Convenient synthesis of diarylpropargyl alcohols

Article abstract of DOI:10.1016/j.mencom.2011.11.016

Reaction between benzophenones and sodium acetylide in THF in the presence of 18-crown-6 gives the corresponding diarylpropargyl alcohols.

Full text of DOI:10.1016/j.mencom.2011.11.016

Mendeleev
Communications
Mendeleev Commun., 2011, 21, 339–340
Convenient synthesis of diarylpropargyl alcohols
Valerii Z. Shirinian,*a Aleksei A. Shimkin,a Artur K. Mailyan,b
Evgeniya S. Leonovab and Mikhail M. Krayushkina
a N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
Fax: +7 499 135 5328; e-mail: shir@ioc.ac.ru
b A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow,
Russian Federation
DOI: 10.1016/j.mencom.2011.11.016
Reaction between benzophenones and sodium acetylide in THF in the presence of 18-crown-6 gives the corresponding diarylpropargyl
alcohols.
The tertiary propargylic alcohols are widely used in the syn-
thesis of photochromic naphthopyrans1 and other heterocyclic
compounds.2 The Meyer–Schuster rearrangement of propargylic
alcohols provides an access to a,b-unsaturated carbonyl com-
pounds.3 Cycloisomerization of prop-2-yn-1-ols leads to furans
or pyrroles,4 benzofurans,5 indoles6 and cyclopentadienes.7 Prop-
argylic alcohols, especially steroid derivatives, often show high
biological activity.8
The usual synthetic strategy for the preparation of prop-2-yn-
1-ols includes interaction between ketone and metal acetylide.
The most frequently used reagents are lithium acetylide (as
ethylenediamine complex),9 sodium acetylide (suspension in
xylene),10 lithium or magnesium derivatives prepared in situ
from acetylene and n-butyllithium or Iotsich reagent.11 While the
application of commercially available acetylides is very attractive,
yields of propargylic alcohols are usually moderate, the large
excess (up to 10 equiv.10(a)) of metal acetylide or passing of
acetylene gas through reaction mixture10(b) being necessary.
Here we report an improved procedure for the synthesis of
diarylpropargyl alcohols using commercially available sodium
acetylide in the presence of 18-crown-6 (Scheme 1).
The reaction of benzophenone 1a with ethylenediamine com-
plex of lithium acetylide in anhydrous THF at room temperature
leads to propargylic alcohol 2a in only 43% yield. The reaction
time was extremely long, while the conversion of the starting
ketone on using of 4 equiv. of lithium acetylide over two weeks
was no more than 60%. Apparently, the complex of lithium
acetylide with ethylenediamine is very stable, in which the C–Li
bond is rather covalent, resulting in poor nucleophilicity of this
acetylene ‘anion’.
To strengthen the nucleophilic properties of acetylide, we
assumed that the more polar bond between metal and carbon atom
is needed. Testing of commercially available sodium acetylide
(as suspension in xylene) brought about much better results:
yield of propargylic alcohol 2a was 75%. We have tested various
reaction conditions (without solvent, in benzene, dioxane, DMSO,
O
HO
NaC CH
Ar1
1a–j
Ar2
Ar1
2a–j
Ar2
18-crown-6, THF
HO
HO
HO
HO
F
OMe
OMe
MeO
OMe
2a, 99%
F
MeO
OMe
MeO
OMe
MeO
OMe
N
OMe
O
2b, 96%
2c, 88%
2d, 96%
HO
HO
HO
OH
N
N
MeO
OMe
N
MeO
OMe
2f, 91%
N
OMe
MeO
2e, 90%
2g, 87%
MeO
OMe
HO
HO
HO
S
N
N
N
F
2h, 92%
2i, 85%
2j, 90%
Scheme 1
© 2011 Mendeleev Communications. All rights reserved.
– 339 –

Mendeleev Commun., 2011, 21, 339–340
References
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In conclusion, we have developed a simple and efficient pro-
cedure for the synthesis of diarylpropargyl alcohols by the reaction
of diarylketones with sodium acetylide in the presence of catalytic
amount of 18-crown-6.
Online Supplementary Materials
Supplementary data associated with this article can be found
in the online version at doi:10.1016/j.mencom.2011.11.016.
†
General procedure for the synthesis of diarylpropargyl alcohols 2a–j.
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Benzophenone 1 (15 mmol or 7.5 mmol for 1g) and 18-crown-6 (0.27 g,
1 mmol) were added to a stirred mixture of sodium acetylide (18% suspen-
sion in xylene, 8 g, 30 mmol) in anhydrous THF (50 ml). The flask was
closed with a stopper; the reaction mixture was stirred for 7 days at room
temperature, and then poured into crushed ice (200 g). The precipitate
was filtered off, washed with water (3×50 ml), and dried in air. If oil
instead of precipitate emerged, the mixture was extracted with ethyl acetate
(3×50 ml). The combined extracts were washed with water (3×50 ml)
and evaporated in vacuo. The crude product was purified by flash chrom-
atography. For the characteristics of all the prepared compounds, see
Online Supplementary Materials.
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Received: 23rd June 2011; Com. 11/3749
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