Preparation of N-Arylquinazolinium Salts via a Cascade Approach

Article abstract of DOI:10.1021/acs.joc.9b00601

An easy manipulation method for the preparation of N-arylquinazolinium salts is described from readily available aryldiazonium salts, nitriles, and 2-aminoarylketones in a one-pot operation. This method relies on the in situ generation of the N-arylnitrilium intermediate from the reaction of aryldiazonium salt with nitrile, which undergoes amination/cascade cyclization/aromatization, leading to N-arylquinazolinium salts in excellent yields. Nucleophilic addition of alkoxide to these N-arylquinazolinium salts provides functionalized dihydro-N-arylquinazoline.

Full text of DOI:10.1021/acs.joc.9b00601

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Note
Preparation of N-Arylquinazolinium Salts via a Cascade Approach
Mani Ramanathan, Jing Wan, and Shiuh-Tzung Liu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00601 • Publication Date (Web): 13 May 2019
Downloaded from http://pubs.acs.org on May 13, 2019
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Preparation of N-Arylquinazolinium Salts via a
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Cascade Approach
Mani Ramanathan, Jing Wan and Shiuh-Tzung Liu*
Department of Chemistry, National Taiwan University, Taipei 106, Taiwan
Corresponding author. E-mail: stliu@ntu.edu.tw
TITLE RUNNING HEAD: Arylquinazolinium Salts
Graphic Abstract (TOC)
___________________________________________________________________
+
-
O
Ar
N
N2 BF4
Nu OR
N
R2
RO-
Ar
H2N
N
R1
R1
RCN
-
R BF4
N
R
R2
R2
R1
One-pot fashion
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ABSTRACT. An easy manipulation method for the preparation of N-arylquinazolinium salts is
described from readily available aryldiazonium salts, nitriles and 2-aminoarylketones in a one-
pot operation. This method relies on the in situ generation of N-arylnitrilium intermediate from
the reaction of aryldiazonium salt with nitrile, which undergoes amination/cascade
cyclization/aromatization leading to N-arylquinazolinium salts in excellent yields. Nucleophilic
addition of alkoxide to these N-arylquinazolinium salts provides functionalized dihydro-N-
arylquinazoline.
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KEYWORDS. Quinazolinium, Diazonium, Cascade reaction, Nitrilium.
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Quinazoline and its derivatives represent a potential class of heterocyclic scaffolds found in
drugs exerting unique pharmacological activities including antiasthmatic,1 antitubercular,2
antiviral,3 anticancer,4 antimalarial,5 antihypertensive6 and anticonvulsant7 properties. In
addition, quinazolines exhibit excellent photophysical properties8 and act as potential ligands in
asymmetric transformations.9 Consequently, numerous synthetic routes have been developed to
access this ubiquitous core.10
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Despite the skeletal diversity in quinazoline, cationic quinazolinium derivatives have rarely
been found in literature.11 Figure 1 summarizes some known quinazolinium species and most of
them are prepared by N-substitution reactions. A chelated palladacycle was used as the substrate
to render the N-arylquinazolinium salts IV in low yields via an insertion of alkyne followed by
depalladation.11d
-
BF4
R
N
R
Br-
RN
Ar
S
R
N
N
N
Cl-
OH
-OH
R'
Ar
N
N
H
N
N
OMe
R = alkyl
N
I
II
III
IV
Figure 1. Some known quinazolinium salts
Aryldiazonium salts are prerogative reagents in synthetic uses.12 In recent years, the use of N-
arylnitrilium intermediates, generated in situ from aryldiazonium salts and nitriles, has received
significant attention due to the applications in the synthesis of various heterocycles.13-14 We
envisioned the possibility of developing a one-pot preparation of substituted N-
arylquinazolinium salts. The unprecedented synthesis was expected to proceed via an initial
formation
of
N-arylnitrilium
intermediate
(V)
followed
by
a
tandem
amination/cyclization/elimination sequences as shown in Scheme 1.
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Scheme 1. Proposed Synthetic Approach to N-arylquinazolinium salts.
5
6
Ph
7
8
9
O
-
N2+BF4
O
R
Ph
N
H2N
N
RCN
-N2
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N
R
V
H
Ph OH
Ph
N
N
N
BF4
R
- H2O
N
R
To explore this feasibility, we investigated the reaction of 1a with 2a in anhydrous MeCN
o
under various conditions (Table 1). When the reaction was carried out at 80 C for 2 h, the
desired product 3a was isolated in 52% yield by the addition of ether to the mixture followed by
a filtration (Table 1, entry 1). To our delight, significant improvement in yield was observed
o
upon increasing the temperature to 120 C (Table 1, entries 3-5). Conducting the reaction for a
longer period led to no further improvement (Table 1, entry 6). Unfortunately, our attempts to
reduce the amount of nitrile in the presence of co-solvents such as DCE, DMSO and toluene
were unfruitful (Table 1, entries 7-10). It is noticed that the yield does not improved by addition
of molecular sieves (Table 1, entry 11) due to the decomposition.
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Table 1. Reaction Optimizationa
5
6
7
-
N2+BF4
O
8
9
MeCN
Ph
H2N
2a
N
-
BF4
N
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1a
3a
entry solvent
T (oC)
80
t (h)
2
Yield (%)b
1
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
52
48
66
63
81
78
NDd
47
15
38
10
2
80
12
3
3
100
100
120
120
120
120
120
120
120
4
5
5
5
6
12
12
12
12
12
12
7c
8c
9e
10c
11f
MeCN/DMSO
MeCN/DCE
MeCN/ DCE
MeCN/toluene
MeCN
aReaction conditions: a mixture of 1a (0.48 mmol), 2a (0.53 mmol), and anhydrous MeCN (2
mL) were heated in a sealed tube. bisolated yields. cMeCN (1 mL) in solvent (2 mL). dND = Not
detected. eMeCN (0.5 mL) in solvent (2 mL). fWith addition of 1.5 g of molecular sieve.
With the optimal conditions, we explored the reaction scope by treating 2a with aryldiazonium
salts of diverse steric and electronic characteristics in anhydrous MeCN (Table 2). A wide range
of substituted aryldiazonium salts were readily participated in the reaction and provided the
corresponding N-arylquinazolinium salts in good to excellent yields (Table 2, entries 1-9). It was
noted that the difference in the substitution pattern of the aromatic ring had no influence on the
conversion. In particular, 2,4,6-trimethylphenyldiazonium and 3,4,5-trimethoxyphenyldiazonium
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salts proceeded smoothly in the reaction and furnished the corresponding salts in good yields
(Table 2, entries 10-11). For a practical utility, treatment of 1j (0.6 g) with 2-
aminobenzophenone (0.56 g) in acetonitrile (12 mL) furnished 3j (0.83 g) in 75% yield.
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Table 2. Reaction scope with various aryldiazonium saltsa
3
4
2
R1
Ph
N
R1
N2+BF4
-
MeCN
5
N
-
2a
6
BF4
1a-k
3a-k
Entry R1 =
Product (yield)
3a (81%)
3b (62%)
3c (74%)
3d (84%)
3e (72%)
3f (71%)
3g (82%)
3h (77%)
3i (74%)
1
R1 = 4-Me
2
R1 = H
3
R1 = 3-Me
4
R1 = 2-Me
5
R1 = 2-MeS
R1 = 3-MeO
R1 = 3,4-(Me)2
R1 = 3,5-(Me)2
R1 = 2,6-(Me)2
R1 = 2,4,6-(Me)3
R1 = 3,4,5-(MeO)3
6
7
8
9
10
11
3j (88%)
3k (76%)
aReaction conditions: a mixture of diazonium salt (0.52 mmol) and 2a (0.57 mmol) in
acetonitrile (2mL) at 120 oC for 5 h. Yields given refer to isolated yields.
On the other hand, aryldiazonium salts with electron-withdrawing functional groups underwent
rapid azo-coupling with 2a leading to 5-(aryldiazenyl)-substituted 2-aminobenzophenones
(Scheme 2).15 Intriguingly, these azo-coupled products (3aa-3ac) could be accessed under mild
conditions.
+
-
Scheme 2. Reactions of 2a with ArN2 BF4 bearing electron-withdrawing groups.
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R1
O
R1
-
N2+BF4
N
Ph
MeCN/PhCN
80 oC, 5 h
N
2a
6
NH2
7
8
9
1
1
1l
3aa
3ab
3ac
, R = 3-Br
, R = 3-Br, 48%
1
1
1m
, R = 4-CO2Et
, R = 4-CO2Et, 56%
1
1
1n
, = R = 4-COPh
, R = 4-COPh, 43%
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Next, we probed the reactivity difference of aryldiazonium salts 1a, 1j, and 1o bearing
substituents in a different electronic nature (Scheme 3). It is known that the hydrolysis of
nitrilium ion into the corresponding amide is a rapid reaction.13c Thus, the measurement of the
amount of amide formation is able to compare the relative rate of reactions. It was observed that
compound 1a and 1j readily reacted with MeCN at room temperature and resulted in a
significant amount of amide upon quenching with water (Scheme 3). Furthermore, the reactivity
of 1j is more active than that of 1a due to the three methyl groups on the ring. In case of 1o with
a fluoro substituent, no amide product (1oA) was observed. These results indicate the formation
of N-arylnitrilium intermediate highly depends on the electronic nature of the aryldiazonium
components. Presumably, the electron withdrawing group at 4-position readily destabilizes the
cationic nature for the substitution.
+
-
Scheme 3. Comparison of reactivity of various ArN2 BF4 toward acetonitrile
O
R1
R1
20 eq.
CH3CN
R1
H2O
-
N2+BF4
N
H
N
fast
rt
First-hour conversion
, R1 = H,
, R1 = H,
36%
1a
1j,
1o
1aA
1 = 2,4,6-Me3 53%
R
1 = 2,4,6-Me3
, R1 = 4-F
1jA,
1oA
R
, R1 = 4-F
0%
Further, we investigated this reaction with a variety of nitriles in combination with
aryldiazonium salts and 2a (Table 3). The reaction proved efficiently with a series of 1o, 2o, 3o
and cyclic aliphatic nitriles furnishing the corresponding 2-alkylated-3,4-diarylquinazolinium
salts in moderate to excellent yields (Table 3, entries 1-8). Sterically demanding pivalonitrile led
to no desired product upon treating 2,4,6-trimethylphenyldiazonium salt (Table 3, entry 6).
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However, the product 4g was successfully isolated albeit with a diminished yield (Table 3, entry
7). To our delight, adiponitrile was also amenable for this transformation to afford the desired N-
arylquinazolinium salt in 82% yield (Table 3, entry 8). Notably, the sensitive cyano group on the
aliphatic chain remains unaffected. Furthermore, benzylnitrile was also participated well in the
reaction and afforded the desired product 4i in moderate yield (entry 9).
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Table 3. Reaction scope with various aliphatic nitrilesa
R1
Ph
R1
-
N2+BF4
RCN
N
2a
N
BF4
R
-
1a 1c
or
4a-i
entry
substituents
R1 = 2,4,6-(Me)3, R = n-Pr
yieldb
1
2
3
4
5
6
7
8
9
4a, 84%
R1 = 2,4,6-(Me)3, R = CH2CH2OMe 4b, 44%
R1 = 2,4,6-(Me)3, R = i-Pr
R1 = 2,4,6-(Me)3, R = c-Pr
R1 = 2,4,6-(Me)3, R = c-C6H11
R1 = 2,4,6-(Me)3, R = t-Bu
R1 = 3-Me, R = t-Bu
4c, 76%
4d, 78%
4e, 41%
4f, 0
4g, 31%
4h, 82%
4i, 52%
R1 = 2,4,6-(Me)3, R = (CH2)4CN
R1 = 2,4,6-(Me)3, R = CH2Ph
aReaction conditions: a mixture of diazonium salt (0.52 mmol) and 2a (0.57 mmol) in nitrile
(2mL) at 120 oC for 5 h. bYields given refer to isolated yields.
On the other hand, various substituted benzonitriles were also successfully utilized in this
reaction to furnish 2,3,4-triarylated quinazolinium salts in yields ranging from 49-71% (Table 4).
Together, these unprecedented and diverse N-arylquinolinium salts may find potential
implications for drug library and material applications.16
Table 4. Reaction scope with various aromatic nitrilesa
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3
R1
4
-
N2+BF4
2
R1
ArCN
5
6
2a
N
6
5
7
8
9
N
1a 1b 1j
R2
,
or
-
4
BF4
2
3
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entry
substituents
yieldb
1
2
3
4
5
6
7
R1 = H, R2 = H
4j, 54%
4k, 44%
4l, 71%
4m, 41%
4n, 66%
4o, 67%
4p, 49%
R1 = H, R2 = 2-Me
R1 = 4-Me, R2 = 2-Me
R1 = 2,4,6-(Me)3, R2 = 2-Me
R1 = H, R2 = 4-Me
R1 = H, R2 = 3-Br
R1 = 2,4,6-(Me)3, R2 = 4-F
aReaction conditions: a mixture of diazonium salt (0.52 mmol) and 2a (0.57 mmol) in an
aromatic nitrile (2 mL) at 120 oC for 5 h. bYields given refer to isolated yields.
Finally, we probed the scope with variously substituted 2-aminoarylketones (Scheme 4). It
was noted that, 2-aminoaryl ketone bearing halogens (Cl, F) at various positions of the aromatic
ring were participated in the reaction and conveniently led to the corresponding product in good
yields (Scheme 4, 5a-5c). Notably, multi-halogenated N-arylquinazolinium salt 5e was also
obtained in excellent yield.
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Scheme 4. Reaction of 1j with various 2-aminoarylketones
5
R2
4
6
7
8
9
5
3
2
-
N2+BF4
O
R1
5
8
MeCN
Ar
H2N
2b-2f
6
7
N
R3
120 oC, 5 h
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N
-
BF4
1j
, R3 = 6-Cl, R2 = H, 77%
5a
5b
5c
3
2
, R = 6-Br, R = H, 74%
, R3 = H, R2 = 4-F, 78%
, R3 = H, R2 = 4-Me, 78%
, R3 = 6-Cl, R2 =2'-Cl, 73%
5d
5e
Interestingly, when 2-aminoacetophenone was treated with 1j in MeCN, an inseparable
mixture (60:40) of 5f and 5f’were observed in CD3CN (Scheme 5). However, upon base
treatment, this mixture readily converted into one isomeric form 6.
Scheme 5. Reaction of 1j with 2-aminoacetophenone
O
-
BF4
H3C
H
N
N
N
H2N
1j
Na2CO3
N
Me
N
Me
N
Me
MeCN
120 oC, 5 h
6
5f
60
5f'
40
+
:
(51%)
In contrary to our earlier observations,14a,14d,14f aryldiazonium salt 1p with adjacent phenyl
group, reacted with 2a and MeCN to give 7 in good yield in lieu of 6-methylphenanthridine
(Scheme 6, Eq. 1). Apparently, N-arylnitrilium intermediate is reactive towards amino
nucleophile rather than adjacent phenyl group leading to 7. On the other hand, aryldiazonium salt
with o-ester functionality expeditiously resulted in the formation of 8 (Scheme 6, Eq. 2), unlike
compound 3ab presumably due to the steric hindrance preventing the diazo coupling. Seemingly,
the rate of intramolecular amidation is faster than that of the intermolecular amination/tandem
cyclization/elimination sequences.
Scheme 6. Reactions of 2a with o-functionalized aryldiazonium salts
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N
Ph
N
-
N2+BF4 2a
(1)
MeCN
110 o
5 h
N
Ph
C
-
BF4
Not formed
1p
1q
7
, 76%
Ph
N
-
O
N2+BF4
2a
MeCN
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(2)
N
110 o
5 h
C
CO2Me
CO2Me
N
COPh
-
BF4
N
8
, 77%
Not formed
Further synthetic application using these quinazolinium salts is demonstrated by the
nucleophilic addition of alkoxides leading to the dihydroquinazolines. Typically, reaction of 4d
with sodium methoxide gave 9a in 96% yield. Similarly, compound 4o reacted with ethoxide in
ethanol under ambient temperature provided 9b in 84% yield (Scheme 7). Furthermore, this
dihydroquinazoline could be obtained from a sequential treatment without the isolation of
quinazolinium salt (Scheme 7). Thus, reaction of o-toluenediazonium tetrafluoroborate and 2-
o
amino-5-chlorbenzophenone in acetonitrile at 120 C for 5 h led to the desired quinazolinium
salts, which was stirred in a basic methanol/water solution at room temperature for 12 h to yield
the dihydroquinazoline 9c.
Scheme 7. Structures of 9a-b and direct preparation of 9c.
Et
O
Ph
N
MeO Ph
N
N
N
9b
(84%)
9a
(96%)
Br
MeO Ph
N
O
Cl
1. CH3CN, 120 oC, 5 h
2. CH3OH/NaOH
Cl
+
Ph
NH2
N
-
N2+BF4
9c
(92%)
2b
1d
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In summary, we have disclosed an efficient method to prepare diversely substituted N-
arylquinazolinium salts from readily accessible aryldiazonium salts, nitriles and 2-amino
arylketones in a one-pot manner. Nucleophilic addition of alkoxide toward these quinazolinium
salts giving the dihydroquinazoline derivative provides an alternative to prepare various
quinazolines.
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Experimental Section
General information. 1H and 13C NMR were recorded in a 400 MHZ spectrometer in CDCl3 and
CD3CN referenced to TMS. All the nitriles were dried over activated 4Å molecular sieves and
solid nitriles were purchased and used without any further drying. All the anilines were
commercially purchased and used for diazotization without further purification. Other chemicals
were used as purchased. Flash chromatography was performed using silica gel 230-400 mesh.
Aryldiazonium salts were prepared according to the literature procedure. In cases of known
compounds, their spectral data were compared with the literature values. Melting points were
determined on a Fargo MP-1D instrument. Unless otherwise noted, all the reactions were
performed without any special precautions. Compound 2c was prepared according to the literature
method,17a whereas 2a-2b and 2d-2f were purchased.
General procedure for preparing aryldiazonium tetrafluroborate:
All the substituted aryldiazonium salts were synthesized by following the reported methods.
Spectral data of the compounds are in agreement with those reported in the literature. A typical
procedure for preparing benzenediazonium tetrafluroborate is shown below. The corresponding
aniline (0.93 g, 10 mmol) was dissolved in a mixture of water (4 mL) and 50% aqueous
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hydrofluroboric acid (3.3 mL, 19.3 mmol, 1.92 equiv.). The mixture was cooled to 0 C and a
solution of NaNO2 (0.69 g, 10 mmol in 1.5 mL of water) was added slowly. The resulting
reaction mixture was stirred at 0 oC for 30 min. and the precipitate was collected by filtration.
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The solid product was dissolved in minimum acetone and re-precipitated using diethyl ether to
yield aryldiazonium tetrafluroborate which was dried under vacuum without further purification.
General procedure for the synthesis of N-arylquinazolinium tetrafluoroborates:
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In a dry 10 mL glass sealed tube, aryldiazonium salt (100 mg, 0.52 mmol) and 2-
aminobenzophenone (113 mg, 0.57 mmol, 1.1 eq.) were suspended in 2 mL of anhydrous nitrile.
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The tube was sealed with a Teflon screw cap and heated in an oil bath (120 C) for 5 h. After
cooling to room temperature, reaction mixture was added dropwise to diethyl ether (30 mL)
under vigorous stirring. Resulting solid was filtered and dried under high vacuum to
obtain the title compound.
2-Methyl-3,4-diphenylquinazolin-3-ium tetrafluoroborate (3a).
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124 mg, 62%, off-white solid: mp 228-229 C; H NMR (400 MHz, CD3CN) δ 8.47 (ddd, J =
15.4, 7.8, 1.2 Hz, 1H), 8.32 (d, J = 8.4 Hz, 1H), 7.94 (t, J = 7.6 Hz, 1H), 7.78 (d, J = 8.4 Hz, 1H),
7.53-7.50 (m, 3H), 7.49-7.48 (m, 3H), 7.47-7.43 (m, 2H), 7.40-7.38 (m, 2H), 2.70 (s, 3H);
13C{1H} NMR (100 MHz, CD3CN) δ 169.6, 156.6, 152.5, 143.0, 139.5, 132.6, 132.4, 132.2,
132.1, 131.2, 130.4, 130.2, 129.5, 129.3, 128.1, 123.4, 25.1; HRMS (ESI-TOF) calcd. For
C21H17N2 (M)+ m/z = 297.1392, found 297.1382.
2-Methyl-4-phenyl-3-(p-tolyl)quinazolin-3-ium tetrafluoroborate (3b).
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156 mg, 81%, off-white solid: mp 248-249 C; H NMR (400 MHz, CD3CN) δ 8.45 (t, J = 8.0
Hz, 1H), 8.31 (d, J = 8.4 Hz, 1H), 7.93 (t, J = 8.0 Hz, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.53 (t, J =
7.6 Hz, 1H), 7.46 (t, J = 7.6 Hz, 2H), 7.40 (d, J = 7.6 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 7.29 (d, J
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= 8.0 Hz, 2H), 2.69 (s, 3H), 2.32 (s, 3H); C{1H} NMR (100 MHz, CD3CN) δ 169.7, 156.8,
152.4, 142.9, 142.6, 137.1, 132.5, 132.3, 132.0, 131.5, 130.4, 129.5, 129.4, 129.3, 127.7, 123.5,
25.1, 21.2; HRMS (ESI-TOF) calcd. For C22H19N2 (M)+ m/z = 311.1548, found 311.1551.
2-Methyl-4-phenyl-3-(m-tolyl)quinazolin-3-ium tetrafluoroborate (3c).
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142 mg, 74%, off-white solid: mp 216-217 C; H NMR (400 MHz, CD3CN) δ 8.46 (t, J = 7.6
Hz, 1H), 8.32 (d, J = 8.4 Hz, 1H), 7.94 (t, J = 8.0 Hz, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.54-7.51
(m, 1H), 7.46 (t, J = 6.8 Hz, 2H), 7.42-7.40 (m, 2H), 7.38-7.34 (m, 1H), 7.31-7.24 (m, 3H), 2.72
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(s, 3H), 2.31 (s, 3H); C{1H} NMR (100 MHz, CD3CN) δ 169.5, 156.6, 152.4, 142.9, 141.8,
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139.4, 132.6, 132.5, 132.3, 132.0, 130.8, 130.4, 129.4 (2C), 129.3, 128.4, 124.9, 123.4, 25.0,
21.1; HRMS (ESI-TOF) calcd. For C22H19N2 (M)+ m/z = 311.1548, found 311.1552.
2-Methyl-4-phenyl-3-(o-tolyl)quinazolin-3-ium tetrafluoroborate (3d).
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162 mg, 84%, off-white solid: mp 214-215 C; H NMR (400 MHz, CD3CN) δ 8.49 (ddd, J =
15.6, 7.6, 1.6 Hz, 1H), 8.34 (d, J = 8.8 Hz, 1H), 7.96 (ddd, J = 15.6, 7.8, 1.2 Hz, 1H), 7.80 (dd, J
= 8.8, 0.8 Hz, 1H), 7.57-7.51 (m, 1H), 7.50-7.47 (m, 2H), 7.46-7.42 (m, 3H), 7.41-7.40 (m, 1H),
7.38-7.32 (m, 2H), 2.67 (s, 3H), 2.03 (s, 3H); 13C{1H} NMR (100 MHz, CD3CN) δ 169.4, 156.4,
152.9, 143.3, 138.4, 134.4, 133.1, 132.8, 132.7, 132.4, 132.2, 130.9, 129.5, 129.46, 129.41,
129.1, 128.7, 123.7, 24.5, 17.7; HRMS (ESI-TOF) calcd. For C22H19N2 (M)+ m/z = 311.1548,
found 311.1558.
2-Methyl-3-(2-(methylthio)phenyl)-4-phenylquinazolin-3-ium tetrafluoroborate (3e).
129 mg, 72%, pale yellow solid: mp 263-264 oC; 1H NMR (400 MHz, CD3CN) δ 8.50 (t, J = 7.6
Hz, 1H), 8.34 (d, J = 8.4 Hz, 1H), 7.96 (t, J = 7.6 Hz, 1H), 7.80 (d, J = 8.4 Hz, 1H), 7.59-7.55
(m, 2H), 7.53-7.49 (m, 2H), 7.47-7.43 (m, 3H), 7.40 (d, J = 8.0 Hz, 1H), 7.31 (t, J = 7.6 Hz, 1H),
2.71 (s, 3H), 2.47 (s, 3H); 13C{1H} NMR (100 MHz, CD3CN) δ 170.5, 156.6, 152.7, 143.7,
136.8, 136.3, 132.9, 132.8, 132.4, 130.8, 129.5, 129.3, 129.0 (2C), 128.4, 128.1, 127.3, 123.4,
24.2, 15.2; HRMS (ESI-TOF) calcd. For C22H19N2S (M)+ m/z = 343.1269, found 343.1271.
3-(3-Methoxyphenyl)-2-methyl-4-phenylquinazolin-3-ium tetrafluoroborate (3f).
133 mg, 71%, orange solid: mp 186-187 oC; 1H NMR (400 MHz, CD3CN) δ 8.47 (ddd, J = 15.4,
7.6, 1.6 Hz, 1H), 8.31 (d, J = 8.4 Hz, 1H), 7.94 (ddd, J = 15.6, 8.0, 0.8 Hz, 1H), 7.79-7.76 (m,
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1H), 7.54-7.50 (m, 1H), 7.49-7.41 (m, 3H), 7.40-7.36 (m, 2H), 7.07-7.01 (m, 3H), 3.74 (s, 3H),
2.75 (s, 3H); 13C{1H} NMR (100 MHz, CD3CN) δ 169.8, 161.9, 156.9, 152.8, 143.3, 140.6,
132.8, 132.7, 132.4, 132.3, 130.7, 129.7, 129.6, 129.5, 123.6, 120.4, 118.2, 113.9, 56.9, 25.2;
HRMS (ESI-TOF) calcd. For C22H19N2O (M)+ m/z = 327.1497, found 327.1496.
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3-(3,4-Dimethylphenyl)-2-methyl-4-phenylquinazolin-3-ium tetrafluoroborate (3g).
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153 mg, 82%, off-white solid: mp 218-219 C; H NMR (400 MHz, CD3CN) δ 8.45 (ddd, J =
15.4, 7.6, 1.6 Hz, 1H), 8.30 (d, J = 8.4 Hz, 1H), 7.93 (ddd, J = 15.6, 7.8, 1.2 Hz, 1H), 7.76-7.73
(m, 1H), 7.52-7.50 (m, 1H), 7.48-7.43 (m, 2H), 7.42-7.39 (m, 2H), 7.22 (d, J = 7.6 Hz, 2H), 7.15
(dd, J = 8.0, 2.4 Hz, 1H), 2.70 (s, 3H), 2.21 (s, 6H); 13C{1H} NMR (100 MHz, CD3CN) δ 169.9,
157.2, 152.7, 143.2, 141.5, 140.5, 137.5, 132.8, 132.6, 132.4, 132.1, 130.7, 129.7 (2C), 129.6,
128.9, 125.4, 123.8, 25.3, 20.1, 19.9; HRMS (ESI-TOF) calcd. For C23H21N2 (M)+ m/z =
325.1705, found 325.1697.
3-(3,5-Dimethylphenyl)-2-methyl-4-phenylquinazolin-3-ium tetrafluoroborate (3h).
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144 mg, 77%, off-white solid: mp 225-226 C; H NMR (400 MHz, CD3CN) δ 8.45 (t, J = 7.2
Hz, 1H), 8.30 (d, J = 8.4 Hz, 1H), 7.93 (t, J = 8.0 Hz, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.54-7.51
(m, 1H), 7.48 (t, J = 7.6 Hz, 2H), 7.42-7.40 (m, 2H), 7.12 (s, 1H), 7.07 (s, 2H), 2.72 (s, 3H), 2.25
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(s, 6H); C{1H} NMR (100 MHz, CD3CN) δ 169.4, 156.7, 152.4, 142.8, 141.4, 139.3, 133.1,
132.4, 132.3, 132.0, 130.4, 129.3 (2C), 125.4, 123.4 (2C), 24.9, 21.1; HRMS (ESI-TOF) calcd.
For C23H21N2 (M)+ m/z = 325.1705, found 325.1705.
3-(2,6-Dimethylphenyl)-2-methyl-4-phenylquinazolin-3-ium tetrafluoroborate (3i).
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138 mg, 74%, off-white solid: mp 224-225 C; H NMR (400 MHz, CD3CN) δ 8.51 (ddd, J =
15.4, 7.8, 1.2 Hz, 1H), 8.36 (d, J = 8.4 Hz, 1H), 8.00-7.96 (m, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.59
(t, J = 7.6 Hz, 1H), 7.48-7.46 (m, 2H), 7.42-7.37 (m, 2H), 7.35 (t, J = 8.0 Hz, 1H), 7.22 (d, J =
7.6 Hz, 2H), 2.66 (s, 3H), 2.04 (s, 6H); 13C{1H} NMR (100 MHz, CD3CN) δ 169.0, 156.1, 153.3,
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143.5, 137.7, 134.7, 133.2, 132.8, 132.6, 132.3, 130.2 (2C), 129.5 (2C), 128.3, 123.9, 23.8, 18.3
(2C); HRMS (ESI-TOF) calcd. For C23H21N2 (M)+ m/z = 325.1705, found 325.1715.
3-Mesityl-2-methyl-4-phenylquinazolin-3-ium tetrafluoroborate (3j).
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160 mg, 88%, off-white solid: mp 233-234 C; H NMR (400 MHz, CD3CN) δ 8.50 (t, J = 8.0
Hz, 1H), 8.35 (d, J = 8.4 Hz, 1H), 7.97 (t, J = 8.0 Hz, 1H), 7.83 (d, J = 8.4 Hz, 1H), 7.61 (t, J =
7.6 Hz, 1H), 7.49 (t, J = 7.6 Hz, 2H), 7.40 (d, J = 7.6 Hz, 2H), 7.04 (s, 2H), 2.65 (s, 3H), 2.26 (s,
3H), 1.99 (s, 6H); 13C{1H} NMR (100 MHz, CD3CN) δ 169.6, 156.7, 153.6, 143.8, 143.1, 135.7,
134.6, 133.4, 133.1, 132.9, 131.6, 129.9, 129.86, 129.82, 128.7, 124.3, 24.2, 21.3, 18.5 (2C);
HRMS (ESI-TOF) calcd. For C24H23N2 (M)+ m/z = 339.1861, found 339.1863.
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When the reaction was carried out in a scale of mesitylenediazonium tetrafluoronorate (0.6 g)
and 2-aminobenzophenone (0.56 g) in acetonitrile (12 mL), the desired compound 3j was
obtained (0.83 g) in 75% yield.
2-Methyl-4-phenyl-3-(3,4,5-trimethoxyphenyl)quinazolin-3-ium tetrafluoroborate (3k).
127 mg, 76%, green solid: mp 176-177 C;1H NMR (400 MHz, CD3CN) δ: 8.46 (t, J = 7.2 Hz,
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1H), 8.31 (d, J = 8.4 Hz, 1H), 7.94 (t, J = 8.0 Hz, 1H), 7.79 (d, J = 8.4 Hz, 1H), 7.57-7.54 (m,
1H), 7.51-7.44 (m, 4H), 6.78 (s, 2H), 3.71 (s, 6H), 3.69 (s, 3H), 2.82 (s, 3H); 13C{1H} NMR (100
MHz, CD3CN) δ 169.8, 157.0, 154.9, 152.4, 143.0, 140.3, 134.6, 132.5, 132.3, 132.1, 130.4
(2C), 129.3 (2C), 123.2, 106.2, 61.1, 57.1 (2C), 24.7; HRMS (ESI-TOF) calcd. For C24H23N2O3
(M)+ m/z = 387.1709, found 387.1709.
(E)-(2-Amino-5-((3-bromophenyl)diazenyl)phenyl)(phenyl)methanone (3aa).
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67 mg, 48%, orange solid: mp 137-138 C; H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 1.6 Hz,
1H), 7.94 (dd, J = 9.2, 2.0 Hz, 1H), 7.90 (s, 1H), 7.73-7.69 (m, 3H), 7.55 (t, J = 7.2 Hz, 1H), 7.49
(t, J = 8.0 Hz, 3H), 7.30 (t, J = 8.0 Hz, 1H), 6.79 (d, J = 9.2 Hz, 1H), 6.65 (brs, 2H); C{1H}
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NMR (100 MHz, CDCl3) δ 198.7, 153.7, 153.6, 142.7, 139.4, 134.9, 132.5, 131.5, 130.2, 129.1,
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128.3, 125.7, 124.1, 123.0, 122.4, 117.7, 117.0; HRMS (ESI-TOF) calcd. For C19H1579BrN3O
(M+H)+ m/z = 380.0398, found 380.0375; HRMS (ESI-TOF) calcd. For C19H1581BrN3O (M+H)+
m/z = 382.0378, found 382.0353.
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Ethyl (E)-4-((4-amino-3-benzoylphenyl)diazenyl)benzoate (3ab).
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78 mg, 56%, orange solid: mp 136-137 C; H NMR (400 MHz, CDCl3) δ 8.17 (d, J = 2.4 Hz,
1H), 8.12-8.08 (m, 2H), 7.97 (dd, J = 9.2, 2.4 Hz, 1H), 7.80-7.77 (m, 2H), 7.71-7.69 (m, 2H),
7.56 (ddd, J = 14.6, 7.2, 2.4 Hz, 1H), 7.51-7.47 (m, 2H), 6.79 (d, J = 9.2 Hz, 1H), 6.68 (brs, 2H),
4.37 (q, J = 7.2 Hz, 2H), 1.38 (t, J = 7.2 Hz, 3H); C{1H} NMR (100 MHz, CDCl3) δ 198.7,
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166.1, 155.3, 153.9, 143.0, 139.4, 135.2, 131.5, 131.2, 130.4, 129.1, 128.3, 125.7, 122.1, 117.7,
117.0, 61.1, 14.3; HRMS (ESI-TOF) calcd. For C22H20N3O3 (M+H)+ m/z = 374.1505, found
374.1489.
(E)-(4-((4-amino-3-benzoylphenyl)diazenyl)phenyl)(phenyl)methanone (3ac).
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58 mg, 43%, orange solid: mp 141-142 C;1H NMR (400 MHz, CDCl3) δ 8.19 (d, J = 2.0 Hz,
1H), 8.00 (dd, J = 8.8, 2.0 Hz, 1H), 7.89-7.83 (m, 4H), 7.79 (d, J = 7.2 Hz, 2H), 7.70 (d, J = 7.2
Hz, 2H), 7.60-7.55 (m, 2H), 7.51-7.45 (m, 4H), 6.80 (d, J = 9.2 Hz, 1H), 6.71 (brs, 2H); 13C{1H}
NMR (100 MHz, CDCl3) δ 198.7, 196.0, 154.9, 153.9, 143.0, 139.4, 138.1, 137.5, 135.3, 132.4,
131.5, 131.0, 129.9, 129.1, 128.4, 128.3, 125.7, 122.1, 117.7, 117.0; HRMS (ESI-TOF) calcd.
For C26H20N3O2 (M+H)+ m/z = 406.1556, found 406.1544.
3-Mesityl-4-phenyl-2-propylquinazolin-3-ium tetrafluoroborate (4a).
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162 mg, 84%, off-white solid: mp 149-150 C; H NMR (400 MHz, CD3CN) δ 8.50 (ddd, J =
15.6, 7.8, 1.2 Hz, 1H), 8.37 (d, J = 8.4 Hz, 1H), 7.96 (ddd, J = 15.6, 8.0, 0.8 Hz, 1H), 7.81 (d, J =
7.6 Hz, 1H), 7.62-7.58 (m, 1H), 7.50-7.46 (m, 2H), 7.38 (dd, J = 7.2, 1.6 Hz, 2H), 7.03 (s, 2H),
2.72 (t, J = 7.2 Hz, 2H), 2.62 (s, 3H), 2.07-2.00 (m, 2H), 1.97 (s, 6H), 1.00 (t, J = 7.2 Hz, 3H);
13C{1H} NMR (100 MHz, CD3CN) δ 169.2, 158.5, 153.1, 143.4, 142.8, 134.8, 134.5, 133.1,
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132.7, 132.5, 131.3, 129.6, 129.5, 129.4, 128.6, 123.8, 37.1, 21.0, 20.1, 18.3 (2C), 13.5; HRMS
(ESI-TOF) calcd. For C26H27N2 (M)+ m/z = 367.2174, found 367.2166.
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88 mg, 44%, pale yellow solid: mp 121-122 C; H NMR (400 MHz, CD3CN) δ 8.52 (ddd, J =
15.4, 7.6, 1.6 Hz, 1H), 8.37 (dd, J = 8.4, 0.8 Hz, 1H), 8.00-7.96 (m, 1H), 7.84-7.82 (m, 1H),
7.62-7.58 (m, 1H), 7.51-7.46 (m, 2H), 7.42-7.39 (m, 2H), 7.03 (s, 2H), 4.00 (t, J = 5.6 Hz, 2H),
3.29 (s, 3H), 2.99 (t, J = 6.0 Hz, 2H), 2.26 (s, 3H), 1.98 (s, 6H); 13C{1H} NMR (100 MHz,
CD3CN) δ 169.3, 157.0, 152.9, 143.6, 142.9, 134.8, 134.7, 133.1, 132.9, 132.6, 131.2, 129.6,
129.5, 128.6, 127.0, 123.9, 69.1, 59.1, 35.7, 21.0, 18.3 (2C); HRMS (ESI-TOF) calcd. For
C26H27N2O (M)+ m/z = 383.2123, found 383.2116.
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2-Isopropyl-3-mesityl-4-phenylquinazolin-3-ium tetrafluoroborate (4c).
147 mg, 76%, pale yellow solid: mp 226-227 oC; 1H NMR (400 MHz, CD3CN) δ 8.50 (ddd, J =
15.6, 7.8, 1.2 Hz, 1H), 8.35 (d, J = 8.8 Hz, 1H), 7.96 (ddd, J = 15.4, 7.8, 1.2 Hz, 1H), 7.80 (dd, J
= 8.8, 0.8 Hz, 1H), 7.62-7.57 (m, 1H), 7.50-7.46 (m, 2H), 7.39-7.36 (m, 2H), 7.02 (s, 2H), 3.01
(hept, J = 6.4 Hz, 1H), 2.25 (s, 3H), 1.99 (s, 6H), 1.39 (d, J = 6.4 Hz, 6H); C{1H} NMR (100
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MHz, CD3CN) δ 168.9, 164.1, 153.5, 143.4, 142.7, 134.9, 134.7, 133.0, 132.8, 132.4, 131.2
(2C), 129.4 (2C), 128.8, 123.9, 34.0, 22.8 (2C), 21.0, 18.6 (2C); HRMS (ESI-TOF) calcd. For
C26H27N2 (M)+ m/z = 367.2174, found 367.2179.
2-Cyclopropyl-3-mesityl-4-phenylquinazolin-3-ium tetrafluoroborate (4d).
150 mg, 78%, pale yellow solid: mp 193-194 oC; 1H NMR (400 MHz, CD3CN) δ 8.42 (ddd, J =
15.6, 7.6, 1.6 Hz, 1H), 8.20 (d, J = 8.4 Hz, 1H), 7.87 (ddd, J = 15.4, 7.8, 1.2 Hz, 1H), 7.75-7.37
(m, 1H), 7.61-7.57 (m, 1H), 7.48 (ddd, J = 13.8, 7.2, 1.6 Hz, 2H), 7.41-7.38 (m, 2H), 7.03 (s,
2H), 2.25 (s, 3H), 2.03 (s, 6H), 1.87-1.81 (m, 1H), 1.56-1.53 (m, 2H), 1.29-1.24 (m, 2H);
13C{1H} NMR (100 MHz, CD3CN) δ 168.5, 160.9, 153.8, 143.3, 142.7, 135.1, 134.9, 133.0,
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132.3, 132.0, 131.1, 129.5, 129.1, 128.7 (2C), 123.5, 21.0(2C), 18.4 (2C), 14.6 (2C); HRMS
(ESI-TOF) calcd. For C26H25N2 (M)+ m/z = 365.2018, found 365.2008.
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2-Cyclohexyl-3-mesityl-4-phenylquinazolin-3-ium tetrafluoroborate (4e).
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86 mg, 41%, off-white solid: mp 230-231 C; H NMR (400 MHz, CD3CN) δ 8.49 (ddd, J =
15.6, 7.8, 1.2 Hz, 1H), 8.34 (d, J = 8.4 Hz, 1H), 7.94 (dt, J = 15.4, 1.2 Hz, 1H), 7.79 (d, J = 8.0
Hz, 1H), 7.59 (t, J = 7.6 Hz, 1H), 7.47 (t, J = 8.0 Hz, 2H), 7.38-7.36 (m, 2H), 7.02 (s, 2H), 2.66-
2.59 (m, 1H), 2.26 (s, 3H), 1.98 (s, 6H), 1.90-1.88 (m, 4H), 1.84-1.79 (m, 2H), 1.70-1.68 (m,
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1H), 1.39-1.28 (m, 1H), 1.16-1.05 (m, 2H); C{1H} NMR (100 MHz, CD3CN) δ 168.9, 162.8,
153.5, 143.3, 142.7, 134.9, 134.7, 133.0, 132.8, 132.4, 131.1 (2C), 129.5 (2C), 128.9, 123.9,
44.0, 33.3(2C), 26.4(2C), 26.0, 21.0, 18.7 (2C); HRMS (ESI-TOF) calcd. For C29H31N2 (M)+ m/z
= 407.2487, found 407.2481.
2-(tert-Butyl)-4-phenyl-3-(m-tolyl)quinazolin-3-ium tetrafluoroborate (4g).
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68 mg, 31%, off-white solid: mp 236-237 C; H NMR (400 MHz, CD3CN) δ 8.45 (ddd, J =
15.6, 7.8, 1.2 Hz, 1H), 8.32 (d, J = 8.4 Hz, 1H), 7.93 (ddd, J = 15.2, 7.6, 0.8 Hz, 1H), 7.60 (d, J =
8.4 Hz, 1H), 7.48-7.39 (m, 3H), 7.37-7.27 (m, 4H), 7.25-7.24 (m, 2H), 2.27 (s, 3H), 1.38 (s, 9H);
13C{1H} NMR (100 MHz, CD3CN) δ 171.8, 163.8, 151.9, 143.2, 140.5, 139.8, 133.1, 132.9,
132.1, 132.0, 131.5, 130.5, 130.4, 129.8, 129.4, 129.3, 128.1, 123.7, 43.6, 31.8, 21.3; HRMS
(ESI-TOF) calcd. For C25H25N2 (M)+ m/z = 353.2018, found 353.2016.
2-(4-Cyanobutyl)-3-mesityl-4-phenylquinazolin-3-ium tetrafluoroborate (4h).
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175 mg, 82%, off-white solid: mp 148-149 C; H NMR (400 MHz, CD3CN) δ 8.51 (ddd, J =
15.4, 7.8, 1.2 Hz, 1H), 8.39 (d, J = 8.4 Hz, 1H), 7.97 (ddd, J = 15.6, 7.8, 1.2 Hz, 1H), 7.81 (dd, J
= 8.4, 0.8 Hz, 1H), 7.62-7.58 (m, 1H), 7.50-7.46 (m, 2H), 7.39-7.37 (m, 2H), 7.02 (s, 2H), 2.77
(t, J = 7.2 Hz, 2H), 2.45 (t, J = 6.8 Hz, 2H), 2.25 (s, 3H), 2.16-2.08 (m, 2H), 1.97 (s, 6H), 1.76-
1.68 (m, 2H); 13C{1H} NMR (100 MHz, CD3CN) δ 169.4, 157.9, 153.1, 143.5, 142.9, 134.7,
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134.5, 133.2, 132.9, 132.6, 131.4, 129.7, 129.6, 129.5, 128.6, 123.9, 121.1, 34.7, 25.7, 25.1, 21.1,
18.4(2C), 17.5; HRMS (ESI-TOF) calcd. For C28H28N3 (M)+ m/z = 406.2283, found 406.2269.
2-Benzyl-3-mesityl-4-phenylquinazolin-3-ium tetrafluoroborate (4i).
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111 mg, 52%, off-white solid: mp 188-189 C; H NMR (400 MHz, CD3CN) δ 8.51 (t, J = 7.2
Hz, 1H), 8.35 (d, J = 8.4 Hz, 1H), 7.98 (t, J = 8.0 Hz, 1H), 7.82 (d, J = 8.4 Hz, 1H), 7.58 (t, J =
7.2 Hz, 1H), 7.45 (t, J = 8.0 Hz, 2H), 7.35 (d, J = 7.6 Hz, 2H), 7.30-7.26 (m, 3H), 7.00 (d, J = 6.4
Hz, 2H), 6.95 (s, 2H), 4.26 (s, 2H), 2.27 (s, 3H), 1.72 (s, 6H); 13C{1H} NMR (100 MHz,
CD3CN) δ 169.7, 157.2, 153.0, 143.5, 143.0, 135.0, 134.6, 134.2, 133.1, 133.0, 132.6, 131.2,
130.5, 129.7 (2C), 129.6, 129.4, 128.8, 128.5, 124.1, 42.5, 21.0, 18.2 (2C); HRMS (ESI-TOF)
calcd. For C30H27N2 (M)+ m/z = 415.2174, found 415.2180.
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2,3,4-Triphenylquinazolin-3-ium tetrafluoroborate (4j).
125 mg, 54%, brown solid: mp 220-221 oC; 1H NMR (400 MHz, CD3CN) δ 8.52 (ddd, J = 15.4,
7.8, 1.2 Hz, 1H), 8.42 (d, J = 8.4 Hz, 1H), 8.03 (ddd, J = 15.4, 7.8, 1.2 Hz, 1H), 7.89 (dd, J = 8.8,
0.8 Hz, 1H), 7.54-7.46 (m, 4H), 7.44-7.39 (m, 4H), 7.36-7.31 (m, 4H), 7.23-7.17 (m, 3H);
13C{1H} NMR (100 MHz, CD3CN) δ 169.9, 156.0, 152.2, 143.3 (2C), 139.8, 134.2, 133.3,
132.4, 132.2, 131.5, 131.4, 130.8, 130.4, 130.1, 129.9, 129.6, 129.5, 129.2, 123.7; HRMS (ESI-
TOF) calcd. For C26H19N2 (M)+ m/z = 359.1548, found 359.1535.
3,4-Diphenyl-2-(o-tolyl)quinazolin-3-ium tetrafluoroborate (4k).
150 mg, 63%, brown solid: mp 217-218 oC; 1H NMR (400 MHz, CD3CN) δ 8.54 (ddd, J = 15.6,
8.0, 1.6 Hz, 1H), 8.44-8.41 (m, 1H), 8.06 (ddd, J = 15.4, 8.0, 0.8 Hz, 1H), 7.95-7.92 (m, 1H),
7.55-7.51 (m, 2H), 7.48-7.38 (m, 3H), 7.33-7.28 (m, 3H), 7.28-7.23 (m, 2H), 7.20-7.13 (m, 3H),
7.11-7.09 (m, 1H), 2.35 (s, 3H); 13C{1H} NMR (100 MHz, CD3CN) δ 170.3, 155.8, 152.0, 143.3
(2C), 139.4, 137.8, 133.5, 132.5, 132.3, 131.6, 131.5 (2C), 130.9, 130.6, 130.1, 129.9, 129.5
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(2C), 129.4, 126.3, 124.0, 20.1; HRMS (ESI-TOF) calcd. For C27H21N2 (M)+ m/z = 373.1705,
found 373.1710.
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4-Phenyl-2-(o-tolyl)-3-(p-tolyl)quinazolin-3-ium tetrafluoroborate (4l).
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163 mg, 71%, off-white solid: mp 197-198 C; H NMR (400 MHz, CD3CN) δ 8.53 (ddd, J =
15.4, 7.8, 1.2 Hz, 1H), 8.41 (d, J = 8.4 Hz. 1H), 8.05 (ddd, J = 15.4, 7.8, 1.2 Hz. 1H), 7.91 (dd, J
= 8.4, 0.8 Hz, 1H), 7.56-7.54 (m, 2H), 7.52-7.48 (m, 3H), 7.35-7.28 (m, 2H), 7.25-7.19 (m, 2H),
7.12 (t, J = 7.2 Hz, 2H), 6.98 (d, J = 8.4 Hz, 2H), 2.34 (s, 3H), 2.12 (s, 3H); 13C{1H} NMR (100
MHz, CD3CN) δ 170.4, 155.9, 151.9, 143.1 (2C), 141.9, 137.7, 137.0, 133.6, 133.4, 132.4, 132.2
(2C), 131.4 (2C), 130.9, 130.6, 130.4, 129.8 (2C), 126.3, 124.0, 21.0, 20.1; HRMS (ESI-TOF)
calcd. For C28H23N2 (M)+ m/z = 387.1861, found 387.1876.
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3-Mesityl-4-phenyl-2-(o-tolyl)quinazolin-3-ium tetrafluoroborate (4m).
87 mg, 41%, off-white solid: mp 191-192 oC; 1H NMR (400 MHz, CD3CN) δ 8.56 (t, J = 7.6 Hz,
1H), 8.44 (d, J = 8.4 Hz, 1H), 8.07 (t, J = 8.0 Hz, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.61 (t, J = 7.2
Hz, 1H), 7.51-7.46 (m, 4H), 7.42-7.34 (m, 2H), 7.02-6.93 (m, 2H), 6.77 (s, 2H), 2.44 (s, 3H),
2.10 (s, 3H), 1.98 (s, 6H); 13C{1H} NMR (100 MHz, CD3CN) δ 170.3, 154.8, 152.6, 143.5,
142.1, 139.4, 135.6, 135.3, 133.6, 133.2, 132.7, 132.6, 131.9, 131.7, 130.5, 130.1, 130.0, 129.7,
129.4, 128.8, 126.0, 124.0, 20.8, 20.4, 18.9 (2C); HRMS (ESI-TOF) calcd. For C30H27N2 (M)+
m/z = 415.2174, found 415.2182.
3,4-Diphenyl-2-(p-tolyl)quinazolin-3-ium tetrafluoroborate (4n).
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157 mg, 66%, off-white solid: mp 201-202 C; H NMR (400 MHz, CD3CN) δ 8.52 (ddd, J =
15.6, 8.0, 1.6 Hz, 1H), 8.42-8.39 (m, 1H), 8.02 (ddd, J = 15.4, 7.6, 0.8 Hz, 1H), 7.88-7.86 (m,
1H), 7.53-7.48 (m, 1H), 7.46-7.43 (m, 4H), 7.42-7.37 (m, 2H), 7.34-7.31 (m, 2H), 7.26-7.21 (m,
3H), 7.20-7.16 (m, 2H), 1.92 (s, 3H); 13C{1H} NMR (100 MHz, CD3CN) δ 170.3, 156.6, 152.7,
143.5 (2C), 142.6, 140.2, 133.6, 132.7, 132.5, 131.7, 131.2, 130.8, 130.4, 130.3, 130.2, 129.8,
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129.3 (2C), 124.0, 21.7; HRMS (ESI-TOF) calcd. For C27H21N2 (M)+ m/z = 373.1705, found
373.1705.
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2-(3-Bromophenyl)-3,4-diphenylquinazolin-3-ium tetrafluoroborate (4o).
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185 mg, 67%, grey solid: mp 240-241 C; H NMR (400 MHz, CD3CN) δ 8.55 (ddd, J = 15.4,
7.6, 1.6 Hz, 1H), 8.44 (d, J = 8.4 Hz, 1H), 8.06 (ddd, J = 15.6, 7.8, 1.2 Hz, 1H), 7.92 (dd, J = 8.4,
0.8 Hz, 1H), 7.66 (t, J = 1.6 Hz, 1H), 7.60-7.57 (m, 1H), 7.56-7.52 (m, 1H), 7.49-7.43 (m, 5H),
7.36-7.34 (m, 2H), 7.29-7.22 (m, 4H); 13C{1H} NMR (100 MHz, CD3CN) δ 170.1, 154.3, 152.1,
143.4, 139.5, 136.0, 134.5, 133.6, 133.4, 132.5, 132.3, 131.6, 131.2, 130.5, 130.3, 130.0, 129.7,
129.5, 129.4, 129.2, 123.8, 122.5; HRMS (ESI-TOF) calcd. For C26H1879BrN2 (M)+ m/z =
437.0653, found 437.0643; HRMS (ESI-TOF) calcd. For C26H1881BrN2 (M)+ m/z = 439.0633,
found 439.0718.
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2-(4-Fluorophenyl)-3-mesityl-4-phenylquinazolin-3-ium tetrafluoroborate (4p).
130 mg, 49%, pale yellow solid: mp 205-206 oC; 1H NMR (400 MHz, CD3CN) δ 8.56 (t, J = 8.0
Hz, 1H), 8.46 (d, J = 8.4 Hz, 1H), 8.05 (t, J = 8.0 Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.62 (t, J =
7.6 Hz, 1H), 7.53-7.48 (m, 4H), 7.41 (d, J = 7.6 Hz, 2H), 7.13 (t, J = 8.8 Hz, 2H), 6.83 (s, 2H),
2.15 (s, 3H), 1.95 (s, 6H); 13C{1H} NMR (100 MHz, CD3CN) δ 169.8, 166.3, 163.8, 154.8,
153.2, 143.7, 142.7, 135.5, 135.1, 133.6, 133.3 (d, J = 7.4 Hz), 132.7, 130.8 (2C), 130.2, 129.9,
129.4 (d, J = 19 Hz), 128.4, 124.1, 116.5 (d, J = 22 Hz), 20.9, 18.8 (2C); HRMS (ESI-TOF)
calcd. For C29H24FN2 (M)+ m/z = 419.1924, found 419.1964.
6-Chloro-3-mesityl-2-methyl-4-phenylquinazolin-3-ium tetrafluoroborate (5a).
152 mg, 77%, off-white solid: mp 225-226 oC; 1H NMR (400 MHz, CD3CN) δ 8.43 (dd, J = 9.2,
2.4 Hz, 1H), 8.34 (d, J = 8.8 Hz, 1H), 7.79 (d, J = 2.0 Hz, 1H), 7.61 (ddd, J = 15.4, 8.2, 1.2 Hz,
1H), 7.51-7.48 (m, 2H), 7.40 (dd, J = 8.4, 1.2 Hz, 2H), 7.04 (s, 2H), 2.65 (s, 3H), 2.25 (s, 3H),
1.98 (s, 6H); 13C{1H} NMR (100 MHz, CD3CN) δ 168.7, 157.0, 152.2, 143.7, 143.0, 138.2,
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135.3, 134.2, 133.4, 131.5, 131.4, 130.5, 129.7, 129.6, 128.0, 125.0, 23.9, 21.0, 18.2 (2C);
HRMS (ESI-TOF) calcd. For C24H2235ClN2 (M)+ m/z = 373.1472, found 373.1475; HRMS (ESI-
TOF) calcd. For C24H2237ClN2 (M)+ m/z = 375.1442, found 375.1443.
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6-Bromo-3-mesityl-2-methyl-4-phenylquinazolin-3-ium tetrafluoroborate (5b).
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160 mg, 74%, grey solid: mp 222-223 oC; 1H NMR (400 MHz, CD3CN) δ: 8.55 (dd, J = 8.8, 2.0
Hz, 1H), 8.25 (d, J = 9.2 Hz, 1H), 7.95 (d, J = 2.0 Hz, 1H), 7.61 (t, J = 7.6 Hz, 1H), 7.49 (t, J =
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7.6 Hz, 2H), 7.41-7.38 (m, 2H), 7.04 (s, 2H), 2.63 (s, 3H), 2.25 (s, 3H), 1.98 (s, 6H); C{1H}
NMR (100 MHz, CD3CN) δ 168.6, 157.1, 152.3, 146.2, 143.0, 135.2, 134.2, 133.9, 133.4, 131.3
(2C), 129.7, 129.6, 127.9, 126.2, 125.3, 23.9, 21.0, 18.2 (2C); HRMS (ESI-TOF) calcd. For
C24H2279BrN2 (M)+ m/z = 417.0966, found 417.0963; HRMS (ESI-TOF) calcd. For C24H2281BrN2
(M)+ m/z = 419.0946, found 419.0948.
4-(4-Fluorophenyl)-3-mesityl-2-methylquinazolin-3-ium tetrafluoroborate (5c).
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147 mg, 78%, off-white solid: mp 238-239 C; H NMR (400 MHz, CD3CN) δ: 8.51 (ddd, J =
15.4, 7.8, 1.2 Hz, 1H), 8.35 (d, J = 8.4 Hz, 1H), 7.99 (ddd, J = 15.6, 8.0, 0.8 Hz, 1H), 7.87 (dd, J
= 8.4, 0.8 Hz, 1H), 7.46-7.42 (m, 2H), 7.26-7.21 (m, 2H), 7.06 (s, 2H), 2.66 (s, 3H), 2.27 (s, 3H),
1.97 (s, 6H); 13C{1H} NMR (100 MHz, CD3CN) δ 168.3, 166.7, 164.2, 156.5, 153.3, 143.6,
142.9, 135.2, 134.2, 132.7 (d, J = 55 Hz), 132.5, 131.4, 129.5, 124.6 (d, J = 3 Hz), 124.0, 116.9
(d, J = 23 Hz), 23.9, 21.0, 18.1 (2C); HRMS (ESI-TOF) calcd. For C24H22FN2 (M)+ m/z =
357.1767, found 357.1768.
3-Mesityl-2-methyl-4-(p-tolyl)quinazolin-3-ium tetrafluoroborate (5d).
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151 mg, 80%, off-white solid: mp 253-254 C; H NMR (400 MHz, CD3CN) δ 8.49 (ddd, J =
15.4, 7.6, 1.6 Hz, 1H), 8.33 (d, J = 8.4 Hz, 1H), 7.96 (ddd, J = 15.4, 8.0, 0.8 Hz, 1H), 7.83 (dd, J
= 8.4, 0.8 Hz, 1H), 7.32-7.27 (m, 4H), 7.05 (d, J = 0.8 Hz, 2H), 2.62 (s, 3H), 2.37 (s, 3H), 2.27
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(s, 3H), 1.98 (s, 6H); C{1H} NMR (100 MHz, CD3CN) δ 169.5, 156.3, 153.1, 144.1, 143.3
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(2C), 142.8, 135.4, 134.3, 132.7, 131.3, 130.1, 129.8, 129.4, 125.5, 124.0, 23.9, 21.5, 21.0, 18.2
(2C); HRMS (ESI-TOF) calcd. For C25H25N2 (M)+ m/z = 353.2012, found 353.2018.
6-Chloro-4-(2-chlorophenyl)-3-mesityl-2-methylquinazolin-3-ium tetrafluoroborate (5e).
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154 mg, 73%, off-white solid: mp 317-318 oC; 1H NMR (400 MHz, CD3CN) δ 8.46 (dd, J = 9.2,
2.0 Hz, 1H), 8.38 (d, J = 8.8 Hz, 1H), 7.81 (d, J = 2.0 Hz, 1H), 7.66-7.58 (m, 2H), 7.41-7.37 (m,
1H), 7.27 (dd, J = 8.0, 1.2 Hz, 1H), 7.12 (s, 1H), 7.00 (s, 1H), 2.69 (s, 3H), 2.26 (s, 3H), 2.10 (s,
3H), 1.99 (s, 3H); 13C{1H} NMR (100 MHz, CD3CN) δ 165.8, 158.0, 152.1, 144.3, 143.0, 139.0,
135.3, 135.2, 134.8, 134.3, 133.1, 132.1, 131.9, 131.5, 131.3, 131.2, 129.8, 128.6, 126.8, 124.5,
24.1, 21.0, 18.4, 18.1; HRMS (ESI-TOF) calcd. For C24H2135Cl2N2 (M)+ m/z = 407.1082, found
407.1066; HRMS (ESI-TOF) calcd. For C24H2137Cl2N2 (M)+ m/z = 409.1052, found 409.1042.
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3-Mesityl-2-methyl-4-methylene-3,4-dihydroquinazoline (6).
60 mg, 51%, viscous oil: 1H NMR (400 MHz, CD3CN) δ 7.54 (dd, J = 8.0, 1.2 Hz, 1H), 7.34 (td,
J = 15.0, 1.6 Hz, 1H), 7.28 (dd, J = 8.0, 1.2 Hz, 1H), 7.14 (td, J = 15.0, 1.6 Hz 1H), 7.00 (s, 2H),
4.52 (d, J = 2.0 Hz, 1H), 3.38 (d, J = 2.4 Hz, 1H), 2.32 (s, 3H), 2.14 (s, 6H), 1.88 (s, 3H);
13C{1H} NMR (100 MHz, CD3CN) δ 154.1, 140.9, 140.7, 138.7, 135.4, 134.9, 130.3, 130.1,
125.6, 125.4, 122.9, 121.7, 80.3, 22.7, 21.0, 17.2 (2C); HRMS (ESI-TOF) calcd. For C19H21N2
(M+H)+ m/z = 277.1705, found 277.1697.
3-([1,1'-Biphenyl]-2-yl)-2-methyl-4-phenylquinazolin-3-ium tetrafluoroborate (7).
o
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123 mg, 76%, off-white solid: mp 305-306 C; H NMR (400 MHz, CD3CN) δ 8.44 (ddd, J =
15.6, 7.8, 1.2 1H), 8.30 (d, J = 8.4 Hz, 1H), 7.89-7.83 (m, 2H), 7.68-7.63 (m, 3H), 7.53 (tt, J =
15.2, 1.2 Hz, 1H), 7.49-7.47 (m, 1H), 7.37-7.32 (m, 2H), 7.30-7.20 (m, 4H), 6.72-6.70 (m, 2H),
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6.33 (dd, J = 7.4, 1.3 Hz, 1H), 2.96 (s, 3H); C{1H} NMR (100 MHz, CD3CN) δ 169.3, 157.2,
152.5, 143.4, 137.9, 136.5, 136.3, 133.2, 133.0, 132.9, 132.2, 131.6, 130.5, 130.2, 130.1, 129.8,
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129.6, 129.5, 129.2, 129.1, 128.0, 122.7, 25.9; HRMS (ESI-TOF) calcd. For C27H21N2 (M)+ m/z
= 373.1705, found 373.1707.
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3-(2-Benzoylphenyl)-2-methylquinazolin-4(3H)-one (8).17b
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104 mg, 77%, pale yellow solid: mp 161-162 oC; 1H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 8.0
Hz, 1H), 7.74 (d, J = 7.2 Hz, 2H), 7.71-7.58 (m, 3H), 7.56-7.51 (m, 2H), 7.48 (d, J = 7.6 Hz,
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1H), 7.39-7.30 (m, 4H), 2.36 (s, 3H); C{1H} NMR (100 MHz, CDCl3) δ 195.0, 162.0, 154.7,
147.5, 137.0, 136.6, 134.4, 133.2, 132.2, 130.7 (2C), 130.3, 129.6, 128.6, 128.3, 126.9, 126.8,
126.2, 120.4, 24.3; HRMS (ESI-TOF) calcd. For C22H17N2O2 (M+H)+ m/z = 341.1290, found
341.1284.
2-Cyclopropyl-3-mesityl-4-methoxy-4-phenyl-3,4-dihydroquinazoline (9a).
Compound 4d was dissolved in anhydrous methanol (10 mL) under N2. NaOMe
(weighed in glove box) (60 mg, 5eq) was added in one portion. Resulting mixture was
stirred for 12h and the excess methanol was removed under reduced pressure. Residue
was diluted with DCM (40 mL) and washed with water (10 mL) and brine (10 mL).
Removal of solvents and purification by silica gel column chromatography (5% to
10%-EA : Hexane) provided the 9a (84 mg, 96%) as off-white solid. mp 139-140 oC; 1H
NMR (400 MHz, CDCl3) δ 7.36-7.27 (m, 4H), 7.06-6.97 (m, 4H), 6.87 (dd, J = 8.0, 1.2 Hz, 1H),
6.76 (s, 1H), 6,42 (s, 1H), 2.99 (s, 3H), 2.57 (s, 3H), 2.10 (s, 3H), 1.64 (s, 3H), 1.33-1.25 (m,
1H), 1.17-1.12 (m, 1H), 1.00-0.94 (m, 1H), 0.71-0.64 (m, 1H), 0.55-0.49 (m, 1H); 13C{1H} NMR
(100 MHz, CDCl3) δ 159.3, 144.4, 140.6, 138.0, 137.6, 136.9, 136.8, 129.2, 129.0, 128.7, 128.6,
127.4, 126.1, 124.0, 123.1, 122.6, 93.1, 50.1, 20.6, 20.2, 18.9, 13.6, 8.8, 7.9; HRMS (ESI-TOF)
calcd. For C27H29N2O (M+H)+ m/z = 397.2280, found 397.2288.
2-(3-Bromophenyl)-4-ethoxy-3,4-diphenyl-3,4-dihydroquinazoline (9b).
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The procedure is similar to that for 9a except using 4o and sodium ethoxide as reagents. 62 mg,
84%, brown oil; 1H NMR (400 MHz, CDCl3) δ 7.64-7.63 (m, 1H), 7.45-7.43 (m, 1H), 7.38-7.34
(m, 2H), 7.32-7.27 (m, 2H), 7.26-7.21 (m, 2H), 7.08-7.00 (m, 5H), 6.94 (t, J = 8.0 Hz, 1H), 6.86-
6.80 (m, 2H), 6.79-6.71 (m, 1H), 6.32-6.30 (d, J = 6.0 Hz, 1H), 3.77-3.69 (m, 1H), 3.28-3.20 (m,
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1H), 1.27 (t, J = 6.8 Hz, 3H); C{1H} NMR (100 MHz, CDCl3) δ 154.0, 144.2, 142.0, 140.9,
139.2, 132.2, 131.5, 130.5, 130.0, 129.1, 129.0, 128.5, 128.1, 127.9, 127.7, 127.1, 126.3, 125.5,
124.9, 124.6, 121.8, 91.6, 57.7, 15.0; HRMS (ESI-TOF) calcd. For C28H2479BrN2O (M+H)+ m/z
= 483.1072, found 483.1059; HRMS (ESI-TOF) calcd. For C19H1581BrN3O (M+H)+ m/z =
485.1052, found 485.1044.
6-Chloro-4-methoxy-2-methyl-4-phenyl-3-(o-tolyl)-3,4-dihydroquinazoline (9c).
In a dry 10 mL glass sealed tube, 2-toluenediazonium tetrafluoroborate (100 mg, 0.48 mmol)
and 5-chloro-2-aminobenzophenone (123 mg, 0.53mmol, 1.1 eq.) were suspended in anhydrous
acetonitrile (2 mL). The tube was sealed with a Teflon screw cap and heated in an oil bath (120
o
C) for 5 h. After cooling, diethyl ether (50 mL) was added dropwise to the reaction
mixture. The quinazolinium salt was obtained by filtration and the solid was then dissolved in
methanol (6 mL) with NaOH (85 mg, 2.12 mmol). After stirring at room temperature
for 12 h, solvents were removed under reduced pressure and the residue was extracted
with DCM (30 mL x 2). Organic layer was washed with water (10 mL) and brine (10
mL). The organic layer was dried over MgSO4. Removal of solvents and purification
by silica gel column chromatography (5% to 10%-EA:Hexanes) provided 9c (71mg,
1
92%) as pale yellow oil. H NMR (400 MHz, CDCl3) δ 7.32-7.26 (m, 4H), 7.13 (ddd, J =
15.2, 8.2, 1.2 Hz, 1H), 7.07-7.03 (m, 3H), 7.02-6.99 (m, 2H), 6.84 (dd, J = 7.6, 0.8 Hz, 1H),
6.80-6.79 (m, 1H), 3.12 (s, 3H), 1.93 (s, 3H), 1.68 (s, 3H); C{1H} NMR (100 MHz, CDCl3) δ
13
156.2, 142.0, 141.4, 138.1, 136.2, 130.5, 130.0, 129.7, 129.2, 128.2, 128.1, 127.7, 126.5 (2C),
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126.2, 125.0, 124.5, 91.3, 49.6, 23.6, 17.6; HRMS (ESI-TOF) calcd. For C23H2235ClN2O (M+H)+
m/z = 377.1421, found 377.1426; HRMS (ESI-TOF) calcd. For C23H2237ClN2O (M+H)+ m/z =
379.1391, found 379.1400.
9
ASSOCIATED CONTENT
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Supporting Information
Spectra for all new compounds. The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.xxxxxx
AUTHOR INFORMATION
Corresponding Author
*E-mail: stliu@ntu.edu.tw
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank the Ministry of Science and Technology, Taiwan (Grant No. MOST107-2113-M-002-
005) for the financial support. We also thank “National Taiwan University Mass Spectrometry-
based Proteomics Core Facility” for the measurement of ESI mass data.
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