Alkylation with 1-butyl alcohol

The nucleophUic reactivity in neutral medium has been used extensively to prepare various thioethers of thiazole (122). In acidic medium, alkylation may be performed with alcohols (123, 124). An unexpected reaction encountered was the decarboxylation of 2-mercapto-4-methyl-5-thiazolecarboxyhc acid (60) when treated with butyl alcohol under acidic conditions (Scheme 27) (123). Reaction between A-4-thiazoline-2-thione... 

The anti-Markovnikov alkylation of phenol (PhOH) with /-butyl alcohol (/-BuOH) can be achieved in supercritical water at 673 K in the absence of an added catalyst. 

Under appropriate conditions activated thiazoles are alkylated at the 5-position 2-amino 4-methylthiazole is alkylated in the 5-position by heating with /-butyl alcohol in sulfuric acid (24). Under similar conditions 4-methyl-2-phenylthiazole is alkylated by cyclohexanol. 2-Acetylamino-4-methylthiazole reacts with dimethylamine and formaldehyde to afford the corresponding Mannich base (25). 2-Hydroxy-4-methyIthiazole fails to react when submitted to Friedel-Crafts benzoylation conditions whereas it reacts normally in Gatter-mann and in Reimer-Tiemann formylation reactions yielding the 5-formyl derivative (26). 2,4-Dimethylthiazole undergoes perfluoroalkylation when heated at 200 °C for 8 h in a sealed tube with perfluoropropyl iodide and sodium acetate (27). 

N-Sitylimine 89 in ether at -78°C was asymmetrically alkylated with butyl-Uthium in the presence of the diUthium alkoxide of the chiral diol 93 (76%, 62% ee) (Scheme 27) [76]. Addition of the preformed (-)-sparteine (19)-BuLi complex to benzaldehyde N-diisobutylaluminoimine 90, prepared in situ from partial reduction of benzonitrile with diisobutylaluminum hydride, in pentane at -78°C gave the primary amine 92 in good ee (70% yield, 74% ee) [77]. The use of polymer-supported amino alcohol 94 in THF at -78°C allows the asymmetric alkylation of an M-borylimine 91 to give the primary amine 92 with 44% ee [77]. 

A method of preparation of 2-pyridone from pyridine in 50% overall yield via the N-oxide and XII-424 is recommended by Chumakov. The 2-pyridone, free of water and acetic acid, is prepared from XII-424 by heating with -butyl alcohol. When an alkyl group occupies the 2- or 4-position (e.g., XII-425 to Xn-427) substitution at the a-position of the side-chain predominates and is usually accompanied by some reaction at the... 

We can extend the general principles of electrophilic addition to acid catalyzed hydration In the first step of the mechanism shown m Figure 6 9 proton transfer to 2 methylpropene forms tert butyl cation This is followed m step 2 by reaction of the car bocation with a molecule of water acting as a nucleophile The aUcyloxomum ion formed m this step is simply the conjugate acid of tert butyl alcohol Deprotonation of the alkyl oxonium ion m step 3 yields the alcohol and regenerates the acid catalyst... 

We now have a new problem Where does the necessary alkene come from Alkenes are prepared from alcohols by acid catalyzed dehydration (Section 5 9) or from alkyl halides by dehydrohalogenation (Section 5 14) Because our designated starting material is tert butyl alcohol we can combine its dehydration with bromohydrm formation to give the correct sequence of steps... 

Propylene oxide [75-56-9] is manufactured by either the chlorohydrin process or the peroxidation (coproduct) process. In the chlorohydrin process, chlorine, propylene, and water are combined to make propylene chlorohydrin, which then reacts with inorganic base to yield the oxide. The peroxidation process converts either isobutane or ethylbenzene direcdy to an alkyl hydroperoxide which then reacts with propylene to make propylene oxide, and /-butyl alcohol or methylbenzyl alcohol, respectively. Table 1 Hsts producers of propylene glycols in the United States. 

All lation of Aromatic Amines and Pyridines. Commercially important aromatic amines are aniline [62-53-3] toluidine [26915-12-8], phenylenediamines [25265-76-3], and toluenediamines [25376-45-8] (see Amines, aromatic). The ortho alkylation of these aromatic amines with olefins, alcohols, and dienes to produce more valuable derivatives can be achieved with soHd acid catalysts. For instance, 5-/ f2 butyl-2,4-toluenediamine (C H gN2), which is used for performance polymer appHcations, is produced at 85% selectivity and 84% 2,4-toluenediamine [95-80-7] (2,4-4L)A)... 

The A-ring of the 17-ol (25) derived from equilenin 3-methyl ether is reduced rapidly under Birch reduction conditions, since the 1,4-positions are unsubstituted. The B-ring is reduced at a much slower rate, as is characteristic of aromatic compounds in which 1,4-reduction can occur only if a proton enters an alkylated position. Treatment of (25) with sodium and t-butyl alcohol in ammonia reduces only the A-ring to afford the corresponding 1,4-dihydro compound in over 85% yield.On the other hand,... 

In this regard Gedye et al. studied reactions of alkyl halides with bases in which the amounts of elimination and substitution were compared and a Diels-Alder reaction in which the ratio of endo to exo adducts was investigated [71]. In the first set of experiments, the ratios of elimination to substitution products for the reactions of 1-and 2-bromooctane with methoxide ion in methanol and with tert-butoxide ion in tert-butyl alcohol, obtained under MW heating in a sealed Teflon container, were compared with those found using normal reflux conditions (Scheme 4.25). 

Diethyl 7V-(t-butoxycarbonyl)phosphoramidate 18 is obtained from diethyl phospho-ramidate by successive treatment with oxalyl chloride and t-butyl alcohol. It forms a stable non-hydroscopic sodium salt, which reacts with a variety of alkyl halides in benzene in the presence of tetrabutylammonium bromide under phase-transfer conditions to give the corresponding TV-alkyl derivatives. The latter are cleaved by hydrogen chloride in benzene to yield amine hydrochlorides (equation 16)48. 

Symmetrical and unsymmetrical carbonates have also been obtained from the reaction of chloroformates with alcohols under soliddiquid conditions [55], and the reaction of carbamoyl fluorides with alcohols produces alkyl carbamates [58]. r-Butyloxycarbonylation of alcohols and phenols is effected by trans-esterification of di-r-butyl carbonate under basic phase-transfer catalysed conditions [59]. Yields tend to be high for the reaction with the phenols (>85%), but only moderate with the alcohols (30-81%). 

Alcohols, their corresponding olefins and alkyl cations are in equilibrium, with the alcohol generally predominating over the olefin (Purlee et al., 1955 Taft and Riesz, 1955 Boyd et al., 1960). The alkyl cation concentration is extremely low and this species never exists as more than a transient intermediate whose relation to the solvent is little known. In 5% H2SO4 the ratio of alcohol to olefin is about 1200 to 1 at 50° for the isobutylene-tertiary butyl alcohol system (Taft and Riesz, 1955). As the temperature increases the ratio of alcohol to olefin at equilibrium decreases (Boyd et al., 1960). This can be illustrated by examining the position of equilibrium in equation (8). Values of Kp, [alcohol (1)]/ [olefin (g)], were shown to vary from 5 54 at 50° to 1-34 at 70°. The equilibrium constant [alcohol (l)]/[olefin (1)] can be calculated from... 

Alkyl cations are thus not directly observed in sulphuric acid systems, because they are transient intermediates present in low concentrations and react with the olefins present in equilibrium. From observations of solvolysis rates for allylic halides (Vernon, 1954), the direct observation of allylic cation equilibria, and the equilibrium constant for the t-butyl alcohol/2-methylpropene system (Taft and Riesz, 1955), the ratio of t-butyl cation to 2-methylpropene in 96% H2SO4 has been calculated to be 10 . Thus, it is evident that sulphuric acid is not a suitable system for the observation of stable alkyl cations. In other acid systems, such as BFj-CHsCOOH in ethylene dichloride, olefins, such as butene, alkylate and undergo hydride transfer producing hydrocarbons and alkylated alkenyl cations as the end products (Roberts, 1965). This behaviour is expected to be quite general in conventional strong acids. 

Isobutylene is the most chemically reactive of the butylene isopiers. If the objective is just to get the isobutylene out of the C4 stream, it can be removed by reaction with methanol (CH3OH) to make MTBE (methyl tertiary butyl ether), by reaction with water to make TBA (tertiary butyl alcohol), by polymerization, or by solvent extraction. After that, butene-1 can be removed by selective adsorption or by distillation. That leaves the butene-2 components, together with iso- and normal butane, which are generally used as feed to an alkylation plant. 

A variety of other carbon nucleophiles have been alkylated with alcohols including malonate esters, nitroaUcanes, ketonitriles [119, 120], barbituric acid [121], cyanoesters [122], arylacetonitriles [123], 4-hydroxycoumarins [124], oxi-ndoles [125], methylpyrimidines [126], indoles [127], and esters [128]. Selected examples are given in Scheme 35. Thus, benzyl alcohol 15 could be alkylated with nitroethane 147, 1,3-dimethylbarbituric acid 148, phenylacetonitrile 149, methyl-pyrimidine 150, and even f-butyl acetate 151 to give the corresponding alkylated products 152-156. 

In the presence of tellurium tetrachloride, aromatic hydrocarbons are alkylated with reactive alkylating agents such as benzylic or t-butyl alcohols and chlorides. The yields are high with toluene but only moderate for benzene, p-xylene and anisole. Equivalent and catalytic amounts of tellurium tetrachloride, respectively, are required for the alcohols and... 

In addition to alkylation with alkyl halides, electrophilic amination has been achieved with di-(/< /r-butyl) azodi-carboxylate <2004HCA1016>, and reactions with aldehydes have generated alcohol derivatives <1999JOC8668, 2003TL671>. Dialkylation at the 5-position has also been achieved <1998TA3881>. 

Birch reduction-alkylation of (2S)-2-methoxymethyl-l-(2-phenylbenzoyl)pyrrolidine (1) gives products 2 in high diastereoselectivities29. In contrast to the previous examples, only one double bond remains in the product (if one equivalent of rm-butyl alcohol is used as proton donor). Formally this procedure is a stereoselective cis addition, and is thus particularly useful. Thus, two stereogenic centers are created in the same reaction step with high diastereoselectivities. Subsequent hydrolysis furnishes acids, whereas reaction with methyllithium yields chiral ketones29. 

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