George W. Kabalka' and Herbert C. Hedgecock, Jr. University of Tennessee Knoxville. 37916
I
The Hydroboration-Oxidation of Alkenes A convenient anti-Markownikoff
hydration experiment The hydroboration reaction has hecome an important tool in the repertoire of the synthetic organic c h e m i ~ tT. ~h e resultant oreanoboranes can he readilv converted to a variety of synth;?tically important compo"nds such as alcohols, aldehydes, esters, etc. Indeed, the numher of recently reported reactions involving organohoranes as alkylating aeents is irn~ressive.3.~ T h e authors of current undergraduate organiE textbooks have recognized the utility of the organoboranes and are providing increased coverage of their role in synthesis. Unfortunately the organic laboratory manuals have not followed suit. %lost undergraduate manuals omit even the simple hydrohurntion-uxidation sequence which provides for the anti-Markownikoff hydration of alkenes?" 3RCH=CH,
+
BHB
Ether
(RCH,CHAB
There have been a numher of valid reasons for the omission of this reaction sequence: (1) the necessary borane solutions have been somewhat difficult to prepare, requiring the m---e of metal hvdrides:, (2) .-~. - - -~~~~~~ . . the borane solutions have been difficult to store, requiring dry, oxygen free conditions a t O°C; (3) the standard oxidation procedure has required the use of 30% hydrogen peroxide solutions or peracids. Consequently the hydroboration reaction and the reactions
Presented in part at the 26th ACS Southeastern Regional Meeting, Norfolk, Virginia, October 1974. 1 To whom correspondence should be addressed. 2 Brown, Herbert C., "Hydroboration," W. A. Benjamin, New York, 1962. Brown, Herbert C., "Boranes in Organic Chemistry," Cornell University Press,Ithaca, N.Y., 1972. Kabalka, G. W., Intm-Science Chem. Report 7.57 (1973). 5 For simplicity, the hydroborating agent is represented as BH.. In actual fact it is the dimer, B2H6, unless the solvent is a good Lewis base such as tetrahydrofuran or dimethylsulfide. In these cases the hydrohorating agent is BHrTHF or BHrS(CHd2, respectively. "be use of BH3 produces 94% of the primary alcohol along with 6%of the secondary alcohol. Lane. C. F.. J. O m Chem.. 39,1437 (1974). sKabalka, G. W., and Hedgecock, H., J. 0%. Chem., 40 (12), (1975). Although we report the first use of trimetby1amine-Noxide dihydrate as an efficient reagent for the oxidation of organoboranes, the difficult to prepare, anhydrous amine oxides have been used in organoborane oxidations. See: Kaster, R., and Morita, Y., Angew. Chem., Internat. Ed., 5,580 (1966). We have successfully utilized toluene, xylene, heptane, diethyl ether, tetrahydrofuran, and diglyme in this reaction sequence. The choice of solvent depends on the separation techniques employed for product isolation. As an example xylene (bp 138'C) is difficult to separate from 1-hexanol (bp 136%) via distillation but chromatography affords a simple separation. 'O To obtain a convenient oxidation rate (1hr) the temperature should he kept above 100°C during the oxidation. Consequently the higher boiling solvents such as diglyme (bp 162W are convenient for the undergraduate laboratory. We have, however, achieved high conversions in refluxing diethyl ether over a 24-hr period.
Conversion of Alkenas to Alcohols Via
Aikene
Product Alcohol
1-ostene I-hexene cyclohexene norbornene
1-octanol l-hexanal cyclohexanol norbornanol
Hydroboration-Oxidation yield ( % W BH,.SlCH,)I/ (CH,),&-0
Yield (%Wb utilizing BH,.THF/ H20,
85c 8 S 93
8 9 8 9 90 100
100
Yield determined via gar ChromatograPhY. b Yields are those obtained by students In our laboratory. C 4 - 6 % o f the recondarv alcohol is also formed.
of organoboranes have traditionally been relegated to studies in advanced lahoratory courses. Recent advances in organoborane chemistry have significantly altered this situation. We present here a hydrohoration-oxidation sequence that can he readily performed in an undergraduate organic lahoratory in two 3-hour laboratory periods. The experiment utilizes commercially available. stable reaeents (moderatelv oriced) and standard lah" oratory glassware. The reactions involve the use of the stable borane dimethvlsulfide comolex as the hvdroboratine agent7 and t ~ i m e t i ~ l a m i n e - N - o i i ddihydratk e as the ox; dizing agent.s
..
3CH,,(CH,),CH=CH9
[CH,(CH,),CH&B
+
+
BH,.S(CH&
-
+
3CFN(CHJ,
+
H,O
3CH,(CH2hOH
+
(CH&Nt
T h e reaction is a eeneral one and a number of alkenes can he hydrated. ~urrhermore,the conversion can he accomolished in a varietv of non-orotic solventsg and a t a variety bf temperatnres.lO' T h e following experiment is representative. Due to the evolution of dimethylsulfide and trimethylamine, the reaction must be performed in a hood.
Experimental Reagents All reagents are available from Aldrich Chemical Company and can be used without further purification. Apparatus A standard, single necked, 200-ml round bottomed flask fitted with a Claisen adapter was employed. A reflua condenser fitted with a drying tube was attached to one side of the Claisen adapter and a gas inlet tube was attached to the other. Conversion of l-Octene to l-Octanol (Hood!) A solution of 1-octene (10.0 g, 88 mmole) in 50 ml of diglyme (2methoxyethyl ether) is added to the reaction flask. The system is flushed with an inert gas such as nitrogen or carbon dioxide." The flask is then cooled in an ice bath. The reflux condenser is removed momentarily and the neat borane dimethylsulfide (3.0 ml, 32 and the conmmole) is added all at once to the octene s~lution'~ denser replaced. At this stage the flushing with inert gas may be discontinued or allowed to proceed. The ice bath is removed and
Volume 52, Number I I, November 1975
/ 745
the reaction allowed to warm to room temperature with occasional swirling. After a total reaction time of 1 hr the hydroboration is complete. Water (2.0 ml) is added dropwise through the reflux condenser to destroy the excess hydride (some foaming occurs). A few boiling chips are then added followed by trimethylamine-Noxide dihydrate (10.0 g, 90 mmole). The Claisen adapter is removed and the reflux condenser is attached to the flask directly. The mixture is slowly heated to a gentle reflua for 1 hr (some foaming occurs). The mixture is then cooled to room temperature and the p r d u c t isolated. (The mixture may be stored at this point.) The reaction mixture is transferred to a separatory funnel containing 100 ml of ether. The mixture is extracted five times with equal volumes of water to remove the diglyme. The ether layer is dried aver anhydrous magnesium sulfate and the product isolated by distillation. The distillation yields 8.7 g (75%) of l-oetanal, bp 103°C at 26 mm Hg (water aspirator).13 Discussion T h e yields of alcohols from the corresponding alkenes via t h e ~ r o c e d u r eoutlined are at least a s eood as those reported for t h e standard hydration procedure utilizing B H r T H F as t h e hydrohorating agent a n d aqueous peroxide as t h e oxidizing agent. Our results are summarized in t h e tahle. T h e advantages of this procedure are t h e stability, commercial availability in pure form, a n d solubility of t h e reagents involved. T h e only restriction t h a t we find is t h e necessity of a n efficient hood to remove t h e gaseous effluents. T h e hydrohoration of alkenes utilizing horane di-
746 / Journal of ChemicalEducation
methylsulfide opens t h e major new area of organoborane chemistry t o t h e undergraduate laboratory. 'l During the hydroboration an inert, dry atmosphere is important. We found small cylinders of nitrogen to be convenient. We have also found that carbon dioxide works mite well. The COI eas n~ ran be generared quite readily by plncmg Dry Ice in a separate round hutturned flnck connected to the gas inlet tube via rubhrr tuhinx. The rntr of CO1 rvulution can br controlled by means of a warm water bath. We have found borsne dimethylsulfide to he remarkably stable (refrigerated samples show no hydride loss after a year's storage). We dispense it from a buret fitted only with a drying tube. The student can transfer it via small flasks or vials even under atmospheric conditions. The loss of hydride due to oxygen and moisture is insignificant (less than 5%)if the manipulations are carried out quickly (less than 5 mid. We destroy the excess horane dimethylsulfide remaining in the buret at the end of the laboratory period by slowly adding it to a beaker of ice water (Hwd!). In an attempt to gauge the dangers involved, we have "spilled" a few milliliters of horane dimethylsulfide into large watchglasses. It does not inflame. The reagent slowly reacts with moisture to form a white crusty material. Caution! The borane dimethylsulfide is presumably toxic and laboratory cleanliness should he emphesized. l3 Glpe analysis of the crude reaction mixture indicated a 94% yield of 1-and 2-odanols (ratio of 94x3,respectively). Glpe analysis of the distilled product indicates a 5% yield of 2-odanol as the major impurity. ~
~~~
.
