Iminium salts hydrolysis

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). 

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 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,... 

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). 

After its isolation, the structure of alkaloid deplancheine (7) was unambiguously proved by several total syntheses. In one of the first approaches (14), 1,4-dihydropyridine derivative 161, obtained by sodium dithionite reduction of A-[2-(indol-3-yl)ethyl]pyridinium salt 160, was cyclized in acidic medium to yield quinolizidine derivative 162. Upon refluxing 162 with hydrochloric acid, hydrolysis and decarboxylation took place. In the final step of the synthesis, the conjugated iminium salt 163 was selectively reduced to racemic deplancheine. 

Hydrolytic conditions are tolerated by dihydrobenzoxazines, and this allows the selective hydrolysis of the ester group of 243 into the free acid with 10% sodium hydroxide <1983JHC45>. The nitrile of 244 was converted into the iminium salt followed by hydrolysis to give the ester 70 <1987M273>. Conversion of 245 into an iminium salt followed by base treatment to give the a-ethoxy enamine then allows cyclization with an aldehyde to give product 246 as shown in Scheme 27 <1986H(24)3483>. 

The 6//-l,3-thiazin-6-iminium hydroperchlorate salts 78-81 give interesting products when treated with nucleophiles <2003H(60)2273>. Hydrolysis of 6-imino-6//-l,3-thiazine hydroperchlorate 78 affords (2Z,4Z)-2-cyano-5-hydroxy-5-phenyM-azapenta-2,4-dienethioamide 82 in excellent yield, while treatment with morpholine gives 2-(morpholinomethylene)malononitrile 83 and thiobenzamide. The 5-(ethoxycarbonyl) -(methylthio)-2-aryl-6/7-l,3-thiazin-6-iminium salts 79 and 80 react with hydroxide or morpholine to afford ethyl 4-(methylthio)-2-aryl-6-thioxo-l,6-dihydropyrimidine-5-carboxylates 84 and 85. In the case of the 4-chloro analogue 80, the (Z)-ethyl 2-(5-(4-chlorophenyl)-37/-l,2,4-dithiazol-3-ylidene)-2-cyanoacetate 87 is also formed for the reaction with sodium hydroxide. The 1,2,4-dithiazoles 86 and 87 can be obtained as the sole product when 79 and 80 are treated with sodium acetate in DMSO. Benzoxazine 88 is isolated when the iminium salt 81 is treated with morpholine or triethylamine. Nitrile 89 is formed as a ( /Z)-mixture when 6-imino-67/-l,3-thiazine hydroperchlorate 79 is reacted with triethylamine and iodomethane in methanol <2003H(60)2273>. 

The formation of NNN, NNK, and NNA from nicotine probably involved the intermediacy of cyclic iminium salts, as shown in Figure 5 (28). These salts can undergo hydrolysis to the free amines which are nitrosated, or at near neutral pH, can be directly nitrosated to give nitrosamines. The formation of nitrosamines from iminium salts under neutral conditions has been demonstrated in at least two studies and is of interest because iminium salts are known to be intermediates in the mammalian metabolism of nicotine (26,29,30,31). The possibility that tobacco bacteria could nitrosate nicotine via this pathway is currently under investigation. 

The photochemical electrocyclization of conjugated iminium salts 160, formed by protonation of 2-azadienes 159, led to isoquinolin-4-ones 162, presumably through hydrolysis and oxidation of the dihydroisoquinoline intermediates 161 (85TL5213) (Scheme 39). A closely related reaction served as the key step for a short synthesis of the pentacyclic marine alkaloid ascididemin as reported by Moody, Rees, and Thomas [90TL(31)4375 92T3589] the central reaction involves a 67r-electron pho-tocyclization of a syn- aza stilbene in sulfuric acid. 

Reaction of an alkene with keteniminium salts resulted in [2 + 2]-cycloaddition reactions (see Section 1.3.5.3). Hydrolysis of the intermediate cyclobutanone iminium salts 3 gave the cy-clobutanone 4.- 12 316 The cyclobutanone iminium salts are usually not isolated since they hydrolyze on aqueous workup. 

Epoxynitrone (742) can be transformed to a positively charged heterodiene (743) using CF3S03SiMe3 or CF3S03Si(Bu )Me2 as electrophilic reagents (79HCA205). The diene adds to isolated double bonds to afford oxazines such as (744) via an inverse electron demand Diels-Alder pathway. Subsequent addition of cyanide to the iminium salt leads to a stable derivative (745) which can be converted through its mesylate (746) to an a-methylene y-lactone (747) on base treatment followed by acid hydrolysis (Scheme 171). 

Other classical synthetic approaches to 2-furanamine have failed, including the Curtius method and Beckmann rearrangement of 2-benzoylfuran oxime. However, hydrazinolysis of AT-(2-furyl)phthalimide, obtained from phthalimide and 2,5-dimethoxy-2,5-dihy-drofuran, gives 2-furanamine which was not isolated but detected by GLC-MS and H NMR spectroscopy. The latter reveals the absence of imino tautomers (75AP713). The chemistry of 2-dialkylamino-5-phenylfurans is typical of enamines protonation occurs on carbon to produce iminium salts. They are stable to base but afford 5-phenylfuran-2(3//)-one on hydrolysis with dilute acid. 2-Morpholino-5-phenylfuran couples with diazonium salts and affords Diels-Alder adducts with maleic anhydride and IV-phenylmaleimide (73JCS(P1)2523). 

Imidate salts hydrolysis, 118-144 syn and anti, 120 isomerization, 142 B-lactam, 142 Iminium salts, 211-221 Imino-ethers, 147 lodolactonization, 169 Ionic state of tetrahedral intermediates, 65, 105-106, 119 Ionophore A-23187, 13 Isochromane-3-one, 70 Isocyanate, 300 Isonitrile, 296... 

Here again, loss of Y = H would result in rearomatization and formation of 12, but in the case of Y = Me, this cannot occur. However, assistance by the amine nitrogen lone pair can aid the rearomatization process, producing the copper-bound phenol product and an imininm salt. Hydrolysis during the workup procedure could release the 2-meth-ylphenol product and result in a retro-Mannich reaction to give the observed secondary amine (PY2) and formaldehyde. A small amount (<10%) of N—Me—PY2 is often observed as a byproduct and its yield is at the expense of the PY2 and formaldehyde thus, it appears to be derived from direct reduction of the intermediate iminium salt [167],... 

When cesium fluoride is used instead of zinc chloride, a diaminomethane derivative is obtained, whose formation is explained by the addition of the iminium salt to the secondary amine resulting from its hydrolysis.219... 

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