Camphor-borneol, reduction

Borneol and isoboineol are respectively the endo and exo forms of the alcohol. Borneol can be prepared by reduction of camphor inactive borneol is also obtained by the acid hydration of pinene or camphene. Borneol has a smell like camphor. The m.p. of the optically active forms is 208-5 C but the racemic form has m.p. 210-5 C. Oxidized to camphor, dehydrated to camphene. 

The reduction of camphor with lithium aluminum hydride gives 90% isobor-neol and 10% borneol. Explain these results. 

Camphene is a solid terpene. The dextro variety d-camphene is found in camphor, ginger and spike oils, and the levo variety, 1-camphene is in citrondla and valerian oil and in French and American turpentine. Bornylene does not occur in nature but has been prepared from the alcohol corresponding to it known as Borneol or Borneo camphor. This, as previously stated, may be prepared from pinene so that Bornylene itself may be made from pinene. Fenchene, also, is not found in nature but is obtained by reduction of fenchone a terpene ketone found in fennel oil and in Thuja oil. 

In a thermodynamically controlled reaction, 3-oxo-e.vo-tricyclo[4.2.1.02 s]nonane is converted to e. vo-3-hydroxy-e.vo-tricyclo[4.2.1.02,5]nonane (85-95%). With sodium borohydride the ewfo-alcohol is obtained185. For example, the Meerwein-Ponndorf-Verley reduction of camphor yields a 70 30167 (75 2525, 69 31 186) mixture of the exo- and endol,7,7-trimethylbi-cyclo[2.2.1]heptan-2-ols (isoborncol and borneol). The equilibrium has been established to give a 29 71 mixture of isoborneol and borneol183, giving another example where the Meerwein-Ponndorf-Verley reduction leads predominantly to the less stable product. 

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-... 

The problem of the stereospecificity of the method arises when reduction of the keto group leads to formation of a new asymmetric carbon atom or of new cyclic cis-trans-isomers. Although a mixture of the epimeric cis-trans-isomers is obtained in many cases, one form is often favored or indeed may be formed exclusively. It transpires that the more stable isomer is usually formed from sterically unhindered ketones, and that hydrogen is usually added to the unhindered side of ketones that are strongly sterically hindered. Thus, on reduction of camphor a 94% yield is obtained of a mixture of borneol (10%) and iso-borneol (90%) in which the ra-isomer patently preponderates.359... 

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. 

An informative and amusing background to that unique material, camphor, has appeared. Its preparation by Oppenauer oxidation of the epimeric borneols occurs without epimerization. Epimerization does not occur in the presence of potassium t-butoxide in t-butyl alcohol, but it does with potassium isopropoxide in propan-2-ol." The reaction of camphor with phosphoric acid yields a complex mixture of m- and p-cymenes, 3,4-dimethylethylbenzene, 1,2,3,4-and 1,2,3,5-tetramethylbenzene, fenchone, carvenone, and carvacrol. A very detailed examination of the metal-ammonia reduction has revealed an intermediate camphor analogue of pinacol formed by association of a camphor anion radical with the metal cation. This intermediate was isolated and characterized. Other effects are discussed, such as that of adding a large excess of metal salt (LiBr, KBr, or NH Cl)." ... 

As you know from your general chemistry course, an oxidation of one compound must be accompanied by a reduction of another compound. In the present experiment the oxidation of borneol (a secondary alcohol) to camphor (a ketone) must be accompanied by a reduction of Cr + (orange color) to Cr + (green color). 

Part C. Percentages ot Isobomeol and Borneol Obtained from the Reduction of Camphor... 

Your instructor will advise you of the method you should use to analyze the products from the sodium borohydride reduction of camphor. Each method yields the percentages of isobomeol and borneol obfained. 

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... 

Aldehydes and ketones of wide variety such as caproaldehyde, benzaldehyde, 2-heptanone, and norcamphor utilize 1 equiv of hydride in THF and are reduced rapidly and quantitatively to the corresponding alcohols at 15 2 °C. The hindered ketone, 2,2,4,4-tetramethyl-3-pentanone, which is inert to 9-BBN [5], however, is rapidly reduced with Li9-BBNH. Reduction of camphor gives 91% isoborneol and 9% borneol (Eq. 25.13). 

Figure 9.11 Borneol, which Is obtained by reduction from the camphor tree found in Borneo and Sumatra... 

The bulk of the oil boiled between 190 and 220. The following ter-penes were identified in the oil o-pinene, y8-pinene, 1-limonene, dipen-tene, and X-terpinene. A considerable amount of a-terpinene was found (this had previously been identified by Teeple), as well as borneol and methyl-chavicol. Fenchyl alcohol was also found as a constituent of the oil, and traces of camphor and cineol. The presence of fenchyl alcohol is of particular interest as it occurs in the inactive variety. It is well known that this body results from the reduction of fenchone, but it has never before been discovered as a natural constituent of an essential oil The table below shows the character of the fenchyl alcohol occurring in this oil and of those prepared by the reduction of active and inactive fenchone. 

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