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An Efficient and Quick Laboratory Scale Method forthe Ethynylation of Some Aliphatic and CycloaliphaticCarbonyl CompoundsHermann D. Verkruijsse a , Wim de Graaf a & Lambert Brandsma aa Department of Metal-mediated Synthesis, State University, Padualaan 8, 3584, CH Utrecht,The NetherlandsPublished online: 19 Dec 2006.

To cite this article: Hermann D. Verkruijsse , Wim de Graaf & Lambert Brandsma (1988): An Efficient and Quick LaboratoryScale Method for the Ethynylation of Some Aliphatic and Cycloaliphatic Carbonyl Compounds, Synthetic Communications: AnInternational Journal for Rapid Communication of Synthetic Organic Chemistry, 18:2, 131-134

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SYNTHETIC COMMUNICATIONS, 1 8 ( 2 ) , 131-134 (1988)

AN EFFICIENT AND QUICK LABORATORY SCALE METHOD

FOR THE ETHYNYLATION OF SOME ALIPHATIC AND CYCLOALIPHATIC CARBONYL COMPOUNDS.

Hermann D. Verkruijsse, Wim de Graaf and Lambert Brandsma*,

Department of Metal-mediated Synthesis, State University, Padualaan 8, 3584 CH Utrecht, The Netherlands.

Summary

A number of aliphatic and cycloaliphatic carbonyl compounds have been

ethynylated in tetrahydrofuran at atmospheric pressure using uncomplexed

potassium tert-butoxide as a catalyst.

Ethynylation of carbonyl compounds can be effected by a number of

well-established complementary methods such as the reaction with an alkali

acetylide in liquid ammonia or with the Grignard compound HCrCMgBr in

tetrahydrofuran. In addition industrial methods are available in which the carbonyl

compound is coupled with acetylene in the presence of alkali hydroxide or copper

salts (see the reviews 192).

* To whom correspondence should be adressed.

131

Copyright @ 1988 by Marcel Dekker, Inc.

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132 VERKRUIJSSE, DE GRAAF AND BRANDSMA

Steroid ketones have been ethynylated in THF in the presence of mixtures of

tertiary alkoxides and the corresponding alcohols 3. We obtained poor results in

attempts to mono-ethynylate higher aliphatic and cycloaliphatic ketones under the

influence of this basic system (mixtures of unconverted ketones, aldol-condensation

products, etc.). However, when a solution of the commercially available

uncomplexed t-BuOK in THF was saturated at -2o'C with acetylene and a higher

aliphatic ketone or cycloaliphatic ketone with a medium ring size was gradually

added while continuing the introduction of acetylene, the ethynyl carbinols were

obtained in excellent yields. Even the aldehyde (CH3)3CCH=O,which gave

unsatisfactory results in the reaction with HCKMgBr in THF, gave a reasonable

yield of the corresponding alcohol. With benzaldehyde an intractable brown reaction

mixture was formed. Although somewhat less than stochiometrical amounts of

t-BuOK gave also good results in most cases, the highest yields were obtained

when using 1: 1 molar ratios of the base and the carbonyl Compound.

t-BuOK HCECH + R ~ R ~ C = O ------+ HCK-C(R~)(R~)OH

THF. 0- 15°C

This procedure is particularly suitable for the preparation of a number of ethynyl

carbinols on a laboratory scale (up to 1 molar or, if desired, more) and is much

quicker than the Grignard method (laborious preparation of HCgMgBr 4, and the

liquid ammonia method (time consuming distiilative separation of the carbinol and

the C=O compound reformed from the enolate in the hydrolysing procedure). The

ethynylation of cyclododecanone, dl-camphor, p-ionone and acetophenone

appeared to be very incomplete, possibly due to extensive formation of the enolates.

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ALIPHATIC AND CYCLOALIPHATIC CARBONYL COMPOUNDS 133

Procedure

In a 1 liter four-necked round-bottomed flask, equipped with a dropping funnel,

a gas inlet tube, an efficient mechanical stirrer and a thermometer-gas outlet

combination, was placed a solution of 0.30 mol of t-BuOK in 250 ml of THF.

Acetylene (from a cylinder; freed from acetone by passing it through two traps

cooled at -78°C) was introduced for - 10 min at a rate of 1 l/min (flow meter) with

vigorous stining and cooling in a bath at 0°C. Subsequently the carbonyl compound

(0.30 mol) was added dropwise over 15 min while continuing the intrcduction of

acetylene at a rate of -400 ml/min. The gelatinous suspension gradually cleared and

a colorless or light-brown solution was formed. During the addition the temperature

of the mixture was gradually lowered to between 10 and 15°C or, in the case of

(CH3)3CCH=O, to 5'C. After completion of the addition the introduction of

acetylene was continued for an additional 5 min, then the solution was poured into

300 ml of an aqueous solution of 40 g of NH4Cl. After swirling (some dissolved

acetylene may escape) and successively shaking, the layers were separated and the

aqueous phase was extracted three times with ether. The combined (unwashed)

organic solutions were dried well over MgS04, after which the greater part of the

solvents was distilled off at atmospheric pressure through a 40-cm Vigreux column.

The remaining liquid was carefully distilled in a vacuum. The following carbinols

(all pure according to GLC and lH NMR, IR (no C=O at -1700 crn-l) were

obtained in -90% yields, (the volatile compound R1 = H, R2 = r-Bu was isolated in

-70% yield). Their physical properties (b.p., nD) correspond with those reported in

the literature295.

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134 VERKRUIJSSE. DE GRAAF AND BRANDSMA

I Compound boiling point

"C/ mm Hg

52/40

45/15

60/15

75/15

92/15

55/15

901 15

---

1.4441

1.4748

m.p. -30°C

1.4897

1.4355

1.4426

1.

2.

3.

4.

5 .

References

a. Ziegenbein, W., "Einfuhrung der Athinyl- und Alkinyl-Gruppe in organische

Verbindungen", Verlag-Chemie, Weinheim, (1963); b. Ziegenbein, W. in

Viehe, H.G. (ed), "Chemistry of Acetylenes", Marcel Dekker, New York,

(1969).

Brandsma, L., "Preparative Acetylenic Chemistry", Elsevier, Amsterdam,

(1971); revised edition to appear in 1988.

Burtner, R.R. and Gentry, R.E., J. Org. Chem., (1960), E, 582; for a

procedure see ref [ 1 a], p. 1 12.

Skattebd, L.; Jones, E.R.H.; Whiting, M.C., Org. Synth. Coll. Vol. IV,

(1963), 792.

Johnson, A.W., "Acetylenic Compounds", Vol. I, Edward Arnold Co.,

London, ( 1946).

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