Trimethylsilyl cyanide addition to carbonyl compounds under neutral condition catalyzed by iodine

Article abstract of DOI:10.1080/713744569

Reaction of trimethylsilyl cyanide with aliphatic or aromatic aldehydes and ketones in the presence of a catalytic amount of elemental iodine produced the corresponding cyanohydrin trimethylsilyl ethers in very short time and high yields.

Full text of DOI:10.1080/713744569

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Phosphorus, Sulfur, and Silicon and the Related
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Trimethylsilyl Cyanide Addition to Carbonyl Compounds
Under Neutral Condition Catalyzed by Iodine
Najmedin Azizi a & Mohammad R. Saidi a
a Sharif University of Technology , Tehran, Iran
Published online: 27 Oct 2010.
To cite this article: Najmedin Azizi & Mohammad R. Saidi (2003) Trimethylsilyl Cyanide Addition to Carbonyl Compounds
Under Neutral Condition Catalyzed by Iodine, Phosphorus, Sulfur, and Silicon and the Related Elements, 178:10, 2111-2115,
DOI: 10.1080/713744569
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Phosphorus, Sulfur, and Silicon, 178:2111–2115, 2003
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Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500390221564
TRIMETHYLSILYL CYANIDE ADDITION TO
CARBONYL COMPOUNDS UNDER NEUTRAL
CONDITION CATALYZED BY IODINE
Najmedin Azizi and Mohammad R. Saidi
Sharif University of Technology, Tehran, Iran
(Received February 18, 2003; accepted March 25, 2003)
Reaction of trimethylsilyl cyanide with aliphatic or aromatic aldehydes
and ketones in the presence of a catalytic amount of elemental iodine
produced the corresponding cyanohydrin trimethylsilyl ethers in very
short time and high yields.
Keywords: Carbonyl compound; cyanohydrin trimethylsilyl ether;
iodine; trimethylsilyl cyanide
Cyanohydrins are valuable intermediates for the synthesis of vari-
ous chiral compounds such as α-hydroxycarbonyl derivatives and β-
aminoalcohols.1 Although the addition of cyanide to carbonyl com-
pounds is a known reaction, it has been the subject of renewed interest
due to the role of cyanohydrin as a versatile intermediate in organic
synthesis.
A variety of catalysts has been reported for trimethylsilyl cyanide
addition to carbonyl compounds,2 including different Lewis acids,3 ti-
tanium and ruthenium Schiff base complexes,4 Cu(OTf)2,5 18-crown-6
complexes of potassium and cesium,6 tetracyano-ethylene,7 solid acidic
montmorillonite, and solid bases such as CaO and MgO.8 Several opti-
cally active catalysts for asymmetric cyanohydrin formation also were
used.9 Although these procedures improved the addition process, in
most cases reaction with ketone did not take place or required forceful
conditions and prolonged reaction time.
We are grateful to the Research Council of Sharif University of Technology for fi-
nancial support. We also thank Volkswagen-Stiftung, Federal Republic of Germany for
financial support towards the purchase of chemicals.
Address correspondence to Mohammad R. Saidi, Department of Chemistry, Sharif
University of Technology, PO Box 11365-9516, Tehran, Iran. E-mail: saidi@sharif.edu
2111

2112
N. Azizi and M. R. Saidi
RESULTS AND DISCUSSION
In connection with our interest for trimethylsilyl cyanide addition to
the iminium salts,10 we now report a new, rapid, convenient, and mild
method using iodine as an efficient catalyst for addition of trimethylsi-
lyl cyanide (TMSCN) to the carbonyl functional group. Thus treatment
of aldehydes and ketones with TMSCN in the presence of 0.2 equiva-
lents of elemental iodine in dichloromethane afforded the corresponding
cyanohydrins in 86–97% yields under neutral and mild condition in a
very short time. A wide variety of aldehydes and ketones were caused
to react with TMSCN in the presence of a catalytic amount of iodine
to produce the corresponding cyanohydrins (Scheme 1). The results are
shown in Table I.
SCHEME 1
The data in Table I clearly show that cyclohexanone and differ-
ent type of aldehydes were converted successfully to the correspond-
ing cyanohydrin trimethylsilyl ethers almost instantly with high to
nearly quantitative yields at room temperature. Due to the neutral
and exceptionally mild reaction condition, no by-product was observed.
Dichloromethane was the best solvent for this reaction. The yields of
the cyanohydrin trimethylsilyl ethers in other solvent such as ace-
tonitrile are lower. Both aromatic and aliphatic aldehyds reacted with
TMSCN under these conditions to give the corresponding cyanohydrin
trimethylsilyl ethers (Table I). The reaction proceeded smoothly at am-
bient temperature and has the advantages of operational simplicity,
improved yields, enhanced rates and simple experimental work up
SCHEME 2

Trimethylsilyl Cyanide Addition to Carbonyl Compounds
2113
procedures. The generality of this reaction is evident from the results
summarized in Table I.
The role of iodine could be the formation of trimethylsilyl iodide11
or [ArCH OSiMe3]+ in the initial step and subsequently producing
a weakly solvated anion, which displays high reactivity toward the
carbonyl group in aldehyde or ketone. A plausible mechanism for this
transformation is shown in Scheme 2.
TABLE I Cyanosilylation of Aldehydes
and Ketons in the Presence of Element
Iodine
Entry
Substrate
Product
Yield (%)a
aisolated yields.

2114
N. Azizi and M. R. Saidi
CONCLUSION
In conclusion, the iodine as catalyst is an efficient, mild, readily avail-
able, and cheap reagent for TMSCN addition to aliphatic or aromatic
aldehydes and ketones. The reaction condition is neutral and exception-
ally mild with no by-product and with high yields of the cyanohydrin
trimethylsilyl ethers. Both aromatic and aliphatic aldehydes reacted
with TMSCN under these conditions and at ambient temperature.
EXPERIMENTAL
General
All the yields refer to isolated products. All compounds were character-
ized on the basis of their spectroscopic data (IR, NMR) and by compari-
son with those reported in the literature.2a,8b IR spectra were taken on
a Matt Son 1000 Unicam FTIR, 1H and 13C NMR spectra were recorded
on a Bruker AC 80 or Bruker 500 MHz Ultra Shield. Mass spectra were
obtained on Fisson 800 Trio, and GC-Mass HP 5973 MSD. All reactions
were performed under argon. Most aldehydes were distilled before use.
Chemicals were purchased from Fluka or Merck.
General Procedure for Trimethylsilyl Cyanide Addition
to Carbonyl Compounds
Iodine (0.2 mmol) was added to the mixture of aldehyde (1 mmol)
and TMSCN (1.3 mmol) in dry CH2Cl2 and the mixture was stirred at
room temperature for 3 min. Then the resulting mixture was quenched
quickly with aqueous sodium thiosulphate and extracted with ethyl ac-
etate (2 × 15 ml), the combined organic layers washed quickly with a
5% solution of NaHCO3 and dried over anhydrous sodium sulphate.
Solvent was evaporated under reduced pressure and the crude mate-
rial was purified by chromatography on silica gel eluting with petroleum
ether/ethyl acetate, or washing with petroleum ether if needed. All com-
pounds were characterized on the basis of their spectroscopic data (IR,
NMR) and by comparison with those reported in the literature.2a,8b
The prolonged washing with 5% solution of NaHCO3 produced the cor-
responding cyanohydrins.
Selected spectroscopic data: Cyanohydrin trimethylsilyl ether 3a, 1H
NMR (500 MHz, CDCl3), δ, 0.23 (s, 9H), 5.54 (s, 1H), 7.28–7.92 (m,
5H); 13C NMR (125 MHz, CDCl3), δ, 0.1 (CH3), 64.1 (CH), 119.4 (CN),
126.8 (CH), 127.12 (CH), 129.4 (CH), 136.7 (C); IR, (CH2Cl2), ν, 2248
(CN), 1072 (C O) cm−1. Cyanohydrin trimethylsilyl ether 3d, 1H NMR

Trimethylsilyl Cyanide Addition to Carbonyl Compounds
2115
(500 MHz, CDCl3) δ, 0.22 (s, 9H), 3.82 (s, 3H), 5.46 (s, 1H), 6.90 (m, 2H)
7.40 (m, 2H); 13C NMR (125 MHz, CDCl3), δ, 0.1 (CH3), 55.6 (CH3), 63.2
(CH), 114.7 (C), 119.9 (CN), 128.3 (CH), 128.8 (CH), 132.1 (CH), 160.2
(C); IR, (CH2Cl2), ν: 2232 (CN), 1160 (C O) cm−1
.
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