Alcohols phenols, synthesis

For the classical Williamson synthesis an alcohol is initially reacted with sodium or potassium to give an alkoxide, e.g. 1. Alternatively an alkali hydroxide or amide may be used to deprotonate the alcohol. Phenols are more acidic, and can be converted to phenoxides by treatment with an alkali hydroxide or with potassium carbonate in acetone. ... 

Alternatively, the Sn2 nucleophilic substitution reaction between alcohols (phenols) and organic halides under basic conditions is the classical Williamson ether synthesis. Recently, it was found that water-soluble calix[n]arenes (n = 4, 6, 8) containing trimethylammonium groups on the upper rim (e.g., calix[4]arene 5.2) were inverse phase-transfer catalysts for alkylation of alcohols and phenols with alkyl halides in aqueous NaOH solution to give the corresponding alkylated products in good-to-high yields.56... 

The three-component synthesis of benzo and naphthofuran-2(3H)-ones from the corresponding aromatic alcohol (phenols or naphthols) with aldehydes and CO (5 bar) can be performed under palladium catalysis (Scheme 16) [59,60]. The mechanism involves consecutive Friedel-Crafts-type aromatic alkylation and carbonylation of an intermediate benzylpalla-dium species. The presence of acidic cocatalysts such as TFA and electron-donating substituents in ortho-position (no reaction with benzyl alcohol ) proved beneficial for both reaction steps. 

Abstract The basic principles of the oxidative carbonylation reaction together with its synthetic applications are reviewed. In the first section, an overview of oxidative carbonylation is presented, and the general mechanisms followed by different substrates (alkenes, dienes, allenes, alkynes, ketones, ketenes, aromatic hydrocarbons, aliphatic hydrocarbons, alcohols, phenols, amines) leading to a variety of carbonyl compounds are discussed. The second section is focused on processes catalyzed by Pdl2-based systems, and on their ability to promote different kind of oxidative carbonylations under mild conditions to afford important carbonyl derivatives with high selectivity and efficiency. In particular, the recent developments towards the one-step synthesis of new heterocyclic derivatives are described. 

Acetals and ketals are very important protecting groups in solution-phase synthesis, but only a few constructs have been used as linkers in solid-phase synthesis (Tab. 3.3). The THP-linker (22) (tetrahydropyran) was introduced by Ellman [54] in order to provide a linker allowing the protection of alcohols, phenols and nitrogen functionalities in the presence of pyridinium toluene sulfonate, and the resulting structures are stable towards strong bases and nucleophiles. Other acetal-linkers have also been used for the attachment of alcohols [55, 56]. Formation of diastereomers caused by the chirality of these linkers is certainly a drawback. Other ketal tinkers tike... 

Phenolic resins (Baekeland) Neoarsphenamine (Ehrlich) Aldehydes, alcohols (Oxo synthesis) Insulin (Banting)... 

Since the first synthesis of organogermanium nitrogen derivatives it was found that the Ge—N bonds display high reactivity, especially an easy protolysis with water, alcohols, phenols, carboxylic acids, hydrohalic acids, SH-, NH-, PH- and CH-acids, etc36,37,77,346,347. All these reactions were initiated by electrophilic attack of the reactant proton on the nitrogen atom76,468,469. 

A synthesis of [3]-fused furans involving a ring enlargement can be effected by the treatment of a-alkynyl-a-cyclopropylcycloalkanones with an electron-rich Au(l) catalyst in the presence of a suitable nucleophile (Equation 18) <2006AGE6704>. The nucleophiles that can be used include alcohols, phenols, carboxylic acids, indole, and 2-pyrrolidone. Open-chain ketones as well as other ring sizes react with comparable yields. Silver and lanthanide triflates are also effective catalysts for this transformation. 

The principle of the carbon synthesis is shown in Fig. 1. Suitable carbon sources such as sucrose, furfuryl alcohol, phenol-resin monomers and acetylene gas are converted to carbon frameworks inside mesoporous silica template by pyrolysis. An effective method for the restriction of carbonization to inside the template is to incorporate a suitable catalyst such as Al, Sn and Fe onto the silica pore walls prior to the use as template. The template after the carbonization is removed using ethanol-water solution of HF or NaOH. 

Preparation.- Trialkyl or triaryl phosphites and trithiophosphites (55) can be obtained in 50-90% yields from white phosphorus, carbon tetrachloride, triethylamine, and the appropriate alcohol, phenol, or thiol in a polar aprotic solvent such as dimethylformamide. A series of racemic phenylbis(dialkylamino)phosphines (56) have been prepared in a one-pot synthesis as shown the bulk of the dicyclohexyl-amino group prevents substitution of the second chlorine atom, and the products (56) are claimed to be stable to air and moisture. In a one-pot synthesis tris(diethylamino)-phosphine has been treated successively with three different alcohols to give a 89% yield of the thiophosphate (57) after oxidation with sulphur. ... 

Palladium-phosphine complexes such as Pd [PPh3 ]4 or, most conveniently, Pd(OAc)2 and PPh3 are used. Usually, these telomers are obtained in high yields. Nucleophiles such as water, carboxylic acids, alcohols, phenols, ammonia, amines, enamines, nitroalkanes, and active methylene and methyne compounds participate in telomerization. Also, carbon monoxide and hydrosilanes are involved in the reaction to give telomers. These easily available telomers are trifunctional and extremely useful starting materials for simple synthesis of certain types of natural products. 

The a-iodoalkyltin compounds described above react readily with a variety of nucleophiles (alcohols, phenols, thiols, amides etc.) to give further types of a-functionally-substituted compounds R 3SnCHRX (Scheme 6-1).11 26 These will then react with butyl-lithium to give the reagents LiCHRX (Section 22.1) which will react in turn with carbon electrophiles to extend the carbon chain, and this methodology has been exploited extensively in organic synthesis. 

The first totally synthetic route to a solvent in the United States was the synthesis of isopropyl alcohol from propylene by Melco Chemical Corporation in 1917. In 1928 Union Carbide made acetone from isopropyl alcohol the synthesis of acetone in the cumene-to-phenol process came much later and now is the source of about 85% of acetone production. In 1927 Du Pont began the synthesis of methanol. Synthetic ethyl alcohol was made from ethylene by Union Carbide in 1929. Specialized books on ethyl alcohol (14. 15) and isopropyl alcohol (16) give many details on the manufacture, properties, and uses of these major products. 

NuH = Alcohols, phenol, and amines Scheme 1.22 (a-c) Palladium-catalyzed carbonylative synthesis of indoles and thiophenes. 

The optimum isomer distribution requires a low o-cymene content, since o-cymene is intricate to oxidize and inhibits the oxidation of the other cymenes. In practice, a mixture of 3% o-cymene, 64% m-cymene and 33% p-cymene is used. The oxidation of the cymene mixture is carried out to a peroxide content of around 20%, whereas the degree of oxidation of cumene in phenol synthesis is around 30%. In addition to cresols, the acid-cleaved reaction mixture contains acetone and unconverted cymene together with a wide range of co-products, such as isopropylbenzaldehyde, isopropylbenzyl alcohol, methyl acetophenone and isopropyltolyl alcohol. The m-/p-cresol mixture is over 99.5% pure the m-/p-ratio is 1.5 1. 

Monomer Synthesis. Sila[l]ferrocenophane monomers such as (43) are readily available on a substantial laboratory scale (>100 g) from the reaction of dilithioferrocene tetramethylethylenediamine (fcLi2-TMEDA) with the appropriate dichloroorganosilane (166). Spirocyclic sila[l]ferrocenophanes such as (45) and (46) are also easily synthesized (167). Sila[l]ferrocenophane monomers with alkoxy, aryloxy, and amino substituents at silicon are readily accessible through reaction of dichlorosila[l]ferrocenophane with the appropriate alcohol, phenol or amine in the presence of base (168). 

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