Cymenes

Submitted by D. E. Pearson, Robert D. Wysonc, and J. M. Finkei 1 Checked by Richard A. Haggard and W. D. Emmons 

Caution It is necessary to carry out the entire operation including the workup in a well-ventilated hood. Rubber gloves and safety glasses should be worn (Note I). 

Anhydrous hydrogen fluoride (135 ml., approx. 7 moles) is liquefied by passing the gas through an 8-ft. spiral of i-in. I.D. copper tubing surrounded by an isopropyl alcohol-dry ice bath (Note 2). The liquid is delivered to a 500-ml. polyethylene 

In the event of accidental contact of hydrogen fluoride with the skin, the affected area must be washed immediately and 

If one half the given quantity of hydrogen fluoride is used, all other factors being kept the same, the m-cymene formed contains as much as 5% of -cymene. 

---

Triethylamine in THF can be used as the external base to deprotonate triazolium salts. The resulting NHCs were complexed in situ, e.g., to [(/7 -cymene)RuCl2]2, [(/ -cod)RhCl]2, and [(/ -C5Me5)RhCl2]2. Sodium carbonate in water/ DMSO deprotonates imidazolium iodides in the presence of mercury(II) dichloride to give [Hg(NHC)2][Hgl3Cl]. " A pyridine-functionalized imidazolium salt was deprotonated by lithium diisopropylamide (LDA) in THF and attached in situ to [(p -cod)Pd(Me)Br] [Eq.(17)]. After abstraction of the bromide anion with silver(I) a tetranuclear ring is formed. 

R =R = Et]. The methyl-containing starting material after a similar sequence of transformations but with nickel chloride gives the nickel analogue of 7 [ML = = Ru(/7 -cymene) M = Ni, R = R = H R =... 

The ruthenium complex 76 reacted with equimolar amounts of [M(acac)L2] (M = Rh, L2 = cod or (CO)2 M = Ir, L = CO) to give the corresponding heterodinuclear complexes [(r 6-p-cymene)(pz)Ru(/x-pz)2ML2]. The latter compounds gave cationic derivatives of formula [(r/6-/7-cymene)(Hpz)Ru(/i-pz)2ML2](BF4) when treated with an equimolar amount of HBF4. An X-ray crystal structure determination was performed for the cationic complex having M = Irand L = CO (108). 

The catalytic activity of [RuCl(=C=C=CPh2)(7 -/ >-cymene)(PCy3)][PF6] under... 

Another potential approach towards 1 was reported by Seido et al. utilizing an asymmetric reduction of the ketone (57 Scheme 15) as the key step. Acylation of the lithium enolate of methyl phenylacetate with the imidazolide, obtained by treatment of the acid 56 with A, V -carbonyldiimidazole, gave the ketoester 57 in 66.4% yield. Asymmetric reduction of 57 with [RuI(/7-cymene)(5)-binap]I, tin chloride, and cam-phor-lO-sulfonic acid in methanol at 80 °C afforded the alcohol 58 as a mixture of syn and anti forms in 87.4% yield. The ratio of syn to anti isomers was 76.3 23.7 and the enantiomeric purity of each form was 95.6% ee and 97.8% ee, respectively. Tosylation of 58 with p-toluenesulfonyl chloride and pyridine in the presence of catalytic amounts of DMAP yielded a diastereomeric mixture of tosylate 59 in 61.8% yield. Deprotection of the /V-Cbz group in 59 by hydrogenation over 5% Pd-C followed by cyclization of the resulting amino tosylate 60 with potassium carbonate in methanol furnished methylphenidate as a mixture of erythro and threo isomers in a 7 3 ratio and 77.5% yield. 

As mentioned before, of the constituents of thyme oil, thymol (91) was the most active, followed by carvacrol (92), borneol (93),/7-cymene (37), a-pinene (13) and camphene (94). When mixtures of these 6 materials were made and the antibacterial activity evaluated, the results were quite unexpected. The antibacterial activity of the mixtures was less than that of the essential oil of thyme. This suggests that the minor compounds play a significant role in the biological activity [121]. 

Cymene can be obtained from toluene and isopropyl alcohol in the presence of phosphoric acid, the yield then being 80%.658 The use of boron trifluoride and phosphoric oxide is illustrated in the following preparation of 5ec-butyl-benzene 655... 

Cymene selectivity and service time are drastieally enhanced when adding a Ce promotor. Initial p-eymene selectivity is up to 50.1%, versus 16.9% for the unpromoted catalyst. However, p-cymene selectivity decreases after 6 h time on... 

On the other hand, the reaction of [(/7-cymene)Ru(/i-Cl)2]2 with the chiral chelating ligands 3.17 and 3.18 remarkably gave the respective cationic complexes 3.19 and 3.20 as single disatereomers (Figure As stated in the beginning of this section chiral... 

Martins, I. M., Rodrigues, S. N., Barreiro, M. R, and Rodrigues, A. E. (2012). Release studies of thymol and /7-cymene from polylactide microcapsules. Industrial and Engineering Chemistry Research, 51, 11565-11571. 

---