Quaternary ammonium salts. Hofmann elimination

The amino functional group is not commonly encountered in steroid synthesis except perhaps in steroidal alkaloids. However, certain elimination reactions have been shown to have theoretical and limited preparative importance, largely due to the efforts of McKenna and co-workers. The Hofmann rule for 2 elimination predicts that alkaline elimination of quaternary ammonium salts will occur towards the carbon carrying the most hydrogen atoms cf. the converse Saytzeff orientation, above). In cyclohexyl systems, the requirement for diaxial elimination appears to be important, as in other 2 eliminations, and the Hofmann rule frequently is not obeyed [e.g., (116) (117)]. 

Amine oxides 2, which can be prepared by oxidation of amines 1, react upon heating to yield an olefin 3 and a hydroxylamine 4. This reaction is called the Cope elimination reaction,and as a synthetic method is a valuable alternative to the Hofmann degradation reaction of quaternary ammonium salts. 

The preparation of an alkene 3 from an amine 1 by application of a /3-elimination reaction is an important method in organic chemistry. A common procedure is the Hofmann elimination where the amine is first converted into a quaternary ammonium salt by exhaustive methylation. Another route for the conversion of amines to alkenes is offered by the Cope elimination. 

The Hofmann elimination reaction is not often used today in the laboratory, but analogous biological eliminations occur frequently, although usually with protonated ammonium ions rather than quaternary ammonium salts. In the biosynthesis of nucleic acids, for instance, a substance called adenylosuccinate... 

Qiana, structure of, 836 Quantum mechanical model, 4-6 Quartet (NMR), 460 Quaternary ammonium salt. 917 Hofmann elimination and, 936-937... 

Aryl vinyl ketones are produced thermally from the corresponding quaternary ammonium salts via Hofmann elimination. However, the conjugated ketones are heat-sensitive and polymerization is difficult to avoid. Traditional preparations afforded only moderate yields. Microwave conditions were established for Hofmann eliminations, performed essentially quantitatively, by batch or continuous processes. 

Base-catalysed quaternary ammonium salts give alkenes and 3° amines. This reaction is known as Hofmann elimination or Hofmann degradation. Amines can readily be converted to quaternary ammonium salt by the treatment of excess primary alkyl halides, and then Ag20 and H2O. Quaternary ammonium salts undergo E2 elimination, when heated with NaOH to give alkenes and tertiary amines. Thermal decomposition of a quaternary ammonium salt by NaOH to an alkene is known as Hofmann elimination. 

Base catalyzed Hofmann elimination carried out on the quaternary ammonium salts (61) gives (62). Good nucleophiles, but relatively weak bases, add at room temperature to the activated double bond of (62), affording (rans-4,5-dihydro-l,2,3-triazoles (63) (80JHC267). 

Hofmann elimination (Section 24.7) a method for effecting the elimination reaction of an amine to yield an alkene. The amine is first treated with excess iodomethane, and the resultant quaternary ammonium salt is heated with silver oxide. 

Exposure of quaternary ammonium salt 163 to NaOMe gives methyl orthoester 37 and ketene acetal 54 as the consequence of a competing Hofmann-type elimination (Equation 33). Elution of 163 as a methanol solution through an anion-exchange resin (Dowex-550-OH, MeOH) leads exclusively to ketene acetal 54 in 89% yield <2004AGE1117>. 

However, quaternary ammonium salts having a 3-hydrogen atom undergo elimination with base to give alkene and tertiary amine. The reaction is known as the Hofmann elimination . ... 

The evidence suggests that 2-propanamine interacts with the protons associated with the framework Fe atoms to form 2-propyl ammonium cations which maintain 2-propanamine in the zeolite to high temperatures. Above approximately 600K, the decomposition rate for these cations to form propene and ammonia becomes appreciable. The decomposition reaction is very similar to the Hofmann elimination reaction found for quaternary ammonium salts and provides indirect evidence that ammonium ions are involved in the reaction. When Fe is removed from the framework of the molecular sieve, the associated proton site is lost, along with the capability for forming the ammonium ion and carrying out the reaction at that site. 

Thermal decomposition of quaternary ammonium salts and bases is most valuable in structural investigations of amines, particularly heterocyclic secondary amines (Hofmann exhaustive methylation). The course of the elimination (A or B) is determined by the nature of the four alkyl groups on the nitrogen atom. The reaction has found little use in the synthesis of pure olefins. The yields are low even when three of the alkyl groups are methyl radicals. Carbon-skeleton rearrangement does not occur. Thus, the only olefin obtained by pyrolysis of pinacolyltri-methylammonium hydroxide, (CHj),CCH(CHj)N(CHj)j OH, is /-butylethylene (50%). ... 

The Hofmann fission of quaternary ammonium salts displays some unusual features in the steroid field. The elimination is normally of E2 character, and in acyclic structures gives olefinic products according to the familiar Hofmann rule [ 14]. The behaviour of 3-trimethylammonium steroidal salts is unexceptional [32, 3 ] the axial 3u compounds in the 5a-series giving A -olefins (5), or in the case of compounds already unsaturated at C-C 6) (6), the A -dienes (7). The 3j8-trimethylammonium-5a compounds are stable to bases, or... 

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. 

A Pyrrolidine is a secondary amine and reacts with two moles of methyl iodide to form a quaternary ammonium salt, compound A. The analytical data for compound B shows that it has one double bond equivalent which is present as an alkene. Consequently, compound B has been formed from compound A by a Hofmann elimination ... 

The only way around this obstacle is to convert NH2 into a better leaving group. The most common method to accomplish this is called a Hofmann elimination, which converts an amine into a quaternary ammonium salt prior to P elimination. 

What is the stereochemistry of the alkene formed from the Hofmann elimination of each quaternary ammonium salt H... 

Hofmann elimination (Section 25.12) An E2 elimination reaction that converts an amine into a quaternary ammonium salt as the leaving group. The Hofmann elimination gives the less substituted alkene as the major product. 

Cyclopropene (533) has been prepared by Hofmann elimination of the quaternary ammonium salt (532) (equation 139). Decomposition of 532at 90-100°C was... 

The most commonly used quaternary ammonium salts are tetrabutylammonium perchlorate (TBAP), tetrafluoroborate (TBAT), the halides (TBACl, TBAB, and TBAI), and the corresponding tetraethylammonium salts, such as the perchlorate (TEAP), but also the tetramethyl- or tetrapropylammonium salts have been employed the former cannot undergo a base-promoted Hofmann elimination. However, evidence has been found for the formation of trimethylammonium methylide [460]. In nonpolar solvents it may be necessary to employ tetrahexyl- or tetraoctylammonium salts. The tetraalkylammonium ions are soluble in many nonaqueous media, and they may be extracted from an aqueous solution by means of chloroform or methylene chloride [461,462], and tetraalkylammonium salts may thus be prepared by ion extraction [462]. Tetrakis(decyl)ammonium tetra-phenylborate is soluble even in hexane [442,443]. 

In E2 elimination with bases like KOH and CH30Na, most alkyl halides give Saytzeflf orientation. Certain other compounds (quaternary ammonium salts, Sec. 23.5, for example) give Hofmann orientation. Alkyl sulfonates fall in between. With each kind of compound, orientation is affected—sometimes drastically—by the choice of base and solvent, and by stereochemistry. (The percentage of 1-hexene from 2-hexyl chloride, for example, jumps from 33% in CH ONa/ CH3OH to 91% in /-BuOK//-BuOH, evidently for steric reasons.) In all this, we should remember that orientation is a matter of relative stabilities of competing transition states these stabilities are determined by electronic factors—alkene character and carbanion character—with superimposed conformational factors. 

Hofmann elimination from quaternary ammonium salts. Discussed in Sec. 23.5. H... 

Quaternary ammonium salts. Exhaustive methylation. Hofmann elimination... 

The synthesis of stereodefined acyclic alkenes via 3-elimination reactions—such as (1) dehydration of alcohols, (2) base-induced eliminations of alkyl halides or sulfonates (tosyl or mesyl esters), and (3) Hofmann eliminations of quaternary ammonium salts—often suffers from a lack of regio- and stereoselectivity, producing mixtures of isomeric alkenes. 

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