Olefins with formamide

Another relatively simple system for the epoxidation of tri- and c/r-disubstituted olefins is formamide-hydrogen peroxide in an aqueous medium. This reagent has the advantage of being pH-independent, which makes it attractive for biochemically mediated transformations. No reaction was observed in the case of /ran.v-disubstituted and terminal olefins. With bifunctional alkenes, the more reactive double bond is selectively epoxidized [95TL4015]. 

From a practical point of view, isocyanates, together with carbamates and ureas (Chapter 3), are the most important organic products discussed in this book. Their synthesis from nitroarenes has indeed been the subject of many patents. There are also limited examples of aliphatic isocyanates obtained by this route. Organic mono- and diisocyanates may be prepared in a continues liquid phase method by treating the appropriate amine with phosgene. However, the reaction is rather complex [6] and, besides the use of the dangerous phosgene, the formation of the corrosive hydrochloric acid creates several problems. Aliphatic isocyanates can also be obtained from olefins with isocyanate ion in the presence of a salt of a coordination compound of palladium or platinum [7], from olefins with isocyanic acid in the vapour phase over Pt/ALOs [8], and from formamides, by oxidation over a silver catalyst [9]. Apparently only the last reaction seems to have some potential practical applications [10]. 

In the examples, a nitro group is substituted for a hydrogen atom, and water is a by-product. Nitro groups may, however, be substituted for other atoms or groups of atoms. In Victor Meyer reactions which use silver nitrite, the nitro group replaces a hahde atom, eg, I or Br. In a modification of this method, sodium nitrite dissolved in dimethyl formamide or other suitable solvent is used instead of silver nitrite (1). Nitro compounds can also be produced by addition reactions, eg, the reaction of nitric acid or nitrogen dioxide with unsaturated compounds such as olefins or acetylenes. 

Ritter Reaction (Method 4). A small but important class of amines are manufactured by the Ritter reaction. These are the amines in which the nitrogen atom is adjacent to a tertiary alkyl group. In the Ritter reaction a substituted olefin such as isobutylene reacts with hydrogen cyanide under acidic conditions (12). The resulting formamide is then hydroly2ed to the parent primary amine. Typically sulfuric acid is used in this transformation of an olefin to an amine. Stoichiometric quantities of sulfate salts are produced along with the desired amine. 

Photolytic Reaction in Sunlight A mixture of olefin (0.01 mole), formamide (40 g), r-butyl alcohol (20 ml), and acetone (5 ml) is placed in a Pyrex Erlenmeyer flask, which is then flushed with nitrogen, stoppered, and situated in direct sunlight for 1 day. A solution of olefin (0.04 mole), /-butyl alcohol (25 ml), and acetone (5 ml) is then added in four equal portions at 1-day intervals, and finally, the flask is left in sunlight for an additional 2 days. Work-up of the solutions as in the above procedure gives the desired amide in comparable yields. 

Some studies seeking preferred conditions for this reaction have been made. Optimum yields are obtained when the amount of water present is appreciable, and it was noted that the rate of hydrogen evolution increases with increasing water content. A 75% formic acid system appears generally preferred. Under the reaction conditions examined by the submitters, olefins, ketones, esters, amides, and acids are inert, but nitro compounds are reduced to the formamide derivative. 

Formylation of olefins can be accomplished with N-disubstituted formamides and POCl.v201 This is an aliphatic Vilsmeier reaction (see 1-15). Vilsmeier formylation can also be performed on the a position of acetals and ketals, so that hydrolysis of the products gives keto aldehydes or dialdehydes 202... 

Further hydrolysis of the compound 55 with 7% HCl-MeOH followed by treatment with MsCl-pyridine and then with LiCl in dimethyl-formamide (DMF) (90-100°, 18 hr) afforded a monomesylate [56, mp 253-254° (as hydrochloride)] via deacetyldeoxyyuzurimine (57) and dimesylate (58). In the NMR spectrum of 56, a broad singlet resulting from two olefinic protons was observed at 5.93. Finally, catalytic hydrogenation of this compound over Pt02 gave yuzurimine-B mesylate (54) which was directly obtained from yuzurimine-B on mesylation with MsCl-pyridine. 

The C-Si bond of an SMA can also be cleaved by oxidizing reagents like cerium ammonium nitrate (CAN). Starting from (V-bis(trimethylsilyl)methylazetidinones, treatment with CAN probably leads to the oxidation product of the two C-Si bonds, i.e., the corresponding disilylketal that is hydrolyzed into the formamide to give the N-H azetidinones (yields >80%). This constitutes an alternate and more efficient way to sequential fluoride-induced desilylation. Peterson olefination, ozonolysis, and formamide decomposition when deprotection of bis(trimethylsilyl)methylated azetidinones into NH-azetidinones is required.228,230... 

Friedman and Shechter (27) found that substituted formamides undergo similar reactions with olefins in the presence of peroxides at elevated temperatures to give products resulting from the addition of both CON (CH3)2 and HCON (CH3)CH2 radicals to the olefins,... 

Since it has been observed that the hydrogen atoms attached to nitrogen in amines were not easily abstractable in free radical reactions (6, 74), it may be assumed that the aldehydic part of the formamide molecule will be more reactive in the photoaddition reactions than the amino function, thus leading to the following addition reaction with terminal olefins,... 

A study of the photoaddition of formamide to olefins was undertaken with the aim of finding a new process for converting olefins to higher amides and possibly further to amines by reduction or by the use of the Hofmann rearrangement. Since hydrolysis of the amides to the corresponding carboxylic acids can be effected by standard procedures, this reaction provides a new process for carboxylation of olefins under mild conditions at room temperature. A similar reaction has been shown to take place in a thermal process, using peroxides as initiators (60). 

Since the addition of formamide to olefins is induced photochemically as well as by peroxides at elevated temperatures, it may be safe to assume that we deal here with a free radical reaction. Let us apply this assumption to interpret the results. A reasonable free radical derived from formamide would be a carbamoyl radical CONH2 which can be formed by loss of a hydrogen atom from formamide. Experimental data show that irradiation of formamide in the presence of acetone and in the absence of an olefin leads to the formation of considerable amounts of oxamide. 

In fact, alkylated succinamides were isolated in some cases, though in very poor yields, and result from radical combination, which is a chain termination step. The experimental observations, i.e. the formation of (a) 1 1 adducts, (b) telomeric products, (c) alkylated succinamides, and (d) oxamide (when an olefin is absent), are consistent with a free radical mechanism. The telomeric products obtained support the assumption that we deal here with a chain reaction, because they are characteristic products of this type of reaction. Another proof for the chain reaction mechanism is the fact that when benzophenone is used as a photoinitiator (vide infra), the amount of benzpinacol formed is smaller than the amount of the 1 1 addition product of formamide and olefin (16). Quantum yield determinations will supply extra evidence for the validity of a chain reaction mechanism for this photoaddition reaction. 

The reaction of formamide with aromatic compounds under ultraviolet irradiation is still unexplored and only preliminary results have so far been obtained. In the cases already studied it has been found that this reaction must be sensitized with a ketonic sensitizer, usually acetone, in order to take place. The mechanism of the photoamidation of aromatic compounds certainly differs from the one of simple olefins. The detailed mechanism still awaits further experimental evidence, and in some cases involves, most probably, radical combinations and not addition of radical to unsaturated systems. Interactions of the excited sensitizer with aromatic compounds, having in some cases triplet energies similar or just a bit higher than those of the sensitizers used, must be brought into consideration. Experimentally it has been shown that the photosensitized amidation of benzene leads to benzamide (11),... 

The N-alkylation of amides followed by hydrolysis furnishes a good route for making secondary amines. The formyl, acetyl, and aryl-sulfonyl " derivatives of amines are best suited for alkylation (method 358). Hydrolysis is accomplished by refluxing concentrated hydrochloric acid alone or in acetic acid. N-Alkyl-formamides prepared by the addition of olefins to nitriles (method 355) are hydrolyzed with aqueous alkali. Similar hydrolytic procedures... 

The reaction is an equilibrium that can be shifted to the right by introduction of a base sodium acetate is one of the reagents of choice with branched olefins.4 For unbranched alkenes, dimethyl-formamide is preferred.5 Inorganic bases have also been used6 but are less satisfactory. Addition of copper(I) chloride7 improves the yields, since any Pd (II) that is reduced by the olefin (which in turn is converted into an aldehyde or ketone) is reoxidized. 

The application of ethylene in Heck reactions often shows different activities from other olefins, because of Wacker-type side reactions. It was found, however, that iodo- and acceptor-substituted bromoarenes are cleanly converted in aqueous media to the corresponding styrenes utilizing a palladiium-TPPMS complex [13]. Furthermore, high-purity 0- and p-vinyltoluenes were prepared in a dimethyl-formamide/water mixture with palladium tri(o-tolyl)phosphine complexes [14]. Here, the role of water may be the dissolution of the inorganic base (potassium carbonate) in the organic media. 

A pyridal formate group is used for hydroesterification of an olefin (Equation (42)). Use of a benzyl ester in place of the pyridyl group gave 0% yield. Pyridyl formamides were also found to give hydroamidation products with high linear/branched ratios. "" ... 

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