Hydrogen halides synthesis

Alcohols react with hydrogen halides to yield al kyl halides The reaction is useful as a synthesis of al kyl halides The reactivity of hydrogen halides de creases in the order HI > HBr > HCI > HF Alcohol re activity decreases in the order tertiary > secondary > primary > methyl... 

When applied to the synthesis of ethers the reaction is effective only with primary alcohols Elimination to form alkenes predominates with secondary and tertiary alcohols Diethyl ether is prepared on an industrial scale by heating ethanol with sulfuric acid at 140°C At higher temperatures elimination predominates and ethylene is the major product A mechanism for the formation of diethyl ether is outlined m Figure 15 3 The individual steps of this mechanism are analogous to those seen earlier Nucleophilic attack on a protonated alcohol was encountered m the reaction of primary alcohols with hydrogen halides (Section 4 12) and the nucleophilic properties of alcohols were dis cussed m the context of solvolysis reactions (Section 8 7) Both the first and the last steps are proton transfer reactions between oxygens... 

Both reactants m the Williamson ether synthesis usually originate m alcohol pre cursors Sodium and potassium alkoxides are prepared by reaction of an alcohol with the appropriate metal and alkyl halides are most commonly made from alcohols by reaction with a hydrogen halide (Section 4 7) thionyl chloride (Section 4 13) or phosphorus tri bromide (Section 4 13) Alternatively alkyl p toluenesulfonates may be used m place of alkyl halides alkyl p toluenesulfonates are also prepared from alcohols as their imme diate precursors (Section 8 14)... 

Phosphoms halides are subject to reactions with active hydrogen compounds and result in the elimination of hydrogen halide. They are convenient reagents in the synthesis of many esters, amides, and related compounds. However, because the involved hydrogen halide frequendy catalyzes side reactions, it is usually necessary to employ a hydrogen halide scavenger to remove the by-product. 

A particular case of the synthesis of isoxazoles via -diketone derivatives is the preparation of 3-halogenoisoxazoles (11) from -nitroketones (9) treated with hydrogen halides. This inter-... 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

Me, m-OMe, m-Cl, m-CF3, etc.) have been prepared by hydrolysis of the corresponding X-C6H4Si(OMe)3 compounds in an H20/MeOH mixture. Again, the formation of an alcohol, MeOH, rather than a hydrogen halide is beneficial in the synthesis of such sensitive triols (102). 

A simple and atom-economical synthesis of hydrogen halide salts of primary amines directly from the corresponding halides, which avoids the production of significant amounts of secondary amine side products, has been described by researchers from Bristol-Myers Squibb [227]. Microwave irradiation of a variety of alkyl halides or tosylates in a commercially available 7 m solution of ammonia in methanol at 100-130 °C for 15 min to 2.5 h followed by evaporation of the solvent provided the corre-... 

Ethers may be prepared by (1) dehydration of alcohols and (11) Williamson synthesis. The boiling points of ethers resemble those of alkanes while their solubility Is comparable to those of alcohols having same molecular mass. The C-O bond In ethers can be cleaved by hydrogen halides. In electrophilic substitution, the alkoxy group activates the aromatic ring and directs the Incoming group to ortho and para positions. 

Precursor y-halogeno alcohols are frequently prepared by the classic sequence of addition of hydrogen halide to a,/3-unsaturated aldehydes, ketones, acids or esters, followed by Grignard reaction or hydride reduction. Recently a novel and general synthesis of 3-methoxyoxetanes from 3-phenylseleno-2-propenal was reported. This method comprises a sequence of Grignard addition to the aldehyde function, treatment with two equivalents of MCPBA, and then reaction with methanolic sodium hydroxide (equation 78) (80JOC4063). 

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. 

Compounds of the type L-BH2X can be prepared by the reaction of the appropriate amine borane and hydrogen halides or halogens. The synthesis of the trimethylamine iodoborane [25741-81-5] adduct (eq. 8) yields a precursor for the preparation of the trimethylamine isocyanoborane [60045-36-5] adduct as shown in equation 9 (15). 

Synthesis of Heterocycles by Intramolecular Acylation of Nitrile-Hydrogen Halide Adducts ... 

A number of reactivity studies have been performed on 6 and 8 and indicate a strongly polar (if not ionic) Mn—E bond Mn "—E,+ (E = In, Tl). Thus heterolytic bond dissociation occurs in polar ligating solvents such as MeCN or DMF, and halogens, hydrogen halides, and alkyl halides readily add across the metal-metal bond in a manner consistent with the polarity described above (13,13a,18). In the thallium example, however, the reactions are generally more complicated and result in T1(I) salts [e.g., Eq. (3)], and metal exchange reactions are also more facile, e.g., the synthesis of 6 from 8 and indium metal. In general, therefore, the chemistry of 6 and 8 is consistent with predominantly ionic behavior. 

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