Bomeol oxidation

Camphor was originally obtained from the camphor tree Lauras eamphora in which it appeared in the optically active dextro-rotary form. Since about 1920 the racemic ( ) mixture derived from oil of turpentine has been more generally used. By fractional distillation of oil of turpentine the product pinene is obtained. By treating this with hydrochloric acid, pinene hydrochloride (also known as bomyl chloride) may be produced. This is then boiled with acetic acid to hydrolyse the material to the racemic bomeol, which on oxidation yields camphor. Camphor is a white crystalline solid (m.p. 175°C) with the structure shown in Figure 22.3. 

SCHEME 122. Selective oxidation of bomeols and menthols with immobiUzed Mo catalysts and TBHP... 

Bomeol is oxidized to camphor with chromic or nitric acid dehydration with dilute acids yields camphene. Bomeol is readily esterified with acids, but on an industrial scale bornyl esters are prepared by other routes. For example, levorotatory bomeol is synthesized industrially from levorotatory pinenes by Wagner Meerwein rearrangement with dilute acid, followed by hydrolysis of the resulting esters [86]. 

In the presence of chiral polymerization catalysts, enantiomeric monomers are consumed at different rates (Scheme 75). Enantiomer-selective polymerization of racemic propylene oxide catalyzed by a diethylzinc-(-f)-bomeol system is a classical example of such kinetic resolution H 176). The polymeric product has an [a]D of +7.4°. The mechanism... 

The glucuronic acid moiety of bomyl /9-D-glucuronide excreted as a metabolite of bomeol by man or rabbit was shown by Pryde and Williams20 to have a pyranoid structure. The glucuronide, on treatment with methyl iodide and silver oxide, gave crystalline bomyl 2,3,4-tri-O-methyl-jS-D-glucuronide methyl ester. This was converted to a mixture of a and (8 anomers of methyl tri-O-methyl-D-glucuronides by the action of 0.2 N sulfuric acid in methanol at 100° under pressure. Oxidation of... 

Bomeol, the structure of which is given in text Figure 26.7, is a secondary alcohol. Oxidation of bomeol converts it to the ketone camphor. 

As with trifluoroacetic anhydride, activation of dimethyl sulfoxide with thionyl chloride must be carried out at low temperatures as the reaction is highly exothenmic. Besides the higher yields, a further advantage of thionyl chloride to activate dimethyl sulfoxide over anhydrides is the lack of Pummerer rearrangement products or of esters formed as by-products (as long as Ae reactions are carried out below -60 C). This is amply demonstrated by the oxidation of (-)-bomeol which proceeds in an excellent 99% yield (equation 12). ... 

Constitution of Camphor.—The constitution of camphor and of Bomeol has been established by Kompa s synthesis of camphoric acid which is obtained by the oxidation of camphor. 

Synthesis of Camphor.— The relationship of camphor to pinene, the terpene present in turpentine, is of especial interest and importance in connection with its synthesis. Pinene is the unsaturated di-cyclic terpene related to the saturated di-cyclic terpene pinane (p. 823). In both of these terpenes the di-cyclic arrangement is different from that in camphane and Bornylene in that the isopropyl group in forming the secondary cycle joins the meta carbons instead of the para. Now pinene, by addition of hydrogen chloride, forms a hydrochloride which has been referred to as artificial camphor. This hydrochloride is identical with the hydrochloric acid ester of Bomeol and may be converted into Bomeol by hydrolysis. Now as Bomeol can be oxidized to camphor we may thus obtain true synthetic camphor from pinene. The reactions, involving an intermediate product and then rearrangement of the secondary cycle in pinene, are as follows ... 

Under comparatively drastic reaction conditions, camphor is oxidized with ring cleavage to give camphoric acid (69). Alternatively, bomeol may be used as starting material. Both enantiomers are commercially available. As oxidants nitric acid is most frequently used the best results are obtained when ammonium vanadate is added as a catalyst68. The ( + )-enantiomer was used for the preparation of monoperoxycamphoric acid, which is an isomeric mixture and difficult to separate69. The peracid has been applied with limited success as an enantioselective epoxidation reagent (Section D.4.5.2.). 

In a more recent paper CeUa and McGrath report that alcohols can be oxidized inMCPBAin purified THF, with hydrochloric acid (10 mole %) as the only catalyst. Yields of ketones are high (75-95%) for unhindered secondary alcohols, but significantly lower for even slightly hindered alcohols (bomeol -> camphor, 23% yield). A further limitation is that the method is not suitable for acid-sensitive substrates. 

Oxidation of Alcohols to Aldehydes and Ketones. Hyper-valent iodine compounds have powerful oxidizing capabilities. However, IBX possesses different properties than many similar oxidants, such as the related analogs iodoxybenzene and m-iodoxybenzoic acid. Until recently, the major application of IBX was its use in DMSO for the oxidation of primary alcohols to aldehydes at room temperature, without the danger of over-oxidation to carboxylic acids. The related iodo-oxy reagents oxidize benzyl alcohols to benzaldehydes at elevated temperatures in benzene (80 °C, 5-10 h) or in acetic acid (rt, 24 h), while IBX oxidizes the same compounds in 15 min (or less) at room temperature. IBX is equally effective for the oxidation of secondary alcohols to ketones under analogous conditions. Even sterically hindered alcohols are readily oxidized. Bomeol undergoes smooth oxida-... 

Lang PT, Harned AM, Wissinger JE. Oxidation of bomeol to camphor using Oxone and catalytic sodium chloride a green experiment for the undergraduate organic chemistry laboratory. J Chem Educ 2011 88 652-6. 

Wolfgang Oppolzer s muscone synthesis is the first enantioselective macrocycli-sation. [195] It starts with pentadec-14-ynal, which is converted by hydro-boration and transmetaUation into the corresponding organozinc compound. The ring closure takes place in the presence of catalytic amounts of a diethylzinc/ (-)ejco-3-(diethylamino)bomeol adduct. After work-up, the cyclic allyl alcohol is obtained in 75 % yield and with an ee of 92 %. The hydroxy-group directs the diastereoselective cyclopropanation (Simmons-Smith reaction). The final steps are a Swern oxidation and selective ring-opening of the cyclopropane under Birch conditions. 

Phytochemistry The plant contains tanshinones (Sairafianpour et al. 2001). Water-distiUed essential oils from leaves collected in Arslonbob (Kyrgyzystan) contained cineole, pinene, epi-13-manool, bomyl acetate, camphene, camphor, caryo-phyllene, caryophyUene oxide, humulene, caryophylladienol, bomeol, and other compounds (Basher et al. 1997). 

Tsuruta et al. (1963) prepared optically active poly (propylene oxide) from one mole of diethylzinc and two moles of (- -)-bomeol or (—)-menthol. They interpreted the catalyst activity as due to monomeric or dimeric zinc dialkoxide and that anionic coordinated polymerization took place by a four-membered ring intermediate similar to (LXV). The proximity of the optically active alkoxide to the point of reaction was thought to cause the asymmetric synthesis. 

An Oxidation-Reduction Scheme Bomeol, Camphor, Isohomeol... 

This experiment will illustrate the use of an oxidizing agent (pyridinium chiorochromate) for converting a secondary alcohol (borneoi) to a ketone (camphor). The camphor is then reduced by sodium borohydride to give the isomeric alcohol isohomeol. The spectra of bomeol, camphor, and isoborneol will be compared to detect stmctural differences and to determine the extent to which the final step produces a pure alcohol isomeric with the starting material. 

Instructors may notice that PCC replaces bleach for the oxidation of bomeol to camphor. After several years of doing this in our own laboratory classes, and accepting advice from other instructors, we finally gave up on the green oxidation. Results were too variable PCC has became the reagent of choice. It is widely shown in lecture textbooks. We reluctantly gave up on bleach oxidation ... 

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