Synthesis of β-ionone

Article abstract of DOI:10.1081/SCC-100000202

Preparation of β-ionone by a reaction sequence starting from acetone is described.

Full text of DOI:10.1081/SCC-100000202

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SYNTHESIS OF β-IONONE#
Parimi V.S.N. Vani a , Asiya Seema Chida a , Rajagopal Srinivasan a , Malapaka
Chandrasekharam a & Ashok Kumar Singh b
a Bio-Organic Laboratory, Division of Organic Chemistry-III, Indian Institute of Chemical
Technology, Hyderabad, 500 007, India
b Bio-Organic Laboratory, Division of Organic Chemistry-III, Indian Institute of Chemical
Technology, Hyderabad, 500 007, India
Published online: 16 Aug 2006.
To cite this article: Parimi V.S.N. Vani , Asiya Seema Chida , Rajagopal Srinivasan , Malapaka Chandrasekharam &
Ashok Kumar Singh (2001): SYNTHESIS OF β-IONONE# , Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 31:2, 219-224
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SYNTHETIC COMMUNICATIONS, 31(2), 219–224 (2001)
SYNTHESIS OF β-IONONE#
Parimi V. S. N. Vani, Asiya Seema Chida, Rajagopal
Srinivasan, Malapaka Chandrasekharam,
and Ashok Kumar Singh∗
Bio-Organic Laboratory, Division of Organic Chemistry-III,
Indian Institute of Chemical Technology,
Hyderabad-500 007, India
ABSTRACT
Preparation of β-ionone by a reaction sequence starting from
acetone is described.
We were interested to find a convenient synthetic route to prepare β-ionone,
which is an important building block in our approach towards vitamin-A and (RS)-
abscisic acid syntheses. Many patented reports for the synthesis of β-ionone, along
with a few published reports regarding synthesis of β-ionone through ꢀ-ionone,
are available in the literature (1). β-Ionone has received considerable attention
because of its wide use in cosmetics (7), food flavoring (8), as a bactericide (9),
andanantagonist(10). Inthisreportwepresentaconvenientandpracticalsynthesis
of the title compound (Scheme 1).
Acetone is reacted with sodium acetylide at −50◦C to form the acetylenic
alcohol 1 in 87.9% yield. The resulting acetylenic alcohol underwent partial re-
duction using Lindlars catalyst at room temperature to afford the substituted allyl
alcohol 2. The allylic rearrangement of compound 2 is carried out using either HCl
# IICT communication number 4541.
∗ To whom correspondence should be addressed.
219
Copyright ꢀ 2001 by Marcel Dekker, Inc.
www.dekker.com
C

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VANI ET AL.
Reagents and conditions: (a) Acetylene, NH3, NaNH2 or Acetylene, Na, THF or Acetylene,
NaNH2, THF at −50◦C, 5 h; (b) H2/Lindlar, Hexane, rt, 10 h, atm. pressure; (c) 37% HCl,
0◦C, 1 h; (d) 48% HBr, 0◦C, 0.5 h; (e) CH3COONa, TEBA, 4.5 h; (f) 10% NaOH, reflux,
2.5 h; (g) MnO2, Petroleum ether, rt, 17 h; (h) 200◦C/40atm, 1.5 h or (i) LiCl, Toluene,
Hydroquinone, reflux, after work up (ii) 1,2-dichlorobenzene, LiCl, 135◦C; (i) Acetone,
NaOMe, −10–(−5)◦C, 1h; (j) H2SO4, Hexane-Acetone.
Scheme 1.
or HBr at 0◦C for 1 h to obtain 3a and 3b, respectively. The allyl chloride 3a under-
went nucleophilic substitution with sodium acetate in presence of TEBA as PTC
for 4.5 h to afford the acetate 4 in 96.4% yield. Our procedure for this conversion
is more efficient compared to the earlier reports. Hydrolysis of acetate 4 with 10%
sodium hydroxide solution under refluxing conditions for 2.5 h gave allyl alcohol
5 in 95% yield, which was subjected to allylic oxidation with MnO2 in petroleum
ether at RT for 17 h, resulting the α,β-unsaturated aldehyde 6.Allylic alcohol 5 and
the aldehyde 6 were reacted using LiCl catalyst to form citral 7 according to litera-
ture procedure, which involved Claisen followed by Cope rearrangements. Citral 7
underwent condensation reaction with acetone to form the alcohol 8. Finally, com-
pound 8 was subjected to smooth cyclization in H2SO4 to give β-ionone (9) in 75%
yield. Synthesis of β-ionone has been achieved from acetone in nine steps via citral.
EXPERIMENTAL
Preparation of 3-Methyl-1-butyn-3-ol (1)
In a 5-L, three-necked, round-bottom flask fitted with a cold finger, dropping
funnel, and a gas bubbler NaNH2 (273 g, 7 mol) and ammonia (3 L) is collected

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221
at −50◦C. Acetylene gas is passed for 30 min. To this mixture was added acetone
(530 mL) during 3 h at the same temperature. After completion of this addition,
the cooling bath was removed and the mixture kept at room temperature overnight.
Stirring of the mixture continued for 30 min at 25◦C, then it was quenched with
10% H2SO4 (500 mL), and 35% H2SO4 (1300 mL). The aqueous layer was ex-
tracted with CH2Cl2; the organic layer was concentrated under reduced pressure
and purified by distillation at 104–105◦C. Yield: 87.9% (516.9 g). IR (Neat, νmax
)
cm−1: 3302 1H NMR (400 MHz/CDCl3) ppm: δ 1.55 (s, 6H); 1.95 (brs, 1H); 2.40
(s, 1H). MS-EI (m/e): 84 (M+); 69 (M+-CH3); 67 (M+-OH).
Preparation of 3-Methyl-1-butene-3-ol (2)
Procedure I
Compound 1 (70 g, 0.833 mol), Lindlar catalyst (7 g), and hexane (210 mL)
are taken in a 1-L round-bottom flask and maintained at room temperature for 10 h
under H2 atmosphere. Filtered and purified by distillation over a column packed
with glass beads, pure fraction was collected at 97◦C. Yield: 91.1% (65.3 g). IR
1
(Neat, νmax) cm−1: 3540 H NMR (400 MHz/CDCl3) ppm: δ 1.30 (s, 3H); 1.50
(s, 3H); 2.50 (brs, 1H); 4.95 (d, J = 7.4 Hz, 1H); 5.15 (d, J = 14.8 Hz, 1H); 5.95
(dd, J = 14.8, 7.4 Hz, 1H). MS-EI (m/e): 86 (M+); 71 (M+-CH3); 69 (M+-OH).
Procedure II
The above procedure was followed using Compound 1 (52 g, 0.619 mol),
Lindlar catalyst (4.6 g), quinoline (2.6 g) and petroleum ether (75 mL) to afford
compound 2. Yield: 99% (53.46 g).
Preparation of 1-Chloro-3-methyl-2-butene (3a)
Compound 2 (13 g, 0.1511 mol) in a 100-mL round-bottom flask was mixed
with 37% aq. HCl (44.2 mL, 0.44 mol) at 0◦C and stirred at the same temperature
for 1 h. The organic layer was separated, washed with water (2 × 20 mL), dried over
anhy. Na2SO4 and distilled at 109◦C to obtain product 3a. Yield: 96.3% (15.2 g).
1H NMR (200 MHz/CDCl3) ppm: δ 1.75 (s, 3H); 1.80 (s, 3H); 4.05 (d, J = 7.78 Hz,
2H), 5.45 (t, J = 7.78 Hz, 1H). MS-EI (m/e): 104, 105 (M+).
Preparation of 1-Bromo-3-methyl-2-butene (3b)
Vinyl alcohol 2 (13.49 g, 0.1568 mol) was placed in a 250-mL round-bottom
flask and cooled to 0◦C. Then 48% aq. HBr (62.7 mL) was slowly introduced

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VANI ET AL.
into the reaction flask and the resulting mixture stirred for 30 min at the same
temperature. The organic layer was separated and the aqueous layer extracted with
CH2Cl2. The combined organic layer and extracts were dried over anhy. Na2SO4,
concentrated under reduced pressure, and distilled off at 59◦–60◦C. Yield: 90%
1
(21.03 g). Rf = 0.8 (Petroleum ether) H NMR (200 MHz/CDCl3) ppm: δ 1.70
(s, 3H); 1.75 (s, 3H); 3.95 (d, J = 6.74 Hz, 2H); 5.50 (t, J = 6.74 Hz, 1H). MS-EI
(m/e): 148, 150 (M+).
Preparation of 1-Acetoxy-3-methyl-2-butene (4)
Compound 3a (4.27 g, 0.0408 mol), NaOAc (3.868 g, 0.0471 mol), TEBA
(0.1044 g, 0.00045 mol) were heated in a 50-mL round-bottom flask for 4.5 h
at 95◦–105◦C, then extracted with DCM (3 × 10 mL) and concentrated under
vacuum. Yield: 96.4% (5.04 g) Rf = 0.75 (Ethyl acetate-Petroleum ether, 1:4)
b.p.: 160◦C/10 mm IR (Neat, νmax) cm−1: 3300, 1720. 1H NMR (200 MHz/CDCl3)
ppm: δ 1.75 (s, 3H); 1.80 (s, 3H); 2.05 (s, 3H); 4.55 (d, J = 6.9 Hz, 2H); 5.35 (t,
J = 6.9 Hz, 1H). MS-EI (m/e): 128 (M+); 113 (M+-CH3).
Preparation of Allyl Alcohol 5
Compound 4 (13.4 g, 0.1046 mol) and 10% NaOH solution (4.4 mL) were
heated at 100◦C for 2.5 h. The organic layer was separated and the aqueous
layer extracted with DCM (2 × 250 mL). The extracts were combined with the
organic layer, dried (Na2SO4), and concentrated under reduced pressure. Dis-
tillation at 137◦C gave pure compound 5. Yield: 95% (8.6 g). IR (Neat, νmax
)
1
cm−1: 3332. H NMR (200 MHz/CDCl3) ppm: δ 1.65 (s, 3H); 1.72 (s, 3H);
1.95 (brs, 1H); 4.05 (d, J = 8 Hz, 2H); 5.35 (t, J = 8 Hz, 1H). MS-EI (m/e): 86 (M+);
71 (M+-CH3).
Preparation of 3-Methyl-2-butenal (6)
Compound 5 (28.2 g, 0.327 mol) and MnO2 (71.2 g, 0.819 mol) were taken
in petroleum ether (300 mL) and stirred at room temperature for 7 h, filtered, and
the filtrate concentrated to give crude product compound 6, which was distilled
1
off at 132◦–133◦C. Yield: 95% (26.12 g) IR (Neat, νmax) cm−1: 1682. H NMR
(200 MHz/CDCl3) ppm: δ 1.70 (s, 3H); 1.75 (s, 3H); 5.90 (d, J = 9.37 Hz, 1H);
9.95 (d, J = 9.37 Hz, 1H). MS-EI (m/e): 84 (M+), 69 (M+-CH3).
Preparation of Compound 8
Compound 7 (7.49 g, 0.0493 mol) and acetone (13 mL, 0.1778 mol) were
taken in a round-bottom flask and cooled to −10◦C. To this was added NaOMe

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223
(0.8862 g, 0.0164 mol), slowly maintaining the temperature below −5◦C over
a period of 30 min, and stirring continued for 30 min at the same temperature.
The reaction was quenched with aq. tartaric acid solution (1.107 g of tartaric
acid dissolved in 7.38 mL of water), extracted with ethyl acetate (3 × 30 mL),
and concentrated to give alcohol 8 Yield: 92% (9.538 g) Rf = 0.47 (Ethyl acetate-
Petroleum ether, 1:4) 1H NMR (200 MHz/CDCl3) ppm: δ 1.60 (s, 3H); 1.65 (s, 3H);
1.70 (m, 2H); 1.90, 1.95 (s, 3H, two sets); 2.20 (m, 4H); 2.25, 2.30 (s, 3H, two
sets); 2.60 (br s, 1H); 5.05 (br s, 1H); 6.05 (m, 2H). MS-EI (m/e): 210 (M+); 193
(M+-OH).
Preparation of β-Ionone 9
Hexane (3.6 mL) and H2SO4 (5.16 mL) were taken in a round-bottom flask
and the contents were cooled to −10◦C and stirred for 10 min. Then compound
8 (3.1 g, 0.0162 mol) in hexane (4 mL) was added within 15 min and stirring
continued for 30 min. The reaction mixture was neutralized with 18% NaOH
solution until the pH = 7 at −10◦C. The reaction mixture was extracted with DCM
(2 × 25 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure.
Yield: 75% (2.325 g) Rf = 0.53 (Ethyl acetate-Petroleum ether, 1:9) b.p.: 138◦–
1
140◦C/10 mm IR (Neat, νmax) cm−1: 1693, 1673. H NMR (200 MHz/CDCl3)
ppm: δ 1.05 (s, 6H); 1.46 (m, 2H); 1.60 (m, 2H); 1.73 (s, 3H); 2.05 (m, 2H);
2.25 (s, 3H); 6.07 (d, J = 16.8 Hz, 1H); 7.20 (d, J = 16.8 Hz, 1H). MS-EI (m/e):
192 (M+); 177 (M+-CH3); 123 (M+-C4H5O).
ACKNOWLEDGMENTS
PVSNV and ASC thank Dr. K. V. Raghavan, Director, IICT, Hyderabad
for allowing them to work on this project and for financial support.
REFERENCES
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3. Szmidt, B.; Beldowicz, M.; Wisniewski, G.; Gora, J.; Antczak, U.; Kalemba,
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7. Kobayashi, T.; Ueno, I.; Kobayashi, T. Jpn. Kokai Tokkyo Koho JP 04,
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Accepted April 11, 2000

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