1- isoquinoline methiodide

Based on isoquinoline methiodide, I from the acid chloride, II from the acid plus oarbodiimide. 

In 1964 Grewe et al.bb reported that when a mixture of isoquinoline methiodide and benzaldehyde is hydrogenated in the presence of alkali, a 64% yield of 4-benzyl-2-methyl-1,2,3,4-tetrahydroiso-quinoline can be isolated. It was postulated that reduction of isoquinoline methiodide occurs to form the 1,2-dihydroisoquinoline, which then condenses with the benzaldehyde to form 81 and this is immediately further reduced. With isoquinoline itself and a variety... 

The transformation of isoquinolinium salts into naphthalene derivatives described in connection with berberine (c/. Section 11) may have general applicability since similar reaction of isoquinoline methiodide gave -naphthyl acetate, albeit in small yield (see ref. 362). 

Isoquinoline methiodide reacted with LiAlH4 in abs. ether, cooling occasionally with ice water —2-methyl-l,2-dihydroisoquinoline. Y ca. 70%. (F. e. s. H. Schmid and P. Karrer, Helv. 32, 960 (1949).)... 

It is well established that sodium in liquid ammonia reduction of tetrahydrobenzyl-isoquinoline methiodides leads to cleavage of the C-1 to N-2 bond see K. W. Bentley and A. W. Murray, J. Chem. Soc., 2501 (1963). 

A novel preparative synthesis of aporphines which should prove of appreciable utility in the future involves the cathodic cyclization of a l-(o-iodo-benzyl)isoquinoline methiodide salt. Gottlieb and Neumeyer have shown that electrolysis of l-(o-iodobenzyl)isoquinoline methiodide in dry acetonitrile containing tetraethylammonium bromide, and using a mercury cathode, furnished an 867o yield of the yellow didehydroaporphine which was reduced over Adams catalyst in methanolic hydrochloric acid to produce aporphine hydrochloride. The formation of didehydroaporphine proceeds via two one-electron reduction steps as shown below. 10,11-Dimethoxyaporphine was also prepared by this route. 

A soln. of Na in anhydrous methanol added slowly to an ice-cooled soln. of isoquinoline methiodide and methyl cyanoacetate in the same solvent, and stirred 3 hrs. in the cold 10-carbomethoxy-10-cyano-8,17-dimethyl-8,17-diazadibenzo-[c,j]tetracyclo[7.3.1.02,9.07,l6]tridecane. Y 75%. F. e. s. W. R. Schleigh, J. Heterocyclic Chem. 9, 675 (1972). 

Isoquinoline methiodide and o-nitrotoluene added to a warm stirred soln. of Na in abs. ethanol, and kept 18 hrs. at 25 l-(2-nitrobenzal)-2-methyl-... 

Methiodides have been prepared from perhydropyrido[2,l-b][l,3]ox-azines (61AP65 63AP38) and 9,10-dimethoxy-2,3,4,6,7,llb-hexahy-dro[l,3]oxazino[2,3-a]isoquinolines (66AP817 85AJC1591). In the reaction of perhydropyrido[2,l-b][l,3]oxazine and methyl iodide, two methiodides (42%, mp 138-139°C and 7.5%, mp 224-225°C) were obtained (61AP65). 

Isoquinolinium salts are reduced to 2-alkyl-1,2-dihydroisoquinoline derivatives by sodium dithionite,6 lithium aluminum hydride7,8 (LAH), or dialkyl aluminum hydrides.9 LAH is preferred7 to dithionite since it leads to purer products, and will reduce those salts that are inert to dithionite (e.g., papaverine methiodide). Isoquinoline itself10,11 and 3-methyl-6,7-methylenedioxyisoquinolinelz (5) can be reduced to the 1,2-dihydroisoquinoline with LAH, as can isoquinoline... 

Methiodide and ethiodide salts were prepared from perhydropyrido[2,l-c][l,4]oxazines [58N516 60AP(293)74 63AP(296)38], from 1,3,4,6,7, llh-hexahydro-[l,4]oxazino[3,4-a]isoquinolines (67BRP1094470, 67NEP 6611733 85AJC1591), and from perhydropyrido[l,2,3-de]-l,4-benzoxazine (44HCA1756) with alkyl iodides. 

The presence of an oxindole nucleus in mitraphylline is established by the results of zinc dust distillation. The basic products include isoquinoline and 3,4-diethylpyridine, while the neutral fraction affords 3-spirocyclopropano-oxindole (IV), mp 179°-181° (55, 56). This degradation product is of the greatest importance in this series of alkaloids it was first obtained from the calcium oxide distillation of rhynchophyllic acid (19), and has since been obtained by zinc dust distillation of uncarine-A (58), by hydrogenation and pyrolysis of uncarine-A methiodide (59), and by zinc dust distillation of formosanine (uncarine-B) (60). The structure of this neutral degradation product was first proposed by Wenkert and Reid (61), who pointed out that its properties were very similar to those... 

This tends to weaken the hypothesis that halogenation at C-3 of quinoline and at C-4 of isoquinoline involves covalent intermediates of the type shown in 13 and 14. No spectral evidence for these hypothetical adducts has as yet been obtained for the parent heterocycles and the assumption that pyridinoid methiodides may involve covalent species86 has now been shown to be mistaken.26 The spectral shifts seem best explained by charge-transfer ion pairs [Eq. (18)] ... 

In a similar way, microwave heating was used to aid the synthesis of compounds 53 from the l,3-azaphospholo[5,l- 7]-isoquinolines. When iodomethane was used as coreactant, instead of sulfur, the analogous phosphonium methiodides were obtained <2002X1573, 2003HAC560>. 

The first total synthesis of ( + )-dauricine was reported by Kametani and Fukumoto in 1964 (18,19). Arndt-Eistert reaction of homoveratryl-amine with the acid chloride XIX afforded the amide XXII. Bischler-Napieralski cyclization of the above amide gave the dihydro isoquinoline derivative XXIV, the methiodide of which when reduced with zinc dust and ethanol-hydrochloric acid afforded + )-dauricine. The identity of the synthetic product with ( )-dauricine w as concluded through a comparison of its physical properties (spectra and chromatographic behavior) with those of an authentic sample of the alkaloid. Melting-point determination of a mixture of derivatives of the two specimens is not recorded. 

A new electroreductive method for the synthesis of tetrahydro-phthalide-iso-quinolines is also known If isoquinolinium methiodide is used in the reaction the 1,2-dihydrophthalide isoquinoline is obtained... 

This plant yielded the first 1-phenyltetrahydroisoquinoline alkaloid to be found in nature. Spectral data indicated that it was l-(3,4-methylenedioxyphenyl) -2-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroiso -quinoline, C19H29O4N (mp 101° [ajj) -t-54°) and a synthesis of the diform confirmed this structure (XLVI). The amide resulting from the reaction of piperonoyl chloride with 3,4-dimethoxyphenethylamine was cyclized by means of phosphorus oxychloride. The resulting dihydro-isoquinoline was converted to methiodide and the latter reduced with sodium borohydride. The resulting dZ-base (mp 117°) was identical in spectral properties with the natural alkaloid 66). 

More recently, the preparative value of VOCl3 and VOF3-TFA in chemical oxidation has been demonstrated (see Section III, on the pro-aporphine and promorphinane alkaloids) (415,462). Some other authors used the purified enzyme horseradish peroxidase (463). By this method the aporphine base (besides the quaternary dibenzopyrrocoline) is readily obtained from (S)-( + )-laudanosoline hydrobromide or from (/ )-(—)-laudanosoline methiodide with retention of the absolute configuration. The synthesis of 6a,7-dehydroaporphine bases was also carried out by making use of the benzyne reaction (439). Reduction of these substances affords the corresponding aporphine bases (439). The synthesis of isoquinoline alkaloids by lead tetraacetate oxidation was reviewed by Umezawa and Hoshino (343). 

Stannylated azines have been widely used for cross-coupling. Al-Oxides of tri(n-butyl)stannylated pyridine, quinoline, and isoquinoline and tti(n-butyl)stannylated N-methiodides of pyridine and quinoline have been coupled with heteroaryl halides (Scheme 61). The use of tosylate as a counterion for the quatemized salts 149 and 150 minimized decomposition of the stannane whereas iodide anion promotes destannyla-tion.f ... 

Stermitz and his collaborators constructed the benzylisoquinoline methiodides necessary for conversion to the unsymmetrically substituted pavines platycerine and munitagine by way of a Reissert compound. Alkylation of the Reissert compound derived from the isoquinoline 2 with the appropriately... 

Displacement of the initially formed methiodide was observed when dimsyl sodium was used to cyclize the C-6 phenolic and the non phenolic bromobenzyl-isoquinolines 10 and 11 (Scheme 8.2). ... 

Corydamine, C20H18N2O4, incorporates a bis(methylenedioxy)-3-aryl-isoquinoline system with an 7V-methylaminoethyl side chain. Reductive methylation of corydamine led to the tertiary base 5 which was converted by quaternization and Hofmann elimination to the isoquinolinostyrene 6. iV-Methylation of 6 followed by borohydride reduction gave rise to the known anhydroprotopine-B. Alternatively, when the methiodide of 5 was pyrolyzed in dimethylformamide, the protoberberine salt coptisine iodide was obtained. ... 

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