Researchers - Khalid Mirza & Marshall Moritz



To convert DL-α-methylbenzyl alcohol to acetophenone using NaH, following a recently published JACS protocol


Sodium hydride is added to a stirred THF solution of α-methylbenzyl alcohol at 0 C. After stirring for 12min the bath was removed and the mixture was allowed to warm to room temperature. Aliquots were removed over the course of the reaction, and NMRs were taken after adding benzene-d6 without quenching.
The glassware set up:

Taking an aliquot:

During the run


DL-α-methylbenzyl alcohol
HNMR(100uL in 700uL CDCl3)
HNMR(100uL in 700uL CDCl3 & 300uL THF)

UCExp243-1A - 0min
UExp243-2A - 2min
UExp243-3A - 6min
UExp243-4A - 11min
UExp243-5A - 18min
UExp243-6A - 36min
UExp243-7A - 72min
UExp243-8A - 144min
UExp243-9A - 288min
UExp243-10A - 460min
UCExp243-11A - 1123min [18h 43min]
Final Product- after quenching and work-up.
Overlay of the alcohol, ketone and the Product - HNMR
Overlay of the alcohol, ketone and the Product - IR


The reaction was monitored by NMR without quenching. Even after 19 hours, no new peaks were observed. Acetophenone is expected to show peaks at about 2.6 and 7.9 ppm (ChemSpider). Note there appears to be about 2% of acetophenone in the starting material (see first 2 NMRs in the Results section). These peaks are too small to observe in the monitoring NMRs.
Wang reported a 75% GC yield of acetophenone (JACS supplementary material), which we clearly have not reproduced. Totally Synthetic reported a 15% NMR yield for the 4-chloro derivative (see post).
In a comment on Carbon-Based Curiosities, European Chemist points to a 1965 paper where oxidants on the surface of NaH are likely responsible for oxidative behavior (Lewis JOC). This would certainly explain why some researchers are reporting some oxidation products but with widely divergent yields.


We were not able to reproduce the oxidation of α-methylbenzyl alcohol using NaH.


12:30 Flame dried all the glassware to be used.
13:00 Obtained Sodium hydride (48mg, 2mmol, 95%, dry powder stored under N2 in a glove-box, purchased from Sigma-Aldrich) in a vial flushed with N2, screw capped tightly and parafilmed.
13:30 Obtained THF (20mL, dry and stored under N2), placed in an ice bath. Obtained DL-α-methylbenzyl alcohol from the stockroom.
15:15 Set-up the glassware assembly, with N2 flow about 2 bubbles /sec, rb flask sitting in an ice bath-(inside temp had already dropped to 12C)
15:20 Obtained ten clean and dry NMR tubes with caps, rinsed with 100uL C6D6 each. These tubes were labeled 1-10
15:40 Increased the N2 flow in to the rb flask and then pipetted out DL-α-methylbenzyl alcohol (120.7uL 1mmol) in to the flask on a stir plate and stir bar spinning in it. As soon as the liquid was pipetted in the flask, it was stoppered.
15:45 Unseald THF and NaH and pipetted THF (1mL) in to NaH vial. Screw capped the vials and vortexed it for about 2-3s. Then immediately pipetted out the solution from the vial in to the alchol in the 3-neck flask under N2. Almost all NaH had been transferred in to the fask...rinsed the vials, containing remaining NaH a further four times and pipetted out the solution in to flask each time. immediately after the N2 flow was normalized (2 bubbles / sec). The temperature of the reaction mixture was reacorded as 1C.
15:45 Soon after the first transfer of NaH/THF solution, an aliquot of 100uL was pipetted out from the flask (now containing 1mmol alcohol, 1mL NaH/THF solution) in to the NMR tube containing C6D6 (400uL) UCExp243-1A...[ * indicates - I got help from my lab-mate Marshall Moritz, who stayed with the reaction for the next 2.5h removing aliquots for me to obtain NMRs- great help, Thanks man!- Each time he removed an aliquot, he increased the N2 pressure and soon after turned the pressure back to about 2 bubble/sec]
15:46 Rushed to obtain a HNMR of the sample...was unable to get good shims on the took almost 4min to get the spectrum.-also labled UCExp243-1A. [I'm going to take this as 0min]
15:47 Removed another 100uL aliqout of the reaction mixture* UCExp243-2A .
15:55 Obtained HNMR of UCExp243-2A [2min]
15:57 Removed the ice bath from under the reaction flask and let it stir at room temperature under N2.
15:51 Removed another 100uL aliqout of the reaction mixture, UCExp243-3A* and obtained an HNMR at 16:00 [6min]
15:56 Transferred an aliquot (100uL) of the reaction mixture, UCExp243-4A* and obtained an HNMR at 16:06 [11min]
16:03 Transferred an aliquot (100uL) of the reaction mixture, UCExp243-5A* and obtained an HNMR at 16:14 [18min]
16:21 Transferred an aliquot (100uL) of the reaction mixture, UCExp243-6A* and obtained an HNMR at 16:27 [36min]
16:53 Recorded a video of the the reaction mixture stirring at room temperature
16:57 Transferred an aliquot (100uL) of the reaction mixture, UCExp243-7A* and obtained an HNMR at 17:05 [72min]
18:09 Transferred an aliquot (100uL) of the reaction mixture, UCExp243-8A* and obtained an HNMR at 18:09 [144min]
20:33 Transferred an aliquot (100uL) of the reaction mixture, UCExp243-9A and obtained an HNMR at 20:38 [288min]
23:25 Transferred an aliquot (100uL) of the reaction mixture, UCExp243-10A and obtained an HNMR at 23:33 [min]
10:28 Transferred an aliquot (100uL) of the reaction mixture, UCExp243-11A* and obtained an HNMR at 10:40 [18h 43min]
12:50 Quenched the reaction mixture by adding as saturated solution of ammonium chloride (5mL). The reaction mixture was left stirring at room temperature under N2.
14:00 Stopped stirring the reaction mixture and poured it out in to a 100mL separatory funnel.
14:10 Added 15mL ethylacetate to it with 10mL distilled water..shook the flask vigorously and left it for the organic layer to separate out.
14:15 Drained out the aqueous layer and added 10mL water to the sep-funnel containing the organic layer..mixed the added water with organic layer..and waited for the layers to separate-out.
14:25 Collected the aqueous layer together with the previously collected aq. layer..added 15mL ethyl acetate to the combined aqueous layers. The organic layer from the sep-funnel was drained-off in to a clean erlenmeyer flask.
14:40 The combined aq. layer with ethyl acetate was poured in to the separatory funnel. After shaking vigorously waited for the layers to separate out.
14:55 Drained the aqueous layer out and collected the organic with the previously obtained organic layer.
15:10 The combined organic layer was washed with brine (25mL) in a separatory funnel. The organic layer was then collected.
15:30 The resultant organic layer was dried over anydrous MgSO4.
15:45 Filtered out MgSO4, and collected pale colored liquid in a pre-weighed 250mL one neck round bottom flask.
15:50 The rb flask was set on a rotory evaporator at 80C, connected to a high vac.
16:00 Turned off the heater on the evaporator, left the residue on the rotory evaporator on the vacuum pump.
17:30 Removed from the high vac and obtained a oily yellow liquid, UCExp243-2-1 (73.1mg)
18:00 Obtained HNMR of UCExp243-2-1 and IR on a Perkin Elmer Spectrum 1- FTIR on an ATR.