Expedient base-mediated desulfitative dimethylamination, oxidation, or etherification of 2-(Methylsulfanyl)-3,5-dihydro-4 H -imidazol-4-one scaffolds

Article abstract of DOI:10.1055/s-0033-1338499

The dimethylamino functionality is generally introduced onto the 3,5-dihydro-4H-imidazol-4-one skeleton by treatment of a halogenated derivative with low-boiling dimethylamine at a high temperature and pressure. The corresponding aliphatic ethers are usua

Full text of DOI:10.1055/s-0033-1338499

PAPER
▌2405
paper
Expedient Base-Mediated Desulfitative Dimethylamination, Oxidation, or
Etherification of 2-(Methylsulfanyl)-3,5-dihydro-4H-imidazol-4-one Scaffolds
Functionalization of 3,5-Dihydro-4H-imidazol-4-ones
Shahnawaz Khan,a Vikas Tyagi,a Rohit Mahar,b Vikas Bajpai,b Brijesh Kumar,b Prem M. S. Chauhan*a
a
Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, 226 001, India
Fax +91(522)2623405; E-mail: premsc58@hotmail.com; E-mail: prem_chauhan_2000@yahoo.com
b
Sophisticated Analytical Instrument Facility, CSIR-Central Drug Research Institute, Lucknow, 226 001, India
Received: 30.01.2013; Accepted after revision: 03.06.2013
avoid the difficulties of handling low-boiling dimethyl-
Abstract: The dimethylamino functionality is generally introduced
amine and the low yields of the reaction, N,N-dimethyl-
onto the 3,5-dihydro-4H-imidazol-4-one skeleton by treatment of a
formamide, in the presence of a base, has been used as a
halogenated derivative with low-boiling dimethylamine at a high
temperature and pressure. The corresponding aliphatic ethers are
source of the dimethylamine functionality.6
usually prepared by Williamson ether synthesis, but the available
transition-metal-catalyzed methods require highly toxic reagents
for the synthesis of biologically important heterocycles,7
(such as dimethyl sulfate or methyl halides) and expensive metal
catalysts, and they entail harsh reaction conditions and complex
workups. A simple and efficient method is described for base-
Our ongoing research program to develop novel strategies
and our previous report on the dimethylamination of
heterocycles8 prompted us to examine the substitution-
dependent desulfitative dimethylamination and oxidation
reactions of 2-(methylsulfanyl)-3,5-dihydro-4H-imidaz-
ol-4-one derivatives (Scheme 1).
mediated desulfitative dimethylamination, oxidation, or etherifica-
tion at the C2-position of the 2-(methylsulfanyl)-3,5-dihydro-4H-
imidazol-4-one scaffold by using potassium carbonate and aqueous
N,N-dimethylformamide or an aliphatic alcohol.
Key words: heterocycles, aminations, etherifications, oxidations,
ketones, amines, ethers
R1
N
NMe2
N
O
The dimethylamino group is a common functional group
that is present in a variety of natural products and synthet-
ic molecules.1 For example, indole alkaloids isolated from
the tunicate Dendrodoa grossularia contain dimethylami-
no groups (Figure 1); among these, alkaloid 1 shows mod-
erate cytotoxicity towards the L1210 leukemia cell lines
(4–10 μg/mL) and greater cytotoxicity for the MCF7 and
WiDr cell lines (≤10 ng/mL).2 Additionally, the pyrro-
lopyrimidine 4 (Figure 1), a lead compound in the devel-
opment of potent inhibitors of the interaction of the tumor
suppressor protein p53 with MDMX and MDM2 proteins,
contains a dimethylamino group.3 The dimethylamino
group is also found in a number of important drugs.4
R2
dimethylamination
R1
R1
R3
H
N
N
N
O
S
N
R2
O
O
R2
etherification
R1
H
N
O
N
O
R2
oxidation
The dimethylamino functionality is generally introduced
by treatment of a halogenated compound with low-boiling
dimethylamine at high temperature and pressure.5 To
Scheme 1 Three approaches towards desulfitative replacement reac-
tions
Me2N
NMe2
N
NMe2
O
N
NMe2
O
N
N
O
NH
O
O
N
O
NH
N
N
N
O
O
N
N
N
H2N
H
N
H
H
1
2
3
4
Figure 1 Natural products and bioactive molecule containing a dimethylamino group
SYNTHESIS 2013, 45, 2405–2412
Advanced online publication: 11.07.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1338499; Art ID: SS-2013-N0091-OP
© Georg Thieme Verlag Stuttgart · New York

2406
S. Khan et al.
PAPER
idazol-4-one derivatives by using a base and N,N-
dimethylformamide or an aliphatic alcohol is shown in
Scheme 1.
H
N
N
K2CO3, DMF–H2O
140 °C, MW, 1 h
Initially, we examined the desulfitative dimethylamina-
tion of 5-benzylidene-2-thioxoimidazolidin-4-one (5)
with N,N-dimethylformamide as the amine source and po-
tassium carbonate as the base under the microwave condi-
tions, but the yield of product 6 was poor (12%) (Scheme
2).
NMe2
S
N
H
N
H
O
O
6
5
Scheme 2 Desulfitative dimethylamination of 5-benzylidene-2-
thioxoimidazolidin-4-one
Interestingly, the S-methyl derivative of substrate 5, pre-
pared by methylation with iodomethane in acetone, gave
a higher yield of the dimethylamino derivative 6. Encour-
aged by these results, we used the S-methyl derivative 7a
to explore the optimal reaction conditions for dimethyl-
amination with N,N-dimethylformamide as the amine
source. The presence of water was found to be essential
(Table 1). When anhydrous N,N-dimethylformamide was
Aliphatic etherification is a difficult task in synthetic or-
ganic chemistry.9 The conventional method for this reac-
tion is the Williamson ether synthesis, which uses highly
toxic reagents, such as dimethyl sulfate and methyl ha-
lides, and generates stoichiometric quantities of inorganic
salts.10 In addition, various transition-metal-catalyzed
methods have been reported for the preparation of aliphat-
ic ethers.11 Although efficient, these methods require ex-
pensive metal catalysts and entail anhydrous and harsh
reaction conditions and complex workup procedures.
Simple and efficient protocols for etherification are there-
fore required. In this context, we report an efficient meth-
od for the etherification of 2-(methylsulfanyl)-3,5-
dihydro-4H-imidazol-4-one derivatives at the C-2 posi-
tion by using an aliphatic alcohol in the presence of potas-
sium carbonate. A general strategy for base-mediated
desulfitative dimethylamination, oxidation, or etherifica-
tion reactions of 2-(methylsulfanyl)-3,5-dihydro-4H-im-
Table 2 Scope of the Desulfitative Dimethylamination and Oxida-
tion Reactions of 2-(Methylsulfanyl)-3,5-dihydro-4H-imidazol-4-
ones
R1
R1
R1
H
N
N
N
N
NMe2
O
SMe
+
N
N
R2
O
O
O
R2
R2
8a–o
7a–o
9a–o
Substratea R1
R2
Yieldb (%) Yieldb (%)
of 8a–o of 9a–o
Table 1 Optimization of Conditions for the Desulfitative Dimethyl-
amination and Oxidation Reactions
7a
7b
7c
7d
7e
7f
Ph
H
H
H
H
H
H
H
H
81
78
61
77
57
61
79
59
0c
12
3,4-(MeO)2C6H3
2-naphthyl
4-MeOC6H4
4-O2NC6H4
3,4,5-(MeO)3C6H2
4-BnOC6H4
2-BrC6H4
traced
–
H
N
N
N
base, solvent
O
+
NMe2
SMe
18
trace
0
temp, MW, 40 min
N
H
N
H
N
H
O
O
O
7a
8a
9a
7g
7h
7i
Entrya
Base
Solvent
Yieldb (%) Yieldb (%)
of 8a
of 9a
14
74
70
61
72
59
64
72
3,4-(MeO)2C6H3 4-MeOC6H4CH2 0e
1
2
3
4
5
6
7
8
–
DMF
–
–
7j
4-BnOC6H4
Ph
Ph
–
–
–
–
–
–
K2CO3
K2CO3
K2CO3
Na2CO3
KOH
DMF
34
81
0c
73
57
–
trace
–
7k
7l
Bn
Me
Me
DMF–H2O
H2O
4-PrC6H4
2-FC6H4
–
7m
7n
7o
DMF–H2O
DMF–H2O
1,4-dioxane
1,4-dioxane
–
3,4-(OCH2O)C6H3 Me
Ph Me
19
74
61
K2CO3
Na2CO3
a Reaction conditions: Substrate 7a–o (1 equiv), K2CO3 (2 equiv),
DMF–H2O (1:1; 2 mL), 140 °C, MW, 40 min.
b Yield of isolated product.
–
a Reaction conditions: 7a (1 equiv), K2CO3 (2 equiv), solvent (2 mL),
140 °C, MW, 40 min.
c Product 9 was not observed.
d Product 9 was obtained in a trace amount.
e Product 8 was not observed.
b Yield of isolated product.
c The starting material was recovered.
Synthesis 2013, 45, 2405–2412
© Georg Thieme Verlag Stuttgart · New York

PAPER
Functionalization of 3,5-Dihydro-4H-imidazol-4-ones
2407
used at 140 °C, the reaction was incomplete and the di- dergoes base-mediated decarbonylation to give product
methylamino product 8a was obtained in low yield (entry G.12
2), but when water and N,N-dimethylformamide were
used in a ratio of 1:1, the yield of 8a increased to 81% (en-
try 3). However, when water was used as the sole solvent,
the diketone product 9a was obtained in trace amounts
We have also applied our optimized condition to the
Biginelli multicomponent reaction (MCR) product 1013
and the pyrazolopyrimidine derivative 12 (Scheme 3).
There are few reports of direct amination at the C2-posi-
(entry 4). Various bases gave good to excellent yields in
tion of Biginelli MCR-type products. Moreover, a dimeth-
the dimethylamination reaction with N,N-dimethylform-
ylamino group at the C6-position of pyrazolopyrimidine
derivatives is generally introduced by reaction of the cor-
amide (entries 3, 5 and 6). Of these bases, potassium car-
bonate was the base of choice, giving the product 8a in
81% yield (entry 3). The reaction failed to proceed in the
absence of a base (entry 1). It is interesting to note that
when N,N-dimethylformamide was replaced with 1,4-di-
oxane, the reaction was completed in straightforward
responding halogenated pyrazolopyrimidine with an
amine.14 To our delight, the respective products 11 and 13
were obtained in good yields under our optimized condi-
tions (Scheme 4).
manner to give the diketone 9a exclusively in good yield
(entry 7).
Cl
Cl
Next, we examined the effects of substituents in the 1-po-
sition. When a substituent was present in the 1-position,
the oxidative product was formed as the major product,
whereas in the absence of this substitution, the dimethyl-
aminated product was formed exclusively (Table 2). Hav-
ing identified the optimal protocol for dimethylamination,
we applied it to substrates 7a–o, and we obtained the cor-
responding dimethylamino products in good yields.
O
O
K2CO3, DMF–H2O (1:1)
MW, 140 °C, 40 min
O
N
O
N
N
H
NMe2
N
H
SMe
10
11, 63%
SMe
N
NMe2
N
A plausible mechanism for the oxidation and dimethyl-
amination at the C2-position of 2-(methylsulfanyl)-3,5-
dihydro-4H-imidazol-4-one moiety by N,N-dimethyl-
formamide–water involves two paths (Scheme 3; paths 1
and 2). In path 1, nucleophilic substitution of substrate A
by water molecules at the C2-position gives the desulfita-
tive oxidized product B, which subsequently tautomerizes
to form the stable product C. In path 2, carbonylation of
K2CO3, DMF–H2O (1:1)
MW, 140 °C, 40 min
N
N
N
N
N
SMe
N
SMe
H
H
12
13, 57%
Scheme 4 Dimethylamination of Biginelli MCR product 10 and pyr-
azolopyrimidine derivative 12
2-(methylsulfanyl)-3,5-dihydro-4H-imidazol-4-one
D
We decided to apply the experience that we gained from
the above study to the etherification of 2-(methylsulfa-
nyl)-3,5-dihydro-4H-imidazol-4-ones at the C2-position
proceeds with cleavage of N,N-dimethylformamide to
give the carbonylated intermediate E. Subsequent nucleo-
philic attack by dimethylamine, formed by the cleavage of
N,N-dimethylformamide, gives intermediate F, which un-
OH
Me2NH
R1
–
R1
H
N
N
N
O
SMe
O
O
SMe
path 1
N
path 2
R = H
O
SMe
N
N
N
R = Me
O
SMe
N
R
Me
A
R1
H
R1
D
O
E
Me2N
H
R1
R1
N
N
O
NMe2
O
NMe2
tautomerization
N
NH
base
– CO
N
N
O
OH
O
O
O
N
H
N
R1
H
G
R1
Me
C
Me
B
F
Scheme 3 A plausible mechanism for substituent-dependent desulfitative dimethylamination and oxidation reactions of 2-(methylsulfanyl)-
3,5-dihydro-4H-imidazol-4-ones
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 2405–2412

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S. Khan et al.
PAPER
by using alcohols. To identify suitable conditions for the
etherification, we chose the imidazolone 14a and butanol
as model coupling partners, and we examined the reaction
in the presence of various bases and at various tempera-
ture (Table 3). Of the three bases that we examined, potas-
sium carbonate was found to be the best, giving ether 15a
in 83% yield when butanol was used as the solvent at
160 °C (Table 3, entry 2). Sodium carbonate and potassi-
um hydroxide gave poor yields of 15a (entries 3 and 4),
and the reaction did not proceed in the absence of a base
(entry 1). With potassium carbonate as the base, reducing
the reaction temperature to 140 °C or 120 °C gave signif-
icantly lower yields of 15a (entries 5 and 6). The reaction
proceeded to completion within 45 minutes under micro-
wave conditions at 160 °C, whereas in the absence of mi-
crowave irradiation, it took 16 to 18 hours to reach
completion.
Table 4 Scope of the Desulfitative Etherification of 2-(Methylsulfa-
nyl)-3,5-dihydro-4H-imidazol-4-ones
R1
R1
N
N
N
N
OR3
SMe
O
O
R2
R2
14
15
Entrya R1
R2
R3
Temp
(°C)
Yieldb
(%)
1
2
4-O2NC6H4
Ph
Me
Me
Me
Ph
Bu
Bu
Bu
Bu
Bu
Pr
160
160
160
160
160
130
120
130
130
130
130
130
89
88
81
62
78
69
67
53
62
74
71
62
3
3,4-(OCH2O)C6H3
3,5-(MeO)2C6H3
4-PrC6H4
4
5
Me
Me
Me
Me
Me
Me
Me
Me
Table 3 Optimization of Reaction Condition for the Desulfitative
Etherification
6
3,4-(OCH2O)C6H3
4-O2NC6H4
2-naphthyl
4-Me2NC6H4
4-O2NC6H4
4-PrC6H4
NO2
NO2
7
Et
8
Pr
9
Pr
N
N
N
base, BuOH
OBu
10
11
12
Pr
SMe
N
temp, MW, 45 min
O
O
Me
Pr
Me
Ph
Pr
14a
15a
a Reaction conditions: 14 (1 equiv), K2CO3 (2 equiv), R3OH (2 mL),
120–160 °C, MW, 45 min.
Entrya
Base
Temp (°C)
Yieldb (%)
b Yield of isolated product.
c
1
2
3
4
5
6
–
160
160
160
160
140
120
–
K2CO3
Na2CO3
KOH
K2CO3
K2CO3
83
69
31
43
16
amine. Additionally, etherification of 2-(methylsulfanyl)-
3,5-dihydro-4H-imidazol-4-ones at the 2-position was
readily achieved by using an aliphatic alcohol and potas-
sium carbonate under mild conditions, providing access to
extra diversity at this position.
All reagents and solvents were purchased from commercial sources
and used without purification. H NMR spectra were recorded at
a Reaction conditions: 14a (1 equiv), K2CO3 (2 equiv), BuOH (3 mL),
120–160 °C, MW, 45 min.
1
300 or 400 MHz with Bruker Avance DRX-300 or DRX-400 spec-
trometers and 13C NMR spectra were recorded at 50, 75, or 100
MHz with Bruker Avance DRX-200, DRX-300 or DRX-400 spec-
trometers in deuterated solvents with TMS as internal reference.
Mass spectra and high-resolution mass spectra were recorded in the
ESI (positive ion) mode with Micromass Quattro II and Jeol JMS
T100LC Accu TOF spectrometers, respectively. Microwave reac-
tions were conducted by using a Biotage Initiator in 10-mL glass
tubes sealed with Teflon septa and placed in the cavity of the micro-
wave oven. The progress of the reaction was routinely monitored by
TLC on precoated silica gel plates.
b Yield of isolated product.
c No reaction.
Having identified the optimal protocol, we extended it to
the etherification of various substituted 2-(methylsulfa-
nyl)-3,5-dihydro-4H-imidazol-4-one scaffolds with vari-
ous aliphatic alcohols, and we obtained the corresponding
ethers in moderate to good yields (Table 4).
In summary, we have developed an efficient method for
the substitution-dependent dimethylamination or oxida- 5-Alkylidene-2-(dimethylamino)-3,5-dihydro-4H-imidazol-4-
ones (8a–h), 5-alkylideneimidazolidine-2,4-diones (9a,i–o), and
tion of substituted 2-(methylsulfanyl)-3,5-dihydro-4H-
imidazol-4-one scaffolds at the C2-position by using a
mixture of N,N-dimethylformamide and water in the pres-
Related Compounds (11 and 13); General Procedure
A 10-mL glass reaction vial containing a stirring bar was charged
with the 2-(methylsulfanyl)-3,5-dihydro-4H-imidazol-4-one 7a–o,
ence of potassium carbonate. This protocol provides a Biginelli MCR product 10, or pyrazolopyrimidine derivative 11
(100 mg, 1 equiv), followed successively by K2CO3 (2 equiv) and
1:1 DMF–H2O (3 mL). The vial was sealed tightly with a Teflon
straightforward method for dimethylamination using N,N-
dimethylformamide instead of low-boiling dimethyl-
Synthesis 2013, 45, 2405–2412
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Functionalization of 3,5-Dihydro-4H-imidazol-4-ones
2409
septum and heated in the cavity of the microwave oven at 140 °C for
40 min. When the reaction was complete (TLC), the solvent was
evaporated under reduced pressure and the residue was purified by
flash column chromatography (silica gel, hexane– EtOAc).
2-(Dimethylamino)-5-(3,4,5-trimethoxybenzylidene)-3,5-di-
hydro-4H-imidazol-4-one (8f)
Bright-yellow solid; yield: 60 mg (61%); mp 194–197 °C.
FTIR (KBr): 3442, 1649, 1371, 1248, 1125, 894 cm–1.
1H NMR (300 MHz, CDCl3): δ = 11.24 (br s, 1 H), 7.50 (s, 2 H),
6.26 (s, 1 H), 3.79 (s, 6 H), 3.68 (s, 3 H), 3.09 (s, 6 H).
13C NMR (75 MHz, CDCl3): δ = 172.9, 159.7, 153.4, 152.9, 141.0,
5-Benzylidene-2-(dimethylamino)-3,5-dihydro-4H-imidazol-4-
one (8a)
Yellow solid; yield: 80 mg (81%); mp 160–163 °C.
FTIR (KBr): 3434, 3116, 1706, 1667, 1599, 1447, 898, 769, 693
cm–1.
1H NMR (300 MHz, CDCl3): δ = 11.35 (br s, 1 H), 8.23 (d, J = 6.0
137.3, 132.1, 111.5, 107.8, 107.4, 60.5, 56.0, 37.1.
HRMS (ESI): m/z [M + H]+ calcd for C15H20N3O4: 306.1454; found:
306.1441.
Hz, 2 H), 7.82–7.65 (m, 3 H), 6.28 (s, 1 H), 3.12 (s, 6 H).
13C NMR (75 MHz, CDCl3): δ = 172.1, 160.3, 155.7, 143.7, 140.3,
129.9, 125.4, 124.9, 107.8, 36.9.
HRMS (ESI): m/z [M + H]+ calcd for C12H14N3O: 216.1137; found:
5-[4-(Benzyloxy)benzylidene]-2-(dimethylamino)-3,5-dihydro-
4H-imidazol-4-one (8g)
Yellow solid; yield: 78 mg (79%); mp 148–150 °C.
FTIR (KBr): 3434, 1653, 1601, 1450, 1238, 999, 894 cm–1.
216.1142.
1H NMR (300 MHz, CDCl3): δ = 11.12 (br s, 1 H), 8.00 (d, J = 7.8
Hz, 2 H), 7.47–7.33 (m, 5 H), 7.03 (d, J = 8.7 Hz, 2 H), 6.28 (s, 1
H), 5.13 (s, 2 H), 3.08 (s, 6 H).
13C NMR (75 MHz, CDCl3): δ = 173.1, 158.1, 137.4, 131.9, 129.3,
128.8, 128.3, 128.1, 115.2, 111.5, 69.6, 37.2.
5-(3,4-Dimethoxybenzylidene)-2-(dimethylamino)-3,5-dihydro-
4H-imidazol-4-one (8b)
Yellow solid; yield: 76 mg (78%); mp 184–186 °C.
FTIR (KBr): 3420, 2934, 1612, 1443, 1262, 1150, 1024, 894 cm–1.
1H NMR (400 MHz, CDCl3): δ = 11.1 (s, 1 H), 8.09 (s, 1 H), 7.39
(d, J = 7.6 Hz, 1 H), 6.92 (d, J = 8.0 Hz, 1 H), 6.24 (s, 1 H), 3.76 (s,
3 H), 3.75 (s, 3 H), 3.05 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 172.6, 159.0, 148.7, 140.2, 129.6,
123.9, 113.4, 112.2, 111.9, 55.8, 55.5, 37.1.
HRMS (ESI): m/z [M + H]+ calcd for C14H18N3O3: 276.1348; found:
276.1340.
HRMS (ESI): m/z [M + H]+ calcd for C19H20N3O2: 322.1556; found:
322.1551.
5-(2-Bromobenzylidene)-2-(dimethylamino)-3,5-dihydro-4H-
imidazol-4-one (8h)
Pale-yellow solid; yield: 58 mg (59%); mp 170–172 °C.
FTIR (KBr): 3120, 1718, 1661, 1597, 1251, 897 cm–1.
1H NMR (300 MHz, CDCl3): δ = 11.3 (br s, 1 H), 8.86 (br s, 1 H),
7.63 (d, J = 7.8 Hz, 1 H), 7.41 (t, J = 7.2 Hz, 1 H), 7.15 (t, J = 7.2
Hz, 1 H), 6.54 (s, 1 H), 3.11 (s, 6 H).
13C NMR (75 MHz, CDCl3): δ = 172.8, 160.7, 143.6, 135.5, 133.0,
131.7, 128.8, 128.0, 124.4, 107.2, 37.4.
2-(Dimethylamino)-5-(2-naphthylmethylene)-3,5-dihydro-4H-
imidazol-4-one (8c)
Yellow solid; yield: 60 mg (61%); mp >200 °C.
FTIR (KBr): 3405, 2934, 1615, 1435, 1277, 1114, 898, 769 cm–1.
1H NMR (400 MHz, CDCl3): δ = 11.3 (s, 1 H), 8.97 (br s, 1 H), 8.22
(s, 1 H), 7.92 (d, J = 8.0 Hz, 1 H), 7.81 (d, J = 7.6 Hz, 1 H), 7.59–
7.49 (m, 3 H), 7.02 (s, 1 H), 3.11 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 173.2, 160.4, 142.9, 133.8, 131.9,
131.6, 129.2, 128.6, 127.8, 126.8, 126.2, 123.2, 105.0, 37.3.
HRMS (ESI): m/z [M + H]+ calcd for C16H16N3O: 266.1293; found:
266.1286.
HRMS (ESI): m/z [M + H]+ calcd for C12H12BrN3O: 293.0164;
found: 293.0172.
5-Benzylideneimidazolidine-2,4-dione (9a)
White solid; yield: 64 mg (72%); mp 164–166 °C.
FTIR (KBr): 3211, 3051, 2368, 1770, 1656, 1450, 1379, 1255, 878,
769, 654 cm–1.
1H NMR (300 MHz, DMSO-d6): δ = 11.2 (s, 1 H), 10.5 (s, 1 H),
7.62 (d, J = 7.2 Hz, 2 H), 7.42–7.32 (m, 3 H), 6.4 (s, 1 H).
13C NMR (75 MHz, DMSO-d6): δ = 165.1, 155.2, 132.5, 128.9,
128.3, 127.8, 127.5, 107.8.
2-(Dimethylamino)-5-(4-methoxybenzylidene)-3,5-dihydro-4H-
imidazol-4-one (8d)
Yellow solid; yield: 75 mg (77%); mp 177–181 °C.
FTIR (KBr): 3424, 1610, 1343, 1262, 1050, 1014, 894 cm–1.
1H NMR (300 MHz, CDCl3): δ = 11.1 (s, 1 H), 8.04 (d, J = 8.1 Hz,
2 H), 6.94 (d, J = 8.1 Hz, 2 H), 6.43 (s, 1 H), 3.77 (s, 3 H), 3.07 (s,
6 H).
13C NMR (75 MHz, CDCl3): δ = 172.3, 158.7, 158.5, 139.7, 131.5,
128.8, 113.8, 111.4, 55.0, 36.7.
HRMS (ESI): m/z [M + H]+ calcd for C10H9N2O2: 189.0659; found:
189.0657.
5-(3,4-Dimethoxybenzylidene)-3-(4-methoxybenzyl)imidazoli-
dine-2,4-dione (9i)
White solid; yield: 68 mg (74%); mp 177–180 °C.
FTIR (KBr): 3195, 1761, 1718, 1440, 1248, 1150, 1028 cm–1.
1H NMR (400 MHz, CDCl3): δ = 10.7 (s, 1 H), 7.23 (t, J = 8.4 Hz,
3 H), 7.14 (s, 1 H), 6.97 (d, J = 8.4 Hz, 1 H), 6.89 (d, J = 8.8 Hz, 2
H), 6.52 (s, 1 H), 4.57 (s, 2 H), 3.81 (s, 3 H), 3.77 (s, 3 H), 3.70 (s,
3 H).
13C NMR (100 MHz, CDCl3): δ = 164.4, 159.1, 155.5, 150.0, 149.2,
129.4, 129.1, 125.8, 125.0, 123.7, 114.4, 113.1, 112.2, 111.3, 56.1,
56.0, 55.5, 41.2.
HRMS (ESI): m/z [M + H]+ calcd for C13H16N3O2: 246.1243; found:
246.1237.
2-(Dimethylamino)-5-(4-nitrobenzylidene)-3,5-dihydro-4H-im-
idazol-4-one (8e)
Yellow solid; yield: 57 mg (57%); mp 188–190 °C.
FTIR (KBr): 3446, 1613, 1327, 1100, 887 cm–1.
1H NMR (300 MHz, CDCl3): δ = 11.5 (s, 1 H), 8.27–8.15 (m, 4 H),
HRMS (ESI): m/z [M + H]+ calcd for C20H21N2O5: 369.1450; found:
6.29 (s, 1 H), 3.15 (br s, 6 H).
13C NMR (75 MHz, CDCl3): δ = 171.9, 160.7, 145.2, 144.7, 143.6,
369.1451.
130.0, 123.5, 106.7, 36.9.
HRMS (ESI): m/z [M + H]+ calcd for C12H13N4O3: 261.0988; found:
261.0971.
5-[4-(Benzyloxy)benzylidene]-3-phenylimidazolidine-2,4-dione
(9j)
White solid; yield: 64 mg (70%); mp 167–171 °C.
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FTIR (KBr): 3224, 1718, 1414, 1248 cm–1.
HRMS (ESI): m/z [M + H]+ calcd for C11H11N2O2: 203.0821; found:
203.0811.
1H NMR (300 MHz, CDCl3): δ = 10.9 (s, 1 H), 7.70 (d, J = 8.4 Hz,
2 H), 7.51–7.35 (m, 10 H), 7.10 (d, J = 8.4 Hz, 2 H), 6.63 (s, 1 H),
5.18 (s, 2 H).
13C NMR (75 MHz, CDCl3): δ = 163.7, 159.2, 154.4, 137.2, 132.3,
131.8, 129.2, 128.9, 128.4, 128.2, 127.3, 125.9, 124.9, 115.6, 110.8,
69.8.
Ethyl 4-(4-Chlorophenyl)-2-(dimethylamino)-6-methyl-1,4-di-
hydropyrimidine-5-carboxylate (11)
Pale-yellow solid; yield: 62 mg (74%); mp >200 °C.
FTIR (KBr): 3422, 2949, 1658, 1439, 1216, 1088, 702 cm–1.
1H NMR (300 MHz, CDCl3): δ = 10.4 (br s, 1 H), 7.43 (t, J = 7.2
Hz, 4 H), 5.46 (s, 1 H), 4.11 (d, J = 6.0 Hz, 2 H), 3.15 (s, 6 H), 2.52
(s, 3 H), 1.16 (d, J = 6.30 Hz, 3 H).
HRMS (ESI): m/z [M + H]+ calcd for C23H19N2O3: 371.1396; found:
371.1411.
13C NMR (75 MHz, CDCl3): δ = 164.8, 150.0, 146.7, 140.9, 133.1,
129.1, 128.7, 104.0, 60.7, 51.2, 39.8, 17.9, 14.4.
3-Benzyl-5-benzylideneimidazolidine-2,4-dione (9k)
White solid; yield: 55 mg (61%); mp 189–192 °C.
HRMS (ESI): m/z [M + H]+ calcd for C16H21ClN3O2: 322.1322;
found: 322.1314.
FTIR (KBr): 3429, 2927, 1656, 1403, 1006 cm–1.
1H NMR (400 MHz, CDCl3): δ = 10.8 (s, 1 H), 7.65 (d, J = 7.6 Hz,
2 H), 7.43–7.26 (m, 8 H), 6.58 (s, 1 H), 4.67 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 163.9, 154.9, 136.4, 132.7, 129.5,
128.7, 128.6, 128.5, 127.5, 127.4, 126.4, 109.9, 41.3.
HRMS (ESI): m/z [M + H]+ calcd for C17H15N2O2: 279.1134; found:
N,N-Dimethyl-6-(methylsulfanyl)-1H-pyrazolo[3,4-d]pyrimi-
din-4-amine (13)
Yellow solid; yield: 56 mg (62%); mp 184–186 °C.
FTIR (KBr): 3432, 3115, 1585, 1329, 948, 771 cm–1.
1H NMR (400 MHz, CDCl3): δ = 13.2 (s, 1 H), 8.06 (s, 1 H), 3.27
279.1136.
(s, 6 H), 2.46 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 167.2, 156.1, 134.4, 97.6, 13.4.
HRMS (ESI): m/z [M + H]+ calcd for C8H12N5S: 210.0813; found:
210.0820.
3-Methyl-5-(4-propylbenzylidene)imidazolidine-2,4-dione (9l)
Light-yellow solid; yield: 64 mg (72%); mp 160–164 °C.
FTIR (KBr): 3224, 2929, 1713, 1461, 1161, 1020, 825, 649 cm–1.
1H NMR (300 MHz, CDCl3): δ = 10.6 (s, 1 H), 7.54 (d, J = 7.8 Hz,
2 H), 7.22 (d, J = 7.5 Hz, 2 H), 6.49 (s, 1 H), 2.94 (s, 3 H), 2.57 (d,
J = 7.2 Hz, 2 H), 1.61 (q, J = 1.61 Hz, 2 H), 0.89 (t, J = 7.2 Hz, 3 H).
3-Substituted 2-Alkoxy-5-(alkylidene)-3,5-dihydro-4H-imidaz-
ol-4-ones (15a–l); General Procedure
A 10-mL glass reaction vial containing a stirring bar was charged
successively with the substituted imidazolone 14 (100 mg, 1 equiv),
K2CO3 (2 equiv), and alcohol R3OH (3 mL). The vial was sealed
tightly with a Teflon septum and heated in the cavity of the micro-
wave oven at 120–160 °C for 45 min. When the reaction was com-
plete (TLC), the solvent was evaporated under reduced pressure and
the residue was purified by flash column chromatography (silica
gel, hexane–EtOAc).
13C NMR (75 MHz, CDCl3): δ = 164.7, 155.7, 143.4, 130.7, 129.9,
129.2, 126.4, 110.0, 37.5, 24.6, 24.3, 14.0.
HRMS (ESI): m/z [M + H]+ calcd for C14H17N2O2: 245.1290; found:
245.1285.
5-(2-Fluorobenzylidene)-3-methylimidazolidine-2,4-dione (9m)
White solid; yield: 52 mg (59%); mp 172–174 °C.
FTIR (KBr): 3430, 1718, 1657, 1010, 763 cm–1.
1H NMR (400 MHz, CDCl3): δ = 10.8 (s, 1 H), 7.46–7.39 (m, 3 H),
7.11 (s, 1 H), 6.47 (s, 1 H), 2.91 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 164.5, 163.9, 161.5, 135.6, 135.6,
131.0, 130.9, 128.1, 126.2, 108.1, 24.7.
HRMS (ESI): m/z [M + H]+ calcd for C11H10FN2O2: 221.0726;
2-Butoxy-3-methyl-5-(4-nitrobenzylidene)-3,5-dihydro-4H-im-
idazol-4-one (15a)
Light-yellow solid; yield: 97 mg (89%); mp 143–146 °C.
FTIR (KBr): 3445, 2942, 1577, 1335, 1100, 814 cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.24–8.20 (m, 4 H), 6.87 (s, 1 H),
4.63 (t, J = 6.3 Hz, 2 H), 3.12 (s, 3 H), 1.91–1.82 (m, 2 H), 1.53–
1.46 (m, 2 H), 1.05 (t, J = 7.2 Hz, 3 H).
found: 221.0720.
13C NMR (75 MHz, CDCl3): δ = 169.3, 164.7, 147.3, 141.6, 141.4,
131.7, 123.8, 117.9, 70.5, 30.8, 25.7, 19.2, 13.8.
HRMS (ESI): m/z [M + H]+ calcd for C15H18N3O4: 304.1297; found:
304.1285.
5-(1,3-Benzodioxol-5-ylmethylene)-3-methylimidazolidine-2,4-
dione (9n)
White solid; yield: 57 mg (64%); mp 193–196 °C.
FTIR (KBr): 3222, 1757, 1718, 1457, 1254, 1031, 646 cm–1.
1H NMR (400 MHz, CDCl3): δ = 10.6 (s, 1 H), 7.26 (s, 1 H), 7.13
(t, J = 7.6 Hz, 1 H), 6.94 (d, J = 8.0 Hz, 1 H), 6.45 (s, 1 H), 6.04 (s,
2 H), 2.92 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 164.7, 155.7, 148.2, 148.1, 127.3,
125.5, 125.4, 110.2, 109.2, 109.1, 101.9, 24.6.
HRMS (ESI): m/z [M + H]+ calcd for C12H11N2O4: 247.0719; found:
247.0720.
5-Benzylidene-2-butoxy-3-methyl-3,5-dihydro-4H-imidazol-4-
one (15b)
White solid; yield: 99 mg (88%); mp 101–103 °C.
FTIR (KBr): 3424, 2956, 1722, 1579, 1476, 1302, 948, 683 cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.09 (d, J = 7.2 Hz, 2 H), 7.42–
7.28 (m, 3 H), 6.94 (s, 1 H), 4.60 (t, J = 6.6 Hz, 2 H), 3.10 (s, 3 H),
1.89–1.80 (m, 2 H), 1.58–1.46 (m, 2 H), 1.05 (t, J = 7.5 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 169.6, 162.9, 138.4, 134.8, 131.5,
129.1, 128.6, 121.6, 69.8, 30.8, 25.4, 19.1, 13.8.
5-Benzylidene-3-methylimidazolidine-2,4-dione (9o)
White solid; yield: 63 mg (72%); mp 180–184 °C.
FTIR (KBr): 3427, 1658, 1462, 999, 765 cm–1.
HRMS (ESI): m/z [M + H]+ calcd for C15H19N2O2: 259.1447; found:
259.1441.
1H NMR (400 MHz, CDCl3): δ = 10.7 (s, 1 H), 7.62 (d, J = 7.6 Hz,
2 H), 7.40–7.29 (m, 3 H), 6.50 (s, 1 H), 2.93 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 164.7, 155.8, 133.3, 129.9, 129.2,
128.9, 127.2, 109.7, 24.7.
5-(1,3-Benzodioxol-5-ylmethylene)-2-butoxy-3-methyl-3,5-di-
hydro-4H-imidazol-4-one (15c)
White solid; yield: 87 mg (81%); mp 107–110 °C.
FTIR (KBr): 3431, 2942, 1585, 1485, 1257, 1028 cm–1.
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Functionalization of 3,5-Dihydro-4H-imidazol-4-ones
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1H NMR (300 MHz, CDCl3): δ = 7.95 (s, 1 H), 7.35 (d, J = 7.8, 1
H), 6.86–6.82 (m, 2 H), 6.01 (s, 2 H), 4.57 (t, J = 6.3, 2 H), 3.10 (s,
3 H), 1.86 (t, J = 6.9 Hz, 2 H), 1.55 (q, J = 7.5, 2 H), 1.04 (t, J = 7.2
Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 169.4, 162.1, 148.4, 147.8, 136.7,
129.2, 127.1, 121.6, 110.5, 108.3, 101.2, 69.6, 30.6, 25.3, 19.0,
13.7.
FTIR (KBr): 3427, 2934, 1720, 1575, 1371, 1150, 803 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.83 (d, J = 7.6, 1 H), 8.35 (d,
J = 8.4 Hz, 1 H), 7.86–7.79 (m, 3 H), 7.58–7.48 (m, 3 H), 4.53 (t,
J = 6.8 Hz, 2 H), 3.12 (s, 3 H), 1.91–1.82 (m, 2 H), 1.07 (t, J = 7.2
Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 169.5, 163.3, 139.0, 133.7, 132.4,
130.4, 130.1, 129.6, 128.8, 126.5, 125.7, 125.6, 123.3, 116.8, 71.4,
25.4, 22.0, 10.2.
HRMS (ESI): m/z [M + H]+ calcd for C16H19N2O4: 303.1345; found:
303.1339.
HRMS (ESI): m/z [M + H]+ calcd for C18H19N2O2: 295.1447; found:
295.1439.
2-Butoxy-5-(3,4-dimethoxybenzylidene)-3-phenyl-3,5-dihydro-
4H-imidazol-4-one (15d)
5-[4-(Dimethylamino)benzylidene]-3-methyl-2-propoxy-3,5-di-
hydro-4H-imidazol-4-one (15i)
Light-yellow solid; yield: 65 mg (62%); mp 156–159 °C.
Light-yellow solid; yield: 65 mg (62%); mp 115–117 °C.
FTIR (KBr): 3429, 2925, 1721, 1594, 1267, 1148, 930, 730 cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.01 (s, 1 H), 7.40–7.26 (m, 6 H),
6.91 (s, 1 H), 6.82 (d, J = 8.4 Hz, 1 H), 4.52 (t, J = 6.6, 2 H), 3.86
(s, 3 H), 3.83 (s, 3 H), 1.77–1.68 (m, 2 H), 1.41–1.31 (m, 2 H), 0.89
(t, J = 7.5 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 168.1, 160.5, 150.3, 148.8, 135.6,
132.3, 129.0, 127.8, 127.7, 125.8, 125.8, 122.7, 113.6, 110.9, 69.7,
55.8, 55.6, 30.5, 19.0, 13.6.
FTIR (KBr): 3458, 2924, 1709, 1599, 1360, 1145, 677 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.97 (d, J = 8.4 Hz, 2 H), 6.89 (s,
1 H), 6.68 (d, J = 8.0 Hz, 2 H), 4.48 (t, J = 5.6, 2 H), 3.06 (s, 3 H),
2.98 (s, 6 H), 1.87–1.82 (m, 2 H), 1.05 (t, J = 6.8 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 169.5, 160.7, 150.8, 134.3, 133.0,
123.1, 122.7, 111.7, 70.8, 40.0, 25.2, 22.1, 10.3.
HRMS (ESI): m/z [M + H]+ calcd for C16H22N3O2: 288.1712; found:
288.1704.
HRMS (ESI): m/z [M + H]+ calcd for C22H25N2O4: 381.1814; found:
381.1808.
3-Methyl-5-(4-nitrobenzylidene)-2-propoxy-3,5-dihydro-4H-
imidazol-4-one (15j)
2-Butoxy-3-methyl-5-(4-propylbenzylidene)-3,5-dihydro-4H-
imidazol-4-one (15e)
Yellow solid; yield: 77 mg (74%); mp 166–169 °C.
White solid; yield: 84 mg (78%); mp 92–94 °C.
FTIR (KBr): 3442, 2963, 1729, 1577, 1493, 1334, 1154, 923, 692
cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.20–8.14 (m, 4 H), 6.83 (s, 1 H),
4.56 (t, J = 6.4 Hz, 2 H), 3.11 (s, 3 H), 1.94–1.85 (m, 2 H), 1.08 (t,
J = 7.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 169.0, 164.5, 146.9, 141.3, 141.2,
131.5, 123.6, 117.6, 72.0, 25.4, 22.0, 10.2.
FTIR (KBr): 3405, 2929, 1718, 1479, 1302, 1150, 948, 684 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.88 (d, J = 7.8 Hz, 2 H), 7.09 (d,
J = 8.1 Hz, 2 H), 6.79 (s, 1 H), 4.44 (t, J = 6.6 Hz, 2 H), 2.94 (s, 3
H), 2.50 (t, J = 7.2 Hz, 2 H), 1.74 (q, J = 6.6 Hz, 2 H), 1.65–1.47
(m, 2 H), 1.44–1.31 (m, 2 H), 0.91–0.85 (m, 6 H).
13C NMR (75 MHz, CDCl3): δ = 169.5, 162.3, 144.0, 137.6, 132.2,
131.3, 128.6, 121.6, 69.5, 38.0, 30.6, 25.2, 24.3, 19.0, 13.8, 13.7.
HRMS (ESI): m/z [M + H]+ calcd for C14H16N3O4: 290.1141; found:
290.1135.
HRMS (ESI): m/z [M + H]+ calcd for C18H25N2O2: 301.1916; found:
301.1904.
3-Methyl-2-propoxy-5-(4-propylbenzylidene)-3,5-dihydro-4H-
imidazol-4-one (15k)
5-(1,3-Benzodioxol-5-ylmethylene)-3-methyl-2-propoxy-3,5-di-
hydro-4H-imidazol-4-one (15f)
Yellow solid; yield: 74 mg (71%); mp 113–116 °C.
Yellow solid; yield: 72 mg (69%); mp 131–133 °C.
FTIR (KBr): 2932, 1718, 1578, 1486, 1371, 1150, 948 cm–1.
FTIR (KBr): 2888, 1706, 1586, 1484, 1258, 1037, 941 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.96 (d, J = 8.4 Hz, 2 H), 7.19 (d,
J = 8.0 Hz, 2 H), 6.90 (s, 1 H), 4.51 (t, J = 6.8 Hz, 2 H), 3.08 (s, 3
H), 2.60–2.53 (m, 2 H), 1.89 (q, J = 7.2 Hz, 2 H), 1.66–1.60 (m, 2
H), 1.06 (t, J = 7.2 Hz, 3 H), 0.94 (t, J = 7.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 169.8, 162.5, 144.3, 137.7, 132.4,
131.5, 128.9, 122.1, 71.4, 38.2, 29.9, 24.5, 22.2, 13.9, 10.4.
1H NMR (300 MHz, CDCl3): δ = 7.93 (s, 1 H), 7.34 (d, J = 7.8 Hz,
1 H), 6.85–6.81 (m, 2 H), 5.99 (s, 2 H), 4.53 (t, J = 6.6 Hz, 2 H),
3.09 (s, 3 H), 1.94–1.82 (m, 2 H), 1.09 (t, J = 7.2 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 169.4, 162.1, 148.4, 147.8, 136.7,
129.2, 127.0, 121.5, 110.5, 108.3, 101.2, 71.2, 25.2, 22.0, 10.2.
HRMS (ESI): m/z [M + H]+ calcd for C15H17N2O4: 289.1188; found:
289.1182.
HRMS (ESI): m/z [M + H]+ calcd for C17H23N2O2: 287.1760; found:
287.1756.
2-Ethoxy-3-methyl-5-(4-nitrobenzylidene)-3,5-dihydro-4H-im-
idazol-4-one (15g)
Yellow solid; yield: 67 mg (67%); mp 175–177 °C.
5-Benzylidene-3-methyl-2-propoxy-3,5-dihydro-4H-imidazol-
4-one (15l)
Yellow solid; yield: 65 mg (62%); mp 96–98 °C.
FTIR (KBr): 2998, 1723, 1655, 1568, 1336, 1151, 1015, 688, 572
cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.18–8.15 (m, 4 H), 6.81 (s, 1 H),
4.66 (q, J = 6.9 Hz, 2 H), 3.08 (s, 3 H), 1.51 (t, J = 7.2 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 169.0, 164.4, 147.0, 141.3, 141.2,
131.5, 123.5, 117.5, 66.5, 25.4, 14.3.
FTIR (KBr): 2927, 1720, 1572, 1370, 1150, 944, 686 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.05 (d, J = 7.6 Hz, 2 H), 7.38–
7.28 (m, 3 H), 6.90 (s, 1 H), 4.51 (t, J = 6.8 Hz, 2 H), 3.06 (s, 3 H),
1.88–1.82 (m, 2 H), 1.06 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 169.6, 162.8, 138.4, 134.8, 131.4,
129.0, 128.6, 121.6, 71.4, 29.8, 22.1, 10.3.
HRMS (ESI): m/z [M + H]+ calcd for C14H17N2O2: 245.1290; found:
245.1285.
HRMS (ESI): m/z [M + H]+ calcd for C13H14N3O4: 276.0984; found:
276.0980.
3-Methyl-5-(2-naphthylmethylene)-2-propoxy-3,5-dihydro-4H-
imidazol-4-one (15h)
Yellow solid; yield: 55 mg (53%); mp 143–146 °C.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 2405–2412

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S. Khan et al.
PAPER
S.; Chauhan, S. S.; Chauhan, P. M. S.; Shakya, N.; Verma,
A.; Gupta, S. J. Med. Chem. 2009, 52, 5793. (e) Kumar, R.;
Chauhan, P. M. S. Tetrahedron Lett. 2008, 49, 5475.
(f) Porwal, S.; Kumar, R.; Maulik, P. R.; Chauhan, P. M. S.
Tetrahedron Lett. 2006, 47, 5863.
Acknowledgment
S.K., V.T., and R.M. are grateful to the University Grant Commis-
sion, New Delhi, for financial support. The authors also thank Dr.
Sanjeev K. Shukla, SAIF-CDRI, for providing spectral and analyti-
cal data. The CDRI communication number is 8441.
(8) Agarwal, A.; Chauhan, P. M. S. Synth. Commun. 2004, 34,
2925.
(9) (a) Nel, R. J. J.; de Klerk, A. Ind. Eng. Chem. Res. 2009, 48,
5230. (b) Snelling, J.; Curtis, C. W.; Park, Y. Fuel Process.
Technol. 2003, 83, 219. (c) Watanabe, K.; Yamagiwa, N.;
Torisawa, Y. Org. Process Res. Dev. 2007, 11, 251.
(10) (a) Williamson, A. Justus Liebigs Ann. Chem. 1851, 77, 37.
(b) Reed, C. J.; Gaskell, B. A.; Banger, K. K.; Lock, E. Arch.
Toxicol. 1995, 70, 51. (c) Schwartz, M. D.; Obamwonyi, A.
O.; Thomas, J. D.; Moorhead, J. F.; Morgan, B. W. Am. J.
Ind. Med. 2005, 47, 550.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis. Included
are copies of 1H and 13C NMR spectra of all the compounds.SnuIpfooimnptgrirStanoIuprfio
mtgiornat
References
(1) (a) Dictionary of Natural Products; Vol. 6; Buckingham, J.,
Ed.; Chapman and Hall: London, 1994, 1938.
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