Hoffmann eliminations

Substituted phenyl azides react with acrolein and morpholine to give A -l,2,3-triazolines (743) (Scheme 149). Hoffmann elimination of A -methylmorpholine from the quaternized intermediates (744) by treatment with Ag20 affords 4-methylene triazoles (745) <86JCR(S)132>. 

They generally have reasonable thermal stability. While tetra-alkyl-ammonium salts have limited thermal stability, owing to decomposition via the Hoffmann elimination, [emim][BF4] is reportedly stable up to 300 °C and emim-(CF3S02)2N up to 400 °C. In other words many ionic liquids have liquid ranges of more than 300 °C, compared to the 100 °C liquid range of water. 

A general synthetic approach to the thietes is provided by a Hoffmann elimination from aminothietanes 148 (Eq. 24). Other thiete derivatives... 

Finally it is noted that while the conditions associated with conventional Hoffmann eliminations are obviously much too drastic for preparing heteroannulenes, a rather clever modification of the procedure (one involving the rupture of a cross-link) was successfully applied more than a decade ago to the synthesis of the fully saturated diazonine (120) and its mostly saturated benzo counterpart (121) as well as the partially saturated diazecine (122) and its dibenzo counterpart (123) (69JOC2715, 2720). The fully saturated counterparts of the molecules shown in (121)-(123) were also prepared in that early study. 

Other heterocyclic tertiary amines show a different behavior. Tertiary amines have been used as catalysts in dichlorocyclopropanation of olefins they probably give an ammonium ylide as the first step in the catalytic cycle.262 These ylides are usually unstable and undergo a variety of transformations such as the Stevens rearrangement and the Hoffmann elimination. 

It has already been reported that the weight loss of as-synthesized MMSs depends on the kind of the template used in the synthesis [17]. This is an obvious consequence of the fact that different templates decompose and thermodesorb at different temperatures. However, it was somewhat unexpected that the decomposition/desorption of the same kind of the template may be dramatically influenced by the framework composition of materials [4,10-14]. This can be understood as an influence of the framework structure on the process of Hoffmann elimination of alkylammonium to the corresponding alkene and low molecular weight amine [4,8], This decomposition process leads not only to the elimination of the electrostatic framework-template interactions but also to the formation of decomposition products of lower molecular weight than that of the surfactant. Thus, the framework-surfactant interactions are crucial factors determining the thermogravimetric behavior. 

It is interesting that similar low-temperature weight loss peaks on the DTG curves were also observed for lamellar silicates templated by CTMA+, but the overall shape of the DTG curves was somewhat different [22]. It is not fully clear why these lamellar materials exhibited surfactant decomposition at such low temperatures. This behavior may be related to either properties of their silicate surface or the structural changes in their framework upon heat treatment, or both of these factors, which would promote the Hoffmann elimination at lower temperature [22]. The second of these possible factors may be related to the stress in... 

Vinyl substitutions on alkenes not having their double bonds conjugated with carbonyl groups often proceed more rapidly and give better product yields when the reactions are conducted in the presence of an unhindered secondary amine. Conjugated and nonconjugated dienes are usually only minor products in these cases. The major products normally are allylic amines obtained by nucleophilic attack of the secondary amine upon the ir-allylpalladium intermediates. Since allylic amines may be quatemized and subjected to the Hoffmann elimination, this is a two-step alternative to the direct vinyl substitution reaction.90... 

The molecular mechanism of the Hoffmann elimination involving (iV-Cl)-N-methyl-ethanolamine has been theoretically characterized by using DFT at the B3LYP/ 6-31++G computing level.49 The role of water as a solvent has been analysed by using both discrete and hybrid discrete-continuum models. The rearrangement proceeds by a water-assisted asynchronous concerted mechanism. 

Reetz [13, 65] and also Sivaram [66] have shown that nucleophilic tetrabuty-lammonium salts will initiate living polymerization of acrylates at room temperature. Molecular weights 1500-25,000 are obtained with MWDs of 1.1-1.4. Methyl and ethyl acrylates don t work as well as the more bulky acrylates. Side reactions are end group cyclization and Hoffmann elimination [13] (Scheme 29). 

Reaction with a-silyltertiary aliphatic amines leads to results of the same type, including silyl- and non-sily 1-products, proceeding either from a Stevens rearrangement or a Hoffmann elimination.364... 

Another example is the reaction of benzyne with 1-methyl- (and benzyl)-3, 3-dimethylbenzo[d]-l,3-azasiloline (see their preparation in Section IV.A.2.p). Stevens rearrangement product is obtained (48%) as a single compound. If a Me on nitrogen is replaced by an Et, then Hoffmann elimination occurs.251 It should be noted that an Y-alkyl MSMA is converted into an Y-aryl RSMA in the former case and into a Y-aryl MSMA in the latter case. 

In the case of acyclic compounds there is a strong preference for anti elimination, at least with short-chain alkyl halides. The first example of departure from this norm was observed (Pankova et al., 1967) in the Hoffmann elimination from threo- 2YT -[17] and eryf/iro-[2H]-[17] (Fig. 14). Formation of trans-[ 18] and cis- [18] 9... 

The product, which contains both the double bond and the tertiary amine in an ring-opened structure, can undergo a second Hoffmann elimination. 

We may safely assume that phenanthrene alkaloids with a 2-dimethylamino side chain derive from quaternary aporphinium salts by in vivo Hoffmann elimination. These phenanthrene alkaloids may later be oxidized to the corresponding A -oxides or methylated to give trimethyl 2-(l-phenanthryl)ethylammonium salts. Far more intriguing is the biosynthesis of phenanthrene alkaloids with a 2-monomethylaminoethyl side chain, for which we have four examples A -nor-atherosperminine (13), noruvariopsine (14), secoglaucine (15), and secophoebine (16). One possibility would be direct elimination after protonation of the nitrogen of an aporphine. This transformation would have some similarity to the formation of 167 by acid treatment of 166 18). 

The use of optically active enamines in [2 + 2] cycloadditions with thiocarbonyl 5.5-dioxides gives asymmetric induction in the product thiirane 1,1-dioxides. Thus, when thioformaldehyde S,S-dioxide, generated from methanesulfonyl chloride and triethylamine, is treated with optically active AM-phenylethyl-Af-methylpropanal enamine, a mixture of diastereomeric thietane 1.1-dioxides 6 is formed quantitatively. Removal of the chiral 1-phenylethyl auxiliary followed by Hoffmann elimination gives (-+ )-(5)-2-methyl-2//-thiete 1,1-dioxide (7) with 6% ee1,8. 

Ramos et alP studied the Hoffmann elimination of (A-Cl),A-methylethanolamine in the gas phase and in aqueous solution, i.e., the reaction CH2OH-CH2-NCI-CH3... 

The presence of a solvent may also lead to a reduction in the dipole moment. For the Hoffmann elimination, discussed above, that was studied by Ramos et al., the authors considered the dipole moment for the initial complex consisting of the (N-Cl),A-methylethanolamine, the OH ion, and 0, 1, or 2 water molecules as well as a polarizable continuum describing the rest of the aqueous solvent. They found that it changed from 6.44, via 5.82, to 6.88 D when including 0, 1, or 2 water molecules. For... 

Although the first cyclopropane derivative was obtained as early as 1881, and the parent hydrocarbon just one year later, it was not until 1922 that cyclopropene (1) b ame available. However, Freundler (1897) claimed that the dry distillation of barium furoate led to cyclopropene in addition to furan, but the reaction proved difficult to repeat and the report remains unsubstantiated. Work published by Dem yanov and Doyarenko in 1922 provided the first authenticated synthesis of cyclopropene. These authors found that trimethylcyclopropylammonium hydroxide undergoes Hoffmann elimination by heating to approximately 300°C on platinized clay. This reaction, which parallels the original synthesis of cyclobutene, was subjected to detailed scrutiny in 1941 and under optimum conditions 1 was obtained in a yield of 45 % (equation 1). Despite these early beginnings. 

A second side reaction using this approach is the Hoffmann elimination of the sulfide or amine, during attempted deprotonation of the sulfonium or ammonium salt. This reaction is especially important in the case of ammonium ylides. Finally, another problem which surfaces during the deprotonation step is the formation of a mixture of ylides, e.g. (45) and (46) from (44), which undergo competing rearrangements to give (47) and (48 Scheme 12). ... 

Winterstein esters are easily turned into >-cinnamates by the action of acids (H silica gel) [32]. For preparative purposes the reaction has been carried out using the Hoffmann elimination of the corresponding methylammonium hydroxides [27] or the Cope elimination of the corresponding tf-oxides [SI], The latter procedure is more convenient, since, if the reaction is carried out in THF, elimination of dimethylhydroxylamine takes place spontaneously at room temperature. If only a moderate excess of peracid is employed, the exocyclic double bond at C-4 is not affected [30], The transformation of Winterstein esters into cinnamates can be very useful for separation purposes. Thus, whereas taxine B (2a) and isotaxine B (2b) are difficult to separate by HPLC, their corresponding cinnamates can be separated by column chromatography... 

Thus a support-bound benzylpiperazine (282) was allowed to undergo a Man-nich reaction with formaldehyde and a-keto-aldehyde hydrazones. Upon addition of 1,2-dibromo-ethane (388) the support-bound piperazine tether is N, N -dialky-lated to give a quinuclidinium species (389). Subsequent Hoffmann elimination released a diazaalkadiene (390) from the polymeric support, allowing it to react with isonitriles to give pyrazoles (395). With electron-rich dienophiles, HDA reactions were also reported to have been performed to yield compound (393) (Scheme 80). 

N-Alkylation with methyl iodide followed by Hoffmann elimination in the presence of Hiinig s base allowed the final compounds (565) to be cleaved from the resin. Based on the observed results, the authors concluded that the reaction is unaffected by steric or electronic factors on each component... 

Bis-anion equivalent (Table 8, entry 28) [479] Especially intriguing is the generation of a structure having two potential carbanionic centers on the solid phase (Table 8, entry 28) [479]. Thus, a l-(2-oxopropyl)pyridinium moiety (651) was allowed to react with various chalcones (652) to give compounds (654), attached to the sohd phase via their pyridinium substituents. Hoffmann elimination, driven by aroma-tization, then occurs rapidly to liberate a set of phenols (655) in high yields and purities (Scheme 135). 

Fig. 1.15. C-N bond breaking in HDN of 1.2.3,4-tetrahydroquinoline Hoffmann elimination (top) and nucleophilic substitution (bottom)...

Fig. 1.14. Mechanisms of C-N bond breaking, (a) Hoffmann elimination and (b) Nucleophilic substitution 29...

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