Iminium salts, preparation from amides

Spending thioamides in the best yields. Thiolysis of iminium salts derived from amides and oxalyl chloride or phosphoric trichlorides with ammonium tetra-thiomolybdate 40 occurs below room temperature within 2 h (Eq. 10) [32]. It is advantageous that the by-products are easily separated, although H2S is needed in order to prepare 40. 

Irradiation of matrix-isolated imidazole-2-carboxylic acid gave the 2,3-dihydro-imidazol-2-ylidene-C02 complex (31) characterized by IR spectroscopy and calculated to lie 15.9 kcal mol above the starting material. A series of non-aromatic nucleophilic carbenes (32) were prepared by desulfurization of the corresponding thiones by molten potassium in boiling THF. The most hindered of the series (32 R = Bu) is stable indefinitely under exclusion of air and water and can be distilled without decomposition. The less hindered carbenes slowly dimerize to the corresponding alkenes. Stable aminoxy- and aminothiocarbenes (33 X = O, S) were prepared by deprotonation of iminium salts with lithium amide bases. The carbene carbon resonance appears at 260-297 ppm in the NMR spectrum and an X-ray structure determination of an aminooxycarbene indicated that electron donation from the nitrogen is more important than that from oxygen. These carbenes do not dimerize. 

Various iminium salts have been studied as reagents for the alcohol to halide transformation (see also 1,173) " for example the chloroiminium phospho-chloridates (75a) and chlorides (75b), prepared from amides with POCI3 and SOCI2, respectively, and the bromoiminium bromides (75c), made from (75b) by treatment with HBr, have been used to convert alcohols to the chlorides and bromides (Scheme 36). 

An important application of oxidation of a C-H bond adjacent to a nitrogen atom is the selective oxidation of amides. This reaction proceeds in the presence of ferf-BuOOH as the oxidant and Ru(II) salts. Thus in the example of Eq. (36), the a-tert-butylperoxy amide of the isoquinoline was obtained, which is an important synthetic intermediate for natural products [138]. This product can be conveniently reacted with a nucleophile in the presence of a Lewis add. Direct trapping of the iminium ion complex by a nudeophile was achieved in the presence of trimethylsilyl cyanide, giving a-cyanated amines as shown in Eq. (37) [45]. This ruthenium/peracid oxidation reaction provides an alternative to the Strecker reaction for the synthesis of a-amino acid derivatives since they involve the same a-cyano amine intermediates. In this way N-methyl-N-(p-methoxyphenyl) glycine could be prepared from N,N-dimethyl-p-methoxyaniline in 82% yield. 

The condensation of A-cyanoamidines 713 with chloromethylene-iminium salts 714, prepared in situ from the respective amides R2CONR2 and PC13, provides an efficient, convenient route to many 1,3,5-triazines 715 (Scheme 307) <1980S841, 1981AJC623>. 

Optically active imidazolines are generally obtained from enantiopure 1,2-diamines. For example, chiral ferro-cenylimidazolines are prepared from ferrocenyl carboxylic acid 1241 (Scheme 310). Amide 1242 is activated by 0-alkylation with Et30 BF4, generating iminium ether tetrafluoroborate salt 1243. The formation of the imidazoline ring in 1244 is accomplished by condensation of 1243 with the chiral diamine 1245 at room temperature without the need to isolate the intermediate imidate 1243 <20050L4137>. 

In a search for new methods to generate carbenes, it appeared that readily prepared (from commercially available urea and amides) chloro-amidinium and iminium salts could be interesting precursors [9],... 

Not only the Pinner synthesis provides alkoxymethyleneiminium salts the action of chloroformic acid esters on primary or secondary amides or thioamides ° as well as on lactams is a versatile method to get these salts and from them the imino esters, e.g. (230 equation 125). Primary and secondary amides have been alkylated by several reagents and the iminium salts thus formed were converted to imino esters with the aid of bases. A collection of imino esters prepared by this method can be found in a review the more recent results listed in Table 5 demonstrate the scope of this procedure. 

The reaction of V-cyanocarboximidamide with (chloromethylene)iniinium salts provides another important route to substituted 1,3,5-triazines.394,395 The (chloromethylene)iminium salts are prepared in situ from the corresponding amides, thioamides or dithiocarbamates and phosphoryl chloride, phosphorus pentachloride or phosgene (cf. Houben-Weyl, Vol. E5,... 

Wallach was the first (1874) to report on the transformation of carboxylic acid amides to amide chlorides by treatment with PCls various types of amides were converted by this reagent to chloromethyleneiminium chlorides (30 equation lg). - > Side reactions can include the a-chlorination of the amide chloride. If excess PCIs is used, the formation of iminium salts with complex ions (31) has been reported. The very labile bromomethyleneiminium bromides (32 equation 19) can be obtained by action of PBrs on tertiary amides. The iodomethyleneiminium salt (33) was prepared from DMF and diphosphorus tetraiodide in CS . ... 

Both chlorines in the iminium chloride (27) can be replaced by fluorine, bromine or iodine, giving compounds (58)-(60) (Scheme 3) if the salt is treated with the corresponding hydrogen halide under anhydrous conditions. By chloro-iodo exchange with HI from the 3-chloroacrylamide chloride the corresponding amide iodide (61 equation 37) was prepared. Dimethylformamide chloride (27) is converted by methyl iodide to dimethylformamide iodide (59). Remarkably the difluoro compound (60) is a nonionic, distillable liquid which can be ionized by addition of boron trifluoride. ... 

The reaction of amide chlorides with alcohols to yield alkoxymethyleneiminium salts, e.g. (91) and (92 Scheme 9), is important for the preparation of cations with bulky alkoxy groups, e.g. f-butoxy. These alcoholysis reactions demand the presence of salts with less nucleophilic anions in order to avoid dealkylation of the cations. This difficulty does not arise if the iminium hexachloroantimonates, which are obtained from the chlorides by addition of SbClj, are used for alcoholysis. A convenient route to / -unsubstituted salts (93 equation 54) is the alcoholysis of the formamide-benzoyl chloride adduct. The reaction of phenols with dimethylformamide chloride (27) affords aryloxymethyleneiminium salts (94 equation 55) which are hard to prepare by other methods. By addition of alkynols to the a-ha-loenamine (95) alkoxymethyleneiminium salts have been obtained (equation 56). ... 

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