Hofmann reaction tables

The stability of the base resins produced by the Hofmann reaction was tested by shaking 2.0g lots of H16 in 50 ml of 2% NaOH, 10% NaCl solution. The amine capacity decreased with time as shown in Table III. Because of this instability and the relatively low amine capacities attained, the products were not suitable for the intended applications. 

The versatility of this method for the alkylation of compounds containing active methylene groups is illustrated by Table I. Review articles have recently appeared,34 and the application to the Hofmann carbylamine reaction is described in the following procedure in this volume, p. 96. 

A selective heating in liquid/liquid systems was exploited by Strauss and coworkers in a Hofmann elimination reaction using a two-phase water/chloroform system (Fig. 2.10) [32]. The temperatures of the aqueous and organic phases under micro-wave irradiation were 110 and 55 °C, respectively, due to the different dielectric properties of the solvents (Table 2.3). This temperature differential prevented decomposition of the final product. Comparable conditions would be difficult to obtain using traditional heating methods. A similar effect has been observed by Hallberg and coworkers in the preparation of /3,/3-diarylated aldehydes by hydrolysis of enol ethers in a two-phase toluene/aqueous hydrochloric acid system [33],... 

In media of low proton availability (MeCN, dmf, hmpa)762, ylide formation was found and products derived from the radical cleavage of the phosphonium ion have been observed. The initial cation would interfere in the reaction process as an acid. A competition can exist between the one-electron pathway (dimerization, disproportionation of R ) and the two-electron pathway (ylide formation, Hofmann degradation, phosphine oxide formation) (Table 24). 

The importance of the base in determining the nature of the transition state and thereby the product can be seen from Table 7.13. When Reaction 7.38 is carried out with KO-/Bu in /-butanol (E2H conditions), 76.9 percent Hofmann olefin is obtained. However, when the same reaction is carried out with +N(Bu)4 Br- (E2C conditions), 97.3 percent Saytzeff product is obtained. The... 

H. C. Brown has suggested that steric factors are of primary and almost sole importance in determining the position of the double bond. According to Brown, Hofmann product predominates when a large leaving group makes it even more difficult for the base to abstract the more hindered protons.96 He has asserted that data similar to those of Table 7.12, which seem at first glance to be contrary to his theory, support it further He says that fluorine takes up more space in the transition state than iodine because fluorine is more solvated.97 However, the entropies of activation for Reaction 7.37 with X = F, Cl, Br, or I are all very similar therefore increased solvation of fluorine seems not to be the proper explanation for the preponderance of Hofmann product when X = F.98... 

With the chiral BINOL-phosphates in hand we started to examine the enantioselective transferhydrogenation of ketimines 1. After reaction optimization, including a survey of different solvents, temperatures, BINOL-phosphates, and Hantzsch dihydropyridines, we found that indeed enantioselectivities are observed and the best selectivities are obtained with Brpnsted acid 5a and Hantzsch ester 2a (Table 2). In general, for the first time, high enantioselectivities and good yields are observed in this newly developed metal-free reduction procedure (Rueping et al. 2005b Hofmann et al. 2005 Storer et al. 2006). 

N-halogenation, 103 Hofmann degradation, 674 hydrolysis, 412, 415 intramolecular condensation, 576 preparation, 416, 426, 565 preparations listed in table 63, 578 reaction, with alcohols, 480 with amines, 568 with isocyanates, 647 with organomagnesium compounds, 335... 

Preference for the Hofmann product olefin (i.e., the olefin with the least number of alkyl substituents and, therefore, the least stable thermodynamically) in reactions where more than one olefin may be formed (i.e., secondary and tertiary esters) was noted by DePuy and King in their early review of ester elimination reac-tions . This preference is apparent from the data of Scheer et al. (Table 3). The observed reaction path ratios (Column 2) may be compared with the simple reaction path degeneracy ratios. Column 3, i.e., statistical ratio = ratio of the number of reactive j -H atoms for each path) and with the ratios of the estimated... 

The leaving groups commonly employed in E2 reactions are listed in Table 2.1. As you can see, they are essentially the same as those displaced in nucleophilic substitution reactions (see Part 2), with two exceptions. First, protonated alcohols are not listed as substrates RX in Table 2.1, because they usually react by the El mechanism (as we shall see later) rather than the E2 mechanism. Secondly, the trimethylammonium and dimethylsulfonium groups have limited importance as leaving groups in substitution reactions, although they are particularly important in elimination reactions. In fact, the reaction involving trimethylammonium is known, after its discoverer, as the Hofmann elimination... 

The data in Table 2.2 are representative of many elimination reactions. The product distribution is found to depend on whether the substrate is neutral (with a halide or sulfonate leaving group) or positively charged (with a —N(CH3)3 or —S(CH3)2 leaving group — which become N(CH3)3 and S(CH3)2 respectively). The empirical rules linking the nature of the substrate and the product distribution are known as Saytzev s rule and Hofmann s rule. 

Carbon isotope effects (kyjku) have been measured for both the beta and alpha carbon atoms in some Hofmann degradations of quaternary ammonium compounds (Table 5). Three methods were used to determine the isotope effects (a) comparison of molar specific activity of reactant remaining after a measured extent of reaction, (b) comparison of molar specific activity of the... 

The most successful method developed for the production of a general-purpose synthetic rubber was the emulsion copolymerization of butadiene and styrene (SBR), which still represents the main process in use today (Blackley, 1975 Hofmann, 1989 Blow, 1971 Brydson, 1981 Bauer, 1979 Sun and Wusters, 2004 Demirors, 2003). The general principles of copolymerization will be discussed in a later section, but it is instructive at this point to examine the other main features of this system. The types of recipes used are seen in Table 2.5 (Bauer, 1979). The recipes shown are to be considered only as typical, as they are subject to many variations. It should be noted that the initiator in the 50°C recipe (hot rubber) is the persulfate, whereas in the 5°C recipe (cold mbber) the initiator consists of a redox system comprising the hydroperoxide-iron(II)-sulfoxylate-EDTA. In the latter case, the initiating radicals are formed by the reaction of the hydroperoxide with the ferrous iron, whose concentration is... 

Thus, essentially all computational studies are in agreement with the assertion that DMSOR follows a two-step associative mechanism, with the second transition state highest in energy and an activation energy of 68-80 kJ mol, ie. close to the experimental estimate of 62 kJ mol". The studies have used a variety of DFT methods and basis sets, cf. Table 7.1. Only the studies by Hofmann gave a somewhat lower barrier of 40 kJ mol . Therefore, we were quite surprised to find that the reaction is extremely sensitive to the details of the calculations. ... 

Scheme 7.29. A representation of two potential pathways for proton loss from a carbocation intermediate on the Sn1-E1 reaction surface. Both pathways are followed. It is supposed that proton loss via the pathway labeled (a), which results in the most highly substituted alkene (the Saytzeff product), occurs preferentially because that is the product formed in highest yield. The alkene resulting from pathway (b), the Hofmann product, is also formed. A. W. Hofmann (1818-1895) was a German chemist who was professor of chemistry at the Royal College of Chemistry in London (1845-1864) and then accepted a post as professor at the University of Berlin. Most of Hofmann s work dealt with amines (Chapter 10). Hofmann found, in contrast to Saytzeff, that the least highly substituted alkene is formed when the elimination is carried out on amine quaternary salts (so-called onium salts). This is, in part, presumably due to the close association between the base and the positively charged onium salt as well as to the removal of the proton in the rate-determining step (cf. the E2 reaction). (Note the 82 18 ratio of products shown here should be considered identical, within experimental error, to the 79 21 ratio of Table 7.9.)...

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