Synthesis of 2-alkyl and 2-aryl pyrimidines from β-chlorovinyl ketones of cyclopentanone type

Article abstract of DOI:10.1081/SCC-100000204

Amidines react in the presence of NaHCO₃ with β-chlorovinyl ketones, prepared regioselectively by the reaction of 2-acetylcyclopentanone-type diketones with PPh₃-CCl₄ in 73-78% yield, to afford 2-alkyl (aryl)-pyrimidines a

Full text of DOI:10.1081/SCC-100000204

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SYNTHESIS OF 2-ALKYL AND 2-ARYL
PYRIMIDINES FROM β-CHLOROVINYL KETONES OF
CYCLOPENTANONE TYPE
Sergey A. Popov a & Alexey V. Tkachev b
a Novosibirsk Institute of Organic Chemistry, Novosibirsk, 630090, Russia
b Department of Natural Sciences, Novosibirsk State University, Russia
Published online: 16 Aug 2006.
To cite this article: Sergey A. Popov & Alexey V. Tkachev (2001) SYNTHESIS OF 2-ALKYL AND 2-ARYL PYRIMIDINES FROM
β-CHLOROVINYL KETONES OF CYCLOPENTANONE TYPE, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 31:2, 233-243, DOI: 10.1081/SCC-100000204
To link to this article: http://dx.doi.org/10.1081/SCC-100000204
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SYNTHETIC COMMUNICATIONS, 31(2), 233–243 (2001)
SYNTHESIS OF 2-ALKYL AND 2-ARYL
PYRIMIDINES FROM β-CHLOROVINYL
KETONES OF CYCLOPENTANONE TYPE
Sergey A. Popov1 and Alexey V. Tkachev2,∗
1Novosibirsk Institute of Organic Chemistry,
Novosibirsk 630090, Russia
2Novosibirsk State University, Department
of Natural Sciences, Russia
ABSTRACT
AmidinesreactinthepresenceofNaHCO3 withβ-chlorovinyl
ketones, prepared regioselectively by the reaction of 2-acetylcyclo-
pentanone-type diketones with PPh3-CCl4 in 73–78% yield, to
afford 2-alkyl (aryl)-pyrimidines annelated with cyclopentane
derivatives in 79–87% yields.
β-Chlorovinyl carbonyl compounds are versatile reagents known to be used
for preparation of aza-heterocycles (1,2), organometallic derivatives (3), cyclo-
pentadienyl complexes (4). Here we report the regioselective synthesis of β-
chlorovinyl ketones from readily accessible chiral β-difunctional derivatives of
monoterpenes limonene and (+)-3-carene (5,6), as well as the simplest analogue
(2-acetylcyclopentanone) and their use for the synthesis of annelated pyrimidines
whose preparation from β-diketones directly by traditional methods results in poor
yields of the desired pyrimidins.
∗ To whom correspondence should be addressed.
233
Copyright ꢀ 2001 by Marcel Dekker, Inc.
www.dekker.com
C

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POPOV AND TKACHEV
We studied the reaction of 2-acetylcyclopentanone-type diketones 1–3 with
PPh3-CCl4 [withCHCl3 asco-solvent(7)]andfoundthatformationofβ-chlorovinyl
ketones proceeds regioselectively to provide good yields of β-chlorovinyl ketones
4, 5 and 6.
Formation of 2 pairs of isomers is possible in the reaction of 2-acetyl
cyclopentanone-type diketones with CCl4-PPh3. According to NMR data, the reac-
tion of diketones 1 or 2 provided a mixture of only 2 isomers 4 or 5 (with carbonyl
in the cyclopentene moiety). Treatment of the mixtures 4a + 4b or 5a + 5b with
ammonium acetate-Et3N gave enaminone 7 [identical to that obtained earlier from
diketone 1 (8)] or enaminone 8 (9) as the only isomers (yields 85% and 83%, corre-
spondingly). So the positional isomers with acetyl group and chlorocyclopentene
moiety are not formed in this reaction in a significant yield (Table 1).
The value of the NMR-1H shifts of the E-methyl group for certain cyclic
isopopylidene-2-enones are 0.19–0.08 ppm less than the corresponding values for

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235
Table 1.
Entry Product
Reaction Conditions
Yield, % The Ratio of the Isomers a:b
1
2
3
4a,b
5a,b
6a
reflux, 5 h
72
78
78
1.0:0.26
1.0:0.69
100:0
12 h at 20◦C→ reflux, 15 min
reflux, 5 h
Z-methyl (10). In the minor isomers 4b and 5b, NMR-1H shifts of the methyl
3H-1 are 2.36 and 2.41 ppm, whereas the corresponding values for major isomers
4a and 5a are 2.46 and 2.53 ppm. Additionally, according to the molecular me-
chanics (MM2) and semi-empirical quantum chemical calculations (AM1, PM3),
E-isomers 4a, 5a are more stable than Z-isomers 4b, 5b [ꢀH◦f 4a − ꢀH◦
=
4b
f
−1.64(MM2), −2.32(AM1), −0.47(PM3)kcal/mol;(ꢀH◦f 5a − ꢀH◦ = −1.54
5b
f
(MM2), −2.35 (AM1), −0.46 (PM3) kcal/mol], and that might be the reason for
predominant formation of the isomers 4a and 5a.
Surprisingly, the single isomer of chlorovinyl ketone 6 was isolated in the
reaction of diketone 3 with PPh3-CCl4, which was proved by NMR (both 1H and
13Cshiftsof themethyl arequite similarto the correspondingvaluesfor compounds
4a, 5a) and preparation of the enaminone 93 (82%) as the single product by the
reaction of 6 with NH4OAc-Et3N. Formation of 1-(2-chloro-cyclopent-1-enyl)-
ethanone type isomers is hardly possible due to steric reasons; moreover, according
to NMR data, diketone 3 exists predominantly as isomer 3a. Taking into account
the NMR data and greater stability of the E-isomer 6a by 1.82 (MM2), 2.28 (AM1),
and 0.59 (PM3) kcal/mol, the most probable structure of the product should be
drawn as 6a.
Cyclopentanoids annelated with the nitrogen containing aromatic systems
(mostly pyridines) are known to be presented in alkaloid series (11). On the other
hand, pyrimidine derivatives fused with alicyclic fragments are the less known
class of compounds (12). The combination of pharmacophoric pyrimidine nuclei
and cyclopentane moiety especially those, which comprise chiral fragments in the
molecule, is of interest from the viewpoint of bioactivity, so we attempted the work
designed at preparation of fused pyrimidines.
Reaction of β-diketones with amidines is one of the most common routes
to pyrimidines. We tried to prepare 2-alkyl- or 2-aryl pyrimidines by the reac-
tion of β-diketones 1 and 3 and 2-acetylcyclopentanone with amidines, but our
attempts were unsuccessful due to the retrocondensation reactions of the named
β-diketones resulted in the ring cleavage. For example, unlike the reaction of
2-formylcyclopentanone with amidines (2), ω-keto esters were the main products
when solutions of diketones 1–3 in n-BuOH or MeOH were treated with amidines
or with carbonates or bicarbonates of amidines (only traces of pyrimidine-type
compounds were detected).

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POPOV AND TKACHEV
The numbering scheme of the carbons does not coincide with the numbering of the
system according to IUPAC and is given for NMR interpretation only.
β-Chlorovinylcarbonylcompoundsareknowntoreactreadilywithamidines
in the presence of NaOH to give 2-substituted pyrimidines in quite good yield (13).
We found that the reaction of chlorovinylketone 6a with amidine hydrochlorides in
the presence of a strong base (like NaOH) was always accompanied with destruc-
tion of cyclopropane ring. Formation of 4,6,6-trimethyl-5,6-dihydro-quinazoline-
type by-products 13 was observed.
The relative amount of the by-product 13 is strongly dependent on the type
of base. Thus, in the reaction of 6a with benzamidine hydrochloride, the ratio
12a:13a was 1:1, 5:1, 50:1 when NaOH, Na2CO3, and NaHCO3, correspondingly,

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237
were used as the base. Generally, when NaHCO3 was used in the reaction of 6a
with amidines, the relative amount of 13 in the mixture of isomers did not exceed
3% and compound 12 was purified readily via crystallization (compound 12c was
purified as adduct with picric acid). Mixtures of the isomers 4 and 5 are less strained
as compared to 6a, so their reactions with amidines are less sensitive to the type of
the base. At the same time, the best yields of annelated pyrimidines in the reactions
of amidines with 4, 5 were obtained in the presence of NaHCO3. Compounds 12
can be easily transformed to 13 by treatment with alkali. Thus, reaction of 12a with
KOH in methanol under reflux for 20 h results in compound 13a (yield 58%). The
transformation 12 → 13 can be explained in terms of nucleophylic rearrangement
of α-cyclopropyl anion:
Thus, in the case of certain terpenoid-based molecules, application of β-
chlorovinyl ketones for the syntheses of fused pyrimidines is advantageous over
the parent diketones (14).
EXPERIMENTAL
General Experimental Procedures
®
Analytical TLC plates were Silufol (Silpearl on aluminum foil, Czech
Republic). Preparative column chromatography was performed on SiO2 (“KSK,”
Russia, 100–200 mesh, air dried, and activated at 140◦C for 5 h) or Al2O3. IR
spectra were recorded on a Specord M-80 spectrometer. UV spectra were obtained
for 1% solutions in EtOH using a Specord UV VIS spectrometer. A Polamat A
polarimeter was used to measure optical rotation at 578 nm. Melting points were
measured using a Kofler melting point apparatus. Mass spectra were obtained on
a Finnigan MAT 8200 instrument using the Electron Impact Ionization technique
(50◦–150◦C, 70 eV). 1H and 13C NMR spectra were recorded at room temperature
for 5–10% solutions in CDCl3-CCl4 (2:3 v/v) using standard Bruker NMR Soft-
ware System on a Bruker AC 200 instrument (1H 200.13 MHz, 13C 50.32 MHz)
locked to the deuterium resonance of the solvent. Chemical shifts were calculated

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POPOV AND TKACHEV
relative to the solvent signal (CDCl3) used as the internal standard: δH 7.24 ppm
and δC 76.90 ppm.
Diketones 1 and 3 were prepared by known methods (6,8) from ( )-3-(1-
methyl-ethenyl)-6-oxoheptanenitrile and (1R,3S)-2,2-dimethyl-3-(2-oxo-propyl)-
cyclopropyl]-acetonitrile (purchased from Acros), correspondingly.
Synthesis of β-Chlorovinyl Ketones from Diketones 1, 2, 3
(1R,5R)-2-(1-Chloroethylidene)-6,
6-dimethyl-bicyclo[3.1.0]hexan-3-one 6
A mixture of diketone 3 (20.0 g, 120 mmol) and triphenylphosphane (53.6 g,
204 mmol) in a mixture of CCl4 (80 mL) and CHCl3 (200 mL) was refluxed for
4 h. The mixture was worked according to the procedure described in ref. (7) and
the crude product was distilled in vacuum to afford compound 6 (17.3 g, 78%) as a
pale yellow oil, which was solidified in a refrigerator to give yellow crystals with
m.p. 27◦–28◦C (pentane) and b.p. 85◦–87◦C/6 mm Hg; [α]19 −331 (c 3.5, CHCl3).
IR (CHCl3) νmax = 1715, 1612, 1267, 1235, 1212, 1130, 1102, 1071, 1042, 1012,
927, 873 cm−1. UV (EtOH) λmax = 277 nm (ε 8030). MS (m/z, %): 184.0651
(M+, 100%, C10H13OCl, requires 184.0655), 169 (74), 149 (37), 133 (65), 121
(21), 105 (36), 91 (19), 79 (22), 67 (16), 51 (12). NMR 1H: δ = 0.82 s (3H-10),
1.11 s (3H-9), 1.34 ddd (J = 7.3, 6.5 and 1.0, 1H-6), 2.08 d (J = 7.3, 1H-7), 2.27 dd
(J = 19.5 and 1.0, 1H-5a), 2.49 s (3H-1), 2.56 dd (J = 19.5 and 6.5, 1H-5b). NMR
13C: δ = 15.05 (C-10), 22.49 (C-1), 22.67 (C-6), 24.00 (C-8), 26.71 (C-9), 33.86
(C-7), 39.68 (C-5), 133.67 (C-3 or C-2), 144.20 (C-2 or C-3), 203.06 (C-4).
Amixtureof(E)-( )-2-(1-Chloro-ethylidene)-4-isopropenyl-cyclopentanone
4a and (Z)-( )-2-(1-Chloro-ethylidene)-4-isopropenyl-cyclopentanone 4b (1:0.26
according to NMR) was prepared from diketone 2 by the above method in 72%
yield as yellow oil with b.p. 86◦–90◦C/6mm Hg. IR (CHCl3) νmax = 1714, 1627,
1438, 1404, 1208, 1066, 1004, 971, 897, 785 cm−1. UV (EtOH) λmax = 253 nm
(ε 12280). MS (m/z, %): 184.0653 (M+, 4%, C10H13OCl, requires 184.0655) 169
(7), 149 (8), 144 (20), 142 (62), 121 (7), 118 (10), 116(32), 107 (100), 95 (2), 91
(21), 88 (57), 81 (4), 77 (18), 67 (15), 55(3), 53 (27), 43 (38). Major isomer 4a,
NMR 1H: δ = 1.67 s (3H-9), 2.46 s (3H-1), 4.64 m (1H-10a), 4.68 m (1H-10b);
NMR 13C: δ = 20.48 (C-9), 22.74 (C-1), 36.24 (C-7), 38.82 (C-6), 45.61 (C-5),
110.00 (C-10), 132 87 (C-2), 144.55 (C-3), 145.54 (C-8), 201.82 (C-4).
1
Minor isomer 4b, NMR H: 1.63 s (3H-9), 2.36 s (3H-1); NMR 13C: δ = 20.15
(C-9), 30.00 (C-1), 36.98 (C-7), 41.20 (C-6), 45.44 (C-5), 110.00 (C-10), 136.70
(C-2), 144.55 (C-3), 145.54 (C-8), 194.80 (C-4).
A mixture of (E)-2-(1-Chloro-ethylidene)-cyclopentanone 5a and (Z)-2-(1-
Chloro-ethylidene)-cyclopentanone 5b (1.0:0.69 according to NMR) was pre-
pared from diketone 2 by the above method in 78% yield as yellow oil with

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239
b.p. 58◦–61◦C/5 mm Hg. IR (CHCl3) νmax = 1712 1659, 1625, 1459, 1410, 1211,
1132 cm−1. UV (EtOH) λmax = 251 nm (ε 10200). MS (m/z, %): 144.0337 (M+,
100%, C7H9OCl, requires 144.0342), 129 (81), 116 (12), 102 (17), 88 (27), 81
1
(30), 65 (44), 53 (32), 43 (59). Major isomer 5a, NMR H: δ = 2.53 t (J = 2.3,
3H) NMR 13C: δ = 19.53 (C-7), 23.59 (C-1), 32.14 (C-6), 41.61 (C-5), 133.85
(C-2), 145.13 (C-3), 203.63 (C-4). Minor isomer 5b, NMR 1H: δ = 2.41 s (3H).
NMR 13C: δ = 20.82 (C-7), 31.05 (C-1), 33.27 (C-6), 42.20 (C-5), 138.16 (C-2),
141.24 (C-3), 194.80 (C-4).
Synthesis of Pyrimidines from Chlorovinyl Ketones 4, 5 and 6
A solution of a chlorovinyl ketone 4, 5 or 6 (10 mmol) in MeOH (10 mL) was
added to a stirred mixture of an amidine hydrochloride (15 mmol) and NaHCO3
(50 mmol) in MeOH (75 mL). The reaction mixture was stirred at ambient temper-
ature for 5 h and then refluxed for 2 h. The solvent was distilled off and the residue
was treated with water (150 mL) and extracted with CHCl3 (2 × 20 mL). Then the
combined organic extracts were treated according to the following procedures.
2-Methyl pyrimidines 10c and 12c
The combined extracts were washed with 1M H2SO4 (3 × 20 mL). The com-
bined aqueous extracts were neutralized with aq. NH4OH (50 mL) and extracted
with CHCl3 (3 × 30 mL). The combined chloroform extracts were concentrated at
reduced pressure followed by chromatography on a short alumina column (EtOAc)
to afford pure compounds. An analytical sample of compound 12c was obtained
by additional purification via adduct with picric acid.
2-Aryl pyrimidines 10a, 10b, 11a, 12a and 12b
The combined extracts were washed with 1M H2SO4 (2 × 20 mL), dried over
Na2SO4, and concentrated at reduced pressure to afford the crude pyrimidines,
which were then purified by chromatography on a short alumina column (EtOAc)
and crystallized from MeCN to give pure pyrimidines 10a, 10b, 11a, 12a
or 12b.
The reaction in the presence of NaOH or Na2CO3 was carried out by adding
a stirring solution of a chlorovinyl ketone 3 or 4 (10 mmol) in MeOH (10 mL) to a
stirred mixture of an amidine hydrochloride (15 mmol) and NaOH (15 mmol) or
Na2CO3 (50 mmol) in MeOH (75 mL), followed by isolation (described above)
and analysis of the reaction mixture by NMR.
( )-6-Isopropenyl-4-methyl-2-phenyl-6,7-dihydro-5-H-cyclopentapyrimi-
dine 10a, yield 83%, pale yellow needles with m.p. 78◦–79◦C (pentane). IR

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POPOV AND TKACHEV
(CHCl3) νmax = 1647, 1566, 1439, 1392, 1224, 1206, 1179, 1070, 1027, 897 cm−1
.
UV (EtOH) λmax = 260 nm (ε 17180). MS (m/z, %): 250.1473 (M+, 96%,
C17H18N2, requires 250.1470), 235 (22), 221 (4), 209 (12), 194 (9), 180 (2), 167
(5), 146 (5), 131 (5), 118 (1), 104 (15), 91 (16), 77 (14), 65 (8), 53 (7), 43 (1).
1
NMR H: δ = 1.73 s (3H-9), 2.35 s (3H-1), 2.5–3.2 m (5H, H-5,6,7), 4.73 dm
(J = 0.9, H-10a), 4.76 m (H-10b), 7.25–7.45 m (3H, Ar-H), 8.25–8.45 m (2H,
Ar-H). NMR 13C: δ = 19.81 (C-9), 20.75 (C-1), 32.34 (C-7), 37.92 (C-5), 42.68
(C-6), 109.32 (C-10), 127.10 (4C, aromatic carbons), 128.68 (C-15), 128.82 (C-3),
137.32 (C-12), 145.38 (C-8), 159.98 (C-11 or C-2), 161.78 (C-2 or C-11), 171.57
(C-4).
(
)-6-Isopropenyl-4-methyl-2-(4-nitro-phenyl)-6,7-dihydro-5H-cyclopen-
tapyrimidine 10b, yield 81%, pale yellow needles, dec. at ≈110◦C. IR (CHCl3)
νmax = 1648, 1578, 1521, 1421, 1393, 1347, 1214, 1106, 1014, 697, 870, 853cm−1
.
UV (EtOH) λmax = 299 nm (ε 18860). MS (m/z, %): 295.1317 (M+, 96%,
C17H18N3O2, requires 295.1321) 280 (27), 266 (4), 248 (15), 239 (12), 207 (5),
219 (3), 193 (3), 167 (2), 149 (2), 146 (3), 131 (4), 118 (1), 104 (4), 91 (15), 79
(5), 77 (7), 65 (6), 53 (6). NMR 1H: δ = 1.79 s (3H-9), 2,46 s (3H-1), 2.71–2.33 m
(5H-5,6,7), 4.82 m (H-10a), 4.79 m (H-10b), 8.16 m (2H, Ar-H), 8.52 m (2H,
Ar-H). NMR 13C: δ = 20.65 (C-9), 21.62 (C-1), 33.41 (C-7), 38.86 (C-5), 43.67
(C-6), 110.47 (C-10), 123.18(2C, C-14, 16), 128.69 (2C, C-13, 17), 131.19 (C-3),
146.01 (C-8), 148.77 (C-15), 160.78 (C-11 or C-2), 161.55 (C-2 or C-11), 173.13
(C-4).
( )-6-Isopropenyl-2,4-dimethyl-6,7-dihydro-5-H-cyclopentapyrimidine10c,
yield84%, paleyellowoil. IR(CHCl3)νmax = 1647, 1585, 1566, 1434, 1409, 1227,
1207, 1161, 1088, 1024, 932, 896 cm−1. UV (EtOH) λmax = 213 nm
(ε 5560), 260 nm (ε 4582). MS (m/z, %): 188.1296 (M+, 77%, C12H16N2, re-
quires 188.1314), 187 (100), 173 (49), 146 (25), 132 (32), 118 (5), 105 (19), 91
(16), 79 (11), 65 (9), 53 (9). NMR 1H: δ = 1.54 s (3H-9), 2.12 s (3H-1), 2.44 s (3H-
12), 2.45–2.9 m (5H-5,6,7) 4.53 m (1-10a), 4.56 m (H-10b). NMR 13C: δ = 20.34
(C-1), 21.06 (C-9), 25.17 (C-12), 33.12 (C-7), 38.66 (C-5), 43.49 (C-6), 110.02
(C-10), 128.09 (C-3), 146.12 (C-8), 160.54 (C-11 or C-2), 165.94 (C-2 or C-11),
172.14 (C-4).
4-Methyl-2-(4-nitro-phenyl)-6,7-dihydro-5H-cyclopentapyrimidine 11b,
yield 79%, pale yellow crystals with m.p. 172◦–174◦C (CH3CN). IR (CHCl3)
νmax = 1714, 1627, 1439, 1404, 1373, 1214, 1208, 1146, 1066, 1004 cm−1. UV
(EtOH)λmax=299nm(ε 17910). MS(m/z, %):255.0968(M+, 100%, C14H13N3O2,
requires 255.1008), 225 (11), 214 (18), 209 (43), 179 (8), 166 (10), 150 (14), 125
(4), 103 (10), 91 (3), 76 (8), 65 (13), 53 (5). NMR 1H: δ = 2.19 tt (J = 8.0 and 7.6,
2H-6), 2.48 s (3H-1), 2.92 t (J = 7.6, 2H-5 or 2H-7), 3.03 t (J = 8.0, 2H-7 or 2H-5),
8.23 m (2H, Ar-H), 8.56 m (2H, Ar-H). NMR 13C: δ = 21.72 (C-1), 21.78 (C-6),
28.22 (C-7), 34.00 (C-5), 123.37 (2C, aromatic carbons), 128.72 (2C, aromatic
carbons), 132.05 (C-3), 144.18 (C-9), 160.81 (C-8), 161.99 (C-2), 174.42 (C-4).

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241
(1aR,6aR)-1,1,2-Trimethyl-4-phenyl-1,1a,6,6a-tetrahydro-3,5-diaza-cyclo-
propa[a]indene 12a, yield 86%, white crystals with m.p. 74◦–75◦C (pentane-
toluene) and [α]21 +160 (c 1.3, CHCl3). IR (CHCl3) νmax = 1560, 1448, 1421,
1398, 1300, 1214, 119, 1075, 1042, 1020, 927, 864 cm−1. UV (EtOH) λmax
=
274 nm (ε 57780). MS (m/z, %): 250.1468 (M+, 96%, C17H18N2, requires
250.1470), 235 (100), 208 (18), 194 (52), 167 (3), 132 (3), 117 (5), 104 (9),
91 (21), 77 (12), 65 (6), 51 (4). NMR 1H: δ = 0.64 s (3H-10), 1.17 s (3H-9), 1.54
ddd (J = 6.7, 6.7 and 1.0, 1H-6), 2.08 dd (J = 6.7 and 1.4, 1H-7), 2.48 s (3H-10),
2.82 ddd (19.0, 1.4 and 1.4, 1H-5a), 3.15 dd (J = 19.0 and 7.3, 1H-5b), 7.36 m (3H,
Ar-H), 8.36 m (2H, Ar-H). NMR 13C: δ = 14.00 (C-10), 21.68 (C-1), 22.22 (C-8),
26.50 (C-6), 26.71 (C-9), 32.01 (C-7), 33.90 (C-5), 127.94 (C-15), 128.00 (2C,
aromatic carbons), 129.57 (2C, aromatic carbons), 131.02 (C-3), 138.06 (C-12),
160.97 (C-11), 161.94 (C-2), 174.77 (C-4).
(1aR,6aR)-1,1,2-Trimethyl-4-(4-nitro-phenyl)-1,1a,6,6a-tetrahydro-3,5-di-
azacyclopropa[a]indene 12b, yield 87%, pale yellow crystals with m.p. 149◦–
151◦C (dec., MeCN) and [α]21 +145 (c 0.4, CHCl3). IR (CHCl3) νmax = 1600,
1574, 1556, 1521, 1420, 1397, 1212, 1102, 1044, 1010 cm−1. UV (EtOH) λmax
=
313 nm (19390). MS (m/z, %): 295.1329 (M+, 99.6%, C17H18N3O2, requires
295.1321), 280 (100), 253 (18), 239 (74), 234 (15), 219 (6), 207 (8), 193 (16), 166
(2), 150 (1), 132 (2), 116 (7), 105 (5), 91 (22), 77 (10), 65 (8), 51 (4). NMR 1H: δ =
0.65 s (3H-10), 1.21 s (3H-9), 1.64 dm (J = 6.6, 1H-6), 2.14 d (J = 7.0, 1H-7), 2.51 s
(3H-1), 2.85 d (J = 19.0, 1H-5a), 3.16 dd (J = 19.0 and 7.0, 1H-5b). NMR 13C:
δ = 14.05 (C-10), 21.65 (C-1), 22.66 (C-8), 26.73 (C-9), 26.90 (C-6), 32.13 (C-7),
33.91 (C-5), 123.23 (2C, aromatic carbons), 128.61 (2C, aromatic carbons), 132.72
(C-3), 143.79 (C-12), 148.71 (C-15), 159.61 (C-11), 161.49 (C-2), 175.22 (C-4).
(1aR,6aR)-1,1,2,4-Tetramethyl-1,1a,6,6a-tetrahydro-3,5-diaza-cyclopropa-
[a]indene 12c. Yield 82% as pale yellow oil. [α]24 +99 (c 2.7, CHCl3). IR (CHCl3)
νmax = 1722, 1585, 1566, 1411, 1298, 1225, 1122, 1046, 966, 927, 874, 828 cm−1
.
UV (EtOH) λmax = 230 nm (ε 7084), 273 nm (ε4106). MS (m/z, %): 188.1305
(M+, 77%, C12H16N2, requires 188.1314), 173 (100), 159 (3), 146 (25), 132 (97),
117 (7), 105 (15), 91 (26), 77 (12), 65 (10), 61 (76). NMR 1H: δ = 0.62 s (3H-10),
1.18 s (3H-9), 1.54 ddd (J = 6.8, 6.8 and 1.4, 1H-6), 2.08 dd (J = 6.8 and 1.4,
1H-7), 2.40 s (3H-1), 2.56 s (3H-12), 2.74 ddd (J = 19.0, 1.4 and 1.4, 1H-5α),
3.08 dd (J = 19.0 and 6.8, 1H-5β). NMR 13C: δ = 13.73 (C-10), 20.61 (C-1), 21.15
(C-8), 25.20 (C-12), 26.11 (C-6), 26.59 (C-9), 32.50 (C-7), 33.65 (C-5), 129.56
(C-3), 160.64 (C-11 or C-2), 164.81 (C-2 or C-11), 174.41 (C-4).
4,6,6-Trimethyl-2-phenyl-5,6-dihydro-quinazoline 13a. Potassium hydrox-
ide (1.0 g, 18 mmol) was added to a solution of phenyl pyrimidine 12a (0.060 g,
0.24 mmol) in MeOH (15 mL) and the mixture was stirred under reflux for 20 h.
The solvent was distilled off and the residue was diluted with water and taken
up in CH2Cl2 (3 × 10 mL). The combined extracts were dried over Na2SO4 and
concentrated under reduced pressure. The residue was crystallized to afford 35 mg

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242
POPOV AND TKACHEV
(58 %) of the title compound as white crystals with m.p. 67◦–69◦C (hexane-t-Bu-
O-Me). IR (CHCl3) v/cm−1 1629, 1556, 1468, 1397, 1361. UV (EtOH) λmax/nm
252 (ε 42200). MS (m/z, %): 250.1453 (M+, 70%, C17H18N2, requires 250.1470),
235 (27), 221 (3), 209 (10), 194 (100), 132 (3), 104 (7), 91 (21), 77 (11), 65 (9).
1
NMR H: 1.11 s (6H-9,10), 2.50 s (3 H-1), 2.69 s (2H-7), 6.50 d (J = 9.8, 1H-
5), 6.24 d (J = 9.8, 1H-6). NMR 13C: 21.17 (C-1), 26.64 (C-9,10), 29.56 (C-8),
37.14 (C-7), 126.27 (C-5), 128.18 (C-13, 15, 17), 129.63 (C-14, 16), 131.37 (C-3),
138.39 (C-12), 148.36 (C-6), 161.36 (C-11), 162.25 (C-2), 175.09 (C-4).
Synthesis of Enaminones 7, 8, and 9
Ammonium acetate (1.0 g, 13 mmol) and Et3N (2.0 g, 20 mmol) were added
to a stirred solution of a chlorovinylketone 4 or 5 or 6 (1.6 mmol) in MeOH (10 mL)
and the reaction mixture was stirred at ambient temperature for 12 h. The solvent
was distilled off under reduced pressure and the residue was treated with water
(60 ml) and extracted with CH2Cl2 (2 × 30 mL). The combined organic extracts
were dried over Na2SO4 and concentrated in vacuum followed by chromatography
on a short alumina column (EtOAc) to afford enaminones 7, 8, 9 as pale yellow
crystals identical to those described previously (8).
ACKNOWLEDGMENTS
The authors thank the Russian Foundation for Basic Research (grant no. 98-
03-32910 a) and INTAS (grant # 97-0217) for the financial support of this work.
REFERENCES
1. Nesmeyanov, A.N.; Kochetkov, N.K. Dokl. Acad Nauk SSSR 1951, 77, 65.
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122, 959.
3. Minkin, V.I.; Sadekov, I.D.; Rivkin, B.B.; Zakharov, A.V.; Nivorozhkin, V.L.;
Kompan, O.E.; Struchkov, Yu.T. J. Organomet. Chem. 1997, 536, 2233.
4. Gompper, R.; Kottmair, E. Z. Naturforsch., B 1990, 45, 6833.
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9. Greenhill, J.V.; Ramli, M.; Tomassini, T. J. Chem. Soc. Perkin Trans. I 1975,
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243
10. Horibe, I.; Shigemoto, H.; Tori, K. Tetrahedr. Lett. 1975, 2840.
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Accepted April 11, 2000

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