Isoquinoline derivatives

The Pictet-Gams method involves the cyclization of P-hydroxy- or P-methoxy- P-phenethylamides, and produces the isoquinoline derivative rather than the reduced form. A further extension of method is based on a metboxyetbyl amine. 

Uses. Isoquinoline and isoquinoline derivatives are usehil as corrosion inhibitors, antioxidants, pesticides, and catalysts. They are used in plating baths and misceUaneous appHcations, such as in photography, polymers, and azo dyes (qv). Numerous derivatives have been prepared and evaluated as pharmaceuticals. Isoquinoline is a main component in quinoline stiH residue bases, which are sold as corrosion inhibitors and acid inhibitors for pickling iron and steel. 

A number of isoquinoline derivatives have fungicidal properties, eg, 1,2,3,4-tetrahydroisoquinoiines bearing acyl nitrogen substituents like (36) [41910-26-3] (189). Substituted isoquinolines (37) have proved to be effective in controlling undesired vegetation, insects, acarina, and fungi (190). 

Isoquinolines are used in catalytic (191), photographic (192), and dye appHcations (193). A great many alkaloids and synthetic medicinal compounds are isoquinoline derivatives. The principal dmgs containing this stmcture marketed in the United States are Hsted in Table 4. 

Table 4. Isoquinoline-Derived Drugs Marketed in the United States ...

Praziijuantel. This drug (1), C H24N202, can be used to treat schistosomiasis caused by any one of the three major species. Pra2iquantel is an acylated pyta2ino—isoquinoline derivative that has replaced the traditional (and more toxic) trivalent antimonial compounds. 

The only other synthesis of a benzo fused derivative involves the pyridazino[4,3-cjisoquinoline series, the isoquinoline derivative (377) reacting with hydrazine to give (378) (74YZ607), although an s-triazolo-fused pyrido[2,3-tf Ipyridazine was obtained in the reaction of l-amino-3-iminoisoindolenine with hydrazine and formic acid (56GEP951993). 

There exist many types of azoloquinolines, and therefore it is necessary to define the objects of interest to be described in this review. The tricyclic azoloquinolines reviewed in this article have an azole ring fused to the benzene ring of quinoline (not isoquinoline derivatives) in positions / g, and h. This means that the benzene ring is between azole and pyridine rings, and all of them are ortho-peri condensed. The azole and benzene rings do not have a common heteroatom, and also a carbon... 

Substituted 4-aryl-1 -oxo-1,2-dihydropyrazino[l, 2-i]isoquinolinium salts 402 were obtained when 3-substituted isoquinolines 401 were cleaved from a polymer by treatment 25% TFA (00MIP5). c/i-3,lla-H-3-Phenyl-1,2,3,4,11,11 fl-hexahydropyrazino[l, 2-i]isoquinoline-1,4-dione (404) formed when isoquinoline derivative 403 was cleaved from a resin with 25% TFA during an automated solid-phase synthesis (98BMCL2369). 

Hasrat JA, De Bruyne T, De Backer JP, Vauquelin G, Vlietinck AJ. Isoquinoline derivatives isolated from the fruit of Annona muricata as 5-HTergic 5-HT1A receptor agonists in rats unexploited antidepressive (lead) products. J Pharm Pharmacol 1997 49 1145-1149. 

Cyano-4-hydroxypyridazino[l,6- ]quinolinium betaine 67 could be isolated from the reaction mixture of 1-amino-2-ethoxycarbonylquinolinium mesitylensulfonate and acrylonitrile in a few percent. Reaction of the 2-amino-1-ethoxycarbonylisoquinolinium salt with acrylonitrile afforded only a pyrazolo[5,l- ]isoquinoline derivative. 

The relative configurations and predominant conformations of [l,2,3]oxathiazino[4,3- ]isoquinoline derivatives 177-182 were studied by means of H and 13C NMR spectroscopy with the applications of DNOE, 2D HSC, and 2D-COSY measurements. Their stereostructure includes an equilibrium between the conformers cis-1, trans and cis-2. In the /ra -structure, the B/C rings are trans-ane-WatcA with H-l lb and the N-5 lone electron pair trans-diaxial. In the cis structures, the hetero-rings are air-anellated in the cis-1 conformation C-l is in inside position, while in cis-2... 

Figure 8 Stereochemical features of [1,2,3]oxathiazino[4,3-a]isoquinoline derivatives.

Benzo derivatives of the pyrido[l,2-f][l,3,2]oxazaphosphorine ring system, [l,3,2]oxazaphosphorino[4,3- ]isoquino-lines 195, 196, were synthesized by the reaction of hydroxyethyl isoquinoline derivatives 183, 184 with phenylphos-phonic dichloride, bis(2-chloroethyl)phosphonic dichloride or phosphoryl chloride. In almost all cases, the products were formed in about a 1 1 diastereomeric ratio. The only exception observed was when phosphoryl chloride was used as the reagent (X = C1) in this reaction one single diastereomer 196 (R2 = R3 = H) was obtained (Scheme 28) <2000JST(554) 119, 2000JOC316>. 

The mechanism of palladium-catalyzed intramolecular cyclization of o-bromo(aminoalkyl)benzenes has been discussed earlier (see Scheme 50 in Section IV,A,4). An example illustrating the use of this approach for the synthesis of 2,3,4,5-tetrahydro-l//-2-benzazepin-l-ones is given in Scheme 17386 and examples indicating the synthesis of isoquinoline derivatives are given earlier (see Scheme 146 in Section V,A,4). 

Kobayashi and co-workers have described a new synthesis of a range of 1,4-disubstituted isoquinoline derivatives 117 <06S2934>. Initially, a lithium halogen exchange of 118 was performed to form 119, followed by treatment with a variety of nitriles 120 resulting in 1,4-disubstituted isoquinolines 117. 

The preparation of chiral isoquinoline derivatives continued to be investigated. Sulfanamide 59 was prepared by addition of a lateral lithiated o-toluonitrile with the corresponding sulfinimine. Treatment of 59 with MeLi followed by acidification afforded cyclic imine 60. Reduction of imine 60 with liAlHi/MejAl afforded the trans-1,3 derivative, and... 

Diels-AIder reactions were utilized to prepare isoquinoline derivatives. Various tetrahydroisoquinoline-3-carboxylic acid derivatives were prepared by an enyne metathesis followed by a Diels-AIder reaction. For example the enyne 71 was treated with Grubb s catalyst to afford diene 72 in 65% yield. Subsequent Diels-AIder reaction and oxidation gave tetrahydroisoquinoline 73 in 93% yield <0OCC5O3>. Dihydrosoquinoline 75 was prepared... 

Similarly, ketimines (benzylimines of aromatic ketones) undergo the rhodium-catalyzed ortho-alkenylation with alkynes to give or/ o-alkenylated aromatic ketones after hydrolysis.61 This method is applied to an efficient one-pot synthesis of isoquinoline derivatives by using aromatic ketones, benzylamine, and alkynes under Rh catalysis (Equation (55)). 

Thus, the 2-hydrazinopyridone compound 89 was transformed to the corresponding fused tetrazolo[l,5- ]pyridine 90 in 61% yield <2000J(P1)3686>, and the partially saturated 1-hydrazinoisoquinoline compound 91 when reacted with nitric acid gave the appropriate tetrazole 92 in 64% yield <1994KGS511>. In the case of the acylhydrazino isoquinoline derivative 93, a deprotection of the hydrazine group was carried out first followed by treatment with... 

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