Formamides with alkenes

The chain addition of formamide to alkenes is a closely related reaction. It results in the formation of primary amides. The reaction is carried out with irradiation in acetone. The photoexcited acetone initiates the chain reaction by abstracting hydrogen from formamide ... 

The Ritter reaction is a method for creating amides beginning with alkenes or alcohols (2° or 3°) and cyanide (Reddy, 2003). Preparation of a formamide is shown below ... 

Formylation of alkenes can be accomplished with N-disubstituted formamides and POCl3. ° This is an aliphatic Vilsmeier reaction (see 11-15). Vilsmeier formylation can also be performed on the ot position of acetals and ketals, so that hydrolysis of the products gives keto aldehydes or dialdehydes ... 

Nitroalkanes react with Jt-deficient alkenes, for example, p-nitro ketones are produced from a,P-unsaturated ketones [41], whereas allylic nitro compounds have been prepared via the Michael-type addition of nitroalkanes with electron-deficient alkynes (Table 6.19). The reaction in either dimethylsulphoxide [42] or dimethyl-formamide [43] is catalysed by potassium fluoride in the presence of benzyltriethyl-ammonium chloride the reaction with dimethyl acetylenedicarboxylate is only successful in dimethylsulphoxide [42], Primary nitroalkanes produce double Michael adducts [42,44], A-Protected a-aminoacetonitriles react with alkynes under catalysed solidiliquid conditions to produce the Michael adducts [45] which, upon treatment with aqueous copper(Il) sulphate, are converted into a,p-unsaturated ketones. 

Many carboxylic acids lose carbon dioxide on either direct or sensitized irradiation, and in some cases (4.10 the evidence points to the operation of an initial electron-transfer mechanism rather than primary a-deavage. Cleavage occurs readily with acyl halides, and this can [ead to overall decarbonylation (4.11). Aldehydes also cleave readily, since the (0=)C—H bond is more prone to homolysis than the (0= C-C bond. This offers a convenient method for replacing the aldehydic hydrogen by deuterium in aromatic aldehydes (4.12. and a similar initial reaction step accounts for the production of chain-Iengtheped amides when formamide is irradiated in the presence of a terminal alkene (4.13). 

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]. 

This resonance representation correctly predicts a planar amide nitrogen atom that is sp2 hybridized to allow pi bonding with the carbonyl carbon atom. For example, formamide has a planar structure like an alkene. The C—N bond has partial double-bond character, with a rotational barrier of 75 kJ/mol (18 kcal/mol). 

Table 8 summarizes further examples of the nucleophilic addition of hydrogen fluoride to pcrhalogenated alkenes with potassium fluoride in formamide. 

Table 8. Hydrofluorination of Alkenes with Potassium Fluoride/Formamide...

Further, alkene reacts with formamides in the presence of Ru3(CO)i2 to give the hydroamidated products (Eq. 11.19). 

Formylation of alkenes can be accomplished with A-disubstituted formamides... 

Since the amides (especially the formamides) are easily cleaved under hydrolysis conditions to amines, the Ritter reaction provides a method for achieving the conversions R OH R NH2 (see 10-32) and alkene R NH2 (see 15-8) in those cases where R can form a relatively stable carbocation. The reaction is especially useful for the preparation of tertiary alkyl amines because there are few alternate ways of preparing these compounds. The reaction can be extended to primary alcohols by treatment with triflic anhydride ° or Ph2CCl" SbClg or a similar salt in the presence of the nitrile. 

Many vinylogous amidinium salts, e.g. (185) and (186) (Scheme 25), are readily available by double formylation of CHa-acidic or alkenic compounds. Reviews on the chemistry of vinylogous amidinium salts are available. The first azavinylogous foimamidinium salt (187 Scheme 26) was prepared in 1960 by reaction of DMF with cyanuric chloride. The mechanism of this reaction has been estab-lished. Based on these findings new methods for the synthesis of these compounds were developed, e.g. the reaction of isocyanatomethyleneiminium salts with tertiary formamides affords salts (187). In the synthesis of the salts (187) cyanuric chloride can be replaced by phosphorus nitride chloride (PNCl2)3. ... 

In the laboratory of T.-L. Ho, the total synthesis of the novel marine sesquiterpene (+)-isocyanoallopupukeanane was completed." In the endgame of the synthesis, it was necessary to install the isocyano group onto the tricyclic trisubstituted alkene substrate so that it will occupy the more substituted carbon atom (according to Markovnikov s rule). The Ritter reaction was chosen to form the required carbon-nitrogen bond. The alkene substrate was dissolved in glacial acetic acid and first excess sodium cyanide followed by concentrated sulfuric acid was added at 0 °C. The reaction mixture was stirred at ambient temperature for one day and then was subjected to aqueous work-up. The product A/-alkyl formamide was subsequently dehydrated with tosyl chloride in pyridine to give rise to the desired tertiary isocyanide which indeed was identical with the natural product. 

C-C double bonds are elTiciently cyclopropanated electrochemically in a one-compartment cell fitted with a sacrificial zinc anode which allowed the formation of organozinc species from geminal dihaloalkanes. Electrolysis of dibromomethane in dichloromethane/dimethyl-formamide as solvent mixture is recommended as the standard condition for electrolysis. The best chemical yields were obtained with allylic alcohols and unfunctionalized alkenes. For example electrolysis of allyl alcohol 23 gave cyclopropane 24 in 70% yield. 

Reactions with zinc were accomplished at room temperature, lower yields of difluorocyclopropanes resulted if solvents other than tetrahydrofuran (diethyl ether, acetonitrile, dimethyl-formamide) were utilized. Experimental data indicate that free carbene is generated by this method. Good yields of 1,1-difluorocyclopropanes were obtained with electron-rich alkenes. ... 

Analogously to conventional reactions 201-203), bis(trimethylsiloxy) alkenes form heterocycles of different classes l,2-bis(trimethylsiloxy)-l-cyclohexene (305) reacts with formamide urea malodinitrile and ethyl (J-amino-crotonate to afford 4,5,6,7-tetrahydrobenzunidazole (309) ° 2-oxo-l, 3,4,5,6,7-hexahydrobenzimidazoIe (317) , 2-aniino-3-cyano-4,5,6,7-tetra-hydro-coumarone (312) and 2-methyl-3-ethoxy-carbonyl-4,5,6,7-tetrahydro-in-dole (373) respectively. 

These reactions are typified by Bredereck s formamide synthesis . This has been applied to the synthesis of 4,5-dimethylimidazole (as its formic acid complex) from acetoin and formamide <91JHC1819>. A similar reaction leads to 5-methylhistamine (243) <8lJHC83l>. 1-Hydroxyimidazoles are accessible in high yield from reaction of nitrosonium fluoroborate with acetonitrile and appropriate alkenes (Scheme 177) <84TL1319>. 

The Ritter reaction proceeds by a nucleophilic addition of hydrogen cyanide followed by the hydrolysis of the intermediate formamide. Higher tertiary alkyl amines are produced using the same method with higher alkenes and alcohol. This is considered the most practical way to produce tertiary amines [99]. 

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. 

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