Alcohols, primary complex

Another situation is observed when salts or transition metal complexes are added to an alcohol (primary or secondary) or alkylamine subjected to oxidation in this case, a prolonged retardation of the initiated oxidation occurs, owing to repeated chain termination. This was discovered for the first time in the study of cyclohexanol oxidation in the presence of copper salt [49]. Copper and manganese ions also exert an inhibiting effect on the initiated oxidation of 1,2-cyclohexadiene [12], aliphatic amines [19], and 1,2-disubstituted ethenes [13]. This is accounted for, first, by the dual redox nature of the peroxyl radicals H02, >C(0H)02 and >C(NHR)02 , and, second, for the ability of ions and complexes of transition metals to accept and release an electron when they are in an higher- and lower-valence state. 

Many transition-metal complexes have been reported as catalysts of this reaction, including [lr(g-Cl)(coe)2]2 [74] and [lrH2(solv.)(PPh3)][SbF6] [75]. The latter catalyst appeared to be a very active and highly selective. The hydroxyl group can be selectively silylated, even in the presence of other potentially reactive C=C and C=0 groups. The order of relative reactivities of alcohol isomers is secondary alcohol > primary alcohol > tertiary alcohol. 

Selective oxidation of alcohols. Primary alcohols are oxidized by this RuCL complex about 50 times as rapidly as secondary alcohols. Use of benzene as solvent is critical lor this high selectivity. Little or no reaction occurs in CH3CN, THF, or DMF. Most oxidants, if they show any selectivity, oxidize secondary alcohols more rapidly than primary ones. However, ruthenium-catalyzed oxidations with N-mcthylmorpholine N-nxide and oxidations with PCC4 proceed about three times as rapidly with primary alcohols as with secondary ones. 

The TV-methoxy-jV-methylamide of tiglic acid (17) is used as an aeylating agent in a procedure developed by Weinreb.9 Lithiated aromatic species 18 attacks Weinreb amide 17 with formation of the chelate 19. which is hydrolyzed to ketone 5. Use of Weinreb amide 17 circumvents the primary threat here multiple addition and formation of a tertiary alcohol. Since complex 19 decomposes only in the course of workup, the ketone 5 itself is protected against further nucleophilic attack.10 "BuLi, LiCl. THF. 0 C->RT 17. 77%. 

Borane also reduces carboxylic acids to primary alcohols. Borane (complex with 1HF see Section 8-7) reacts with the carboxyl group faster than with any other carbonyl function. It often gives excellent selectivity, as shown by the following example, where a carboxylic acid is reduced while a ketone is unaffected. (LiAlH4 would also reduce the ketone.)... 

The same authors [42] reported the synthesis of 1 1 complexes between 2,2 -di(4-hydroxyphenyl)propane (13) and several alcohols, primary amines, hydrazine, and methylhydrazine (14). In this context the structure of the complex 13 14, has been elucidated by means of X-ray crystallography (Scheme 4) [43],... 

Although the cyclic dimers are connected by additional H-bonds, the authors did not observe a super-tetrahedral network. Notably, a 2 1 alcohol-amine complex 14 15, was also observed [41] between 4-methoxyphenol (15) and methylhydrazine (14) (Scheme 5). Thus, a dimer formed by a primary amine and a secondary amine in such cases does not have the general requisites to generate a supramolecular architecture. 

Trimethylsilyl chlorochromate gives good yields for secondary alcohols and benzylic alcohols, but saturated primary alcohols give complex mixtures. It will also oxidise thiols to disulfides, and cleave... 

In contrast to the tertiary alcohols, primary (e.g., ethyl alcohol) and secondary alcohols e.g., isopropyl alcohol) decompose to products at temperatures above 800 °K via complex free radical chain processes . This mechanistic inversion is not surprising. Based on the magnitude of substituent effects in four-center elimination reactions, particularly the variations found in the series r-BuCI, i-PrCl, EtCl - , one would estimate that the isopropyl alcohol unimolecular elimination of water should have an activation energy about 6 kcal.mole higher than that for r-butyl alcohol. The. 4-factor can be estimated by transition state methods, and one obtains for the unimolecular decomposition... 

The TPAP/NMO system [24] and the Dess-Martin periodinane [31] have been widely applied for oxidizing alcohols in complex natural product synthesis. Although both reagents are commercially available, they have so far found relatively little use in carbohydrate chemistry for oxidation of primary alcohols to aldehydes [44,45]. 

Cartoni et al. [88] studied perspective of the use as stationary phases of n-nonyl- -diketonates of metals such as beryllium (m.p. 53°C), aluminium (m.p. 40°C), nickel (m.p. 48°C) and zinc (liquid at room temperature). These stationary phases show selective retention of alcohols. The retention increases from tertiary to primary alcohols. Alcohols are retained strongly on the beryllium and zinc chelates, but the greatest retention occurs on the nickel chelate. The high retention is due to the fact that the alcohols produce complexes with jS-diketonates of the above metals. Similar results were obtained with the use of di-2-ethylhexyl phosphates with zirconium, cobalt and thorium as stationary phases [89]. 6i et al. [153] used optically active copper(II) complexes as stationary phases for the separation of a-hydroxycarboxylic acid ester enantiomers. Schurig and Weber [158] used manganese(ll)—bis (3-heptafiuorobutyryl-li -camphorate) as a selective stationary phase for the resolution of racemic cycUc ethers by complexation GC. Picker and Sievers [157] proposed lanthanide metal chelates as selective complexing sorbents for GC. Suspensions of complexes in the liquid phase can also be used as stationary phases. Pecsok and Vary [90], for example, showed that suspensions of metal phthalocyanines (e.g., of iron) in a silicone fluid are able to react with volatile ligands. They were used for the separation of hexane-cyclohexane-pentanone and pentane-water-methanol mixtures. 

Oxidation of alcohols. The complex oxidizes benzyl alcohol to benzaldehyde in yields as high as 97%, but in general primary alcohols such as 1-butanol are oxidized only in low yields. However, secondary alcohols are oxidized to ketones in satisfactory yield (50-707 ). 

After these initial results by Tsuji, this elementary step was incorporated into a catalytic process by Hata and co-workers at Toray Industries and by Atkins and co-workers at Union Carbide. These groups reported reactions of allylic phenyl ethers, allylic alcohols, and allylic acetates with carboxylates, alcohols, primary and secondary amines, and methyl acetoacetate catalyzed by Pd(0) complexes and precursors to Pd(0) complexes (Equation 20.3). - After these initial reports, early developments focused on reactions of "soft" carbanions derived from 3-dicarbonyl compounds, cyanoesters, and related compounds containing two electron-withdrawing groups attached to the nucleophilic carbon. Although these reactions occur with allylic halides in the absence of a catalyst, these reactions are greatly accelerated by palladium catalysts. Thus, the palladium catalyst allows these reactions to occur under mild conditions with allylic acfetates, which are more accessible than allylic halides, and with selectivities that are altered by the metal catalyst. 

As in the case of sec-alcohols, ruthenium complex has also been investigated as a catalyst in the racemization of primary amines. In fact, Shvo s complex 2 (Figure 14.3) was employed by the Backvall s group as the catalyst of the racemization of amines under transfer hydrogenation conditions [105]. However, temperatures up to 110 °C were required for amine racemization, incompatible with the lipase resolution, and furthermore, side products were formed in the medimn and a hydrogen source was needed. To avoid these drawbacks, the racemization at high temperature was carried out after a first lipase-catalyzed KR, followed by a second KR process, and a hydrogen source such as 2,4-dimethylpentan-3-ol was employed. 

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

The first practical method for asymmetric epoxidation of primary and secondary allylic alcohols was developed by K.B. Sharpless in 1980 (T. Katsuki, 1980 K.B. Sharpless, 1983 A, B, 1986 see also D. Hoppe, 1982). Tartaric esters, e.g., DET and DIPT" ( = diethyl and diisopropyl ( + )- or (— )-tartrates), are applied as chiral auxiliaries, titanium tetrakis(2-pro-panolate) as a catalyst and tert-butyl hydroperoxide (= TBHP, Bu OOH) as the oxidant. If the reaction mixture is kept absolutely dry, catalytic amounts of the dialkyl tartrate-titanium(IV) complex are suflicient, which largely facilitates work-up procedures (Y. Gao, 1987). Depending on the tartrate enantiomer used, either one of the 2,3-epoxy alcohols may be obtained with high enantioselectivity. The titanium probably binds to the diol grouping of one tartrate molecule and to the hydroxy groups of the bulky hydroperoxide and of the allylic alcohol... 

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). 

The conversion of primary alcohols and aldehydes into carboxylic acids is generally possible with all strong oxidants. Silver(II) oxide in THF/water is particularly useful as a neutral oxidant (E.J. Corey, 1968 A). The direct conversion of primary alcohols into carboxylic esters is achieved with MnOj in the presence of hydrogen cyanide and alcohols (E.J. Corey, 1968 A,D). The remarkably smooth oxidation of ethers to esters by ruthenium tetroxide has been employed quite often (D.G. Lee, 1973). Dibutyl ether affords butyl butanoate, and tetra-hydrofuran yields butyrolactone almost quantitatively. More complex educts also give acceptable yields (M.E. Wolff, 1963). 

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