, New
Delhi for funding through the program ORIGIN XII FYP
(CSC-0108). R. L. and V. M thank CSIR, New Delhi for the
Senior Research Fellowships.
73%; white solid; mp 114–1158C; IR (neat): nmax,=3013,
1
2961, 2932, 1670, 1606, 1585, 1557, 1020, 772 cmÀ1; H NMR
(400 MHz, CDCl3): d=8.34 (d, J=7.9 Hz, 1H), 7.78–7.72
(m, 2H), 7.55–7.48 (m, 6H), 4.01–3.96 (m, 2H), 1.63–1.55
(m, 2H), 1.22–1.13 (m, 2H), 0.76 (t, J=7.4 Hz, 3H);
13C NMR (125 MHz, CDCl3): d=161.9, 156.1, 146.9, 135.3,
134.1, 129.6, 128.5, 127.6, 127.2, 126.8, 126.5, 120.7, 45.5,
30.5, 19.7, 13.2; MS (ESI): m/z=279 [M+H]+; HR-MS
(ESI): m/z=279.14776, calcd. for C18H19ON2: 279.14919
[M+H]+.
88
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ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2016, 358, 81 – 89

FULL PAPERS
Rhodium(II)-Catalyzed Carbenoid Insertion of N-Tosylhydrazones
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