Formamides from isonitriles

In related work, solid-phase-mediated synthesis of isonitriles from formamides was achieved by using polystyrene-bound sulfonyl chloride as a suitable supported reagent [115]. The sulfonyl chloride resin could be quantitatively regenerated by treatment of the sulfonic acid resin formed with phosphorus pentachloride (PCI5) in N,N-dimethy]formamide at room temperature. 

Triphenylphosphine/carbon tetrachloride triethylamine Isonitriles from formamides... 

Reactions with cyanuric chloride Isonitriles from formamides s. 17, 546... 

Dicyclohexylurea dissolved in anhydrous pyridine by warming, p-toluene-sulfonic anhydride added, and kept 1 hr. at 20° dicyclohexylcarbodiimide. Y 80%. M. Smith, J. G. Moffatt, and H. G. Khorana, Am. Soc. 80, 6204 (1958). p-Toluenesulfonyl chloride pyridine Isonitriles from formamides s. U, 549... 

A similar cyclization can result from lithiation of an isonitrile lithiation of 553 requires two equivalents of LDA and the organolithium 554 can either be trapped with other electrophiles at low temperature or warmed to give an indole 555 (Scheme 219) . It is quite clear that isonitriles activate purely by conjugation, and indeed they promote deprotonation of methyl groups para to an isonitrile just as well as ortho. The ease with which isonitriles can be made from formamides suggests that these methods could be rather more widely used than they are. 

Tetramethylbutyl isonitrile, from N-( 1,1,3,3-tetramethylbutyl )-formamide and thionyl chloride, 51,31... 

When labeled potassium cyanide reacted with the complex in an aqueous methanol solution, the bromide was rapidly replaced and the labeled cyanide ion entered slowly into the coordination complex. When the reaction was conducted at higher temperatures in ethylene glycol dimethyl ether as the solvent, the label was distributed among the benzyl isonitrile, benzyl formamide, and the polymer resulting from benzyl isonitrile and the iron isonitrile complexes. 

A minor isonitrile named acanthellin-2 with a specific rotation of — 24.1° was reported with no further details except some IR and MS data [3]. Isothiocyanate 15 and formamide 16 were also isolated from Axinella cannabina in a later study, in which isonitrile 14 and isomers 17-19 were also secured [35]. That 17-19 are C4(14)-ene isomers of 14 was concluded after extensive double resonance H NMR experiments. Coupling constants and nOe effects between the affected protons and various substituents of 17 established the relative stereochemistry of this series. 

Several examples of the monocyclic isothiocyano sesquiterpenoids having the bisabolane (83) skeleton are known. Along with the hydrocarbon theonellin (84), isothiocyanate 86 and formamide 87 were obtained from the Okinawan sponge Theonella cf. swinhoei. It seems remarkable, but not unusual, that not only was the amide the major constituent, but the isonitrile 85 was the missing member of the triad [57], Relative stereostructures were indicated by NMR analysis of theonellin formamide (87) and its transformation products. 

In a dehydration reaction (Scheme 12.4), the IR band of the formamide carbonyl group at 1684 cm in (7) decreased and eventually converted to the isonitrile band at 2150 cm in (8) (Fig. 12.8). In a separate example (Scheme 12.5), the conversion of the IR band from the carbonate carbonyl group in (9) to the IR band of the carbamide carbonyl group in (10) can be monitored to assure the reaction completion (Fig. 12.9). Based on FTIR analysis, the reaction time course can be analyzed by integrating peak areas of the IR bands from the starting resin and the product. From the point of view of kinetics, the side reaction product formation can be excluded if the pseudo first order rates of the starting material consumption and the product formation are identical. 

In a simple displacement of benzyl isonitrile by K14CN from II, all the labeled atoms should appear in the isonitrile complex and none in the benzyl isonitrile. But the label was present in all of the products isolated and in each to a different extent. For example, the benzyl isonitrile was more radioactive than the N-benzyl formamide which must have been formed by addition of water to benzyl isonitrile. The results indicate that the internal isomerization (III V, Equation 7), the generation of benzyl isonitrile and N-benzyl formamide, and the polymerization of benzyl isonitrile are concomitant reactions. 

The reaction of -halo carbonyl compounds with primary amides is appropriate for oxazoles containing one or more aryl groups . Ureas form 2-aminooxazoles. Formamide can be used resulting in a free 2-position in the oxazole. A convenient synthesis of 5-substituted-4-cyanooxazoles 223 is based on the condensation of -hydroxy—cyanoenamines 222 with trimethyl orthoformate (Scheme 109). The cyanoenamine intermediates 222 are derived from Lewis acid-catalyzed Passerini reactions between /-butyl isonitrile and aldehydes <2002S1969>. 

Phosgene, as well as the easier to handle diphosgene (chloroformic acid trichloromethyl ester) or triphosgene (carbonic acid bis(trichloromethyl) ester) transform primary, secondary and tertiary amides and thioamides to chloromethyleneiminium chlorides (25 equation 15), whereby the reaction with thioamides is of broader scope and proceeds with fewer side reactions. The amide chlorides derived from primary and secondary amides can lose HCl, giving nitriles or imidoyl halides, respectively. /V-Sub-stituted formamides can be converted to isonitriles via amide halides. ... 

Oxazoles. Oxazoles are formed using this building block on reaction with aldehydes and acid chlorides. The isonitrile is prepared from the corresponding formamide by dehydration with POClj-EtjN. 

Conversion of formamides into isonitrUes. In the course of a synthesis of dihydro-conessine from 3/3-acetoxy-A -bisnorcholenic ticid, Corey and Hertler treated the formamide (1) with tosyl chloride in pyridine in the expectation of merely tosylating the 3 8-hydroxyl group. The product, however, was not (3) but the tosylate isonitrile... 

Polymer-bound isonitrile (423), obtained from TentaGel-NH2 through treatment of the resin with formic acid and acetic anhydride, followed by dehydration of the resulting formamide with tosyl chloride and pyridine, has been employed in the preparation of N-substituted amino add ester [349]. Thus, Ugi MCR, performed in the presence of an alcohol instead of the carboxylic component, gave rise to an imino-ether spedes (426). Several Lewis acids were tested in searching for optimal reaction conditions. Boron trifluoride etherate displayed the better yields in term of desired product of the Ugi-type reaction. Amino acid methyl esters (427) were thus obtained when using methanol as the alcohol component, after deavage from the resin of the intermediate imino-ethers by an acetone/water mixture (Scheme 87). 

---