Halides with alcohols

Sulfonic esters are most frequently prepared by treatment of the corresponding halides with alcohols in the presence of a base. The method is much used for the conversion of alcohols to tosylates, brosylates, and similar sulfonic esters. Both R and R may be alkyl or aryl. The base is often pyridine, which functions as a nucleophilic catalyst, as in the similar alcoholysis of carboxylic acyl halides (10-21). Primary alcohols react the most rapidly, and it is often possible to sulfonate selectively a primary OH group in a molecule that also contains secondary or tertiary OH groups. The reaction with sulfonamides has been much less frequently used and is limited to N,N-disubstituted sulfonamides that is, R" may not be hydrogen. However, within these limits it is a useful reaction. The nucleophile in this case is actually R 0 . However, R" may be hydrogen (as well as alkyl) if the nucleophile is a phenol, so that the product is RS020Ar. Acidic catalysts are used in this case. Sulfonic acids have been converted directly to sulfonates by treatment with triethyl or trimethyl orthoformate HC(OR)3, without catalyst or solvent and with a trialkyl phosphite P(OR)3. ... 

The first palladium-catalyzed formation of aryl alkyl ethers in an intermolecular fashion occurred between activated aryl halides and alkoxides (Equation (28)), and the first formation of vinyl ethers occurred between activated vinyl halides and tin alkoxides (Equation (29)). Reactions of activated chloro- and bromoarenes with NaO-Z-Bu to form /-butyl aryl ethers occurred in the presence of palladium and DPPF as catalyst,107 while reactions of activated aryl halides with alcohols that could undergo /3-hydrogen elimination occurred in the presence of palladium and BINAP as catalyst.110 Reactions of NaO-/-Bu with unactivated aryl halides gave only modest yields of ether when catalyzed by aromatic bisphosphines.110 Similar chemistry occurred in the presence of nickel catalysts. In fact, nickel catalysts produced higher yields of silyl aryl ethers than palladium catalysts.108 The formation of diaryl ethers from activated aryl halides in the presence of palladium catalysts bearing DPPF or a CF3-subsituted DPPF was also reported 109... 

Glycosyl perchlorates are formed on treating glycosyl halides with silver perchlorate in inert solvents, and react readily with alcohols to give glycosides, but they have been reported to explode when heated > so their use in direct displacement reactions has understandably been limited. These esters have, however, presumably been present as intermediates in the many reactions of glycosyl halides with alcohols in which silver perchlorate was used as a catalyst (e.g. Ref. s )). 

From Boron Halides. Using boron halides is not economically desirable because boron halides are made from boric acid. However, this method does provide a convenient laboratory synthesis of boric acid esters. The esterification of boron halides with alcohol is analogous to the classical conversion of carboxylic acid halides to carboxylic esters. Simple mixing of the reactants at room temperature or below in a solvent such as methylene chloride, chloroform, pentane, etc, yields hydrogen halide and the borate in high yield. 

The molecular complexity of molybdenum (IV) alkoxides is determined by the size and ramification of the alkyl group — the polymeric (R = Me), dimeric (CN = 5, two bridging OR-groups, R = Pr ) with a double metal-metal bond, and even monomers (R = Bu ). The first representatives of W(OR)4 homologous series are tetramers with the [Ti4(OMe)16]-type structure. The derivatives of ramified or bulky alcohols are known only as mixed-ligand complexes (such as dimeric solvates of alkoxide halids with alcohols, various alkoxide hidrides and monomeric complexes with phenantroline, see Table 12.19). 

Reaction of phosphorus and sulfur halides with alcohols... 

Treatment of an alkyl halide with alcoholic AgN03 often promotes ionization. 

Phosphites can be very easily prepared by the reaction of a phosphorus halide with alcohol and an organic base, typically triethylamine or pyridine.36 It is generally necessary to use low temperatures and to keep the reaction free from moisture and air. If diols are used, reaction conditions can be adjusted so that oxygen either... 

The following Subsections deal in more detail with the condensation of 0-acetylglycosyl halides with alcohols and phenols, in the presence of different acid acceptors. 

Formation of M-H complexes by refluxing metal halides, or complex halides, with alcohols in the presence of stablizing hands occurs via formation of a metal alkoxide followed by j -hydride elimination . This reaction represents the reverse of insertion of an aldehyde or ketone into an M-H bond. 

Aryl thionoesters (54a) may be prepared by nucleophilic substitution reactions of aryl thiocarbonyl halides with alcohols or phenols for instance, thiobenzoyl chloride (58) condenses with phenol to yield the diaryl ester (54a) (Scheme 30). 

Palladium-catalysed carbonylation of halides, with carbon monoxide, can be used to prepare esters, amides and ketones by trapping the intermediate acylpalladium halide with alcohols,amines and organometal-lics, respectively. Boronic acids are probably the best organometallics for the preparation of ketones, but conditions must be adjusted to give the best selectivity between the acylation reaction and simple Suzuki coupling of the boronic acid with the starting halide. ... 

The carbonylation of aryl halides with alcohols and amines catalysed by palladium complexes with triphenylphosphine ligand is the convergent and direct route to the synthesis of aromatic esters as well as aromatic amides. Even though these palladium complexes are widely employed as the best catalytic system, those catalysts are difficult to separate and reuse for the reaction without further processing. The major drawbacks are oxidation of triphenylphosphine to phosphine oxide, reduction of palladium complex to metal and termination of the catalytic cycle. The phosphine-free, thermally stable and air resistant catalyst (1) containing a carbon-palladium covalent bond (Figure 12.3) has been found to be a highly selective and efficient catalyst for the carbonylation of aryl iodides.[1]... 

Y Ukisu, TJ Miyadera. Hydrogen transfer hydrodechlorination of aromatic halides with alcohols in the presence of noble metal catalysts. Mol. Catal. A Chemical 125 135-142,1997. 

The resulting mechanism is therefore the usual one allowing, e.g., the Williamson ether synthesis through alkylation of alkyl halides with alcohols in the presence of 50% NaOH and Bu4N HS04 as catalyst [27]. 

The coupling of sugar derivatives in solution has been used for the preparation of many individual disaccharides and trisaccharides, usually by the Koenigs Knorr 93,94) and Helferich (95-97) reactions. These are reactions of esterified glycosyl halides with alcohols, catalyzed by silver or mercury ions. However, yields have ordinarily been low, and a mixture of a and /S configurations is usually formed at C-1. (Application of these reactions to polymer formation is discussed below.)... 

The combination of alkali metal salts of carboxylic acids and alkyl halides seldom finds use in ester synthesis owing to low yields. The crucial 0-C bond formation is a hard-soft interaction. In contrast, the efficient reaction of acyl halides with alcohols consists of a hard-hard interaction. 

In chemistry related to the reactions of alkali metal alkoxides with late metal halide complexes, late metal alkoxides have been formed by the reaction of alcohols with metal halides in the presence of a base. This process has been used to form arylpalladium alkoxides during the coupling of aryl halides with alcohols discussed in Chapter 19 (cross-coupling). In addition, Milstein used an intramolecular version of this process to prepare the metallaoxetane in Equation 4.68. ... 

Copper-Catalyzed Coupling of Aryl Halides with Alcohols and Thiols... 

The combination of N,N-dimethylglycine and Cul also catalyzes the coupling of aryl halides with alcohols. The scope of the reaction of aryl iodides with primary aliphatic alcohols in the presence of this catalyst was similar to that of the reaction catalyzed by copper complexes of 1,10-phenanthroline derivatives, but the scope of the reactions catalyzed by the complexes of tetrametlnylphenanthroline was somewhat broader. 

Direct Reactions of Metal Halides with Alcohols (Method D)... 

Scheme 2.1 Schematic of nonhydrolytic hydroxylation reactions, (a) Reaction of metal halides with alcohols coordination of the alcohol to the metal center, followed by elimination of an alkyl halide RX. (b) Guerbet-type reaction of a metal isopropoxide with benzyl...

An outstanding point which emerged from my early work on the interaction of hydroxy compounds and inorganic nonmetal halides, such as thionyl and phosphorus halides, was the vital function of the hydrogen halide formed in the reaction pattern. The interaction of hydrogen halides with alcohols, esters, and ethers has also operational importance. 

Silver oxide or silver carbonate is the catalyst most commonly used for the condensation of acetylglycosyl halides with alcohols or phenols. Except in the case of the lower aliphatic alcohols, the aglycone is dissolved in a dry solvent, which is often an organic base to promote the forward reaction. With phenols, but not alcohols, the use of sodium or potassium hydroxide Reftrtnees p. 15a... 

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