Reactions of 2-Methyl- and 1,2-Dimethyl-1,4,5,6-tetrahydropyrimidine with aroyl chlorides: Diverse reactivities of cyclic ketene N, N -acetals generated in situ

Article abstract of DOI:10.1055/s-0029-1218670

2-Methyl-1,4,5,6-tetrahydropyrimidine reacted with two equivalents of aroyl chloride in tetrahydrofuran-triethylamine to give N,N-diaroyl cyclic ketene N,N-acetals that are inert to excess aroyl chlorides. No carbon-carbon bond was formed in these reactio

Full text of DOI:10.1055/s-0029-1218670

PAPER
1209
Reactions of 2-Methyl- and 1,2-Dimethyl-1,4,5,6-tetrahydropyrimidine with
Aroyl Chlorides: Diverse Reactivities of Cyclic Ketene N,N¢-Acetals Generated
in situ
R
eactionsof
Tetra
u
hydropyrimid
o
ines
w
ithA
r
oyl
C
hlorid
h
es ong Ye,a Sabornie Chatterjee,a Aihua Zhou,b Bobby Lloyd Barker,a Chunlong Chen,c Yingquan Song,a Charles
U. Pittman Jr.*a
a
Department of Chemistry, Mississippi State University, Mississippi State, MS 39762, USA
Pharmacy School, University of Wisconsin-Madison, WI 53706, USA
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA
b
c
Fax +1(662)3257611; E-mail: cpittman@chemistry.msstate.edu
Received 6 November 2009; revised 2 December 2009
The generation of cyclic ketene acetals in situ has re-
Abstract: 2-Methyl-1,4,5,6-tetrahydropyrimidine reacted with two
equivalents of aroyl chloride in tetrahydrofuran–triethylamine to
give N,N¢-diaroyl cyclic ketene N,N-acetals that are inert to excess
aroyl chlorides. No carbon–carbon bond was formed in these reac-
ceived a considerable amount of attention as a means of
simplifying the handling of cyclic ketene acetals and for
forming highly functionalized structures efficiently. 2-
tions. Conversely, 1,2-dimethyl-1,4,5,6-tetrahydropyrimidine re- Methyl-4,5-dihydro-1H-imidazoles and 2-methyl-4,5-di-
acted with three equivalents of aroyl chloride under the same
hydro-1,3-thiazoles give branched or cyclized products,
conditions to give N-aroyl N¢-methyl b,b-dioxo cyclic ketene N,N¢-
respectively, through ketene N,O- and N,S-acetals gener-
acetals, with formation of two carbon–carbon bonds. Various reac-
ated in situ.7 Later, the strong nucleophilicity of ketene
tions of cyclic amidines with aroyl chlorides were observed and are
N,N¢-acetals generated in situ was demonstrated by the
discussed in terms of the effects of the ring size and substituents on
the reactivities of the cyclic ketene N,N¢-acetals generated in situ.
one-pot synthesis of 1,8-naphthyridinetetraones.8 Most
recently, divergent reactions have been observed in the re-
actions of aroyl chlorides with 2-methyl-4,5-dihydro-1H-
Key words: acetals, aroyl chlorides, cyclic amidines, pyrimidines
imidazole (1) and 1,2-dimethyl-4,5-dihydro-1H-imida-
zole (2; Scheme 2).9
A carbon-–carbon double bond with two adjacent heteroa-
toms (N, O, or S) frames the basic structure of a ketene ac-
etal (Scheme 1). The donation of electrons from the lone
O
Ar
pairs of both heteroatoms increases the electron density at
O
O
R = H
the double bond so that it becomes polarized and nucleo-
philic at the b-carbon position. The chemistry of acyclic
ketene acetals has been increasingly studied and applied
in organic synthesis1 since the pioneering work by
McElvain and co-workers2 in the 1930s and 1940s. Cyclic
ketene acetals appeared much later in the literature,3 and
they have been applied in ring-opening and 1,2-vinyl ad-
dition polymerization reactions.4 This delay was a result
of the difficulties involved in preparing, storing, and han-
dling cyclic ketene acetals.4d,f,j,5 Although they have been
studied less, cyclic ketene acetals have an exceptional re-
activity that offers a wide range of possibilities for the use
of these compounds in synthesis.6
N
O
N
58–80%
Ar
Ar
Ar
ArCOCl
3
4
R
N
N
O
Et3N, THF
reflux, 3 h
1, R = H
2, R = Me
O
H
N
R = Me
Ar
Ar
N
36–74%
Me
O
Scheme 2 Divergent reactions of aroyl chlorides with 2-methyl-4,5-
dihydro-1H-imidazole (1) or 1,2-dimethyl-4,5-dihydro-1H-imidazole
(2)
This suggested that the N-substituents have a decisive ef-
fect on the reactivity of the five-membered ketene N,N¢-
acetals formed in these reactions. To investigate the ef-
fects of the ring size on the cyclic ketene N,N¢-acetals, we
sought to expand this chemistry to the six-membered ana-
logues of these compounds. We therefore examined the
reactions of aroyl chlorides with 2-methyl-1,4,5,6-tet-
β
α
X
Y
X
Y
X
Y
X,Y = NR, O, S
Scheme 1 Basic structure of ketene acetals and the origin of their rahydropyrimidine (5) and 1,2-dimethyl-1,4,5,6-tetrahy-
nucleophilicity
dropyrimidine (9).
The reaction of pyrimidine 5 with excess of an aroyl chlo-
ride in refluxing tetrahydrofuran–triethylamine mixtures
did not generate the expected triaroylation product 7
(Table 2). Instead, all the reactions stopped at the diaroy-
SYNTHESIS 2010, No. 7, pp 1209–1216
Advanced online publication: 05.02.2010
DOI: 10.1055/s-0029-1218670; Art ID: M05909SS
x
x
.
x
x
.2
0
1
0
© Georg Thieme Verlag Stuttgart · New York

1210
G. Ye et al.
PAPER
Table 1 Reactions of 2-Methyl-1,4,5,6-tetrahydropyrimidine (5) with Various Aroyl Chlorides
O
Ar
O
O
O
O
ArCOCl
Et3N
N
NH
Ar
N
N
Ar
N
N
Ar
Ar
THF or MeCN
reflux
5
6
7
Entrya
1
Ar
Solvent
THF
Time (h)
Product
6a
6a
6a
6b
6c
Yieldb (%)
85
Ph
3
6
6
3
3
6
3
3
3
3
3
3
3
3
3
3
2
Ph
THF
86
3
Ph
MeCN
THF
85
4
4-ClC6H4
86
5
4-MeOC6H4
4-MeOC6H4
3-MeC6H4
3-BrC6H4
3-FC6H4
THF
87
6
MeCN
THF
6c
85
7
6d
6e
90
8
THF
87
9
THF
6f
90
10
11
12
13
14
15
16
3-MeOC6H4
3-ClC6H4
2-MeC6H4
2-FC6H4
THF
6g
6h
6i
88
THF
89
THF
80
THF
6j
88
2-FC6H4
MeCN
THF
6j
87
2-BrC6H4
2-ClC6H4
6k
6l
85
THF
87
a The ratio 5/aroyl chloride/Et3N was 1:3.5:4 in each case.
b Isolated yield after column chromatography over silica gel.
O
O
lation stage, giving the N,N¢-diaroyl cyclic ketene N,N¢-
acetals 6 (Table 1). This contrasts sharply with the con-
version of the five-membered analogue 1 into the triaroy-
lated product 3 (Scheme 2). Prolonged refluxing (entries
2, 3, and 6) or changing the solvent to more-polar, higher-
boiling acetonitrile (entries 3, 6, and 14) had no effect on
the outcome of the reaction. The six-membered ketene
acetals 6 generated in situ exhibited no nucleophilicity to-
ward additional aroyl chloride in these reaction mixtures,
and 6a–l could be isolated in excellent yields by column
chromatography over silica gel under air. The analogous
reactions of 2-methylimidazoline (1) formed triaroylation
products exclusively in good yields (Scheme 2), and five-
membered N,N¢-diaroyl cyclic ketene N,N¢-acetal inter-
mediates could not be separated by silica gel column chro-
Cl
Cl
Ar
Ar
11
O
9
O
7
6
6
10
O
9
O
1
N
5
N
5
1
N
4
N
10
8
Ar
Ar
9
7
Ar
Ar
2
4
2
3
3
6
8
Figure 1 The structures of ketene acetals 6 and 8 explain their dif-
ferent reactivities with aroyl chlorides; the dihedral angles C7–C6–
N1–C10- and C7–C6–N5–C8 in 6 are expected to be larger than the
corresponding dihedral angles C6–C5–N1–C9 and C6–C5–N4–C7 in
8.
poorer alignment between the lone pairs on the nitrogen
and the carbon–carbon p-bond. For example, the superior
flexibility of six-membered ring in 6 in comparison with
the more-rigid five-membered ring in 8 allows greater re-
laxation of the steric hindrance at the expense of an opti-
mal stereoelectronic alignment. Therefore, poorer
conjugation between the nitrogen lone pairs and the
matography
without
undergoing
ring-opening
hydrolysis.9
These observations show that the six-membered N,N¢-di-
aroyl cyclic ketene N,N¢-acetals 6 are weaker nucleophiles
than their five-membered counterparts 8 (Figure 1). This
reduced nucleophilicity can be explained in terms of a
Synthesis 2010, No. 7, 1209–1216 © Thieme Stuttgart · New York

PAPER
Reactions of Tetrahydropyrimidines with Aroyl Chlorides
1211
carbon–carbon p-bond is expected in the case of 6 in com-
parison with its five-membered-ring analogue 8.
The steric hindrance between the methylene group and the
N-substituents is smaller in ketene acetal 8 than in 6 for
ideally planar geometries (where both nitrogen atoms
have pure sp2 hybridization) because the five-membered
ring is more contracted (the internal angle in the five-
membered ring is 108° compared with 120° in the six-
membered ring). Thus, more space is available for the N-
substituents in 8. The greater hindrance in 6 forces a more
distorted alignment of the nitrogen lone pair with the car-
bon–carbon p-bond. The coincidence of greater steric hin-
drance and the greater ring flexibility in 6 reduces electron
donation from nitrogen to the double bond in 6 in compar-
ison with that in 8, which explains their different reactiv-
ities toward aroyl chlorides.
This analysis is supported by the crystal structure of
ketene acetal 6g (Figure 2). Despite the near-planar con-
figurations of N1 and N2, which show that both are sp2-
hybridized, the exocyclic C6–C21 double bond is remark-
ably distorted out of conjugation with these nitrogen
atoms. The C21–C6–N2–C7 dihedral angle is 64.08°,
whereas the C21–C6–N1–C5 dihedral angle is 25.73°.
This shows that electron donation from the nitrogen lone
pairs is limited. Because no examples of 8 were found and
isolated, no direct comparison of a crystal structure with
that of 6g was possible. However, the crystal structure of
3a (Ar = Ph) was determined (Figure 3). Ketene acetal 3a
has a sterically demanding benzoyl substituent instead of
a hydrogen on the exocyclic methylene carbon (C7), in
addition to a benzoyl group on each nitrogen; it is there-
fore more crowded than 8. Despite the presence of this ex-
tra benzoyl group, the central double bond (C6–C7) aligns
better with nitrogen than the corresponding alignment in
6g.
Figure 3 Crystal structure of ketene acetal 3a. The C7–C6–N2–C19
dihedral angle is 7.83°; the C7–C6–N1–C5 dihedral angle is 37.70°
(CCDC 753287)
In addition to N-aroylation, two new carbon–carbon
bonds were formed on the b-carbon. Most of the reactions
gave good yields after refluxing for three hours. Pro-
longed refluxing resulted in no improvement in the yields
(entries 2, 5, and 8).
Table 2 Reactions of 1,2-Dimethyl-1,4,5,6-tetrahydropyrimidine
(9) with Various Aroyl Chlorides
Ar
Ar
O
O
Ar
O
O
Me
Me
Et3N–THF
reflux, 3 h
N
N
+
N
N
Ar
Cl
9
10
Entrya
Ar
Ph
Ph
Time (h) Product
Yield(%)b
1
2
3
10a
10a
10b
10c
10c
10d
10e
10e
10f
10g
10h
10i
82
81
80
83
83
82
84
86
88
61
79
89
74
12
3
3
4-ClC6H4
4
4-MeOC6H4
4-MeOC6H4
4-MeC6H4
4-FC6H4
3
5
12
3
6
7
3
8
4-FC6H4
12
3
Figure 2 Crystal structure of ketene acetal 6g. The C21–C6–N2–C7
dihedral angle is 64.08°; the C21–C6–N1–C5 dihedral angle is 25.73°
(CCDC 753288)
9
3-FC6H4
10
11
12
13
3-MeOC6H4
3-ClC6H4
3-BrC6H4
3-MeC6H4
3
3
Replacement of the amine hydrogen in 5 by a methyl
group (for example, in 9) significantly enhanced the nu-
cleophilicity of the cyclic ketene N,N¢-acetals generated in
situ (Table 2). 1,2-Dimethyl-1,4,5,6-tetrahydropyrimi-
dine (9) reacts with excess aroyl chloride in refluxing tet-
rahydrofuran–triethylamine to give the corresponding N-
aroyl N¢-methyl b,b-dioxo cyclic ketene N,N¢-acetals 10.
3
3
10j
a The ratio 9/aroyl chloride/Et3N was 1:3.5:4 in each case.
b Isolated yield after column chromatography.
Synthesis 2010, No. 7, 1209–1216 © Thieme Stuttgart · New York

1212
G. Ye et al.
PAPER
Because of the presence of substantial push–pull electron- of chloride to form salt 13. Salt 13 is then deprotonated to
ic character6c,10 in 10, the exocyclic carbon–carbon double give diaroylated cyclic ketene N,N¢-acetal 14. The exocy-
bond character could be low, allowing easy out-of-plane clic b-carbon in 14 is still sufficiently reactive toward a
rotation. We therefore determined the single-crystal struc- third equivalent of aroyl chloride, even though two elec-
ture of 10a (Figure 4). N1, N2, C8, and C16 are nearly tron-withdrawing carbonyl groups are present. Thus, in-
planar with sp2 hybridization. However, the order of the termediate 15 is formed and this is deprotonated to
C8–C16 double bond is reduced by the substantial dihe- generate 10.
dral angle (39.5°) between the plane defined by C7–C8–
C9 and that defined by N1–C16–N2. The reduced p-na-
ture of the C8–C16 bond also gives rise to a longer bond
The ring-opened structure 17 (Scheme 3) was the product
that we expected would be formed, on the basis of the
analogous reactions of 1,2-dimethylimidazoline 2 with
aroyl chlorides to give 4 (Scheme 2). However, 17 was
length (1.42 Å).
not formed because the b-carbon in 14 retained sufficient
nucleophilicity to react with aroyl chlorides faster than the
oxygen of the carbonyl group attached to the b-carbon.
The structures of 14 and 18 are compared in Figure 5 to il-
lustrate the effects of ring size on the chemoselectivity in
reactions with an aroyl chloride. Donation of electrons
from the nitrogen atoms, especially from the methyl-sub-
stituted nitrogen, polarizes the carbon in the b-position in
both 14 and 18. Charge delocalization to the b-keto oxy-
gen depends on the planarity of the a,b-unsaturated carbo-
nyl group. In the five-membered structure 18, this
delocalization is sufficiently significant to permit the O11
atom to compete with the b-carbon as a nucleophile. The
O11 atom is less sterically hindered than the b-carbon C6.
Conversely, delocalization to O12 in the six-membered
structure 14 is diminished in comparison with that in 18
Figure 4 Crystal structure of ketene acetal 10a (CCDC: 682487)
because of the greater steric interactions between the O12
atom and the N-substituents. Aroylation therefore occurs
at the b-carbon (C7).
A possible mechanism accounting for the formation of 10
is proposed (Scheme 3). The aroyl chloride reacts with 9
to generate intermediate 11. Deprotonation of 11 gives the
N-aroyl N¢-methyl cyclic ketene N,N-acetal 12. Unlike the
N,N¢-diaroyl cyclic ketene N,N-acetal 6, which is inert to
The various reactions of aroyl chlorides with 2-methyl-
4,5-dihydro-1H-imidazole (1), 1,2-dimethyl-4,5-dihydro-
1H-imidazole (2), 2-methyl-1,4,5,6-tetrahydropyrimidine
excess aroyl chloride, 12 reacts readily with the second
(5), and 1,2-dimethyl-1,4,5,6-tetrahydropyrimidine (9)
equivalent of aroyl chloride, and this is followed by loss
Ar
Ar
H
N
H
O
O
H2C
O
O
O
O H
O
Me
Me
Me
Me
Me
ArCOCl
Et3N
– Et3N•HCl
ArCOCl
N
N
Ar
N
N
Ar
N
Ar
N
N
Me
Ar
N
N
Cl
Ar
N
N
Cl
Cl
Cl
9
11
12
13
Ar
Cl
Ar
Ar
Ar
Ar
Ar
H
O
O
O
O
Ar
Ar
O
O
Ar
Me
Me
Me
Et3N
N
N
N
N
N
N
O
O
O
–Et3N•HCl
Ar
N
Cl
O
15
10
O
N
O
β
Me ArCOCl
Et3N
– Et3N•HCl
Ar
Ar
Ar
Ar
Ar
Cl
O
O
O
O
O
Me
O
14
O
Ar
O
O
Me
Ar
N
N
Ar
N
N
N
H
Ar
N
Ar
Cl
Me
17
16
Scheme 3 A possible mechanism for the formation of 10
Synthesis 2010, No. 7, 1209–1216 © Thieme Stuttgart · New York

PAPER
Reactions of Tetrahydropyrimidines with Aroyl Chlorides
1213
Melting points were recorded with a Mel-Temp apparatus and are
uncorrected. The Fourier-transform IR spectra were recorded on a
Thermo Nicolet spectrometer as films on KBr plates. The H and
O
Cl
Ar
10
Ar
Ph
O
Ar
10
11
1
Ar
δ6-
9
O
δ-
O 11
O
O 12
8
13C NMR spectra were recorded by using a Bruker model AMX-300
300 MHz spectrometer operating at 300 MHz for 1H and at 75 MHz
for 13C. Chemical shifts are reported in ppm downfield from TMS,
which was used as the internal standard for all the NMR spectra. All
reactions were carried out under N2. THF was distilled from Na
metal/benzophenone under N2. MeCN and Et3N were distilled from
CaH2 under N2. The starting substrates, 2-methyl-1,4,5,6-tetrahy-
dropyrimidine (5) and 1,2-dimethyl-1,4,5,6-tetrahydropyrimidine
(6), were prepared according to literature procedures.6c All other
commercially obtained reagents were used as received. The silica
gel used for the column chromatography was purchased from Ald-
rich Company (70–230 mesh, 60 Å). Crystallographic data for com-
pounds 3a, 6g, and 10a have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publications
CCDC 753287, 753288, and 682487, respectively; copies can be
obtained free of charge on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK [fax: +44(1223)336033 or email:
deposit@ccdc.cam.ac. uk].
7
δ-
1
N
1
7
5
9
6
Ar
N 5
N
N4
3
8
Ar
2
4
2
3
14
18
Figure 5 Structures of 14 and 18 and their effects on the chemo-
selectivities in reactions with aroyl chlorides; the dihedral angle
O12–C11–C7–C6 in 14 is expected to be larger than the dihedral
angle O11–C10–C6–C5 in 18
are summarized in Scheme 4. The positions of aroylation
and the balance between the ring-retention pathway and
the ring-opening pathway depend on the ring size. They
also depend on the nature of the substituents (H, Me, or
aroyl) that are present in the cyclic ketene N,N¢-acetal in-
termediates (8, 18, 6, and 14) that are generated in situ
from the cyclic amidines (1, 2, 5, and 9, respectively).
(2-Methylenedihydropyrimidine-1,3(2H,4H)-diyl)bis(phenyl-
methanone) (6a); Typical Procedure
O
Et3N (0.81 g, 8 mmol) was added to a stirred solution of BzCl (0.492
g, 3.5 mmol) in THF (10 mL) under N2 at r.t. A soln of 2-methyl-
1,4,5,6-tetrahydropyrimidine (0.098 g, 1 mmol) in THF (2 mL) was
then added dropwise at r.t. The mixture was refluxed for 3 h then
cooled to r.t. and filtered. The solid (Et3N·HCl) was washed with
anhyd THF (3 × 10 mL), the filtrate was concentrated, and the resi-
due was purified by flash column chromatography [silica gel, hex-
ane–EtOAc (3:1 to 2:1)] to give 6a as a white solid; yield: 260 mg
(85%); mp 133–135 °C; Rf = 0.46 (hexane–EtOAc, 1:1).
O
O
Ar
O
O
H
N
Ar
Ar
N
N
Ar
Ar
N
Me
O
4
6
(from 18)
Ar
R3
N
Ar
IR (KBr): 3057, 1660, 1642, 1599, 1576, 1473 cm–1.
O
O
Ar
1H NMR (300 MHz, CDCl3): d = 7.50–7.34 (m, 10 H, ArH), 4.79
(s, 2 H, =CH2), 3.79 (t, J = 5.8 Hz, 4 H, NCH2), 2.02 (quin, J = 5.8
Hz, 2 H, CH2CH2CH2).
Ar
O
Me
O
O
R1
R2
N
N
N
N
N
O
( )
Ar
Ar
n
13C NMR (75 MHz, CDCl3): d = 170.0 (CO), 139.8 (C=CH2), 135.1
(ArC), 130.2 (ArC), 128.1 (ArC), 127.6 (ArC), 108.0 (=CH2), 45.5
(NCH2), 23.4 (CH2CH2CH2).
HRMS (ESI): m/z [M + Na]+ calcd for C19H18N2NaO2: 329.1266;
found: 329.1259.
3
10
(from 14)
(from 8)
8, n = 1, R1 = R2 = ArCO, R3 = H (from 1)
18, n = 1, R1 = R3 = ArCO, R2 = Me (from 2)
6, n = 2, R1 = R2 = ArCO, R3 = H (from 5)
14, n = 2, R1 = R3 = ArCO, R2 = Me (from 9)
ArCOCl
Et3N, THF
(2-Methylenedihydropyrimidine-1,3(2H,4H)-diyl)bis[(4-chlo-
rophenyl)methanone] (6b)
1, n = 1, R = H
White solid; yield: 86%; mp 114–116 °C; Rf = 0.49 (hexane–
EtOAc, 1:1).
IR (KBr): 3066, 1653, 1593, 1488 cm–1.
2, n = 1, R = Me
5, n = 2, R = H
9, n = 2, R = Me
R
N
N
( )
n
1H NMR (300 MHz, CDCl3): d = 7.54 (d, J = 8.2 Hz, 4 H, ArH),
7.38 (d, J = 8.2 Hz, 4 H, ArH), 4.84 (s, 2 H, =CH2), 3.79 (t, J = 5.8
Hz, 4 H, NCH2), 2.00 (quin, J = 5.8 Hz, 2 H, CH2CH2CH).
Scheme 4 Diverse reactivities of cyclic ketene N,N¢-acetals genera-
ted in situ by reactions of cyclic amidines with aroyl chlorides
13C NMR (75 MHz, CDCl3): d = 169.0 (CO), 139.8 (C=CH2), 136.7
(ArC), 133.3 (ArC), 129.3 (ArC), 128.6 (ArC), 109.0 (C=CH2),
45.9 (NCH2), 23.6 (CH2CH2CH2).
In conclusion, 2-methyl-1,4,5,6-tetrahydropyrimidine and
1,2-dimethyl-1,4,5,6-tetrahydropyrimidine react differ-
ently with aroyl chlorides, forming N,N¢-diaroyl cyclic
ketene N,N-acetals and N-aroyl N¢-methyl b,b-dioxo cy-
clic ketene N,N¢-acetals, respectively. Ring-size effects
are apparent when these reactions are compared with the
analogous reactions of five-membered substrates. These
divergent reactions to give highly functionalized products
illustrate the rich chemistry that is available through cy-
clic ketene N,N¢-acetal intermediates generated in situ.
Reactions with other electrophiles should be further stud-
ied.
(2-Methylenedihydropyrimidine-1,3(2H,4H)-diyl)bis[(4-meth-
oxyphenyl)methanone] (6c)
White solid; yield: 87%; mp 141–143 °C; Rf = 0.30 (hexane–
EtOAc, 1:1).
IR (KBr): 3105, 1631, 1608, 1510, 1461 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.60 (d, J = 8.2 Hz, 4 H, ArH),
6.89 (d, J = 8.2 Hz, 4 H, ArH), 4.83 (s, 2 H, C=CH2), 3.83 (s, 6 H,
OCH3), 3.81 (t, J = 5.8 Hz, 4 H, NCH2), 1.90 (quin, J = 5.8 Hz, 2 H,
CH2CH2CH2).
Synthesis 2010, No. 7, 1209–1216 © Thieme Stuttgart · New York

1214
G. Ye et al.
PAPER
13C NMR (75 MHz, CDCl3): d = 170.0 (C = O), 161.4 (ArC), 140.9
(C=CH2), 130.6 (ArC), 127.2 (ArC), 113.4 (ArC), 107.5 (C=CH2),
55.3 (OCH3), 46.0 (NCH2), 23.8 (CH2CH2CH2).
HRMS (ESI): m/z [M + Na]+ calcd for C21H22N2NaO4: 389.1477;
found: 389.1470.
(2-Methylenedihydropyrimidine-1,3(2H,4H)-diyl)bis[(3-chlo-
rophenyl)methanone] (6h)
White solid; yield: 89%; mp 140–142 °C; Rf = 0.62 (hexane–
HRMS (ESI): m/z [M + Na]+ calcd for C21H22N2NaO4: 389.1477;
found: 389.1466.
EtOAc, 1:1).
IR (KBr): 3059, 1662, 1641, 1563, 1472 cm–1.
(2-Methylenedihydropyrimidine-1,3(2H,4H)-diyl)bis[(3-
tolyl)methanone] (6d)
White solid; yield: 90%; mp 91–93 °C; Rf = 0.65 (hexane–EtOAc,
1:1).
IR (KBr): 3047, 1663, 1643, 1601, 1584, 1467 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.59–7.30 (m, 8 H, ArH), 4.84 (s,
2 H, C=CH2), 3.77 (t, J = 6.1 Hz, 4 H, NCH2), 2.00 (quin, J = 6.1
Hz, 2 H, CH2CH2CH2).
1H NMR (300 MHz, CDCl3): d = 7.39–7.22 (m, 8 H, ArH), 4.83 (s,
2 H, C=CH2), 3.78 (t, J = 6.1 Hz, 4 H, NCH2), 2.37 (s, 6 H, CH3),
1.99 (quin, J = 6.1 Hz, 2 H, CH2CH2CH2).
13C NMR (75 MHz, CDCl3): d = 168.2 (CO), 139.0 (C=CH2), 136.6
(ArC), 134.1 (ArC), 130.3 (ArC), 129.4 (ArC), 127.6 (ArC), 125.5
(ArC), 108.8 (C=CH2), 45.5 (NCH2), 23.2 (CH2CH2CH2).
13C NMR (75 MHz, CDCl3): d = 170.0 (CO), 139.4 (C=CH2), 137.9
(ArC), 135.0 (ArC), 130.9 (ArC), 128.1 (ArC), 127.9 (ArC), 124.4
(ArC), 107.9 (C=CH2), 45.5 (NCH2), 23.3 (CH2CH2CH2), 21.1
(CH3).
HRMS (ESI): m/z [M + Na]+ calcd for C21H22N2NaO2: 357.1579;
found: 357.1586.
(2-Methylenedihydropyrimidine-1,3(2H,4H)-diyl)bis[(2-
tolyl)methanone] (6i)
Colorless liquid; yield: 80%; Rf = 0.47 (hexane–EtOAc, 1:1).
IR (KBr): 3061, 1773, 1649, 1601, 1489 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.27–7.15 (m, 8 H, ArH), 4.80 (br
s, 2 H, C=CH2), 3.71 (br s, 4 H, NCH2), 2.36 (s, 6 H, CH3), 1.98
(quin, J = 5.4 Hz, 2 H, CH2CH2CH2).
13C NMR (75 MHz, CDCl3): d = 169.8 (C = O), 137.7 (C=CH2),
135.8 (ArC), 134.6 (ArC), 130.4 (ArC), 129.1 (ArC), 125.9 (ArC),
125.6 (ArC), 107.1 (C=CH2), 44.3 (NCH2), 23.3 (CH2CH2CH2),
19.1 (CH3).
(2-Methylenedihydropyrimidine-1,3(2H,4H)-diyl)bis[(3-bro-
mophenyl)methanone] (6e)
White solid; yield: 87%; mp 149–151 °C; Rf = 0.53 (hexane–
EtOAc, 1:1).
IR (KBr): 3072, 1660, 1642, 1563, 1471 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.74 (s, 2 H, ArH), 7.56 (d, J = 7.9
Hz, 2 H, ArH), 7.49 (d, J = 7.9 Hz, 2 H, ArH), 7.27 (t, J = 7.9 Hz, 2
H, ArH), 4.85 (s, 2 H, C=CH2), 3.77 (t, J = 6.0 Hz, 4 H, NCH2), 2.00
(quin, J = 6.0 Hz, 2 H, CH2CH2CH2).
13C NMR (75 MHz, CDCl3): d = 168.1 (CO), 138.9 (C=CH2), 136.8
(ArC), 133.3 (ArC), 130.5 (ArC), 129.7 (ArC), 126.0 (ArC), 122.2
(ArC), 108.9 (C=CH2), 45.6 (NCH2), 23.2 (CH2CH2CH2).
(2-Methylenedihydropyrimidine-1,3(2H,4H)-diyl)bis[(2-fluo-
rophenyl)methanone] (6j)
White solid; yield: 88%; mp 120–122 °C; Rf = 0.61 (hexane–
EtOAc, 1:1).
IR (KBr): 3072, 1652, 1614, 1581, 1491 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.44–7.01 (m, 8 H, ArH), 4.67 (br
s, 2 H, C=CH2), 3.75 (br s, 4 H, NCH2), 2.01 (quin, J = 6.2 Hz, 2 H,
CH2CH2CH2).
13C NMR (75 MHz, CDCl3): d = 164.8 (CO), 157.7 (1JCF = 245.0
Hz, ArC), 137.7 (C=CH2), 131.2 (3JCF = 8.0 Hz, ArC), 128.7 (ArC),
124.0 (ArC), 123.8 (2JCF = 17.1 Hz, ArC), 115.3 (2JCF = 21.3 Hz,
ArC), 105.4 (C=CH2), 43.1 (NCH2), 23.6 (CH2CH2CH2).
(2-Methylenedihydropyrimidine-1,3(2H,4H)-diyl)bis[(3-fluo-
rophenyl)methanone] (6f)
White solid; yield: 90%; mp 99–101 °C; Rf = 0.56 (hexane–EtOAc,
1:1).
IR (KBr): 3075, 1670, 1643, 1586, 1483 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.40–7.09 (m, 8 H, ArH), 4.82 (s,
2 H, C=CH2), 3.79 (t, J = 6.1 Hz, 4 H, NCH2), 2.02 (quin, J = 6.1
Hz, 2 H, CH2CH2CH2).
HRMS (ESI): m/z [M + Na]+ calcd for C19H16F2N2NaO2: 365.1078;
found: 365.1089.
(2-Methylenedihydropyrimidine-1,3(2H,4H)-diyl)bis[(2-bro-
mophenyl)methanone] (6k)
White solid; yield: 85%; mp 135–137 °C; Rf = 0.50 (hexane–
EtOAc, 1:1).
13C NMR (75 MHz, CDCl3): d = 168.7 (4JCF = 2.5 Hz, CO), 162.3
(1JCF = 247.8 Hz, ArC), 139.5 (C=CH2), 137.2 (3JCF = 7.0 Hz, ArC),
130.1 (3JCF = 7.9 Hz, ArC), 123.4 (4JCF = 3.0 Hz, ArC), 117.6
(2JCF = 21.1 Hz, ArC), 115.0 (2JCF = 23.1 Hz, ArC), 108.8 (C=CH2),
45.8 (NCH2), 23.4 (CH2CH2CH2).
IR (KBr): 3054, 1651, 1587, 1469 cm–1.
HRMS (ESI): m/z [M + Na]+ calcd for C19H16F2N2NaO2: 365.1078;
found: 365.1064.
1H NMR (300 MHz, CDCl3): d = 7.53–7.23 (m, 8 H, ArH), 5.51 (s,
1 H, C=CH2), 4.90 (s, 1 H, C=CH2), 3.90 (br s, 2 H, NCH2), 3.46 (br
s, 2 H, NCH2), 2.01 (br s, 2 H, CH2CH2CH2).
(2-Methylenedihydropyrimidine-1,3(2H,4H)-diyl)bis[(3-meth-
oxyphenyl)methanone] (6g)
White solid; yield: 88%; mp 98–100 °C; Rf = 0.38 (hexane–EtOAc,
1:1).
13C NMR (75 MHz, CDCl3): d = 168.1 (CO), 166.7 (CO), 137.8
(C=CH2), 136.4 (ArC), 132.8 (ArC), 130.6 (ArC), 128.7 (ArC),
127.9 (ArC), 127.4 (ArC), 127.2 (ArC), 119.7 (ArC), 118.6 (ArC),
109.3 (C=CH2), 46.8 (NCH2), 43.2 (NCH2), 23.2 (CH2CH2CH2).
IR (KBr): 3070, 1644, 1580, 1487 cm–1.
(2-Methylenedihydropyrimidine-1,3(2H,4H)-diyl)bis[(2-chlo-
rophenyl)methanone] (6l)
Yield: 87%; white solid; mp 129–131 °C; Rf = 0.42 (hexane–
EtOAc, 1:1).
IR (KBr): 3019, 1669, 1645, 1592, 1470 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.32–6.95 (m, 8 H, ArH), 4.88 (s,
2 H, C=CH2), 3.84 (s, 6 H, OCH3), 3.79 (t, J = 6.1 Hz, 4 H, NCH2),
2.02 (quin, J = 6.1 Hz, 2 H, CH2CH2CH2).
13C NMR (75 MHz, CDCl3): d = 169.4 (CO), 158.9 (ArC), 139.0
(C=CH2), 136.1 (ArC), 129.0 (ArC), 119.4 (ArC), 116.0 (ArC),
112.4 (ArC), 107.6 (C=CH2), 55.0 (OCH3), 54.9 (OCH3), 45.4
(NCH2), 23.1 (CH2CH2CH2).
Synthesis 2010, No. 7, 1209–1216 © Thieme Stuttgart · New York

PAPER
Reactions of Tetrahydropyrimidines with Aroyl Chlorides
1215
1H NMR (300 MHz, CDCl3): d = 7.38–7.27 (m, 8 H, ArH), 5.53 (s,
1 H, C=CH2), 4.84 (s, 1 H, C=CH2), 3.91 (br s, 2 H, NCH2), 3.49 (br
s, 2 H, NCH2), 2.03 (br s, 2 H, CH2CH2CH2).
1H NMR (300 MHz, CDCl3): d = 7.39–6.85 (m, 12 H, ArH), 3.58
(m, 4 H, NCH2), 3.12 (s, 3 H, NCH3), 2.37 (s, 3 H, ArCH3), 2.30 (m,
2 H, CH2CH2CH2), 2.20 (s, 6 H, ArCH3).
13C NMR (75 MHz, CDCl3): d = 166.7 (CO), 165.6 (CO), 136.1
(C=CH2), 135.2 (ArC), 130.0 (ArC), 129.1 (ArC), 128.0 (ArC),
126.9 (ArC), 126.2 (ArC), 108.1 (C=CH2), 46.0 (NCH2), 42.6
(NCH2), 22.7 (CH2CH2CH2).
HRMS (ESI): m/z [M + Na]+ calcd for C19H16Cl2N2NaO2: 397.0487;
found: 397.0469.
13C NMR (75 MHz, CDCl3): d = 191.5 (C=C–C=O), 170.8
(NC = O), 167.1 (NC=C), 142.1 (ArC), 140.4 (ArC), 139.2 (ArC),
131.5 (ArC), 129.2 (ArC), 128.4 (ArC), 128.2 (ArC), 128.1 (ArC),
107.9 (NC=C), 49.3 (CONCH2), 42.9 (CH3NCH2), 42.1 (NCH3),
26.4 (CH2CH2CH2), 21.5 (ArCH3), 21.3 (ArCH3).
HRMS (ESI): m/z [M + Na]+ calcd for C30H30N2NaO3: 489.2154;
found: 489.2152.
2-(1-Benzoyl-3-methyltetrahydropyrimidin-2(1H)-ylidene)-1,3-
diphenylpropane-1,3-dione (10a)
Yellowish solid; yield: 82%; mp 228–230 °C; Rf = 0.16 (hexane–
acetone, 1:1).
2-[1-(4-Fluorobenzoyl)-3-methyltetrahydropyrimidin-2(1H)-
ylidene]-1,3-bis(4-fluorophenyl)propane-1,3-dione (10e)
Yield: 84%; yellowish solid; mp 204–206 °C; Rf = 0.23 (hexane–
acetone, 1:1).
IR (KBr): 1660, 1596, 1584, 1574, 1532, 1446 cm–1.
IR (KBr): 1674, 1597, 1504, 1477 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.52–7.03 (m, 15 H, ArH), 3.63 (t,
J = 6.0 Hz, 4 H, NCH2), 3.16 (s, 3 H, NCH3), 2.35 (quin, J = 6.0 Hz,
2 H, CH2CH2CH2).
13C NMR (75 MHz, CDCl3): d = 191.5 (C=C–C=O), 170.7
(NC = O), 167.5 (NC=C), 141.7 (ArC), 134.1 (ArC), 131.6 (ArC),
130.1 (ArC), 129.1 (ArC), 128.1 (ArC), 127.8 (ArC), 127.3 (ArC),
108.0 (NC=C), 49.4 (CONCH2), 42.9 (CH3NCH2), 42.1 (NCH3),
26.1 (CH2CH2CH2).
1H NMR (300 MHz, CDCl3): d = 7.54–6.72 (m, 12 H, ArH), 3.65
(m, 4 H, NCH2), 3.13 (s, 3 H, NCH3), 2.35 (quin, J = 6.6 Hz, 2 H,
CH2CH2CH2).
13C NMR (75 MHz, CDCl3): d = 189.5 (C=C–C=O), 167.2
(NC=C), 164.7 (1JCF = 253.7 Hz, ArC), 163.7 (1JCF = 251.3 Hz,
ArC), 137.5 (4JCF = 2.9 Hz, ArC), 131.6 (3JCF = 9.2 Hz, ArC), 130.3
(3JCF = 8.8 Hz, ArC), 130.1 (4JCF = 3.1 Hz, ArC), 114.9 (2JCF = 22.1
Hz, ArC), 114.4 (2JCF = 21.8 Hz, ArC), 107.3 (NC=C), 49.4
(CONCH2), 43.1 (CH3NCH2), 42.1 (NCH3), 25.9 (CH2CH2CH2).
HRMS (ESI): m/z [M + Na]+ calcd for C27H24N2NaO3: 447.1685;
found: 447.1699.
2-[1-(3-Fluorobenzoyl)-3-methyltetrahydropyrimidin-2(1H)-
ylidene]-1,3-bis(3-fluorophenyl)propane-1,3-dione (10f)
Yellowish solid; yield: 88%; mp 212–214 °C; Rf = 0.24 (hexane–
acetone, 1:1).
2-[1-(4-Chlorobenzoyl)-3-methyltetrahydropyrimidin-2(1H)-
ylidene]-1,3-bis(4-chlorophenyl)propane-1,3-dione (10b)
Yellowish solid; yield: 80%; mp 221–223 °C; Rf = 0.32 (hexane–
acetone, 1:1).
IR (KBr): 1686, 1583, 1522, 1483 cm–1.
IR (KBr): 1668, 1626, 1586, 1524, 1477 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.40–6.71 (m, 12 H, ArH), 3.64
(m, 4 H, NCH2), 3.16 (s, 3 H, NCH3), 2.35 (quin, J = 6.5 Hz, 2 H,
CH2CH2CH2).
1H NMR (300 MHz, CDCl3): d = 7.43–6.98 (m, 12 H, ArH), 3.63 (t,
J = 6.0 Hz, 4 H, NCH2), 3.14 (s, 3 H, NCH3), 2.36 (quin, J = 6.0 Hz,
2 H, CH2CH2CH2).
13C NMR (75 MHz, CDCl3): d = 189.6 (4JCF = 2.0 Hz, C=C–C=O),
169.4 (4JCF = 2.7 Hz, NC=O), 167.0 (NC=C), 161.8 (1JCF = 246.8
Hz, ArC), 143.5 (3JCF = 6.2 Hz, ArC), 135.8 (3JCF = 7.2 Hz, ArC),
129.4 (3JCF = 7.8 Hz, ArC), 129.0 (3JCF = 7.8 Hz, ArC), 124.7
(4JCF = 2.9 Hz, ArC), 123.5 (4JCF = 2.8 Hz, ArC), 119.0 (2JCF = 21.3
Hz, ArC), 117.2 (2JCF = 21.4 Hz, ArC), 116.0 (2JCF = 23.2 Hz, ArC),
114.7 (2JCF = 22.2 Hz, ArC), 107.3 (NC=C), 49.6 (CONCH2), 43.2
(CH3NCH2), 42.2 (NCH3), 25.7 (CH2CH2CH2).
13C NMR (75 MHz, CDCl3): d = 189.9 (C=C–C=O), 169.7
(NC = O), 167.1 (NC=C), 139.7 (ArC), 138.2 (ArC), 136.6 (ArC),
132.3 (ArC), 130.4 (ArC), 129.3 (ArC), 128.1 (ArC), 127.8 (ArC),
107.4 (NC=C), 49.6 (CONCH2), 43.2 (CH3NCH2), 42.2 (NCH3),
26.0 (CH2CH2CH2).
2-[1-(4-Methoxybenzoyl)-3-methyltetrahydropyrimidin-2(1H)-
ylidene]-1,3-bis(4-methoxyphenyl)propane-1,3-dione (10c)
Yellowish solid; yield: 83%; mp 188–190 °C; Rf = 0.15 (hexane–
acetone, 1:2).
2-[1-(3-Methoxybenzoyl)-3-methyltetrahydropyrimidin-2(1H)-
ylidene]-1,3-bis(3-methoxyphenyl)propane-1,3-dione (10g)
Yellowish solid; yield: 61%; mp 188–190 °C; Rf = 0.36 (hexane–
acetone, 1:1).
IR (KBr): 1666, 1587, 1536, 1505 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.50–6.51 (m, 12 H, ArH), 3.82
(s, 3 H, OCH3), 3.69 (m, 8 H, OCH3 and NCH2), 3.58 (t, J = 5.8 Hz,
2 H, NCH2), 3.07 (s, 3 H, NCH3), 2.35 (quin, J = 6.4 Hz, 2 H,
CH2CH2CH2).
13C NMR (75 MHz, CDCl3): d = 191.0 (C=C-C = O), 170.1
(NC = O), 167.2 (NC=C), 162.4 (ArC), 161.2 (ArC), 134.4 (ArC),
131.6 (ArC), 130.4 (ArC), 126.5 (ArC), 113.1 (ArC), 112.5 (ArC),
107.6 (NC=C), 55.3 (OCH3), 49.2 (CONCH2), 42.9 (CH3NCH2),
42.0 (NCH3), 26.5 (CH2CH2CH2).
IR (KBr): 1669, 1621, 1574, 1532, 1482 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.32–6.60 (m, 12 H, ArH), 3.65
(m, 5 H, OCH3 and NCH2), 3.64 (s, 6 H, OCH3), 3.56 (t, J = 6.1 Hz,
2 H, NCH2), 3.09 (s, 3 H, NCH3), 2.30 (quin, J = 6.7 Hz, 2 H,
CH2CH2CH2).
13C NMR (75 MHz, CDCl3): d = 190.9 (C=C–C=O), 170.5
(NC=O), 167.1 (NC=C), 158.7 (ArC), 158.3 (ArC), 142.8 (ArC),
135.2 (ArC), 128.3 (ArC), 127.9 (ArC), 121.3 (ArC), 120.5 (ArC),
118.5 (ArC), 116.1 (ArC), 113.1 (ArC), 112.7 (ArC), 107.7
(NC=C), 54.9 (OCH3), 54.8 (OCH3), 49.2 (CONCH2), 42.8
(CH3NCH2), 41.8 (NCH3), 25.8 (CH2CH2CH2).
2-[1-Methyl-3-(4-methylbenzoyl)tetrahydropyrimidin-2(1H)-
ylidene]-1,3-bis(4-methylphenyl)propane-1,3-dione (10d)
Yellowish solid; yield: 82%; mp 260–262 °C; Rf = 0.13 (hexane–
acetone, 1:1).
2-[1-(3-Chlorobenzoyl)-3-methyltetrahydropyrimidin-2(1H)-
ylidene]-1,3-bis(3-chlorophenyl)propane-1,3-dione (10h)
Yellowish solid; yield: 79%; mp 220–222 °C; Rf = 0.30 (hexane–
acetone, 1:1).
IR (KBr): 1677, 1605, 1587, 1542, 1430 cm–1.
Synthesis 2010, No. 7, 1209–1216 © Thieme Stuttgart · New York

1216
G. Ye et al.
PAPER
IR (KBr): 1678, 1538, 1471, 1455 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.48–6.80 (m, 12 H, ArH), 3.58
(m, 4 H, NCH2), 3.13 (s, 3 H, NCH3), 2.28 (m, 2 H, CH2CH2CH2).
13C NMR (75 MHz, CDCl3): d = 188.9 (C=C–C=O), 169.0
(NC=O), 166.9 (NC=C), 142.6 (ArC), 135.2 (ArC), 133.5 (ArC),
132.9 (ArC), 131.8 (ArC), 129.7 (ArC), 128.8 (ArC), 128.6 (ArC),
127.6 (ArC), 126.8 (ArC), 125.7 (ArC), 106.9 (NC=C), 49.4
(CONCH2), 43.2 (CH3NCH2), 41.9 (NCH3), 25.0 (CH2CH2CH2).
(2) (a) Beyerstedt, F.; McElvain, S. M. J. Am. Chem. Soc. 1936,
58, 529. (b) Barnes, H. M.; Kundiger, D.; McElvain, S. M.
J. Am. Chem. Soc. 1940, 62, 1281. (c) McElvain, S. M.;
Tate, B. E. J. Am. Chem. Soc. 1945, 67, 202. (d) McElvain,
S. M. Chem. Rev. 1949, 45, 453.
(3) (a) Meyers, A. I.; Nazarendo, N. J. Am. Chem. Soc. 1972, 94,
3243. (b) Zhou, A.; Pittman, C. U., Jr. Tetrahedron Lett.
2004, 45, 8899. (c) Quast, H.; Ach, M.; Balthasar, J.;
Hergenröther, T.; Regnat, D.; Lehmann, J.; Banert, K. Helv.
Chim. Acta. 2005, 88, 1589. (d) Roberts, R. M.; Corse, J.;
Boschan, R.; Seymour, D.; Winstein, S. J. Am. Chem. Soc.
1958, 80, 1247. (e) Gruseck, U.; Heuschmann, M. Chem.
Ber. 1987, 120, 2053.
2-[1-(3-Bromobenzoyl)-3-methyltetrahydropyrimidin-2(1H)-
ylidene]-1,3-bis(3-bromophenyl)propane-1,3-dione (10i)
Yellowish solid; yield: 89%; mp 222–224 °C; Rf = 0.26 (hexane–
acetone, 1:1).
(4) For examples, see: (a) Cao, L.; Wu, Z.; Zhu, P. C. Polym.
Prepr. (Am. Chem. Soc., Div. Polym. Chem.) 1999, 39, 406.
(b) Cao, L.; Wu, Z.; Pittman, C. U. Jr. J. Polym. Sci., Part A:
Polym. Chem. 1999, 37, 2841. (c) Cao, L.; Pittman, C. U. Jr.
J. Polym. Sci., Part A: Polym. Chem. 1999, 37, 2823.
(d) Wu, Z.; Cao, L.; Pittman, C. U. Jr. Recent Res. Dev.
Polym. Sci. 1998, 2, 467. (e) Wu, Z.; Cao, L.; Pittman, C. U.
Jr. J. Polym. Sci., Part A: Polym. Chem. 1998, 36, 861.
(f) Zhu, P. C.; Pittman, C. U. Jr. J. Polym. Sci., Part A:
Polym. Chem. 1996, 34, 169. (g) Wu, Z.; Cao, L.; Zhu, P. C.
Polym. Prepr. (Am. Chem. Soc., Div. Polym. Chem.) 1997,
38, 121. (h) Pittman, C. U. Jr.; Wu, Z.; Zhu, P. C. J. Polym.
Sci., Part A: Polym. Chem. 1997, 35, 485. (i) Zhu, P. C.;
Pittman, C. U. Jr. J. Polym. Sci., Part A: Polym. Chem. 1996,
34, 73. (j) Liu, Y.; Pittman, C. U. Jr. J. Polym. Sci., Part A:
Polym. Chem. 1997, 35, 3655.
(5) (a) Zhou, A.; Pittman, C. U. Jr. Tetrahedron Lett. 2005, 46,
3801. (b) Zhu, P. C.; Lin, J.; Pittman, C. U. Jr. J. Org. Chem.
1995, 60, 5729. (c) Wu, Z.; Stanley, R. R.; Pittman, C. U. Jr.
J. Org. Chem. 1999, 64, 8386. (d) Cao, L. PhD Thesis;
Mississippi State University: USA, 1999. (e) Li, H. MS
Thesis; Mississippi State University: USA, 2005. (f) Ye, G.
PhD Thesis; Mississippi State University: USA, 2008.
(6) (a) Gruseck, U.; Heuschmann, M. Tetrahedron Lett. 1987,
28, 6027. (b) Gruseck, U.; Heuschmann, M. Chem. Ber.
1987, 120, 2065. (c) Ye, G.; Henry, W. P.; Chen, C.; Zhou,
A.; Pittman, C. U. Jr. Tetrahedron Lett. 2009, 50, 2135.
(d) Zhou, A.; Cao, L.; Li, H.; Liu, Z.; Pittman, C. U. Jr.
Synlett 2006, 201. (e) Zhou, A.; Cao, L.; Li, H.; Liu, Z.; Cho,
H.; Henry, W. P.; Pittman, C. U. Jr. Tetrahedron. 2006, 62,
4188. (f) Diaz-Ortiz, A.; Diez-Barra, E.; de la Hoz, A.;
Prieto, P.; Moreno, A.; Langa, F.; Prange, T.; Neuman, A.
J. Org. Chem. 1995, 60, 4160.
IR (KBr): 1682, 1652, 1548, 1470 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.68–6.81 (m, 12 H, ArH), 3.79 (t,
J = 6.8 Hz, 2 H, NCH2), 3.66 (t, J = 6.2 Hz, 2 H, NCH2), 3.16 (s, 3
H, NCH3), 2.38 (m, 2 H, CH2CH2CH2).
13C NMR (75 MHz, CDCl3): d = 189.2 (C=C–C=O), 169.1
(NC=O), 167.5 (NC=C), 142.7 (ArC), 135.4 (ArC), 135.2 (ArC),
132.9 (ArC), 131.9 (ArC), 131.0 (ArC), 129.3 (ArC), 129.1 (ArC),
127.7 (ArC), 126.5 (ArC), 121.9 (ArC), 121.3 (ArC), 107.4
(NC=C), 49.7 (CONCH2), 43.4 (CH3NCH2), 42.2 (NCH3), 25.2
(CH2CH2CH2).
2-[1-Methyl-3-(3-methylbenzoyl)tetrahydropyrimidin-2(1H)-
ylidene]-1,3-bis(3-methylphenyl)propane-1,3-dione (10j)
Yellowish solid; yield: 74%; mp 202–204 °C; Rf = 0.16 (hexane–
acetone, 1:1).
IR (KBr): 1644, 1581, 1537, 1478, 1454 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.38–6.56 (m, 12 H, ArH), 3.80 (t,
J = 6.7 Hz, 2 H, NCH2), 3.62 (t, J = 5.8 Hz, 2 H, NCH2), 3.12 (s, 3
H, NCH3), 2.36 (m, 2 H, CH2CH2CH2), 2.30 (s, 3 H, ArCH3), 2.05
(s, 6 H, ArCH3).
13C NMR (75 MHz, CDCl3): d = 191.1 (C=C–C=O), 170.1
(NC=O), 167.0 (NC=C), 141.0 (ArC), 136.8 (ArC), 135.7 (ArC),
133.4 (ArC), 131.8 (ArC), 129.9 (ArC), 129.4 (ArC), 128.3 (ArC),
126.9 (ArC), 126.4 (ArC), 125.9 (ArC), 124.5 (ArC), 107.4
(NC=C), 48.8 (CONCH2), 42.5 (CH3NCH2), 41.3 (NCH3), 25.2
(CH2CH2CH2), 20.5 (ArCH3), 20.3 (ArCH3).
Acknowledgment
The authors acknowledge the educational and general funds of
Mississippi State University for partial financial support of this work.
(7) (a) Tohda, Y.; Kawashima, T.; Ariga, M.; Akiyama, R.;
Shudoh, H.; Mori, Y. Bull. Chem. Soc. Jpn. 1984, 57, 2329.
(b) Zhou, A.; Pittman, C. U. Jr. Synthesis 2006, 37.
(c) Zhou, A.; Pittman, C. U. Jr. Tetrahedron Lett. 2005, 46,
2045.
References
(1) For examples, see: (a) Grainger, R. S.; Welsh, E. J. Angew.
Chem. Int. Ed. 2007, 46, 5377. (b) Wang, S. L. B.; Liu, X.;
Ruiz, M. C.; Gopalsamuthiram, V.; Wulff, W. D. Eur. J.
Org. Chem. 2006, 5219. (c) Martins, M. A. P.; Cunico, W.;
Brondani, S.; Peres, R. L.; Zimmermann, N.; Rosa, F. A.;
Fiss, G. F.; Zanatta, N.; Bonacorso, H. G. Synthesis 2006,
1485. (d) Hamasaki, A.; Ducray, R.; Boger, D. L. J. Org.
Chem. 2006, 71, 185. (e) Rustullet, A.; Alibés, R.;
(8) Ye, G.; Zhou, A.; Henry, W. P.; Song, Y.; Chatterjee, S.;
Beard, D. J.; Pittman, C. U. Jr. J. Org. Chem. 2008, 73, 5170.
(9) Ye, G.; Chen, C.; Chatterjee, S.; Collier, W. E.; Zhou, A.;
Song, Y.; Beard, D. J.; Pittman, C. U. Jr. Synthesis 2010,
141.
(10) For examples, see: (a) Sandström, J.; Sjöstrand, U.;
Wennerbeck, I. J. Am. Chem. Soc. 1977, 99, 4526.
(b) Adhikesavalu, D.; Venkatesan, K. Acta Crystallog., Sect.
C 1983, 39, 1044. (c) Kleinpeter, E.; Schulenburg, A.
Tetrahedron Lett. 2005, 46, 5995.
de March, P.; Figueredo, M.; Font, J. Org. Lett. 2007, 9,
2827. (f) Gompper, R.; Elser, W. Tetrahedron Lett. 1964,
29, 1971. (g) Ziegler, T.; Layh, M.; Effenberger, F. Chem.
Ber. 1987, 120, 1347. (h) Neidlein, R.; Klotz, U. J. Chem.
Ber. 1985, 118, 3217. (i) Gillard, M.; T’Kint, C.; Sonveaux,
E.; Ghosez, L. J. Am. Chem. Soc. 1979, 101, 5837.
(j) Sauer, J.; Heldmann, D. K.; Hetzenegger, J.; Krauthan, J.;
Sichert, H.; Schuster, J. Eur. J. Org. Chem. 1998, 2885.
Synthesis 2010, No. 7, 1209–1216 © Thieme Stuttgart · New York