Quaternary ammonium hydroxide, Hofmann

An alternative bimolecular elimination process involves the thermal decomposition in an atmosphere of nitrogen of a quaternary ammonium hydroxide (Hofmann exhaustive methylation procedure). 

In this reaction two different procedures have been used. The first is the classical Hofmann degradation, which prepares the alkene by thermal decomposition of the quaternary ammonium hydroxide. Hofmann orientation is generally observed in acyclic and Zaitsev orientation in cyclohexyl substrates. The second is the treatment of quaternary ammonium halides with very strong bases, e.g. PhLi, KNH2 in liquid NH3. The formation of the alkene proceeds via an 1 mechanism, which means a syn elimination in contrast to the anti elimination which is observed in most of the classical Hofmann degradations. In some cases this type of elimination can also be accomplished by heating the salt with KOH in polyethylene glycol monomethyl ether. 

Quaternary ammonium hydroxides un dergo elimination on being heated It is an anti elimination of the E2 type The regioselectivity of the Hofmann elimina tion IS opposite to that of the Zaitsev rule and leads to the less highly substi tuted alkene... 

The Hofmann elimination route, of which many versions exist, can be carried out at much lower temperatures in conventional equipment. The PX is generated by a 1,6-Hofmaim elimination of amine from a quaternary ammonium hydroxide in the presence of a base. This route gives yields of 17—19%. Undesired polymeric products can be as high as 80% of the product. In the presence of a polymerization inhibitor, such as phenothiazine, DPXN yields can be increased to 50%. 

Hofmann elimination (Section 22.14) Conversion of a quaternary ammonium hydroxide, especially an alkyltrimethyl-ammonium hydroxide, to an alkene on heating. Elimination occurs in the direction that gives the less substituted double bond. 

ALKENES via HOFMANN ELIMINATION USE OF ION-EXCHANGE RESIN FOR PREPARATION OF QUATERNARY AMMONIUM HYDROXIDES DIPHENYLMETHYL VINYL ETHER... 

The Hofmann elimination is useful synthetically for preparing alkenes since it gives the least substituted alkene. The reaction involves thermal elimination of a tertiary amine from a quaternary ammonium hydroxide these are often formed by alkylation of a primary amine with methyl iodide followed by reaction with silver oxide. The mechanism of the elimination is shown in Scheme 1.13 in this synthesis of 1-methyl-1-... 

The elimination of hydrogen halide from organic halides under basic conditions generates alkenes and is a fundamental reaction in organic chemistry. It is sometimes carried out with a base in aqueous media.14 In contrast, the corresponding Hofmann-type eliminations of quaternary ammonium hydroxides are frequently carried out in aqueous media,15 which will be covered in Chapter 11. 

Hofmann exhaustive methyiation reaction org chem The thermal decomposition of quaternary ammonium hydroxide compounds to yield an olefin and water an exception is tetramethyiammonium hydroxide, which decomposes to give an alcohol. haf-mon ig z6s-tiv. meth-o la-shon re,ak-sh3n )... 

Elimination of the amino group can also be achieved by the Hofmann procedure, namely, by heating the quaternary ammonium hydroxide.33... 

The successful synthesis of furanophane (27) by pyrolysis of the quaternary ammonium hydroxide (28) (60JA1428) has prompted the adaptation of this 1,6-Hofmann elimination procedure to the synthesis of numerous heterophanes (77CRV513,77H(7)81,78T1641). Fluoride anion-induced 1,6-elimination of (29) or (30) gives (27) or (31) and (32), respectively, in good yields (81JOC1043). 

HOFMANN DEGRADATION. Formation of an olefin and a tertiary amine hy pyrolysis of a quaternary ammonium hydroxide useful for the preparation of some cyclic olefins and for opening nitrogen-containing ring compounds. 

HOFMANN RULE. When a quaternary ammonium hydroxide containing different primary alkyl radicals is decomposed, the leasl-substituted olelin is formed preferentially. 

Manufacture. For the commercial production of DPXN (di-/)-xyIylene) (3), two principal synthetic routes have been used the direct pyrolysis of p-xylcnc (4, X = Y = H) and the 1,6-Hofmann elimination of ammonium (HNR ) from a quaternary ammonium hydroxide (4, X = H. Y = NR ). Most of the routes to DPX share a common strategy PX is generated at a controlled rate in a dilute medium, so that its conversion to dimer is favored over the conversion to polymer. 

Quaternary ammonium hydroxides undergo Hofmann elimination when they are heated. A point to be considered here concerns the regioselectivity of Hofmann eliminations it is the less hindered / proton that is removed by the base giving the less substituted alkene. 

Heating of the quaternary ammonium hydroxide results in E2 elimination and formation of an alkene. This elimination of a quaternary ammonium hydroxide is called the Hofmann elimination. 

Elimination of a quaternary ammonium hydroxide with an amine as the leaving group. The Hofmann elimination usually gives the least-substituted alkene. (p. 904)... 

Apart from the reactions of diazonium salts, a number of other reactions are known in which the C-N bond is broken. The best known of these is the Hofmann elimination of quaternary ammonium hydroxides (Scheme 2.37). An amine is converted by methylation with methyl iodide to the quaternary ammonium salt ( exhaustive methylation ). The iodide, on treatment with moist silver oxide, forms the quaternary ammonium hydroxide which undergoes a bimolecular elimination to form an alkene. The bimolecular elimination of onium salts yields the least alkylated alkene. This substitution pattern is determined by the ease with which a hydrogen atom can be attacked by the base. 

The Hofmann degradation of quaternary ammonium hydroxides, which has been used in the preparation of olehns has also been occasionally applied to the synthesis of acetylenes, as shown in equations (94)-(96). Quaternarized enamines are also used... 

The Cope elimination has been used less widely than the Hofmann elimination of quaternary ammonium hydroxides, but in some cases has advantages in terms of the ease of manipulation and lack of product isomerization, e.g. nonconjugated alkenes can be obtained without double Ixmd migration, as in equation (2). ... 

In 1851, A.W. Hofmann discovered that when trimethylpropylammonium hydroxide is heated, it decomposes to form a tertiary amine (trimethylamine), an olefin (propene), and water. Widespread use of this transformation did not occur until 1881, when Hofmann applied this method to the study of the structure of piperidines and nitrogen-containing natural products (e.g., alkaloids). " The pyrolytic degradation of quaternary ammonium hydroxides to give a tertiary amine, an olefin and water is known as the Hofmann elimination. The process involves three steps 1) exhaustive methylation of the primary, secondary or tertiary amine with excess methyl iodide to yield the... 

Sulfonium salts (20) have a non-planar tetrahedral configuration, and consequently the structure is chiral when all the attached groups, namely R, R and R", are different. Such sulfonium salts can generally be resolved into quite stable optical isomers (see Chapter 6, p. 83). Sulfonium salts are analogous to quaternary ammonium salts and the hydroxides are strong bases which behave similarly on heating (cf. the Hofmann elimination of quaternary ammonium hydroxides). 

Hofmann degradation, but this causes confusion with the Hofmann exhaustive methylation, in which a quaternary ammonium hydroxide is... 

Hofmann Rule. In the decomposition of quaternary ammonium hydroxides, that olefin will be formed which will have the smallest number of alkyl groups attached to it. 

Hofmann rule The principal alkene formed in the decomposition of quaternary ammonium hydroxides that contain different primary alkyl groups is always ethylene, if an ethyl group is present. Originally given in this limited form by A.W. Hofmann, the rule has since been extended and modified as follows When two or more alkenes can be produced in a P-elimination reaction, the alkene having the smallest number of alkyl groups attached to the double bond carbon atoms will be the predominant product. This orientation described by the Hofmann rule is observed in elimination reactions of quaternary ammonium salts and tertiary sulfonium salts, and in certain other cases. 

Weinstock and Boekelheide introduced Amberlite IRA-400 (OH ) for conversion of alkyltrimethylammonium iodides into the corresponding quaternary ammonium hydroxides. The procedure is simpler than the conventional silver oxide method and avoids undesirable side reactions sometimes encountered. In the case of a derivative of /3-erythroidine, this technique raised the yield in a Hofmann degradation from 40 to 78%. 

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