Hoffman Reaction

20 g of the 3-L4-(trifluoromethoxy)-phenyl]-propionamide. .. were initially charged in 30 mL.of water. At 60° C., a mixture of 21.1 g of sodium hydroxide, 50 ml of water and 15 g of bromine was added dropwise to this suspension. The mixture was then heated under reflux for 3 hours. The reaction mixture was diluted with 200 mL. of water and then worked up and purified as described in Example 3. This gave 8.8 g of 3-[4-(trifluoromethoxy)-phenyl]-acrylamide which distilled over at from 84 to 87° C. and 11 mbar. According to GC, stated in area percent, the product was 99% pure. This corresponds to a yield of 49% of theory. 

5 grams alpha, a/p/ia-dimethy]-6c a-phenylpropionamide m 420 cc. of water was added to a solution of 87.5 grams of potassiutr hydroxide and 35 grams of bromine in 350 cc. of water. After 2 hour.s. ii 60° C, the product was obtained on crystallization from ethanol, meltiny at 184° C. 

24 grams of the urea derivative obtained as indicated above, wgt well mixed with 96 grams of calcium hydroxide in a flask immersed in an air bath and provided with a dropping funnel the stem of whid. reached the bottom of the flask. The mixture was heated to 240-260° G (inside temperature) for 7 hours during which time 86 cc. of water w u slowly added. The vapors were collectad in a receiver cooled with ic( After extraction with ether and distillation, the product was obtained v a colorless liquid boiling from 80-84° C. at 9 mm. 

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Ammonia has always been the starting material for the synthesis of aliphatic amines. Thus, processes have been developed for the condensation of NH3 with alkyl halides (Hoffman reaction) or with alcohols in the presence of various catalysts. The latter reachon, first discovered by Sabatier in 1909 [8, 9] is nowadays the main method of industrial production of light amines (e.g. methylamines 600 000 t/yr) [5]. 

Hofmann reaction, 76 320. See also Hoffman reaction Hofmann rearrangement, 77 741 Hofmann-type inclusion compounds, 74 171-172... 

A few carboxamides have been prepared. They may be hydrolyzed to carboxylic acids, dehydrated to nitriles, and homoamides also undergo the Hoffman reaction with alkaline sodium hypobromite to produce aminoalkylpurines. Table 31 lists reaction products of some typical purinecarboxamides. 

The alkylation of amines (including polyamines formed by reduction of polypeptides) was a highly popular method of derivatization in peptide chemistry before the appearance of contemporary mass-spectro-metric techniques for analysis of nonvolatile compounds (FFAB, MALDI, etc.). Direct alkylation of amines by alkyl halides (Hoffman reaction) can lead to the final nonvolatile ammonium salts and, hence, other soft reagents must be used. For example, exhaustive methylation can be provided by the mixtures CH20/NaBH4/H+ or CH20/formic add. 

A Hoffman reaction of the azide yields a crosslinked polymer, methacrylate) converts to a hydrazide in a similar manner. ... 

Somewhat similar results are obtained with a Hoffman reaction on polyacrylamide. A Sc/imiVir reaction on poly(acrylic acid) also yields mixed results. When it is run in acetic acid the intermolecular reactions appear to predominate over the intramolecular ones. Also, the products formed in acetic acid have a higher nitrogen content that those formed in dioxane. The NMR spectra show the presence of some acid anhydride groups. This has an additional effect of lowering the yield. 

PTC was successfully applied to a variety of other carbene reactions such as insertion into CH bonds, reactions with primary and secondary amines (giving isonitriles and A -formylated amines, respectively), Schiff bases (to form dichloroaziridine derivatives), some aromatic heterocycles, carbon-carbon triple bonds and with many other 0,N,S and P nucleophiles. In many cases, these reactions are of practical value only when carried out according to PTC methodology. For instance, the NaOH-promoted reaction of chloroform with primary amines leading to isonitriles (the Hoffman reaction), which are important intermediates in organic synthesis, was previously used only as an analytical method (eqs. 115-118). 

A survey of the literature has revealed the synthetic application of the Lessen rearrangement in three main areas (a) as a scale-up alternative to the Curtius and Hoffman reaction (b) for stereospecific transformations (c) in the degradation of studies of peptides and carbohydrates. 

Parks E K, Welller B H, Bechthold P S, Hoffman W F, NIeman G C, Pobo L G and Riley S J 1988 Chemical probes of metal cluster structure reactions of Iron clusters with hydrogen, ammonia and water J. Chem. Rhys. 88 1622... 

For Woodward-Hoffman allowed thermal reactions (such as the conrotatory ring opening of cyclobutane), orbital symmetry is conserved and there is no change in orbital occupancy. Even though bonds are made and broken, you can use the RHF wave function. 

For many reasons, including the Woodward-Hoffman rules that describe the likelihood of reaction based on arguments about the shapes of orbitals, it is desirable to be able to visualize molecular orbitals. 

Hoffman Degradation. Polyacrylamide reacts with alkaline sodium hypochlorite [7681-52-9], NaOCl, or calcium hypochlorite [7778-54-3], Ca(OCl)2, to form a polymer with primary amine groups (58). Optimum conditions for the reaction include a slight molar excess of sodium hypochlorite, a large excess of sodium hydroxide, and low temperature (59). Cross-linking sometimes occurs if the polymer concentration is high. High temperatures can result in chain scission. 

Chemical Properties. Reactions of quaternaries can be categorized iato three types (169) Hoffman eliminations, displacements, and rearrangements. Thermal decomposition of a quaternary ammonium hydroxide to an alkene, tertiary amine, and water is known as the Hoffman elimination (eq. la) (170). This reaction has not been used extensively to prepare olefins. Some cycHc olefins, however, are best prepared this way (171). Exhaustive methylation, followed by elimination, is known as the Hoffman degradation and is important ia the stmctural determination of unknown amines, especially for alkaloids (qv) (172). 

Displacement of a tertiary amine from a quaternary (eq. lb) iavolves the attack of a nucleophile on the a-carbon of a quaternary and usually competes with the Hoffman elimination (173). The counterion greatiy iafluences the course of this reaction. For example, the reaction of propyltrimethylammonium ion with hydroxide ion yields 19% methanol and 81% propylene, whereas the reaction with phenoxide ion yields 65% methoxybenzene and 15% propylene (174). 

One of the first methods of polymerizing vinyl monomers was to expose the monomer to sunlight. In 1845, Blyth and Hoffman [7] obtained by this means a clear glassy polymeric product from styrene. Berthelot and Gaudechon [8] were the first to polymerize ethylene to a solid form and they used ultraviolet (UV) light for this purpose. The first demonstration of the chain reaction nature of photoinitiation of vinyl polymerization was done by Ostromislenski in 1912 [9]. He showed that the amount of poly(vinyl bromide) produced was considerably in excess of that produced for an ordinary chemical reaction. 

Here is where we get back to mechanisms. Whether we are talking about Zaitsev vs. Hoffman elimination reactions or about Markovnikov vs. anti-Markovnikov addition reactions, the explanation of the regiochemistry for every reaction is contained within the mechanism. If we completely understand the mechanism, then we will understand why the regiochemistry had to be the way it turned out. By understanding the mechanism, we eliminate the need to memorize the regiochemistry for every reaction. With every reaction you encounter, you should consider the regiochemistry of the reaction and look at the mechanism for an explanation of the regiochemistry. 

Hazards associated with chemical reactions depend on the energy that can evolve in the course of reaction. The chemical reaction energy is categorized in Table 5.4-32 (based on data of Hoffman, 1985, and Rogers, 1997). 

Syn-Dihydroxylation. When the reaction was first discovered, the syn-dihydroxylation of alkenes was carried out by using a stoichiometric amount of osmium tetroxide in dry organic solvent.56 Hoffman made the observation that alkenes could react with chlorate salts as the primary oxidants together with a catalytic quantity of osmium tetroxide, yielding syn-vicinal diols (Eq. 3.11). This catalytic reaction is usually carried out in an aqueous and tetrahydrofuran solvent mixture, and silver or barium chlorate generally give better yields.57... 

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