Isoborneol, from camphor

Camphor is produced by fractional distillation and crystallization of camphor oil or, synthetically, by dehydrogenation of isoborneol (from isobornyl acetate, see p. 73) over a copper catalyst. 

Brit. pat. 803,178 (1958), Prepn of the /-form by reduction of d-camphor with lithium aluminum hydride Trevoy, Brown, J. Am. Chem. Soc. 71, 1675 (1949). Separation of isoborneol from its ewfo-isomer, borneol, via the p-nitro-benxoare deriv Truett, Moulton, foe. cit. Resolution of the d/-form Pickard, Litflebury, foe, cit. Kenyon, Priston, ibid. 127, 1472 (1925). Configuration (isoborneol = c o-form borneol = eflrfo-form) Toivonen et al, Acta Chem. Scand. 3, 991 (1949), Review J. L. Simonsen, The Terpenes vol. 11 (University Press, Cambridge, 2nd ed., 1949) pp 365-367 A. R, Pinder, The Chemistry of the Terpenes (Chapman Hall, London, I960) pp 22-24, Id, 103, 105-107, 111-... 

Ordinary commercial camphor is (-i-)-cam phor, from the wood of the camphor tree. Cinnamonum camphora. Camphor is of great technical importance, being used in the manufacture of celluloid and explosives, and for medical purposes, /t is manufactured from pinene through bornyl chloride to camphene, which is either directly oxidized to camphor or is hydrated to isoborneol, which is then oxidized to camphor. A large number of camphor derivatives have been prepared, including halogen, nitro and hydroxy derivatives and sulphonic acids. 

Camphor, Cj HjgO, occurs in the wood of the camphor tree Laurus camphora) as dextro-camphor. This is the ordinary camphor of commerce, known as Japan camphor, whilst the less common laevo-camphor is found in the oil of Matricaria parthenium. Camphor can also be obtained by the oxidation of borneol or isoborneol with nitric acid. Camphor may be prepared from turpentine in numerous ways, and there are many patents existing for its artificial preparation. Artificial camphor, however, does not appear to be able to compete commercially with the natural product. Amongst the methods may be enumerated the following —... 

Pinene hydrochloride is prepared in the usual manner from turpentine, and this is allowed to react with acetate of silver. Isobornyl acatate is formed, which is hydrolysed, and the isoborneol oxidised to camphor. Acetate of lead is also used, as is also acetate of zinc. 

Camphor is then obtained from isoborneol by oxidation of the secondary alcohol to a ketone. 

A vast array of chiral auxiliaries have been derived from naturally occurring compounds containing the bicyclo[2.2.1]heptane unit (for review articles, see refs 1 -3). In all cases, the ultimate sources of these auxiliaries are the ketones camphor and fenchone, and the alcohols borneol and fenchol, as at least one enantiomer of each compound is provided in enantiomericaUy pure form by nature. Thus. ( + )-camphor [( + )-2], (-)-borneol [(-)- ], and (+)-fenchonc [( + )-5] are enan-tiomerically pure, convenient and inexpensive starting materials for organic synthesis and deriva-tization to give chiral auxiliaries. Most other compounds of this series are also commercially available, but can be prepared by oxidation or reduction of inexpensive precursors by standard methods. The evo-alcohols, such as the enantiomeric isoborneols, are accessible by standard complex hydride reductions of the ketones. The interconnection between these compounds is shown diagrammatically. 

To the crude (1 fl,2.R,4./ )-2-(l-naphthyl)isoborneol, obtained from 59 mmol of ( + )-camphor as described above, are added 250 mL of pyridine and the mixture is cooled in an ice bath. 22 mL of S0C12 are added rapidly dropwise and the mixture stirred for 1 h. After dilution with 150 mL of H20 and extraction three times with 150-mL portions of petroleum ether, the extracts are washed with 10% aq HC1, sat. aq CuS04, sat. aq NaHCOj, and sat. aq NaCl. The combined organic layers arc dried over anhyd Na2S04 and concentrated in vacuo. The residue is bulb-to-bulb distilled at 0.5Torr to remove camphor and naphthalene. The liquid pot residue weighs 65 g. 

The hydride is added to camphor predominately from the less hindered side of the carbonyl group. This is the side opposite the bridge with the two methyl groups and results in the formation of more isoborneol than borneol. 

Fig. 5. GC-MS chromatogram of the steam distilled volatile oil of the rhizome of C. aeruginosa. Camphor, isoborneol and borneol were eluted at 10.44,10.65 and 10.99min, their LRI were 1150,1160,1177, respectively. GC-MS system 1 pL (split mode 1 100) at 270 °C onto a TR-5 column using helium as a carrier gas at a flow rate of 1 mL.rnin-i. The oven temperature was programmed for 60 - 240 °C (4 °C.min-i) and 240 - 270 ° C (10 C.min-i) then held for 2 min. The detector and interface were maintained at 275 °C and the ion source at 220 °C and the MS scanned in positive ion mode over 35 - 650 m/ z. Obtained from the same instrument as Fig. 1.

Steric Effects.—The consequences upon chemical reaction of non-bonded interactions between enantiomeric pairs of molecules have been discussed an antipodal interaction effect was observed in a reductive camphor dimerization and in a camphor reduction. The full paper on the correlation of the rates of chromic acid oxidation of secondary alcohols to ketones with the strain change in going from the alcohol to the carbonyl product has now appeared. It is concluded that the properties of the product are reflected in the transition state for the oxidation. High yields of hindered carbonyls are available from the corresponding alcohols by reaction with DMSO and trifluoroacetic anhydride (TFAA) indeed, the more hindered the alcohol, the higher the yield of carbonyl compound reported Since the DMSO-TFAA reaction occurs instantaneously at low temperatures (<—50°C), it is possible to oxidize alcohols that form stable sulphonium salts only at low temperature. Thus, ( )-isoborneol reacts at room temperature to give camphene, the product of solvolysis of the sulphonium salt the oxidation product, ( + )-camphor, was obtained by the addition of base at low temperature. 

Camphor, a bicyclic monoterpene, is extracted from the woods of Cinnamomum camphora, a tree located in Southeast Asia and North America. Furthermore, it is also one of the major constituents of the essential oil of common sage (Salvia officinalis). Solid camphor forms white, fatty crystals with intensive camphoraceous odor and is used commercially as a moth repellent and preservative in pharmaceuticals and cosmetics (Wichtel, 2002). In dogs, rabbits, and rats, camphor is extensively metabolized whereas the major hydroxylation products of d- and L-camphor were 5-endo-md 5-ex -hydroxycamphor. A small amount was also identified as 3-e do-hydroxycamphor (Figure 8.2). Both 3- and 5-bornane groups can be further reduced to 2,5-bornanedione. Minor biotransformation steps also involve the reduction of camphor to borneol and isoborneol. Interestingly, all hydroxy-lated camphor metabolites are further conjugated in a Phase II reaction with glucuronic acid... 

The lithium 9-boratabicyclo[3.3.1]nonane (Li 9-BBNH) is prepared [1] by refluxing 1 equiv of 9-BBN with excess of finely divided lithium hydride. The reagent reduces [2] cyclic ketones, and the hydride adds from the less hindered side. For example, camphor on reduction with Li 9-BBNH affords the less stable exo isomer isoborneol in 91% yield (Eq. 26.36). 

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