Environmentally friendly and efficient synthesis of various 1,4-dihydropyridines in pure water

Article abstract of DOI:10.1246/bcsj.79.454

An environmentally friendly and efficient synthesis of a series of 1,4-dihydropyridines was developed by the practical one-pot reactions of aldehydes with ammonium acetate and 1,3-dicarbonyl compounds such as alkyl acetoacetate, 5,5-dimethyl-1,3-cyclohexanedione, 1,3-cyclohexanedione, and 2,4-pentanedione in water without any additives under refluxing conditions.

Full text of DOI:10.1246/bcsj.79.454

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
454 Bull. Chem. Soc. Jpn. Vol. 79, No. 3, 454–459 (2006)
Ó 2006 The Chemical Society of Japan
Environmentally Friendly and Efficient Synthesis
of Various 1,4-Dihydropyridines in Pure Water
ꢀ
Guan-Wu Wang, Jing-Jing Xia, Chun-Bao Miao, and Xue-Liang Wu
Hefei National Laboratory for Physical Sciences at Microscale and Department of Chemistry,
University of Science and Technology of China, Hefei, Anhui 230026, P. R. China
Received August 23, 2005; E-mail: gwang@ustc.edu.cn
An environmentally friendly and efficient synthesis of a series of 1,4-dihydropyridines was developed by the prac-
tical one-pot reactions of aldehydes with ammonium acetate and 1,3-dicarbonyl compounds such as alkyl acetoacetate,
5,5-dimethyl-1,3-cyclohexanedione, 1,3-cyclohexanedione, and 2,4-pentanedione in water without any additives under
refluxing conditions.
1,4-Dihydropyridines are analogues of nicotinamide ade-
nine dinucleotide (NADH) coenzymes. 1,4-Dihydropyridines
Results and Discussion
exhibit a wide range of biological activities such as calcium
channel blockers,1 and today they are widely used in pharma-
cology.2 Hantzsch esters and acridines are two important
NADH models and are useful in organic synthetic chemistry.3
Hantzsch esters, first reported by Hantzsch in 1882,4 were typ-
ically synthesized by the one-pot condensation of an aldehyde
with alkyl acetoacetate and ammonia either in acetic acid or in
alcohol.5 This method usually requires a long reaction time
and affords Hantzsch esters in relatively low yield. Improved
methods for the Hantzsch ester synthesis have been achieved
by the use of autoclave6 and by microwave irradiation.7 More
recently, ammonia has been replaced by urea,8 ammonium
acetate (NH4OAc),8c and ammonium hydrogencarbonate8c in
the microwave-assisted solvent-free synthesis of Hantzsch
esters. All of these methods employ either autoclave or micro-
wave irradiation, and utilize harmful organic solvents in most
cases. A more recent work on the thermal solvent-free synthe-
sis of Hantzsch esters has been reported.9
On the other hand, green chemistry as a kind of environmen-
tal benign chemistry has attracted intensive attention in recent
years. One of the most promising approaches is to utilize water
as the reaction medium, which presents a clean, economical,
and environmental-safe protocol. In fact, more and more reac-
tions have been reported to proceed smoothly and efficiently in
water.10 Furthermore, due to the low solubility of common or-
ganic compounds in water, the use of water as a solvent often
makes the purification of products very easy by simple filtra-
tion or extraction. With this in mind, we investigated organic
reactions in pure water.11 To the best of our knowledge, there
have been no reports on the one-pot synthesis of 1,4-dihydro-
pyridines in pure water without any additives. In this paper, we
report the facile and benign one-pot synthesis of Hantzsch
esters from the reactions of aldehydes with ethyl acetoacetate
and NH4OAc in refluxing water, and extended to the synthesis
of other 1,4-dihydropyridines by replacing ethyl acetoacetate
with other 1,3-dicarbonyl compounds, such as methyl aceto-
acetate, 5,5-dimethyl-1,3-cyclohexanedione, 1,3-cyclohexane-
dione, and 2,4-pentanedione.
Hantzsch esters were synthesized by the one-pot three-com-
ponent condensation of an aliphatic or aromatic aldehyde 1,
ethyl acetoacetate (2), and NH4OAc (3) in refluxing water
for a designated time.
The reaction times, yields, as well as the melting points for
the Hantzsch reaction with the molar ratio of 1, 2, and 3 as
1:4:2 in refluxing water are listed in Table 1. In our protocol,
no organic solvents or additives were used during the reaction
process. Furthermore, since the product is solid and precipitat-
ed out from the reaction mixture, the work-up procedure was
just simple filtration. The desired products of high purity were
obtained by column chromatography or recrystallization.
From Table 1, one can see that both aliphatic aldehydes and
aromatic aldehydes with an electron-withdrawing group or
electron-donating group could be employed in the synthesis
of Hantzsch esters. The synthesized Hantzsch esters are known
compounds, and their identities were confirmed by comparison
of their 1H NMR, 13C NMR, IR spectral data, and melting
points with those reported in the literature.5,8a,8c,12 It is notable
that in the 1H NMR spectra of 4a–4i, the methine proton at C4
shifted downfield more than 1 ppm from that of 4-alkyl to 4-
aryl Hantzsch esters, e.g., 3.82 ppm for 4b versus 4.96 ppm for
4i, probably due to the electron-withdrawing effect of the aro-
matic ring. The IR spectra of 4a–4i displayed similar absorp-
tion patterns, thus indicating the same molecular skeleton.
Acridines, which possess the 1,4-dihydropyridine parent nu-
cleus and are the analogues of Hantzsch esters, have similarities
in structure to the biologically important NADH coenzymes.
Acridines have interesting pharmaceutical properties such as
a positive iontropic effect promoting the entry of calcium to
the intracellular space,13 and 1,8-(2H,5H)-acridinediones are
known as laser dyes.14 10-Unsubstituted 1,8-(2H,5H)-acridine-
diones were synthesized by the adoption of the Hantzsch proce-
dure, i.e., by the thermal reaction of 5,5-dimethyl-1,3-cyclo-
hexanedione (dimedone, 5) with an aldehyde and aqueous am-
monia in ethanol,15 or by the microwave-irradiation-assisted
solvent-free reaction of dimedone with an aldehyde using
NH4OAc supported on neutral or basic alumina and catalytic
Published on the web March 8, 2006; DOI 10.1246/bcsj.79.454

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
G.-W. Wang et al.
Bull. Chem. Soc. Jpn. Vol. 79, No. 3 (2006)
455
Table 1. Reaction Times, Yields, and Melting Points of Hantzsch Ester 4
H R
COOC2H5
CH3
C2H5OOC
CH3
reflux
water
R-CHO + 2 CH3COCH2COOC2H5 + NH4OAc
N
H
1
2
3
4
Reaction
time/h
Entry
R
Product
Yeld/%a)
mp (lit.)/ꢁC
1
2
3
4
5
6
7
8
9
Hb)
CH3
CH3CH2
CH3CH2CH2
C6H5
4-NO2-C6H4
3-NO2-C6H4
4a
4b
4c
4d
4e
4f
4g
4h
4i
2
2
2
4
7
7
7
7
7
84
74
85
96
54
92
90
58
53
183–185 (183–18512)
130–131 (130–1315)
110–111 (111–1135,12
126–128 (125–12712)
156–157 (158–1608a,12
128–129 (128–1308a,12
162–163 (162–1648a,12
158–160 (158–16012)
144–145 (144–1468a,12
c)
)
)
)
)
4-CH3O-C6H4
4-Cl-C6H4
)
a) Isolated yield based on added aldehyde. b) Paraformaldehyde. c) 40% aqueous solution.
Table 2. Reaction Times, Yields, and Melting Points of the 3,4,6,7,9,10-Hexahydro-1,8-(2H,5H)-
acridinediones 6a–6j
O
R
O
O
O
reflux
water
RCHO
+
+
NH4OAc
N
H
1
5
3
6
Reaction
time/h
Entry
R
Product
Yield/%a)
mp (lit.)/ꢁC
1
2
3
4
5
6
7
8
9
10
Hb)
CH3
6a
6b
6c
6d
6e
6f
6g
6h
6i
4
4
4
4
4
4
5
5
4
4
96
80
77
75
90
95
92
91
95
93
>300 (317–31914c
)
)
c)
258–260 (256–25814c
CH3CH2
CH3CH2CH2
C6H5
3-NO2-C6H4
3,4-Cl2-C6H3
4-Cl-C6H4
286–288 (282–28318)
287–289 (286–28718)
272–273 (250–25214c
296–297 (285–28616)
>300
)
297–299 (296–29817)
298–300 (270–27215)
>300 (>30019)
4-CH3O-C6H4
4-CH3-C6H4
6j
a) Isolated yield based on added aldehyde. b) Paraformaldehyde. c) 40% aqueous solution.
N,N-dimethylformamide,16 or using ammonium hydrogencar-
bonate.17 We examined the one-pot thermal synthesis of 1,8-
(2H,5H)-acridinediones in pure water without any additives,
and found that both aliphatic aldehydes and aromatic aldehydes
with an electron-withdrawing or electron-donating group could
be successfully employed.
The reaction times, yields, and melting points of the 3,4,-
6,7,9,10-hexahydro-1,8-(2H,5H)-acridinediones 6a–6j synthe-
sized in refluxing water with the molar ratio of 1 and 5 as 1:2
are listed in Table 2.
The yields of hexahydroacridinediones for the aromatic al-
dehydes are higher than those for aliphatic aldehydes, and
overall better than the yields of Hantzsch esters, reflecting that
dimedone works better than ethyl acetoacetate in the synthesis
of 1,4-dihydropyridine derivatives probably due to the higher
solubility of dimedone in water and higher reactivity than ethyl
acetoacetate. Consistent with this fact, a smaller amount of
dimedone was used in these reactions.
Hexahydroacridinediones 6a–6j, except 6g, have been re-
ported previously;14–19 their identities have been confirmed
1
by their H NMR, 13C NMR, IR spectral, and analytical data.
Again, in the 1H NMR spectra, the methine proton at C9
(5.0–5.2 ppm) of the 9-aryl-substituted hexahydroacridine-
diones 6e–6j shifts downfield by about 1 ppm relative to that
(4.0–4.1 ppm) of 9-alkyl-substituted hexahydroacridinediones
6b–6d due to the electronic effect of the aromatic ring. Fur-
thermore, the splitting patterns of the four methylene groups
change from an AB quartet and a singlet for 6b–6d to two
AB quartets for 6e–6j. This phenomenon has not been noted
before, and previously these peaks were simply assigned as a
multiplet.15,17–19 Furthermore, unlike the reported wide range
of ꢀH (6.4–9.4 ppm) for the NH group of hexahydroacridine-

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
456 Bull. Chem. Soc. Jpn. Vol. 79, No. 3 (2006)
Environmentally Friendly Synthesis of 1,4-Dihydropyridines
Table 3. Reaction Times, Yields, and Melting Points of the 1,4-Dihydropyridines 8a–8i
R1
COR3
R2
R3OC
R2
reflux
water
R1CHO + 2 R2COCH2COR3 + NH4OAc
N
H
1
7
3
8
Reaction
time/min
mp (lit.)
/ꢁC
Entry
R1
R2
R3
Product
Yield/%a)
96
Hb)
CH3
CH3
CH3
CH3
CH3
CH3
OCH3
8a
8b
8c
8d
8e
8f
40
230–231
(231–23321)
139–140
1
2
3
4
5
6
7
8
9
CH3CH2CH2
3-NO2-C6H4
H
OCH3
OCH3
CH3
90
60
40
90
60
40
90
60
80
92
96
81
91
95
83
89
(14022)
210–211
(209–21023)
222–223
(224–22524)
127–129
CH3CH2CH2
3-NO2-C6H4
H
CH3
(127–13225)
212–214
CH3
(211–21226)
273–275
-CH2CH2CH2-
-CH2CH2CH2-
-CH2CH2CH2-
8g
8h
8i
(27027)
221–222
CH3CH2CH2
3-NO2-C6H4
(221–22228)
282–284
(280–28129)
a) Isolated yield based on added aldehyde. b) Paraformaldehyde.
diones, 6a–6j exhibited a broad singlet in a much narrower
range (5.4–6.1 ppm) for the NH group in our hands. The IR
spectra of 6a–6j showed similar absorption patterns, indicating
the similar molecular structures.
benzaldehyde, were selected for this study. We also found that
the reaction time could be shortened when the dosages of 1,3-
dicarbonyl compounds and ammonium acetate were 3 and 4
molar amounts, respectively. The detailed results with the
molar ratio of 1, 7, and 3 as 1:3:4 are summarized in Table 3.
Compounds 8a–8i are known compounds and their molecu-
lar structures have been confirmed by comparison of their
spectral data and melting points with those reported in the lit-
erature.21–29
It should be mentioned that the melting points of 6e, 6f,
and 6i were obviously higher than those reported in the litera-
ture.14c,15,16 However, our measured 13C NMR spectral data
of 6f and 6i are the same as the reported data,15,16 exhibiting
the same identities. The different mp might have resulted from
the presence of an impurity or solvent because even a trace
amount of them would have a great effect on the mp of a com-
pound with high mp, and this phenomenon was confirmed
by the mp measurements of authentic samples from another
source. Careful literature investigation shows that the assigned
6e with a mp of 190–192 ꢁC15,16 has the identical mp of the
corresponding ring-opened tetraketone 9e (vide infra).14c,20
Furthermore, the reported characteristic ꢀH for the C9H group
and ꢀC for the C=O group of the assumed 6e are very different
The reaction process for the mixture of dimedone, aldehyde,
and NH4OAc in refluxing water was followed by 1H NMR,
which indicated that the acridinediones 6 were formed via
tetraketones 9. Take the reaction with 3-nitrobenzaldehyde
1
as an example: For a series of the H NMR spectra of the re-
action mixture, the singlet at 5.54 ppm for the CH group bear-
ing the aromatic ring and the broad peak at 11.89 ppm for the
enolized OH group of the corresponding tetraketone 9f grad-
ually decreased while the peak at 5.17 ppm for the methine
proton of C9 and the broad peak at 5.95 ppm for the NH group
of the acridinedione 6f gradually increased as the reaction pro-
ceeded. This result indicates that the formation of acridine-
diones 6 should be through the condensation of the dimedone
(5) with the aldehyde 1, followed by the addition of another
molecule of 5 to afford the tetraketone 9, and finally cycliza-
tion with NH4OAc (Scheme 1). The reaction mechanism for
other 1,4-dihydropyridines should proceed in the same way.
We have developed a new protocol for the eco-friendly and
efficient synthesis of a series of 1,4-dihydropyridines with po-
tential biological activities. This practical synthesis is realized
by the one-pot reactions of aldehydes with ammonium acetate
1
from those of other analogues;15,16 its H NMR and 13C NMR
spectral data15 are almost the same as those of the correspond-
ing tetraketone 9e, except that the peak at 150.2 ppm was re-
placed by one at 189.4 ppm.20 Thus, the structure of the as-
sumed 6e15,16 should be reassigned as 9e.
We have attempted to extend the above methods for the
synthesis of 1,4-dihydropyridines to other 1,3-dicarbonyl com-
pounds. It was found that methyl acetoacetate, 1,3-cyclohex-
anedione, and 2,4-pentanedione could also react with alde-
hydes and ammonium acetate smoothly to afford 1,4-dihydro-
pyridines with excellent yields in refluxing water. Typical
aldehydes, i.e., paraformaldehyde, butyraldehyde, and 3-nitro-

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
G.-W. Wang et al.
Bull. Chem. Soc. Jpn. Vol. 79, No. 3 (2006)
457
O
R
9
O
O
O
R
O
O
1
4
8
5
NH4OAc
2
3
7
6
RCHO +
10
N
OH HO
H
1
5
9
6
Scheme 1.
acridinedione (6a):14c IR (KBr) ꢁ 3328, 2957, 2928, 1621, 1488,
and 1,3-dicarbonyl compounds such as alkyl acetoacetate, 5,5-
dimethyl-1,3-cyclohexanedione, 1,3-cyclohexanedione, and
2,4-pentanedione in refluxing water. The yields of 1,4-dihydro-
pyridines are generally better than those reported previously.
We do not use any organic solvents or additives in the reaction
process, and employ water as a cheap and ‘‘green’’ solvent for
the reaction medium. The work-up procedure is simple filtra-
tion. Therefore, our current process is a more straightforward
and environmentally benign protocol and can easily be scaled
up for the large-quantity synthesis of various 1,4-dihydropyri-
dines.
1
1381, 1222, 1145 cmꢂ1; H NMR (CDCl3) ꢀ 1.09 (s, 12H, CH3),
2.18 (s, 4H, CH2), 2.27 (s, 4H, CH2), 3.12 (s, 2H, CH2), 5.42 (brs,
1H, NH); 13C NMR (DMSO-d6) ꢀ 18.4, 27.9, 31.9, 39.6, 50.0,
107.3, 150.1, 194.9; Anal. Calcd for C17H23NO2: C, 74.69; H,
8.48; N, 5.12%. Found: C, 74.52; H, 8.52; N, 5.09%.
3,3,6,6,9-Pentamethyl-3,4,6,7,9,10-hexahydro-1,8-(2H,5H)-
acridinedione (6b):14c IR (KBr) ꢁ 3446, 3277, 2957, 2926, 1641,
1
1602, 1486, 1376, 1231, 1145 cmꢂ1; H NMR (CDCl3) ꢀ 1.01 (d,
J ¼ 6:5 Hz, 3H, CH3), 1.08 (s, 6H, CH3), 1.09 (s, 6H, CH3), 2.15
(d, J ¼ 16:5 Hz, 2H, CH2), 2.25 (s, 4H, CH2), 2.31 (d, J ¼ 16:5
Hz, 2H, CH2), 4.01 (q, J ¼ 6:5 Hz, 1H, CH), 5.66 (brs, 1H, NH);
13C NMR (CDCl3) ꢀ 21.7, 22.7, 27.1, 29.6, 32.8, 41.0, 51.2, 114.3,
149.6, 196.4; Anal. Calcd for C18H25NO2: C, 75.22; H, 8.77; N,
4.87%. Found: C, 75.01; H, 8.81; N, 4.82%.
Experimental
General. 1H NMR spectra were recorded on a Bruker Avance-
300 (300 MHz) spectrometer, and chemical shifts (ꢀ) are reported
in parts per million relative to tetramethylsilane and coupling con-
stants (J) in Hz. Splitting patterns are designated as s, singlet; d,
doublet; br, broad. 13C NMR spectra were recorded on a Bruker
Avance-300 (75 MHz) spectrometer with complete proton decou-
pling, and chemical shifts are reported in parts per million relative
to the solvent resonance as the internal standard (CDCl3, ꢀ
77.16 ppm; DMSO-d6, ꢀ 39.52 ppm). IR spectra were taken on a
Bruker Vector-22 spectrometer in KBr pellets and reported in
cmꢂ1. Melting points were determined on an XT-4 apparatus
(Beijing Tech Instrument Co., China). Analytical TLC and col-
umn chromatography were performed on silica gel GF254 and
silica gel H60, respectively.
9-Ethyl-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydro-1,8-(2H,-
5H)-acridinedione (6c):18 IR (KBr) ꢁ 3441, 3283, 2957, 2927,
1643, 1600, 1485, 1383, 1225, 1143 cmꢂ1 1H NMR (CDCl3) ꢀ
;
0.73 (t, J ¼ 7:5 Hz, 3H, CH3), 1.10 (s, 6H, CH3), 1.11 (s, 6H,
CH3), 1.45–1.57 (m, 2H, CH2), 2.19 (d, J ¼ 16:6 Hz, 2H, CH2),
2.27 (s, 4H, CH2), 2.34 (d, J ¼ 16:6 Hz, 2H, CH2), 4.09 (t, J ¼
7:4 Hz, 1H, CH), 5.76 (brs, 1H, NH); 13C NMR (DMSO-d6) ꢀ
9.2, 26.5, 26.8, 27.2, 29.3, 31.8, 39.7, 50.4, 110.1, 150.3, 194.6;
Anal. Calcd for C19H27NO2: C, 75.71; H, 9.03; N, 4.65%. Found:
C, 75.52; H, 9.08; N, 4.61%.
3,3,6,6-Tetramethyl-9-propyl-3,4,6,7,9,10-hexahydro-1,8-
(2H,5H)-acridinedione (6d):18 IR (KBr) ꢁ 3439, 3277, 2954,
2926, 1641, 1600, 1485, 1383, 1229, 1144 cmꢂ1
;
1H NMR
Typical Procedure for the Synthesis of Hantzsch Esters 4.
A mixture of 1 (1 mmol), 2 (520.6 mg, 4 mmol), and 3 (154.2 mg,
2 mmol) in 2 mL of water was vigorously stirred at refluxing tem-
perature for a designated time. The reaction was monitored by
TLC. After the reaction was completed, the reaction mixture was
cooled to room temperature, then filtrated and washed with 10 mL
of water twice. The treatment of 4e, 4h, and 4i was slightly differ-
ent. They needed to be washed with 10 mL of petroleum ether to
remove unreacted reagents after washing with water. The obtained
solid products were nearly pure. The desired products of high pu-
rity were further achieved by column chromatography with petro-
leum ether/ethyl acetate or recrystallization from ethanol.
Typical Procedure for the Synthesis of Acridinediones 6. A
mixture of 1 (0.5 mmol), 5 (140.2 mg, 1 mmol), and 3 (77.1 mg,
1 mmol) in 2 mL of water was vigorously stirred under refluxing
conditions. During the reaction process, 77.1 mg (1 mmol) of 3
was added per hour. The reaction was completed after 4 h as moni-
tored by TLC. Due to the high yields of 6, the work-up procedure
was just simple filtration and washing with 10 mL of water twice.
The obtained solid products were nearly pure. The desired prod-
ucts of high purity were further achieved by column chromatogra-
phy with petroleum ether/ethyl acetate or recrystallization from
ethanol.
(CDCl3) ꢀ 0.82 (t, J ¼ 7:2 Hz, 3H, CH3), 1.11 (s, 12H, CH3),
1.16–1.28 (m, 2H, CH2), 1.38–1.45 (m, 2H, CH2), 2.18 (d, J ¼
16:6 Hz, 2H, CH2), 2.27 (s, 4H, CH2), 2.29 (d, J ¼ 16:6 Hz, 2H,
CH2), 4.09 (t, J ¼ 4:9 Hz, 1H, CH), 5.67 (brs, 1H, NH); 13C NMR
(DMSO-d6) ꢀ 14.3, 18.1, 26.1, 26.5, 29.3, 31.9, 37.5, 39.7, 50.4,
110.7, 150.2, 194.6; Anal. Calcd for C20H29NO2: C, 76.15; H,
9.27; N, 4.44%. Found: C, 75.98; H, 9.32; N, 4.40%.
3,3,6,6-Tetramethyl-9-phenyl-3,4,6,7,9,10-hexahydro-1,8-
(2H,5H)-acridinedione (6e):14c IR (KBr) ꢁ 3435, 3283, 2956,
2921, 1639, 1606, 1480, 1368, 1217, 1140 cmꢂ1
;
1H NMR
(CDCl3) ꢀ 0.97 (s, 6H, CH3), 1.09 (s, 6H, CH3), 2.16 (d, J ¼
16:5 Hz, 2H, CH2), 2.24 (d, J ¼ 16:5 Hz, 2H, CH2), 2.25 (d, J ¼
16:4 Hz, 2H, CH2), 2.39 (d, J ¼ 16:4 Hz, 2H, CH2), 5.08 (s, 1H,
CH), 5.83 (brs, 1H, NH), 7.06 (t, J ¼ 7:2 Hz, 1H, ArH), 7.19 (t,
J ¼ 7:5 Hz, 2H, ArH), 7.33 (d, J ¼ 7:1 Hz, 2H, ArH); 13C NMR
(CDCl3) ꢀ 27.2, 29.7, 32.7, 33.7, 40.6, 51.1, 113.2, 126.1,
128.0, 128.1, 146.8, 149.9, 196.3; Anal. Calcd for C23H27NO2:
C, 79.05; H, 7.79; N, 4.01%. Found: C, 78.80; H, 7.79; N, 4.08%.
3,3,6,6-Tetramethyl-9-(3-nitrophenyl)-3,4,6,7,9,10-hexahydro-
1,8-(2H,5H)-acridinedione (6f):16 IR (KBr) ꢁ 3435, 3270, 3184,
1
2958, 1647, 1609, 1487, 1364, 1345, 1224, 1144 cmꢂ1; H NMR
(CDCl3) ꢀ 0.98 (s, 6H, CH3), 1.10 (s, 6H, CH3), 2.16 (d, J ¼
16:4 Hz, 2H, CH2), 2.25 (d, J ¼ 16:4 Hz, 2H, CH2), 2.36 (d, J ¼
17:7 Hz, 2H, CH2), 2.48 (d, J ¼ 17:7 Hz, 2H, CH2), 5.17 (s, 1H,
3,3,6,6-Tetramethyl-3,4,6,7,9,10-hexahydro-1,8-(2H,5H)-