Alcohols Experimental Procedures

Unfortunately, in most cases not all the available information on a reaction is given in the reaction equation in a publication, and even less so in reaction databases. To obtain a fuller picture of the reaction that was performed, the text describing the experimental procedure in the publication or a lab journal) would have to be consulted. Reaction products that are considered as trivial, such as water, alcohol, ammonia, nitrogen, etc., are generally not included in the reaction equation or mentioned in the text describing the experimental work. This poses serious problems for the automatic identification of the reaction center. It is highly desirable to have the full stoichiometry of a reaction specified in the equation. 

The experimental procedure to be followed depends upon the products of hydrolysis. If the alcohol and aldehyde are both soluble in water, the reaction product is divided into two parts. One portion is used for the characterisation of the aldehyde by the preparation of a suitable derivative e.g., the 2 4-dinitrophenylhydrazone, semicarbazone or di-medone compound—see Sections 111,70 and 111,74). The other portion is employed for the preparation of a 3 5-dinitrobenzoate, etc. (see Section 111,27) it is advisable first to concentrate the alcohol by dis tillation or to attempt to salt out the alcohol by the addition of solid potassium carbonate. If one of the hydrolysis products is insoluble in the reaction mixture, it is separated and characterised. If both the aldehyde and the alcohol are insoluble, they are removed from the aqueous layer separation is generally most simply effected with sodium bisulphite solution (compare Section Ill,74),but fractional distillation may sometimes be employed. 

The role of yeast in fermenting dough maturation is even less clear. The alcohol and carbon dioxide developed during fermentation must influence the elastic properties of the protein matrix. However, experimental procedures that would permit this to be checked in the absence of yeast have not been developed. 

Rearrangements and other side-reactions are rare. The ester pyrolysis is therefore of some synthetic value, and is used instead of the dehydration of the corresponding alcohol. The experimental procedure is simple, and yields are generally high. Numerous alkenes have been prepared by this route for the first time. For the preparation of higher alkenes (> Cio), the pyrolysis of the corresponding alcohol in the presence of acetic anhydride may be the preferable method." The pyrolysis of lactones 9 leads to unsaturated carboxylic acids 10 ... 

For the formation of oxepincarbaldehydes by oxidation of the corresponding alcohols, see Section A.3.1.1.1. and Houben-Weyl, Vol. 4/1 b, p 519 Vol.6/4, p468. For an experimental procedure for the reduction of oxepincarboxylates with lithium alanate to give the corresponding alcohols, see Houben-Weyl, Vol.6/4, p468f. 

Di-2-propenyltin dibromide, available from 2-propenyl bromide and tin powder, reacts with aldehydes in the presence of monosodium (+)-diethyl 2,3-dihydroxybutanedioate to give ho-moallylic alcohols in good yields with 42-71% ee the experimental procedure is relatively straightforward98. 

The reaction proceeds with high regioselectivity for oxidation at the less substituted a-carbon. Methanol is commonly used as the solvent, although higher alcohols are also used for some detailed experimental procedures refer to the literature60,61. Some examples of compounds prepared via electrochemical alkoxylation are ... 

A facile method for the oxidation of alcohols to carbonyl compounds has been reported by Varma et al. using montmorillonite K 10 clay-supported iron(III) nitrate (clayfen) under solvent-free conditions [100], This MW-expedited reaction presumably proceeds via the intermediacy of nitrosonium ions. Interestingly, no carboxylic acids are formed in the oxidation of primary alcohols. The simple solvent-free experimental procedure involves mixing of neat substrates with clayfen and a brief exposure of the reaction mixture to irradiation in a MW oven for 15-60 s. This rapid, ma-nipulatively simple, inexpensive and selective procedure avoids the use of excess solvents and toxic oxidants (Scheme 6.30) [100]. Solid state use of clayfen has afforded higher yields and the amounts used are half of that used by Laszlo et al. [17,19]. 

The advantages of the carbon tetrahalide-organophosphine-alcohol reaction to prepare halides are simplicity of experimental procedure good yields relatively mild, essentially neutral reaction conditions absence of allylic rearrangements. The reaction proceeds with inversion of configuration and is a useful simple device for converting optically active alcohols to chiral halides in high optical purity.12-22... 

The reaction of acceptor-substituted carbene complexes with alcohols to yield ethers is a valuable alternative to other etherification reactions [1152,1209-1211], This reaction generally proceeds faster than cyclopropanation [1176], As in other transformations with electrophilic carbene complexes, the reaction conditions are mild and well-suited to base- or acid-sensitive substrates [1212], As an illustrative example, Experimental Procedure 4.2.4 describes the carbene-mediated etherification of a serine derivative. This type of substrate is very difficult to etherify under basic conditions (e.g. NaH, alkyl halide [1213]), because of an intramolecular hydrogen-bond between the nitrogen-bound hydrogen and the hydroxy group. Further, upon treatment with bases serine ethers readily eliminate alkoxide to give acrylates. With the aid of electrophilic carbene complexes, however, acceptable yields of 0-alkylated serine derivatives can be obtained. 

Catalytic hydrogenation is hardly ever used for this purpose since the reaction by-product - hydrogen chloride - poses some inconveniences in the experimental procedures. Most transformations of acyl chlorides to alcohols are effected by hydrides or complex hydrides. Addition of acyl chlorides to ethereal solutions of lithium aluminum hydride under gentle refluxing produced alcohols from aliphatic, aromatic and unsaturated acyl chlorides in 72-99% yields [5i]. The reaction is suitable even for the preparation of halogenated alcohols. Dichloroacetyl chloride was converted to dichloro-... 

The experimental procedure was as follows. One litre of supersaturated aqueous solution was prepared, of which 0.8 was poured Into the crystallizer. After a constant temperature (of 298.2 K) was attained, the solution concentration was determined, and a seed crystal (0.59-0.71 mm) was put Into the solution and was allowed to grow for either 600 or 900 s. The crystal was then taken out of the crystallizer and put Into a 50 ml beaker In which a small quantity of alcohol was placed. The crystal was removed from the beaker and dried In the air for a few mlnltes, then Its weight and surface area were measured. The same crystal was again placed Into the crystallizer and allowed to resume growth. 

The experimental procedure was essentially the same for all substances mentioned, namely, the method used in the case of nitrobenzene. Some complication arises, however, due to the fact that the solids do not disperse as easily in the fermentation mixture. Although the materials were always added in alcoholic solution to the yeast preparation, partial precipitation was unavoidable. With 21.4 g. of nitrosobenzene a yield of 4 g. of aniline was obtained addition of the same quantity of phenylhydroxylamine gave 7.5 g. of aniline. In both cases azobenzene appeared as a by-product and could be isolated in the pure state. Its formation can be readily explained by a condensation of the intermediary nitrosobenzene with the end product aniline. 

Polystyrene-bound allylic or benzylic alcohols react smoothly with hydrogen chloride or hydrogen bromide to yield the corresponding halides. The more stable the intermediate carbocation, the more easily the solvolysis will proceed. Alternatively, thionyl chloride can be used to convert benzyl alcohols into chlorides [7,25,26]. A milder alternative for preparing bromides or iodides, which is also suitable for non-benzylic alcohols, is the treatment of alcohols with phosphines and halogens or the preformed adducts thereof (Table 6.2, Experimental Procedure 6.1 [27-31]). Benzhy-dryl and trityl alcohols bound to cross-linked or non-cross-linked polystyrene are particularly prone to solvolysis, and can be converted into the corresponding chlorides by treatment with acetyl chloride in toluene or similar solvents (Table 6.2 [32-35]). 

Non-activated aryl bromides (but not fluorides) can be used as substrates for palla-dium(0)-catalyzed aromatic nucleophilic substitutions with aliphatic or aromatic amines. These reactions require sodium alcoholates or cesium carbonate as a base, and sterically demanding phosphines as ligands. Moreover, high reaction temperatures are often necessary to achieve complete conversion (Entries 7 and 8, Table 10.4 Experimental Procedure 10.1). Unfortunately, the choice of substituents on the amine... 

Transesterification under strongly basic reaction conditions has been used to acy-late support-bound alcohols with alkyl esters (Entry 10, Table 13.12). For sensitive acids, the Mitsunobu reaction is a particularly mild method of esterification. This reaction gives high yields with support-bound primary aliphatic alcohols and proceeds under essentially neutral reaction conditions (Experimental Procedure 13.4). Mitsunobu esterification of PEG with /V-Fmoc amino acids has also been reported [172]. 

Standard solid-phase peptide synthesis requires the first (C-terminal) amino acid to be esterified with a polymeric alcohol. Partial racemization can occur during the esterification of N-protected amino acids with Wang resin or hydroxymethyl polystyrene [200,201]. /V-Fmoc amino acids are particularly problematic because the bases required to catalyze the acylation of alcohols can also lead to deprotection. A comparative study of various esterification methods for the attachment of Fmoc amino acids to Wang resin [202] showed that the highest loadings with minimal racemization can be achieved under Mitsunobu conditions or by activation with 2,6-dichloroben-zoyl chloride (Experimental Procedure 13.5). iV-Fmoc amino acid fluorides in the presence of DMAP also proved suitable for the racemization-free esterification of Wang resin (Entry 1, Table 13.13). The most extensive racemization was observed when DMF or THF was used as solvent, whereas little or no racemization occurred in toluene or DCM [203]. 

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