Alcohols, primary preparative procedure

Glacial acetic acid, pure or mixed with other solvents, is one of the most attractive solvents for the titration of amines. Commercial acetic acid containing not more than 1% of water (Karl Fischer titration check) can be used in normal practice for the highest accuracy, however, the water content must be lowered to about 0.01% by addition of acetic anhydride and standing for 24 h not more than the stoichiometric amount of acetic anhydride should be used in order to avoid possible reactions with active hydrogen-containing analyte components such as primary or secondary amines or alcohols. A similar procedure is followed in the preparation of perchloric acid titrant from the commercial... 

Acetylenic tertiary alcohols are prepared from sodium acetylides or acetylenic Grignard reagents and ketones in the same manner as described for primary and secondary alcohols (method 88). Dimethylethynylcarbinol is prepared from acetone, aqueous potassium hydroxide, and acetylene in an autoclave at 100° and 300 p.s.i. Ketones ate sometimes treated with an acetylide prepared from acetylene and a solution of sodium or potassium alkoxide in /-amyl alcohol. " Another procedure utilizes... 

The above is a general procedure for preparing trialkyl orthophosphates. Similar yields are obtained for trimethyl phosphate, b.p. 62°/5 mm. triethyl phosphate, b.p. 75-5°/5 mm. tri-n-propyl phosphate, b.p. 107-5°/5 mm. tri-Mo-propyl phosphate, b.p. 83-5°/5 mm. tri-wo-butyl phosphate, b.p. 117°/5-5 mm. and tri- -amyl phosphate, b.p. 167-5°/5 mm. The alkyl phosphates are excellent alkylating agents for primary aromatic amines (see Section IV,41) they can also be ua for alkylating phenols (compare Sections IV,104-105). Trimethyl phosphate also finds application as a methylating agent for aliphatie alcohols (compare Section 111,58). 

The modified procedure involves refluxing the N-substituted phthaUmide in alcohol with an equivalent quantity of hydrazine hydrate, followed by removal of the alcohol and heating the residue with hydrochloric acid on a steam bath the phthalyl hydtazide produced is filtered off, leaving the amine hydrochloride in solution. The Gabriel synthesis has been employed in the preparation of a wide variety of amino compounds, including aliphatic amines and amino acids it provides an unequivocal synthesis of a pure primary amine. 

Usually, organoboranes are sensitive to oxygen. Simple trialkylboranes are spontaneously flammable in contact with air. Nevertheless, under carefully controlled conditions the reaction of organoboranes with oxygen can be used for the preparation of alcohols or alkyl hydroperoxides (228,229). Aldehydes are produced by oxidation of primary alkylboranes with pyridinium chi orochrom ate (188). Chromic acid at pH < 3 transforms secondary alkyl and cycloalkylboranes into ketones pyridinium chi orochrom ate can also be used (230,231). A convenient procedure for the direct conversion of terminal alkenes into carboxyUc acids employs hydroboration with dibromoborane—dimethyl sulfide and oxidation of the intermediate alkyldibromoborane with chromium trioxide in 90% aqueous acetic acid (232,233). 

The above procedure describes the only known preparation of the inner salt of methyl (carboxysulfamoyl)triethylammonium hydroxide and illustrates the use of this reagent to convert a primary alcohol to the corresponding urethane.2 Hydrolysis of the urethane would then provide the primary amine. The method is limited to primary alcohols secondary and tertiary alcohols are dehydrated to olefins under these conditions, often in synthetically useful yields.2... 

The reaction between acyl halides and alcohols or phenols is the best general method for the preparation of carboxylic esters. It is believed to proceed by a 8 2 mechanism. As with 10-8, the mechanism can be S l or tetrahedral. Pyridine catalyzes the reaction by the nucleophilic catalysis route (see 10-9). The reaction is of wide scope, and many functional groups do not interfere. A base is frequently added to combine with the HX formed. When aqueous alkali is used, this is called the Schotten-Baumann procedure, but pyridine is also frequently used. Both R and R may be primary, secondary, or tertiary alkyl or aryl. Enolic esters can also be prepared by this method, though C-acylation competes in these cases. In difficult cases, especially with hindered acids or tertiary R, the alkoxide can be used instead of the alcohol. Activated alumina has also been used as a catalyst, for tertiary R. Thallium salts of phenols give very high yields of phenolic esters. Phase-transfer catalysis has been used for hindered phenols. Zinc has been used to couple... 

Allylic alcohols can be converted to epoxy-alcohols with tert-butylhydroperoxide on molecular sieves, or with peroxy acids. Epoxidation of allylic alcohols can also be done with high enantioselectivity. In the Sharpless asymmetric epoxidation,allylic alcohols are converted to optically active epoxides in better than 90% ee, by treatment with r-BuOOH, titanium tetraisopropoxide and optically active diethyl tartrate. The Ti(OCHMe2)4 and diethyl tartrate can be present in catalytic amounts (15-lOmol %) if molecular sieves are present. Polymer-supported catalysts have also been reported. Since both (-t-) and ( —) diethyl tartrate are readily available, and the reaction is stereospecific, either enantiomer of the product can be prepared. The method has been successful for a wide range of primary allylic alcohols, where the double bond is mono-, di-, tri-, and tetrasubstituted. This procedure, in which an optically active catalyst is used to induce asymmetry, has proved to be one of the most important methods of asymmetric synthesis, and has been used to prepare a large number of optically active natural products and other compounds. The mechanism of the Sharpless epoxidation is believed to involve attack on the substrate by a compound formed from the titanium alkoxide and the diethyl tartrate to produce a complex that also contains the substrate and the r-BuOOH. ... 

Mg or Ca in MeOH, " baker s yeast, Sm/l2, LiMe2NBH3, and tin complexes prepared from SnCl2 or Sn(SR)2. This reaction, combined with RX —+ RN3 (10-65), is an important way of converting alkyl halides RX to primary amines RNH2 in some cases the two procedures have been combined into one laboratory step. Sulfonyl azides (RSO2N3) have been reduced to sulfonamides (RSO2NH2) by irradiation in isopropyl alcohol and with NaH. ... 

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

Metallocene catalysis has been combined with ATRP for the synthesis of PE-fr-PMMA block copolymers [123]. PE end-functionalized with a primary hydroxyl group was prepared through the polymerization of ethylene in the presence of allyl alcohol and triethylaluminum using a zirconocene/MAO catalytic system. It has been proven that with this procedure the hydroxyl group can be selectively introduced into the PE chain end, due to the chain transfer by AlEt3, which occurs predominantly at the dormant end-... 

The preparation of enantiomerically pure chemicals is also the theme of the next group of four procedures. The biopolymer polyhydroxybutyric acid, which is now produced on an industrial scale, serves as the starting material for the large scale synthesis of (R)-3-HYDROXYBUTANOIC ACID and (R)-METHYL 3-HYDROXYBUTANOATE. Esters of (-)-camphanic acid are useful derivatives for resolving and determining the enantiomeric purity of primary and secondary alcohols. An optimized preparation of (-)-(1S,4R)-CAMPHANOYL CHLORIDE is provided. The preparation of enantiomerically pure a-hydroxyketones from ethyl lactate is illustrated in the synthesis of (3HS)-[(tert)-BUTYL-DIPHENYLSILYL)OXY]-2-BUTANONE. One use of this chiral a-hydroxyketone is provided in the synthesis of (2S,3S)-3-ACETYL-8-... 

This one-step procedure is a convenient and general method for the preparation of carbamates. It is substantially simpler, quicker, and safer than the multistep methods hitherto used for the preparation of carbamates of tertiary alcohols. This procedure is applicable to the preparation of carbamates of primary, secondary, and tertiary alcohols and mercaptans, polyhydric alcohols, acetylenic alcohols, phenols, and oximes. It has also been extended to the preparation of carbamyl derivatives (i.e., ureas) of inert (non-basic) amines.10... 

Yields of chlorides are good to excellent for primary and secondary alcohols, but a competing olefin-forming elimination process renders the method of limited value for preparing tertiary chlorides.12 An adaptation of the procedure using carbon tetrabromide allows the synthesis of alkyl bromides. Some examples are the preparation of rt-C5H11Br (97%) and C H6CH2Br (96%).12 Farncsyl bromide has been prepared in 90% yield from fame sol.23... 

The application of phase-transfer catalysis to the Williamson synthesis of ethers has been exploited widely and is far superior to any classical method for the synthesis of aliphatic ethers. Probably the first example of the use of a quaternary ammonium salt to promote a nucleophilic substitution reaction is the formation of a benzyl ether using a stoichiometric amount of tetraethylammonium hydroxide [1]. Starks mentions the potential value of the quaternary ammonium catalyst for Williamson synthesis of ethers [2] and its versatility in the synthesis of methyl ethers and other alkyl ethers was soon established [3-5]. The procedure has considerable advantages over the classical Williamson synthesis both in reaction time and yields and is certainly more convenient than the use of diazomethane for the preparation of methyl ethers. Under liquidrliquid two-phase conditions, tertiary and secondary alcohols react less readily than do primary alcohols, and secondary alkyl halides tend to be ineffective. However, reactions which one might expect to be sterically inhibited are successful under phase-transfer catalytic conditions [e.g. 6]. Microwave irradiation and solidrliquid phase-transfer catalytic conditions reduce reaction times considerably [7]. 

B. General Oxidation Procedure for Alcohols. A sufficient quantity of a 5% solution of dipyridine chromium (VI) oxide (Note 1) in anhydrous dichloromethane (Note 7) is prepared to provide a sixfold molar ratio of complex to alcohol. This excess is usually required for complete oxidation to the aldehyde. The freshly prepared, pure complex dissolves completely in dichloromethane at 25° at 5% concentration to give a deep red solution, but solutions usually contain small amounts of brown, insoluble material when prepared from crude complex (Note 8). The alcohol, either pure or as a solution in anhydrous methylene chloride, is added to the red solution in one portion with stirring at room temperature or lower. The oxidation of unhindered primary (and secondary) alcohols proceeds to completion within 5 minutes to 15 minutes at 25° with deposition of brownish-black, polymeric, reduced chromium-pyridine products (Note 9). When deposition of reduced chromium compounds is complete (monitoring the reaction by gas chromatography or thin-layer chromatography analysis is helpful), the supernatant liquid is decanted from the (usually tarry) precipitate and the precipitate is rinsed thoroughly with dichloromethane (Note 10). 

In 2002, Kanno and Taylor successfully developed a simple one-pot procedure using MnOi/NHiOMe-HCl for the conversion of activated primary alcohols into O-methyl oximes (Scheme 11). They also developed a modification using Amberlyst 15-supported alkoxylamines, which can be employed to prepare other types of 0-aUcyl oximes as well as the parent hydroxylamines. This latter procedure has been used as the cornerstone of an efficient synthesis of the antifungal natural product citaldoxime 11 (Scheme 11). Citaldoxime is an antifungal natural product first obtained as a radiation-induced stress metabolite of Citrus sinensis , and later isolated from the roots of several different citrus plants. ... 

The prominent role of alkyl halides in formation of carbon-carbon bonds by nucleophilic substitution was evident in Chapter 1. The most common precursors for alkyl halides are the corresponding alcohols, and a variety of procedures have been developed for this transformation. The choice of an appropriate reagent is usually dictated by the sensitivity of the alcohol and any other functional groups present in the molecule. Unsubstituted primary alcohols can be converted to bromides with hot concentrated hydrobromic acid.4 Alkyl chlorides can be prepared by reaction of primary alcohols with hydrochloric acid-zinc chloride.5 These reactions proceed by an SN2 mechanism, and elimination and rearrangements are not a problem for primary alcohols. Reactions with tertiary alcohols proceed by an SN1 mechanism so these reactions are preparatively useful only when the carbocation intermediate is unlikely to give rise to rearranged product.6 Because of the harsh conditions, these procedures are only applicable to very acid-stable molecules. 

The bromination with alkali hypobromite in aqueous solution gives good results with (hetero)arylacetylenes, enynes (RCH=CHOCH) and diynes (RC=CC=CH) all acetylenes that are more acidic than those acetylenes in the aliphadc or cycloaliphatic series with an isolated triple bond. For the conjugated systems the hypobromite method is superior to the reaction of metallated acetylenes with bromine. Various acetylenic alcohols are also brominated smoothly, which can be explained in part by their better solubility in water. Since in the case of primary and secondary ethynyl alcohols, oxidation of the alcohol can occur, the use of an excess of hypobromite should be avoided. The best procedure is drop wise additon of a small shot measure of hypobromite ro a mixture of alcohol and water. If the bromoalkynes to be prepared are not too volatile, small amounts of THF or dioxane may be added to effect a better solubility of the alkyne in the aqueous phase. Addition of a co-solvent may also be desired when the starting compound is a solid (e.g. ethynylcyclohexanol). 

Esters of arenesulfonic acids are prepared by reaction of the corresponding alcohol with the arenesulfonyl chloride in the presence of a basic reagent, which has the function of activating the alcohol and binding the hydrogen chloride. The reaction is often carried out with pyridine, which is used as solvent. In the procedure for tosylates of primary aliphatic alcohols, described in A.l. Vogel, A Textbook of Practical Organic Chemistry, an aqueous solution of sodium hydroxide is used. Esters of primary alcohols are formed more easily than secondary-alkyl esters, while tertiary alcohols cannot be esterified under the usual conditions. 

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