Alcohols, Preparation Secondary

In the second step the enol ether introduced with GrignanI reagent 16 is converted into an aldehyde function. For this purpose the secondary alcohol prepared in the first step is mesylated and thus transformed into a good leaving group. 

Protection of the primary and acylation of the secondary alcohol prepares the way for an Ireland-Claisen rearrangement. The E-enolate is produced and the [3,3] sigmatropic rearrangement transmits the chirality across the alkene to set up two new centres. The mechanism of the Ireland-Claisen rearrangement is described above 94 and occurs suprafacially across the backbone of the molecule through a chair-like transition state. We hope you agree both with the relative stereochemistry of the new centres and the E stereochemistry of the new alkene. 

Thus, the chloroformates of primary and secondary alcohols, prepared by reaction of the alcohol with phosgene, are reduced to the corresponding alkane in excellent yield on reaction with tri-n-propylsilane in the presence of t-butyl peroxide at 140 °C yields are low for aryl and benzyl alcohols. A method for the direct replacement of the hydroxy-group of alcohols by alkyl or aryl groups has been described (see Scheme 11, ref. 67). 

List of secondary alcohol preparations presented in Organic Syntheses ... 

Aliphatic hydrocarbons can be prepared by the reduction of the readily accessible ketones with amalgamated zinc and concentrated hydrochloric acid (Clemmensen method of reduction). This procedure is particularly valuable for the prep>aration of hydrocarbons wdth an odd number of carbon atoms where the Wurtz reaction cannot be applied with the higher hydrocarbons some secondary alcohol is produced, which must be removed by repeated distillation from sodium. 

The Dess-Martin periodinane ( DMP ) reagent, U,l-tris(acetyloxy)-l,l-dihydro-l,2-benziodoxol-3(l//)-one, has also been used in several complex syntheses for the oxidation of primary or secondary alcohols to aldehydes or ketones, respectively (e.g., M. Nakatsuka, 1990). It is prepared from 2-iodobenzoic add by oxidation with bromic add and acetylation (D.a Dess, 1983). 

Secondary alcohols may be prepared by two different combinations of Grignard reagent and aldehyde... 

To the synthetic chemist the most important of the reactions m Table 17 1 are the last two the oxidation of primary alcohols to aldehydes and secondary alcohols to ketones Indeed when combined with reactions that yield alcohols the oxidation methods are so versatile that it will not be necessary to introduce any new methods for preparing aide hydes and ketones in this chapter A few examples will illustrate this point... 

It IS often necessary to prepare ketones by processes involving carbon-carbon bond formation In such cases the standard method combines addition of a Gngnard reagent to an aldehyde with oxidation of the resulting secondary alcohol... 

The primary alcohols CH3CH2CH2CH2OH and (CH3)2CHCH20H can each be prepared by hydrogenation of an aldehyde The secondary alcohol CH3CHCH2CH3 can be prepared by hydro... 

Miscellaneous Reactions. Sodium bisulfite adds to acetaldehyde to form a white crystalline addition compound, insoluble in ethyl alcohol and ether. This bisulfite addition compound is frequendy used to isolate and purify acetaldehyde, which may be regenerated with dilute acid. Hydrocyanic acid adds to acetaldehyde in the presence of an alkaU catalyst to form cyanohydrin the cyanohydrin may also be prepared from sodium cyanide and the bisulfite addition compound. Acrylonittile [107-13-1] (qv) can be made from acetaldehyde and hydrocyanic acid by heating the cyanohydrin that is formed to 600—700°C (77). Alanine [302-72-7] can be prepared by the reaction of an ammonium salt and an alkaU metal cyanide with acetaldehyde this is a general method for the preparation of a-amino acids called the Strecker amino acids synthesis. Grignard reagents add readily to acetaldehyde, the final product being a secondary alcohol. Thioacetaldehyde [2765-04-0] is formed by reaction of acetaldehyde with hydrogen sulfide thioacetaldehyde polymerizes readily to the trimer. 

In general, the reactions of the perfluoro acids are similar to those of the hydrocarbon acids. Salts are formed with the ease expected of strong acids. The metal salts are all water soluble and much more soluble in organic solvents than the salts of the corresponding hydrocarbon acids. Esterification takes place readily with primary and secondary alcohols. Acid anhydrides can be prepared by distillation of the acids from phosphoms pentoxide. The amides are readily prepared by the ammonolysis of the acid haUdes, anhydrides, or esters and can be dehydrated to the corresponding nitriles (31). 

Esters of nitro alcohols with primary alcohol groups can be prepared from the nitro alcohol and an organic acid, but nitro alcohols with secondary alcohol groups can be esterified only through the use of an acid chloride or anhydride. The nitrate esters of the nitro alcohols are obtained easily by treatment with nitric acid (qv). The resulting products have explosive properties but are not used commercially. 

Eatty alcohols, prepared from fatty acids or via petrochemical processes, aldol or hydroformylation reactions, or the Ziegler process, react with ammonia or a primary or secondary amine in the presence of a catalyst to form amines (10—12). 

Sulfation by sulfamic acid has been used ia the preparation of detergents from dodecyl, oleyl, and other higher alcohols. It is also used ia sulfating phenols and phenol—ethylene oxide condensation products. Secondary alcohols react ia the presence of an amide catalyst, eg, acetamide or urea (24). Pyridine has also been used. Tertiary alcohols do not react. Reactions with phenols yield phenyl ammonium sulfates. These reactions iaclude those of naphthols, cresol, anisole, anethole, pyrocatechol, and hydroquinone. Ammonium aryl sulfates are formed as iatermediates and sulfonates are formed by subsequent rearrangement (25,26). 

Sulfation andSulfamation. Sulfamic acid can be regarded as an ammonia—SO. complex and has been used thus commercially, always in anhydrous systems. Sulfation of mono-, ie, primary and secondary, alcohols polyhydric alcohols unsaturated alcohols phenols and phenolethylene oxide condensation products has been performed with sulfamic acid (see Sulfonation and sulfation). The best-known appHcation of sulfamic acid for sulfamation is the preparation of sodium cyclohexylsulfamate [139-05-9] which is a synthetic sweetener (see Sweeteners). 

Alkali Metal Xanthates. The commercially available xanthates are prepared from various primary or secondary alcohols. The alkyl group varies from to and the alkah metal may be sodium or potassium. Not all of the commercially available alcohols ia the range are available as... 

Alkali Fusion. Tha alkaU fusion of castor oil using sodium or potassium hydroxide in the presence of catalysts to spHt the ricinoleate molecule, results in two different products depending on reaction conditions (37,38). At lower (180—200°C) reaction temperatures using one mole of alkah, methylhexyl ketone and 10-hydroxydecanoic acid are prepared. The 10-hydroxydecanoic acid is formed in good yield when either castor oil or methyl ricinoleate [141-24-2] is fused in the presence of a high boiling unhindered primary or secondary alcohol such as 1- or 2-octanol. An increase to two moles of alkali/mole ricinoleate and a temperature of 250—275°C produces capryl alcohol [123-96-6] CgH gO, and sebacic acid [111-20-6] C QH gO, (39—41). Sebacic acid is used in the manufacture of nylon-6,10. 

Picolyl ethers are prepared from their chlorides by a Williamson ether synthesis (68-83% yield). Some selectivity for primary versus secondary alcohols can be achieved (ratios = 4.3-4.6 1). They are cleaved electrolytically ( — 1.4 V, 0.5 M HBF4, MeOH, 70% yield). Since picolyl chlorides are unstable as the free base, they must be generated from the hydrochloride prior to use. These derivatives are relatively stable to acid (CF3CO2H, HF/anisole). Cleavage can also be effected by hydrogenolysis in acetic acid. ... 

Codeinone, CjaHijOgN. This ketone (XLVII) corresponds to the secondary alcohol codeine and its stereoisomeride wocodeine. It may be prepared by oxidising codeine with potassium permanganate in acetone or with potassium dichromate in dilute sulphuric acid and in various other ways. Codeinone can be reduced to codeine electrolytically or by chemical methods. It crystallises from alcohol in prisms, m.p. 185-6, [a]J, ° — 205° (EtOH). The hydrochloride, B. HCl. HjO, has m.p. 179-80°, picrate, m.p. 205°, methiodide, B. CHjI. 2H2O, m.p. 180°. 

The important role played by the quinicines (rubatoxanones, quina-toxines) in the syntheses of the dihydrocinchona alkaloids and the possibility that such substances might be used for the preparation of products approaching quinine in therapeutical interest, has led to the production of a large number of quinolyl ketones of various types and the corresponding secondary alcohols, and other derivatives obtainable from them, of which mention may be made of Rubtzov s syntheses of several isomerides of dihydroquinine. ... 

The oxidation of alcohols by treatment of their corresponding chloroform-ates with DMSO and triethylamine has been reported by Barton. Preliminary results indicate this to be a useful method for preparation of aldehydes but cyclic secondary alcohols are converted to ketones in relatively low yields. 

A method that allows for alcohol preparation with formation of new carbon-carbon bonds. Primary, secondary, and tertiary alcohols can all be prepared. 

Picolyl ethers are prepared from their chlorides by a Williamson ether synthesis (68-83% yield). Some selectivity for primary vs. secondary alcohols can be achieved (ratios = 4.3-4.6 1). Picolyl ethers are cleaved electrolytically ( —1.4 V,... 

The application of the AE reaction to kinetic resolution of racemic allylic alcohols has been extensively used for the preparation of enantiomerically enriched alcohols and allyl epoxides. Allylic alcohol 48 was obtained via kinetic resolution of the racemic secondary alcohol and utilized in the synthesis of rhozoxin D. Epoxy alcohol 49 was obtained via kinetic resolution of the enantioenriched secondary allylic alcohol (93% ee). The product epoxy alcohol was a key intermediate in the synthesis of (-)-mitralactonine. Allylic alcohol 50 was prepared via kinetic resolution of the secondary alcohol and the product utilized in the synthesis of (+)-manoalide. The mono-tosylated 3-butene-1,2-diol is a useful C4 building block and was obtained in 45% yield and in 95% ee via kinetic resolution of the racemic starting material. 

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