Alcohols, general secondary

Low-molecular-weight products, generally secondary metabolites such as alcohols, carboxyhc and an iino acids, antibiotics, and vitamins, can be recovered using many of the standard operations such as liquid-hquid extraction, adsorption and ion-exchange, described elsewhere in this handbook. Proteins require special attention, however, as they are sufficiently more complex, their function depending on the integrity of a delicate three-dimensional tertiaiy structure that can be disrupted if the protein is not handled correctly. For this reason, this section focuses primarily on protein separations. Cell separations, as a necessary part of the downstrean i processing sequence, are also covered. 

AC2O, Pyr, 20°, 12 h, 100% yield. This is one of the most common methods for acetate introduction. By running the reaction at lower temperatures good selectivity pan be achieved for primary alcohols over secondary alcohols. Tertiary alcohols are generally not acylated under these conditions. 

STEP 2. The experiments with ethanol, n-propanol, isopropanol, and n-butanol already described or mentioned indicate that a variety of alcohols can be used in the second step. It appears that unhindered primary and secondary alcohols generally will be suitable. 

The addition of alkoxides to 2-nitro-l-phenylthio-l-alkenes affords P-nitro-aldehyde acetals.276 The reaction of the same nitroalkenes with amines gives nitroenamines.270 They are important intermediates for organic synthesis and are generally prepared by the reaction of nitroalkanes with triethylorthoformate in the presence of alcohols or secondary amines.2"1 0 The methods of Eqs. 4.20 and 4.21 have some merits over the conventional methods, for variously substituted (3-nitro-aldehydes acetals or nitroenamines are readily prepared by these methods. 

Tertiary Alkyl Alcohols. Tertiary alkyl alcohols generally undergo facile reduction when treated with acids in the presence of organosilicon hydrides.127,136 This comparative ease of reduction reflects the enhanced stability and ease of formation of tertiary alkyl carbenium ions compared with primary and secondary carbenium ions. Thus, treatment of 1-methylcyclohexanol with mixtures of triethylsilane and aluminum chloride in dichloromethane produces near quantitative yields of methylcyclohexane with or without added hydrogen chloride in as little as 30 minutes at room temperature, in contrast to the more vigorous conditions needed for the reduction of the secondary alcohol cyclohex-anol.136... 

Tungsten-catalysed oxidation of alcohols by hydrogen peroxide is achieved in high yield in the presence of tetra-n-butylammonium hydrogen sulphate [20-22]. Secondary alcohols are converted into ketones (>90%) [e.g. 21], but primary alcohols generally are oxidized completely to the carboxylic acids [21], Aldehydes are also oxidized to the carboxylic acids [e.g. 21]. In contrast, using procedure 10.7.8.B, which is adaptable to scale up, benzyl alcohols are converted into the aldehydes benzoic acids are only formed with an excess of hydrogen peroxide [22],... 

The order of acidity of various liquid alcohols generally is water > primary > secondary > tertiary ROH. By this we mean that the equilibrium position for the proton-transfer reaction (Equation 15-1) lies more on the side of ROH and OHe as R is changed from primary to secondary to tertiary therefore, tert-butyl alcohol is considered less acidic than ethanol ... 

However, the reactivities of primary alcohols are much lower than the reactivities of secondary alcohols. While an increase in reactivity of 2-alcohols with increasing chain length can be expected on the basis of chemical reactivity, the decrease beyond C8 must have another origin, which may be reactant shape selectivity in the TS-1 catalyst. The 2-alcohol generally react faster than the 3-alcohol (Van der Pol et al., 1993b). 

Kinetic resolution of chiral aUylic alcohols.7 Partial (at least 60% conversion) asymmetric epoxidation can be used for kinetic resolution of chiral allylic alcohols, particularly of secondary allylic alcohols in which chirality resides at the carbinol carbon such as 1, drawn in accordance with the usual enantioface selection rule (Scheme I). (S)-l undergoes asymmetric epoxidation with L-diisopropyl tartrate (DIPT) 104 times faster than (R)-l. The optical purity of the recovered allylic alcohol after kinetic resolution carried to 60% conversion is often > 90%. In theory, any degree of enantiomeric purity is attainable by use of higher conversions. Secondary allylic alcohols generally conform to the reactivity pattern of 1 the (Z)-allylic alcohols are less satisfactory substrates, particularly those substituted at the /1-vinyl position by a bulky substituent. 

Oxidation of alcohols. 1 Secondary alcohols are oxidized to carbonyl compounds by Clayfen in pentane or hexane under vigorous stirring. Primary benzyl alcohols are oxidized satisfactorily, but primary aliphatic alcohols are oxidized to complex mixtures. Isolated yields are generally>80%. Nitrite esters (RONO) have been identified as intermediates. 

In general, secondary and tertiary alcohols do not give satisfying results in fluorination reactions with sulfur tetrafluoride when elimination reactions are possible they become an important side reaction, e.g, with secondary substrates such as l,1.1.4,4,4-hexafluorobutan-2-ol (2). ... 

Because of its particular solubility and that of the nonomers, a co-solvant has also been used (very often an alcohol). Generally this solvent induces secondary effects according to the solubility of the polymer in the alcohol ... 

The oxidation of secondary alcohols gives good to excellent yields of the corresponding ketones (Eqn. 21.1)28 while primary alcohols are oxidized to the aldehydes at low conversions and the acids at high conversions. 22.28 Secondary alcohols on the second carbon atom (P) of a chain react more rapidly than primary alcohols while secondary alcohols on other carbon atoms of the chain (y) react more slowly. 28-29 The general order for the oxidation of alcohols on a linear carbon chain is P > a > y.28 The difference in activity between the P and Y alcohols has been ascribed to a difference in the transition state restrictions in these oxidations. These reactions are usually run in moderately dilute solutions at temperatures between 50°-70°C. 

Tri-n-butylstannylpropanol was found to be an excellent catalyst, superior to DBTDL, in catalyzing the reaction of aromatic isocyanates with tertiary alcohols. Generally DBTDL and other dialkyltin catalysts show diminished catalysis with secondary and tertiary hydroxyl groups. 

Reactions of acetyl chloride that are formally analogous to hydrolysis occur with alcohols, mercaptans, and amines primary or secondary compounds form corresponding acetates or amides tertiary alcohols generally yield the tertiary alkyl chlorides. Acetyl chloride can split the ether linkages of many ordinary ethers and acetals. It equilibrates with fatty acids to provide measureable amounts of the mixed acetic—alkylcarboxylic anhydride or acyl chloride, either of which may be employed in esterifications. For example, lauric acid [143-07-7], and acetyl chloride undeigo the reactions... 

Organic isocyanates are very reactive with compounds that possess active hydrogens, as in the case of carboxylic acids, primary and secondary amides, primary and secondary amines, alcohols, phenols, and water. The relative reactivity of these compounds with isocyanate depends upon the nucleophilicity and steric structure of the attacking compound. Primary and secondary amines are typically most reactive, followed by primary alcohols, water, secondary alcohols, and phenols in that general order. Carboxylic acids and amides are the least reactive with isocyanate. Of course, deprotonation may increase nucleophilicity. For example, a phenoxide anion will be much more reactive than a phenol, and probably more reactive than a primary alcohol. Regarding the isocyanate, one should realize that the various NCO groups in pMDI also have variable reactivity. Isocyanate... 

The addition of primary alcohols onto 2 takes place as readily as that of secondary amines. For instance, Marcos et al. [20] built up the natural halimanolide 9 as occurring in Polyalthia langifolia by cyclizing the corresponding alcohol 8 with ylide 2 (Scheme 2, top). A similar butenoHde was prepared likewise by Nishiyama et al. [21]. Tertiary alcohols generally require... 

Open-chain methyl- and ethyl-ketones are readily reduced by TBADH to furnish the corresponding secondary alcohols, generally with excellent specificities [810]. Similarly, co-haloalkyl- [732, 811] and methyl- or trifluoromethyl ketones possessing heterocyclic substituents were converted into the corresponding secondary... 

This substitution reaction provides a useful general route to alkyl halides. Because halide ions are good nucleophiles, we obtain mainly substitution products instead of dehydration. Once again, the reaction rate and mechanism depend on the class of alcohol (tertiary, secondary, or primary). 

Little further was substantiated about cholic acid (or about bile acids generally) for nearly five decades. The name, cholic acid, had become well established, but trivial names based partly on imperfect characterization were common, so that consideration of nomenclature was a part of Wieland s first report on the bile acids in 1912 (56). A review of the evidence then available included that cholic acid was a trihydroxy, monocarboxylic acid and that two of the alcohols were secondary. The final presentation of the structure of cholic acid awaited the correct steroid formulation in 1932 (113, 114). By that time the structural relationship between the sterols and bile acids was well established. The preparation of cholanic acid from cholic acid had been reported in the paper by Wieland and Weil in 1912 (56). The preparation of cholanic acid from cholesterol (through coprostane) was reported in 1919 by Windaus and Neukirchen (55). 

Secondary alcohols generally produce a cloudiness within 3-10 min. The solution may have to be heated to obtain a positive test. 

Figure 8.2. A schematic representation of the results of oxidation of tertiary, secondary, and primary alcohols. Generally, the R groups shown can be alkyl, aryl, and so on, but, except for the primary alcohol (R=H is methanol, CH3OH), not hydrogen (H). Aldehydes are easily oxidized to carboxylic acids. The abbreviation [O] is meant to indicate that oxidation occurs.

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