A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1974, 54, 68
DOI: 10.15227/orgsyn.054.0068
[2,6-Octadiene, 1-chloro-3,7-dimethyl-, (E)-]
Submitted by Gilbert Stork1, Paul A. Grieco2, and Michael Gregson.
Checked by P. A. Aristoff and R. E. Ireland.
1. Procedure
Caution! Hexamethylphosphoric triamide (HMPA) vapors have been reported to cause cancer in rats.3 All operations with hexamethylphosphoric triamide should be performed in a good hood, and care should be taken to keep the liquid off the skin.
A dry, 1-l., three-necked, round-bottomed flask is equipped with an overhead mechanical stirrer, a 125-ml. pressure equalizing dropping funnel fitted with a rubber septum, and a nitrogen inlet tube. The system is flushed with nitrogen, and 15.4 g. (0.100 mole) of geraniol (Note 1), 35 ml. of dry hexamethylphosphoric triamide (Note 2), 100 ml. of anhydrous diethyl ether (Note 3), and 50 mg. of triphenylmethane (Note 4) are placed in the flask. The stirred solution is cooled to 0° with an ice bath, and 63 ml. (0.1 mole) of 1.6 M methyllithium in ether (Note 5) is injected into the addition funnel. The methyllithium solution is added dropwise over a period of 30 minutes. After the addition is complete, the funnel is rinsed by injecting 5 ml. of dry ether.
A solution of 20.0 g. (0.105 mole) (Note 6) of p-toluenesulfonyl chloride in 100 ml. of anhydrous ether is injected into the addition funnel and added over a period of 30 minutes to the stirred, red, 0° reaction mixture. The red color immediately disappears upon addition. After addition is complete, 4.2 g. (0.0990 mole) of anhydrous lithium chloride (Note 7) is added. The reaction mixture is warmed to room temperature and stirred overnight (18–20 hours), during which time lithium p-toluenesulfonate precipitates.
After a total of 20–22 hours, 100 ml. of ether is added, followed by 100 ml. of water. The layers are separated, and the organic phase is washed four times with 100-ml. portions of water, and finally with 100 ml. of saturated sodium chloride. After drying the organic phase over anhydrous magnesium sulfate, the solvent is removed on a rotary evaporator. The crude product is transferred to a 50-ml. flask and distilled through a 20-cm. Vigreux column, yielding 14.1–14.6 g. (82–85%) of geranyl chloride as a colorless liquid, b.p. 78–79° (3.0 mm.) (Note 8) and (Note 9).
2. Notes
1. Geraniol (+99%) can be purchased from the Aldrich Chemical Company, Inc.
2. Hexamethylphosphoric triamide was purchased from the Fisher Scientific Company and the Aldrich Chemical Company, Inc., and distilled from calcium hydride prior to use.
3. Anhydrous ether, available from J. T. Baker Chemical Company, can be used without further drying.
4. Triphenylmethane is available from Eastman Organic Chemicals. Although not necessary, it was used as an indicator to check the molarity of the methyllithium used.
5. Methyllithium (prepared from methyl chloride), available from Foote Mineral Company, can be used without further purification. Attention should be drawn to the following: methyllithium purchased from Alfa Inorganics is prepared from methyl bromide and, thus, produces a mixture of geranyl bromide and chloride.
6. p-Toluenesulfonyl chloride available from either the Aldrich Chemical Company, Inc., or Matheson, Coleman and Bell, Inc., was used without further purification.
7. Available from Alfa Inorganics. If necessary, finely powdered lithium chloride can be dried by heating under vacuum (0.1 mm.) at 100° for several hours.
8. Our sample of geranyl chloride was identical (IR, 1H NMR, and mass spectrum) to a sample prepared by an alternate route (Professor John Hooz, Department of Chemistry, University of Alberta).
9. The IR spectrum (neat) shows major absorptions at 2970, 2920, 2855, 1660, 1450, 1375, 1380, 1255, 835, and 660 cm.−1 The 1H NMR spectrum (CCl4) has a four-line multiplet at δ 1.55–1.85, characteristic of the olefinic methyl protons, two peaks at δ 2.0–2.2, due to the four allylic methylene protons, a d at δ 4.02 (J = 7.0 Hz.), due to the allylic methylene protons adjacent to the chlorine, a very broad t at δ 5.09, and a broad t at δ 5.45. (J = 7.0 Hz.), both due to the vinyl protons.
3. Discussion
The reaction described here illustrates a general procedure for the preparation of allylic chlorides from allylic alcohols without rearrangement and under conditions allowing the retention of sensitive groups.4 For example, the sensitive acetal alcohol I with geraniol geometry was similarly treated with ether-hexamethylphosphoric triamide, with methyllithium in ether, and then with p-toluenesulfonyl chloride and lithium chloride. Workup afforded the corresponding chloride II in 80% yield with no detectable rearrangement. The method was equally successful with the cis-isomer of I.
In addition, 85–90% yields of neryl chloride can be obtained from nerol, the geometrical isomer of geraniol. A modification5 of the above method has appeared which employs methanesulfonyl chloride and a mixture of lithium chloride, N,N-dimethylformamide, and 2,4,6-collidine at 0°; however, its applicability to compounds possessing sensitive groups was not demonstrated.
Initial attempts at preparing γ,γ-disubstituted allyl chlorides employing thionyl chloride in the presence of tri-n-butylamine6 led to appreciable amounts of rearranged (tertiary) halides.
This preparation is referenced from:

References and Notes
  1. Department of Chemistry, Columbia University, New York, New York 10027.
  2. Present address: Department of Chemistry, Indiana University, Bloomington, Indiana 47405.
  3. J. A. Zapp, Jr., Science, 190, 422 (1975).
  4. G. Stork, P. A. Grieco, and M. Gregson, Tetrahedron Lett., 1393 (1969).
  5. E. W. Collington, and A. I. Meyers, J. Org. Chem., 36, 3044 (1971).
  6. See W. G. Young, F. F. Caserio, Jr., and D. D. Brandon, Jr., J. Am. Chem. Soc., 82, 6163 (1960).

Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

geranyl bromide and chloride

diethyl ether (60-29-7)

thionyl chloride (7719-09-7)

sodium chloride (7647-14-5)

nitrogen (7727-37-9)

methyl chloride (74-87-3)

methyl bromide (74-83-9)

Triphenylmethane (519-73-3)

magnesium sulfate (7487-88-9)

N,N-dimethylformamide (68-12-2)

2,4,6-collidine (108-75-8)

geraniol (106-24-1)

Methyllithium (917-54-4)

Lithium chloride (7447-41-8)

calcium hydride (7789-78-8)

Methanesulfonyl chloride (124-63-0)

tri-n-butylamine (102-82-9)

hexamethylphosphoric triamide (680-31-9)

p-Toluenesulfonyl chloride (98-59-9)

Geranyl chloride,
2,6-Octadiene, 1-chloro-3,7-dimethyl-, (E)- (5389-87-7)

acetal alcohol

neryl chloride

nerol (106-25-2)

lithium p-toluenesulfonate