A convenient Pd-mediated oxidation of 4-methylbenzyl alcohol

A mild and convenient Pd-mediated aerobic oxidation of 4-methylbenzyl alcohol is described. We have applied the catalytic system Pd(OAc)2/Et3N to the oxidation of 4-methylbenzyl alcohol to 4-methylbenzyaldehyde. This method has resulted effective at room temperature without oxygen or air stream and without activated molecular sieves.


Introduction
The oxidation of alcohols to carbonyl compounds is a fundamental and important transformation for synthetic chemists in both industry and research laboratories [1,2]. Toxic or/and corrosive co-catalysts, large amounts of additives, expensive chemicals and need of molecular sieves are among the most substantial barriers to import synthetic strategies from laboratory to industry. [3] Of the reported oxidations, basic N-donor ligands [4][5][6] such as Et 3 N in combination with Pd(OAc) 2 have generally provided active catalyst. Here, we have applied the catalytic system Pd(OAc) 2 /Et 3 N to the oxidation of 4-methylbenzyl alcohol because generally, benzylic alcohols with electron-donating groups showed good reactivity [3,7,8]. We have investigated the dependence of conversion percentage on temperature and time.

Experimental
All starting materials and reagents were commercially available and were used without further purification 1 H NMR spectra were recorded on a BRUKER AMX-500 spectrometer in deuterated solvents. J values are given in Hertz. Infrared spectra were recorded as KBr pellets either on a Bio-Rad FTS 135 or a Jasco FT/IR-410 spectrophotometer in the range 4000-600 cm -1 . Electrospray mass spectra were recorded on a Bruker Microtof spectrometer. Elemental analyses were performed on a Carlo Erba EA 1108 analyzer.
Oxidation of 4-methylbenzyl alcohol to 4-methylbenzaldehyde. Since the oxidation of 4-methylbenzyl alcohol to 4-methylbenzaldehyde was the goal of several experiments, the experimental details of each one of them stated below. Experiment 1: Dependence of conversion on temperature. Five solutions of 4methylbenzylalcohol (30 mg, 0.25 mmol), Pd(OAc) 2 (6.1 mg, 0.03 mmol) and Et 3 N (3.5 µl, 0.03 mmol) in tetrahydrofuran (5 mL) were stirred at 10, 20, 40, 60 and 80ºC for 16 h. The resulting orange solutions were centrifuged to separate the very fine black palladium(0) precipitate formed during the heating by palladium acetate decomposition. Then, transparent solutions were concentrated to dryness under vacuum and resulting mixtures were analyzed by NMR. The conversion percentages in obtained crudes were determined by integration of the methyl signal of 4methylbenzaldehyde against the methyl signals of 4-methylbenzylalcohol and 4methylbenzaldehyde.

Results and discussion
Sigman et al. demonstrated aerobic benzyl alcohol oxidation proceeded smoothly even at room temperature by the use of Pd(OAc) 2 /triethylamine as catalyst system [4,5] using activated molecular sieves under a balloon pressure of oxygen. Inspired by those publications, we will explore the dependence of oxidation of 4-methylbenzyl alcohol on temperature and time without oxygen or air stream and without activated molecular sieves.
In order to establish the influence of temperature on the conversion, we have performed an experiment consisting in five reactions of 4-methylbenzylalcohol in THF charged with Pd(OAc) 2 /Et 3 N at 10, 20, 40, 60 and 80ºC for 16 h (experiment 1). Measuring the dependence of conversion percentage on temperature reveals a gradual increasing of the conversion from 80 to 20ºC that falls off considerably at about 10ºC. Fig. 1 shows clearly that room temperature is the most adequate for the oxidation of 4-methylbenzyl alcohol to 16 h reaction. 1 H NMR spectrum of the mixture obtained at room temperature revealed the formation as minor product the active catalyst; in fact it was benzylic alcohol [4,5].  We have also studied t of the catalytic system Pd(OAc) increase gradually from 30 min to 16 h reaction. Since the spectroscopic detection of mixture appears to indicate that this palladium complex is the active catalyst at we have used an equimolar amount of conversion after 24 h reaction methylbenzyl alcohol to 4-methylbenzaldehyde, obtaining at 76% conversion H NMR spectrum of the mixture obtained at room temperature as minor product of Pd(OAc) 2 (Et 3 N) (Fig. 2), ; in fact it was proposed as the active catalyst for the oxidation of Dependence of conversion percentage on temperature after 16h reaction using the H NMR spectrum of Pd(OAc) 2 (Et 3 N). The Et 3 N-methylene proton signals (1) are obscured by the quintuplet signal of dmso-d 6 . The signals corresponding to methyl groups have -methyl) and red (OAc-methyl) colors, respectively. the influence of time (experiment 2) at 20ºC using Pd(OAc) 2 /Et 3 N. Fig. 3 shows that conversion percentages from 30 min to 24 h, although the enhancement is quite low a Since the spectroscopic detection of Pd(OAc) 2 (Et 3 N) mixture appears to indicate that this palladium complex is the active catalyst at we have used an equimolar amount of Pd(OAc) 2 and Et 3 N. This led to reaction.
conversion after H NMR spectrum of the mixture obtained at room temperature which could be for the oxidation of Dependence of conversion percentage on temperature after 16h reaction using the catalytic methylene proton signals The signals corresponding to methyl groups have ºC using 10 mol% that conversion percentages h, although the enhancement is quite low after ) in the reaction mixture appears to indicate that this palladium complex is the active catalyst at 20ºC, This led to a 90% Finally, we have verified that methylbenzylalcohol at room temperature alcohol was oxidized successfully contrast, when we use Pd(OAc)

Conclusions
A convenient aerobic alcohol oxidation, that is effective at room temperature without oxygen or air stream developed. Using a catalyst loading alcohol can be oxidized to 4 h reaction. 1 H NMR sepectroscopy provides evidence that the active catalyst may be Pd(OAc) 2 (Et 3 N).