Improved synthesis of 2-(4-propylphenyl)ethanol

Article abstract of DOI:10.1515/znb-2006-0210

A new procedure for the synthesis of 2-(4-propylphenyl)ethanol is provided. This new procedure significantly reduces side-products as 1-(4-propylphenyl) ethanol and 2-bromoethanol, which are obtained when using the previously known procedure. Only with the new procedure an efficient purification on the large scale needed for avoided-level-crossing muon-spin resonance experiments was possible. Structural details of the title compound could be derived from an X-ray structure analysis of a crystalline derivative, the nitrobenzoyl ester.

Full text of DOI:10.1515/znb-2006-0210

Improved Synthesis of 2-(4-Propylphenyl)ethanol
A. Stephen K. Hashmia, Tobias Burkerta, Jan W. Batsb, and Aleksandra Martyniakc
a Institut fu¨r Organische Chemie, Universita¨t Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart,
Germany
b Institut fu¨r Organische Chemie und Chemische Biologie, Universita¨t Frankfurt,
Marie-Curie-Str. 11, D-60439 Frankfurt, Germany
c Institut fu¨r Physikalische Chemie, Universita¨t Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart,
Germany
Reprint requests to Dr. A. S. K. Hashmi. E-mail: hashmi@hashmi.de
Z. Naturforsch. 61b, 179 – 181 (2006); received November 8, 2005
A new procedure for the synthesis of 2-(4-propylphenyl)ethanol is provided. This new procedure
significantly reduces side-products as 1-(4-propylphenyl)ethanol and 2-bromoethanol, which are ob-
tained when using the previously known procedure. Only with the new procedure an efficient purifi-
cation on the large scale needed for avoided-level-crossing muon-spin resonance experiments was
possible.
Structural details of the title compound could be derived from an X-ray structure analysis of a
crystalline derivative, the nitrobenzoyl ester.
Key words: Alcohols, Epoxides, Esters, Grignard Reagents, Nitro Compounds
◦
Introduction
magnesium salt of 4 upon heating to 95 C or during
the acidic work-up (pouring the hot reaction mixture
directly into the saturated ammonium chloride solu-
tion) by ionization and rearrangement to the more sta-
ble benzylic cation. In order to avoid this, the reac-
tion and the work-up was conducted at room tempera-
ture. Only then the small amounts of impurities formed
could conveniently be removed by column chromatog-
raphy after removal of 6 in high vacuum.
The title compound 4 is a known compound [1]. In
the context of a project investigating the solvation ther-
modynamics of phenyl-substituted alcohols in lamellar
phase surfactant dispersions by avoided-level-crossing
muon-spin resonance [2], we needed to prepare a pure
sample of 1 on an multigram scale and in addition
to obtain detailed spectroscopic characterization and
structural information.
Results and Discussion
Using the original procedure of McKusick [1], the
in situ generation of the Grignard compound 2 from
commercially available 1-bromo-4-propylbenzene (1)
and its reaction with oxirane 3, only material with
significant amounts of side-products as impurities
was obtained. On a multigram scale it was impos-
sible to separate these impurities from the product,
even by column chromatography. As the major side-
products we could identify the known compounds 1-
(4-propylphenyl)ethanol (5) [3] and 2-bromoethanol
(6) [4]. The formation of 6 consumes oxirane at the ex-
pense of the yield of the desired product 4, but the for-
mation of magnesium bromide could not be avoided.
Thus a higher excess of 3 than in the original proce-
A crystal structure analysis would have provided de-
dure was used. Alcohol 5 is probably formed from the tailed structural information, but 4 was a liquid. Thus
c
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180
A. St. K. Hashmi et al. · Improved Synthesis of 2-(4-Propylphenyl)ethanol
◦
˚
Table 1. Selected bond lengths (A) and bond angles ( ) of 8.
Table 2. Crystallographic data for 8.
O(3)-C(8)
C(8)-C(9)
1.4565(17)
1.513(2)
O(3)-C(8)-C(9)
111.93(12)
109.03(12)
118.70(14)
123.23(15)
121.33(12)
112.02(10)
112.97(11)
Empirical formula
Formula weight
Temperature [K]
Wavelength [A]
Crystal system, space group
Unit cell dimensions
C18H19NO4
313.34
156(2)
0.71073
C(8)-C(9)-C(10)
C(9)-C(10)-C(11)
C(15)-C(10)-C(9)
C(14)-C(13)-C(16)
C(13)-C(16)-C(17)
C(16)-C(17)-C(18)
C(9)-C(10)
C(13)-C(16)
C(16)-C(17)
C(17)-C(18)
C(7)-O(3)-C(8)
1.5169(19)
1.5144(16)
1.5203(19)
1.5154(17)
116.04(13)
˚
monoclinic, C2/c
◦
˚
˚
˚
a = 24.732(6) A, α = 90
◦
b = 6.9064(9) A, β = 93.818(12)
◦
c = 18.974(2) A, γ = 90
3
˚
Volume [A ]
3233.7(9)
Z, Calculated density [Mg/m3] 8, 1.287
Absorption coefficient [mm−1] 0.091
F(000)
1328
Crystal size [mm]
θ Range for data collection [ ] 1.65 to 30.96
Limiting indices
0.74×0.70×0.30
◦
−35 ≤ h ≤ 2,
−9 ≤ k ≤ 9,
−26 ≤ l ≤ 26
Fig. 1. Solid state structure of 8.
Reflections collected / unique 25573 / 4701
[R(int) = 0.0293]
91.7 %
Completeness to θ = 30.96
Absorption correction
Empirical, SADABS
(Sheldrick, 2000)
1.000 and 0.872
Full-matrix least-squares on F2
4701 / 0 / 241
Max. and min. transmission
Refinement method
Data / restraints / parameters
Goodness-of-fit on F2
Final R indices [I¿2σ(I)]
R Indices (all data)
1.552
R1 = 0.0576, wR2 = 0.1954
R1 = 0.0763, wR2 = 0.2112
0.593 and −0.323
Largest diff. pea−k3
Fig. 2. Unit cell of 8.
˚
and hole [e·A
]
we decided to prepare a crystalline derivative, which
would at least deliver that information for the 2-(4-
propylphenyl)ethoxy group. We chose an esterification
with 4-nitrobenzoyl chloride (7), which gave a 99%
yield of the desired ester 8 as a slightly yellow solid.
˚
˚
ular contacts are: H2...O1 2.42 A, H6...O2 2.44 A,
˚
˚
H3...O3 2.46 A, H5...O4 2.51 A and H8A...O4
2.43 A. The crystal packing shows three intermolecular
C-H...O contacts with H...O distances between 2.46
and 2.59 A, two intermolecular C-H...π(benzene) in-
teractions with H...Cg distances of 2.83 and 2.84 A
˚
˚
˚
(Cg is the centroid of a benzene ring) and a π ···π con-
˚
tact of 3.52 A between two parallel benzene rings. The
unit cell is shown in Fig. 2. Selected bond lengths and
bond angles of the 2-(4-propylphenyl)ethoxysubstruc-
ture are provided in Table 1.
Experimental Section
Synthesis of 4
From 46.3 g (232 mmol) of 1-bromo-4-propylbenzene (1)
and 5.65 g (232 mmol) of magnesium turnings in diethyl
ether (125 ml), Grignard compound 2 was formed. The re-
action started spontaneously at room temperature and pro-
ceeded under slight reflux. When the formation of 2 was
finished, diethyl ether was added to reach a total volume of
500 ml and an acetone/dry ice condenser was placed on the
flask. Then 12.0 g (272 mmol) of oxirane were added dur-
Single crystals of 8 could be grown from petrol
ether/dichloromethane. The solid state structure is de-
picted in Fig. 1 [5]. Both six-membered rings are pla-
nar, the mean deviations from the planes are 0.002
˚
and 0.001 A, respectively. The angle between the
planes C1/N/O1/O2 and C1/C2/C3/C4/C5/C6 is 8.7◦.
The angle between the planes C4/C7/O3/O4 and
C1/C2/C3/C4/C5/C6 is 0.3◦. The shortest intramolec- ing one hour while stirring. A colourless precipitate formed.
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A. St. K. Hashmi et al. · Improved Synthesis of 2-(4-Propylphenyl)ethanol
181
Stirring was continued overnight, then a hydrolysis with sat- dichloromethane (5 ml) was added within 10 min drop by
urated ammonium chloride solution at room temperature fol- drop. Stirring at 0 ◦C was continued for 15 min, then at
lowed. The aqueous phase was extracted with 3 × 50 ml of room temperature for 45 min. After hydrolysis, from the or-
diethyl ether, the combined organic layers were dried over ganic phase the solvent was removed under reduced pressure.
magnesium sulfate, and the solvent was removed under re- Column chromatography (silica gel, petrol ether/ethyl ac-
duced pressure. Most of 6 was then removed from the crude etate = 20:1) provided 437 mg (99%) of 8 as a slightly yellow
product by applying 0.01 mbar at 30 – 40 ◦C for 24 h. Col- solid. Single crystals for the structure analyis were obtained
umn chromatography of the crude product (silica gel, petrol by slow evaporation of a solution in petrol ether/dichloro-
ether/ethyl acetate = 15:1) delivered 21.1 g (55%) of pure 4 methane at room temperature. Details concerning the crystal
as a colourless liquid. – Rf (PE:EE, 3:1) = 0.23. – IR (film): structure analysis are provided in Table 2. – M. p. 49 ◦C. –
ν = 3306 (O-H), 2956, 2930 (=C-H), 2870 (-C-H), 1514, Rf (PE:EE, 3:1) = 0.42. – IR (film): ν = 1715 (C=O), 1524,
1116, 655 cm−1. – 1H NMR (300.13 MHz, CDCl3): δ =
0.93 (t, 3J = 7.3 Hz, 3 H, Me), 1.42 (bs, 1 H, OH), 1.63
(m, 2 H, CH2-CH2-Me), 2.57 (t, 3J = 7.6 Hz, 2 H, CH2-
CH2-Me), 2.84 (t, 3J = 6.5 Hz, 2 H, CH2-CH2-OH), 3.85 (t,
3J = 6.5 Hz, 2 H, CH2-CH2-OH), 7.14 (s, 4 H, aryl-H). –
13C NMR (62.90 MHz, CDCl3): δ = 14.0 (q, 1 C), 24.7 (t,
1 C), 37.8 (t, 1 C), 48.9 (t, 1 C), 63.9 (t, 1 C), 128.8 (d,
2 C), 129.0 (d, 2 C), 135.7 (s, 1 C), 141.0 (s, 1 C). – MS
(EI, 70 eV): m/z (%) = 164 (51) [M+], 133 (100), 105 (36),
91 (36). – C11H16O (164.2): calcd. C 80.44, H 9.82; found
C 79.91, H 9.88.
1269, 1098, 829, 714 cm−1. – 1H NMR (300.13 MHz,
CDCl3): δ = 0.94 (t, 3J = 7.4 Hz, 3 H, Me), 1.64 (m, 2 H,
CH2-CH2-Me), 2.57 (t, J = 7.6 Hz, 2 H, CH2-CH2-Me), 3.07
(t, 3J = 7.1 Hz, 2 H, CH2-CH2-O), 4.57 (t, 3J = 7.1 Hz,
2 H, CH2-CH2-O), 7.11 – 7.23 (m, 4 H, dialkylaryl-H), 8.13 –
8.32 (m, 4H, nitroaryl-H). – 13C NMR (62.90 MHz, CDCl3):
δ = 13.8 (q, 1 C), 24.51 (t, 1 C), 34.7 (t, 1 C), 37.6 (t, 1 C),
66.4 (t, 1 C), 123.5 (d, 2 C), 128.71 (d, 2 C), 128.73 (d,
2 C), 130.7 (d, 2 C), 134.5 (s, 1 C), 135.7 (s, 1 C), 141.2
(s, 1 C), 150.5 (s, 1 C), 164.6 (s, 1 C). – MS (EI, 70 eV):
m/z (%) = 313 (5) [M+], 150 (6), 146 (100), 117 (64). –
C18H19NO4 (313.3): calcd. C 68.99, H 6.11, N 4.46; found
C 68.93, H 6.11, N 4.46.
Synthesis of 2-(4-propylphenyl)ethyl 4-nitrobenzoate (8)
Acknowledgements
231 mg (1.41 mmol) of 4 were dissolved in dichloro-
This work was supported by the Deutsche Forschungsge-
meinschaft and the Fonds der Chemischen Industrie.
methane (5 ml) and 196 mg (2.47 mmol) of pyridine were
added. At 0 C a solution of 262 mg (1.41 mmol) of 7 in
◦
[4] S.-K. Kang, W.-S. Kim, B.-H. Moon, Synthesis 1161
(1985).
[1] B. C. McKusick, J. Am. Chem. Soc. 72, 1982 (1948).
[2] A. Martyniak, R. Scheuermann, H. Dilger, I. M. Tucker,
T. Burkert, A. S. K. Hashmi, D. Vujosˇevic, E. Roduner,
Physica B, in press (2005).
[3] O. Cervinka, A. Fabryova, I. Brozova, M. Holik,
Collect. Czech. Chem. Commun. 51, 684 (1986).
Y. Kobayashi, K. Kodama, K. Saigo, Org. Lett. 6, 2941
(2004).
[5] Crystallographic data for the structure have been de-
posited with the Cambridge Crystallographic Data
Centre, CCDC-288953. Copies of the data can be ob-
tained free of charge on application to The Director,
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
(Fax: int.code+(1223)336-033; e-mail for inquiry: file-
serv AT ccdc.cam.ac.uk).
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