Org. Synth. 1972, 52, 19
DOI: 10.15227/orgsyn.052.0019
3-BUTYL-2-METHYLHEPT-1-EN-3-OL
[5-Nonanol, 5-(2-propenyl)-]
Submitted by P. J. Pearce
1, D. H. Richards, and N. F. Scilly.
Checked by N. Cohen, R. Lopresti, and A. Brossi.
1. Procedure
A 2-l., four-necked flask equipped with a sealed, Teflon-paddle stirrer, a mercury thermometer, a gas-inlet tube, and a dropping funnel is charged with 1.2 l. of anhydrous tetrahydrofuran (Note 1) and 50 g. (7.1 g.-atoms) of lithium pieces (Note 2) under an atmosphere of prepurified nitrogen. The stirred mixture is cooled to −20° with an acetone dry-ice bath and a mixture of 100 g. (1.00 mole) of methyl methacrylate (Note 3), and 411 g. (3.00 moles) of n-butyl bromide (Note 4) is added dropwise over a period of 3–4 hours. During this addition, an exothermic reaction ensues and is controlled at −20° (Note 5), and on completion of the addition, the vessel is maintained at this temperature, with stirring, for an additional 30 minutes. The contents of the flask are filtered with suction through a 70-mm.-diameter, slit-sieve Buchner funnel, without filter paper, to remove the excess lithium metal. The filtrate is concentrated on a rotary evaporator at aspirator pressure. The residual lithium alcoholate is hydrolyzed by the addition of 1 l. of 10% hydrochloric acid, with ice bath cooling. The liberated alcohol is extracted with two 400-ml. portions of diethyl ether, and the combined ether extracts are washed with two 400-ml. portions of water and dried over 100 g. of anhydrous magnesium sulfate. After suction filtration and removal of the ether on a rotary evaporator at aspirator pressure, the crude alcohol is distilled under reduced pressure through a 40-cm. Vigreux column, yielding 147–158 g. (80–86%) of 3-butyl-2-methyl-1-hepten-3-ol, b.p. 80° (1mm.). The purity of the product, determined by GC analysis, is greater than 99%.
2. Notes
1.
Reagent grade (stabilized) tetrahydrofuran was allowed to stand over molecular sieves for 24 hours, refluxed for 2 hours with
sodium wire, and finally distilled and used within 48 hours. The checkers found that it was convenient simply to percolate the
tetrahydrofuran, after preliminary drying over molecular sieves, through a column of grade I, neutral
aluminum oxide, under
nitrogen, directly into the reaction flask, until the required volume of solvent was collected.
2.
A convenient form of
lithium metal can be purchased from Associated Lead Manufacturers Ltd., 14 Gresham Street, London. A typical analysis shows a purity of 99.6%, and it can be obtained as 1.3-cm.-diameter rod coated with petroleum jelly. A comparable form of
lithium metal can be purchased from Ventron Corporation, Chemicals Division, Beverly, Massachusetts. Preparation for use involves weighing, washing with
petroleum ether (b.p.
40–60°), and cutting the rod by scissors so that the pieces fall into the reaction vessel. The rod is cut into pieces about 0.5 cm. long that have an average weight of 0.3 g. per piece. Since excess
lithium is employed in this reaction, accurate weighing is unnecessary.
3.
Reagent grade methyl methacrylate monomer was dried over powdered
calcium hydride and freshly distilled before use. The checkers found that identical yields could be obtained when
Matheson, Coleman and Bell Chromatoquality methyl methacrylate monomer was used as received with no purification.
4.
Reagent grade n-butyl bromide (greater than 98% pure) was used after drying over molecular sieves.
5.
The reaction is highly exothermic and the submitters have found that isothermal conditions are best maintained by using cooling equipment consisting of a cooling bath seated on a pneumatically operated labjack and controlled by a temperature sensor which is attached to the thermometer dipping into the reaction vessel. This equipment, known as Jack-o-matic, is supplied by Instruments for Research and Industry, Cheltenham, Pennsylvania.
3. Discussion
This method has general applicability in that the carbonyl compound may be an aldehyde, a ketone, or an ester.
2 Similarly, the halide may be chloride, bromide, or iodide, although yields are generally lower with iodides. Alkyl and aryl halides react with equal facility, and the alkyl halide may be primary, secondary, or tertiary. A few examples of the yields obtained with a variety of reagents are given in Table I (the yields quoted are obtained by GC analysis of the reaction mixture using an internal standard).
TABLE I
|
|
Carbonyl Compound
|
Halide
|
Product
|
Yield %
|
|
|
Propionaldehyde
|
Ethyl bromide
|
3-Pentanol
|
90
|
|
Benzaldehyde
|
Chlorobenzene
|
Benzhydrol
|
100
|
|
Di-n-butyl ketone
|
n-Butyl bromide
|
Tri-n-butyl carbinol
|
91
|
|
Ethyl formate
|
n-Butyl bromide
|
5-Nonanol
|
91
|
|
Acrolein
|
Ethyl bromide
|
1-Penten-3-ol
|
90
|
|
Butyraldehyde
|
sec-Butyl bromide
|
3-Methyl-4-heptanol
|
89
|
|
For maximum yield, care must be taken to ensure that the rate of addition of the reagents is not excessive. If this occurs, the alkyllithium is generated in the presence of significant amounts of unchanged alkyl halide, and Wurtz condensation may be favored. The rate of formation of the alkyllithium is proportional to the surface area of the lithium metal; therefore, at a constant rate of addition, an increase in the lithium surface available for reaction will reduce the probability of Wurtz condensation.
Excess alkyl halide is required to compensate for these side reactions; commonly, only a 10–20% excess is used, rather than the 50% quoted in the method above. The yields given in the table are those obtained with 20% excess halide. The submitters have scaled up the reaction by a factor of 40 with no lowering of yield.
The technique is more efficient than the conventional Grignard reaction for three main reasons: (1) it is a one-stage process; (2) the yields are generally higher; and (3) the final product isolation is cleaner and more convenient.
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
petroleum ether
hydrochloric acid (7647-01-0)
ether,
diethyl ether (60-29-7)
Acrolein (107-02-8)
n-butyl bromide (109-65-9)
Ethyl bromide (74-96-4)
sec-Butyl bromide (78-76-2)
Propionaldehyde (123-38-6)
nitrogen (7727-37-9)
benzaldehyde (100-52-7)
chlorobenzene (108-90-7)
sodium wire (13966-32-0)
butyraldehyde (123-72-8)
ethyl formate (109-94-4)
3-Pentanol (584-02-1)
lithium (7439-93-2)
magnesium sulfate (7487-88-9)
5-Nonanol (623-93-8)
aluminum oxide (1344-28-1)
Tetrahydrofuran (109-99-9)
benzhydrol (91-01-0)
calcium hydride (7789-78-8)
methyl methacrylate (80-62-6)
3-BUTYL-2-METHYLHEPT-1-EN-3-OL,
3-Butyl-2-methyl-1-hepten-3-ol
5-Nonanol, 5-(2-propenyl)- (76071-61-9)
1-Penten-3-ol (616-25-1)
3-Methyl-4-heptanol (1838-73-9)
di-n-butyl ketone (502-56-7)
tri-n-butyl carbinol (597-93-3)
Copyright © 1921-, Organic Syntheses, Inc. All Rights Reserved