Alcohols, tertiary degradation

A special category of ethers are trimethylsilyl ethers. Trimethylsilyl ethers of primary alcohols, on treatment with Jones reagent, give acids [590]. On treatment with A-bromosuccinimide under irradiation, trimethylsilyl ethers yield esters [744]. Secondary alkyl trimethylsilyl ethers are converted into ketones by oxidation with both reagents [590, 744, 981]. Oxidation with Jones reagent is regiospecific the 2-ferf-butyldimethylsilyl 11-Krf-butyldiphenylsilyl ether of 2,11-dodecanediol is oxidized only in the sterically less hindered position [590]. Trimethylsilyl ethers of tertiary alcohols are degraded by periodic acid to carboxylic acids with shorter chains [755] (equations 336-339). 

Tertiary alcohols are usually degraded unselectively by strong oxidants. Anhydrous chromium trioxide leads to oxidative ring opening of tertiary cycloalkanols (L.F. Fieser, 1948). 

As with chromic acid, tertiary alcohols are oxidised only very slowly with degradation. The rate expression for oxidation of secondary alcohols is ... 

Epoxides can react with alcohols via acidic or basic catalysed reaction mechanisms. However, since both strong acids and bases will degrade the cell wall polymers of wood, the reaction is usually catalysed via the use of amines, which are more strongly nucleophilic than the OH group. For example, whereas the production of epoxy-phenolic resins requires temperatures in the region of 180-205 °C, reaction between epoxides and primary or secondary amines takes place at 15 °C (Turner, 1967). Reaction of epoxides with wood often involves the use of tertiary amines as catalysts (Sherman etal., 1980). The sapwood is more reactive towards epoxides than heartwood (Ahmad and Harun, 1992). 

This beneficial effect of fluorination on hydrolytic stability has also been demonstrated with the synthetic prostaglandin SC-46275 (Fig. 70). This compound possesses an anti-secretory activity that protects the stomach mucous membrane. However, its clinical development was too problematic because of the instability of the tertiary allyl alcohol in acidic medium (epimerisation, dehydration, etc.). A fluorine atom was introduced on the C-16 methyl to disfavour the formation of the allylic carbocation. This fluorinated analogue possesses the same biological activity, but does not undergo any degradation or rearrangement, and itepimerises only slowly [165]. 

MIESCHER DEGRADATION. Adaptation of the Barbier-Wieland carboxylic acid degradation to pcrmil simultaneous elimination of three carbon atoms, as in degradation of the bile acid side chain to the methyl ketone stage. Conversion of the methyl ester of the bile acid to the tertiary alcohol, followed by dehydration, bromination. dehydrohalogenatinn, and oxidation of the diene yields die required degraded ketone. 

Chlorides can be prepared in this way from primary and secondary, but not tertiary, alcohols. In practice, an equivalent of a weak base, such as pyridine (azabenzene), is added to neutralize the hydrogen chloride that is formed. If the acid is not removed, undesirable degradation, elimination, and rearrangement reactions may occur. 

Methylpropene can be removed from the reaction mixture by distillation and easily is made the principal product by appropriate adjustment of the reaction conditions. If the 2-methylpropene is not removed as it is formed, polymer and oxidation products become important. Sulfuric acid often is an unduly strenuous reagent for dehydration of tertiary alcohols. Potassium hydrogen sulfate, copper sulfate, iodine, phosphoric acid, or phosphorus pentoxide may give better results by causing less polymerization and less oxidative degradation which, with sulfuric acid, results in the formation of sulfur dioxide. 

Unlike the reactions discussed previously in this chapter, oxidation of alcohols involves the alkyl portion of the molecule, or more specifically, the C-H bonds of the hydroxyl-bearing carbon (the a carbon). Secondary alcohols, which have only one such C-H bond, are oxidized to ketones, whereas tertiary alcohols, which have no C-H bonds to the hydroxylic carbon, are oxidized only with accompanying degradation into smaller fragments by cleavage of carbon-carbon bonds. 

Figure 80 Vitamin D analog degradation under aqueous conditions leads to elimination of the tertiary alcohol.

Tertiary hydroxyls can undergo several reactions under acidic conditions to form artifacts in degradation experiments. In acidic acetonitrile/ water solutions, primary, secondary and tertiary alcohols can undergo a Ritter reaction to form amides (Fig. 83). 

Cinnamyl alcohols such as 95 were converted to the corresponding oxetane 96 by reaction with bis-(collidine)bromine(l) hexafluorophosphate (Equation 32) via a 4- r/o-/r7g-electrophilic cyclization <1999JOC81, 2001TL2477>. High yields of oxetanes (up to 88%) were only achieved with tertiary alcohols, with secondary alcohols giving mainly degradation products. 

Parks, G.S., Barton, B. (1928) Vapor pressure data for isopropyl alcohol and tertiary butyl alcohol. J. Am. Chem. Soc. 50, 24—50. Pasanen, M., Uusi-Kyyny, R, Pokki, J.-R, Pakkanen, M., Aittamaa, J. (2004) Vapor-hquid equilibrium for 1-propanol -1- 1-butene, -1- cis-2-butene, -1- 2-methyl-1-propene, -1- fra i-2-butene, -1- -butane, and -1- 2-methyl-propane. J. Chem. Eng. Data 49, 1628-1634. Petriris, V.E., Geankopolis, C.J. (1959) Phase equilibrium in 1-butanol-water-lactic acid system. J. Chem. Eng. Data 4, 197-198. Pitter, P. (1976) Determination of biological degradability of organic substances. Water Res. 10, 231. 

Other oxidations with singlet oxygen are conversions of alkenes into epoxides [43, of secondary alcohols into ketones via alcohol hydroperoxides [44, 45] (equation 9) and the oxidative degradation of tertiary amines to secondary amines [46] (equation 10). 

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