Hydrolysis of iminium salt

The reaction of other nucleophiles such as amines 123,124), hydroxyl-amines, various carbanions, and hydroxide 120) have been tried but not examined in detail. Hydrolysis of iminium salts is covered elsewhere 123). 

The classical Vilsmeier-Haack reaction - involves electrophilic substitution of a suitable carbon nucleophile with a chloromethyleneiminium salt, for example salt (1). Suitable carbon nucleophiles are generally electron-rich aromatic compounds such as V,N-dimethylaniline (2), alkene derivatives such as styrene (3) or activated methyl or methylene compounds such as 2,4,6-trinitrotoluene (4 Scheme I). These compounds (2-4) react with salt (1) giving, after loss of hydrogen chloride, the corresponding im-inium salts (5-7). Hydrolysis of iminium salt (5) affords aldehyde derivative (8) and this transformation (Ar—H - Ar—CHO) is the well-known Vilsmeier-Haack formylation reaction. Hydrolysis of iminium... 

The reaction of iminium salts such as 66 with salts of trichloroacetic acid has been shown to yield amides such as 84 on hydrolysis 126). It was suggested that the reaction proceeds by addition of dichlorocarbene to give an aziridinium intermediate (85), which was opened by trichloroacetate followed by hydrolysis to give the observed products 126). The observed products from the reaction can be accounted for by formation of CCI3,... 

A notable exception is found in the reaction of iminium salt (35) derived from A -phthaloylglycinamide with imines (Scheme 40). The presence of the phthalimido substituent requires a modiflcation of the pro-cedure converting the adduct (36) into the p-lactam (38). While basic hydrolysis destroys compound (36), treatment with sodium hydrogensulfide smoothly gives the azeticUnethione (37) which is readily oxidized to the corresponding 3-lactam (38) with modest overall chemical yield but high enantiomeric purity. 

Reduction of iminium salt (77) is illustrated in equation (34). On hydrolysis (78) is obtained in good yield. ... 

The dienamines (66) and (67) afford the corresponding iminium salts (68) and (69) resulting from disubstitution. Hydrolysis of these salts gives the dialdehyde derivatives (70 35%) and (71 36%) respectively. Salt (68) forms pyridine-3-carbaldehyde (97%) when treated with aqueous ammonium chloride solution. 

Several enamides, for example compound (72 Scheme 5), have been used as precursors to 1 -sub-stituted-2-pyridone derivatives (73) and pyridine-3-carbaldehyde derivatives (74 14-69%). Salt (1) promotes dehydration of tautomers (75b) of 2-acetylbenzamide derivatives (75a) to give enamides (76), which are converted by further reaction with salt U) into iminium salts (77). Hydrolysis of these salts yields aldehydes (78 81-99% Scheme 5). Enecarbamates, such as (79), give formylation products (80 26-94%) in the Vilsmeier-Haack reaction (Scheme 5). ... 

Hydrazones (166) react with chloromethyleneiminium salt (I) giving, after hydrolysis, aldehydes (167 Scheme 12). In this transformation the hydrazones (166) are clearly behaving as aza-enamines. - Hydrazones (168) and (169) react with chloromethyleneiminium salt (1) at both the methyl group and at nitrogen to yield the corresponding iminium salts (170) and (171), which cyclize with loss of dimethylamine to provide iminium salts (172) and (173), respectively. Hydrolysis of these salts (172) and (173) affords pyrazole-4-carbaldehyde derivatives (174) and (175 72-96% Scheme 13). Pr uct (174) can also be prepared from semicaibazone (176). 

The reaction of ketone derivatives (89) with chloromethyleneiminium salt (1) gives iminium salts (90) which yield, after hydrolysis, (3-chloroacrolein derivatives (91 Scheme 7).42 Numerous 3-chloroacrolein derivatives have been prepared by this method and yields are generally moderate to good. 3-Chloroacryl-onitrile derivatives (92) are also available in good yield from iminium salts (90 R2 = H) by treatment with hydroxylamine.43 Ketals (93) can be prepared from iminium salts (90) by treatment with the monosodium salt of ethylene glycol followed by hydrolysis under basic conditions (32-69%).44 If the group R1 in ketone (89) is aromatic and electron rich, then intramolecular electrophilic substitution of iminium salt... 

While the aforementioned mechanism covers all the basis of experimental data, it is long and tedious. In 1961, Le Henaff simplified the mechanism to one that has been widely accepted by the chemistry community. "12 According to Le Henaff, hexaminium salt 2 isomerizes to iminium 7, which undergoes a hydride transfer to provide iminium 12. Hydrolysis of iminium 12 affords hemiaminal 13, which then delivers benzaldehyde 3 and amine 14. 

The copper salt (or copper complex) reacts with Me2PhSi-B(Pin) to deliver the corresponding L-Cu(l)-silane. In parallel, the chiral amine forms the iminium intermediate V with the a,p-unsaturated aldehyde. Next, the catalytic cycles merge and the L-Cu-silane complex stereoselectively reacts with the chiral iminium intermediate V via a possible intermediate W to form a C-Si bond in intermediate X. Subsequent hydrolysis of iminium ion X gives the corresponding P-silyl aldehyde product as weU as regenerate the Cu(I)-silane and the chiral catalyst L37 [115]. 

The alkylation of dienamines has not been studied extensively. Thus the dienamine (44) is reported (43,44) to alkylate at Cj with methyl iodide to give the iminium salt (45), which on hydrolysis gives the alkylated a,)3-unsatur-ated ketone (46). Similar dienamines prepared from A -2-oko steroids. On the other hand, are reported to undergo only N alkylation (45). 

More recently the acylation of aldehyde enamines has been reinvestigated (75) and shown to proceed normally when the enamine is added to the acid chloride. The morpholine enamine of isobutyraldehyde (98), on being added to an ether solution of acetyl chloride, afforded the iminium salt (99), from which the ketoaldehyde (100) was obtained in 66% yield by hydrolysis (75). 

Cleavage of the chiral auxiliary is effected in a three-step procedure commencing with quatemization of the nitrogen with methyl fluorosulfonate, methyl trlfluoromethanesulfonate, or trimethyloxonium tetrafluoroborate. Reduction of the corresponding iminium salt 19 with NaBH4 and acidic hydrolysis of the resulting product affords substituted aldehyde 5 without epimerization of either stereocenter. 

Hydrolysis of 3-[(2,6-dimethoxy-4-pyrimidinyl)hydroxymethyl]perhydro-pyrido[l,2-c]pyrimidin-l-iminium salts 174-177 in boiling cone. HCl afforded the appropriate 3-[(2-hydroxy-6-oxo-l,6-dihydropyrimidin-4-yl) hydroxymethyl] derivative (98TL7021, 00JA5017). 

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