Isoquinoline derivatives reaction

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). 

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. 

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>. 

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... 

In another example increased yields of products are obtained under ultrasonic irradiation in the PTC alkylation of the isoquinoline derivatives using 50% aqueous NaOH as base [125]. Efficient mixing is not easy to achieve for this system under normal reaction conditions due to the viscosity of the aqueous base. In the specific case of alkylation with benzyl chloride ultrasound plus [Et3NCH2Ph] Cl achieved 60% yield in 20 min compared with only 50% in 2 h with stirring (Eq. 3.25). 

If quinoline derivatives are expected to be synthesized by this procedure, the starting cycloalkene should contain a cyclobutene ring. When cyclobutene derivative 65c is reacted with Ig under ethylene gas, isoquinoline derivative 66c is obtained in 60% yield. Furthermore, cyclic amino acid ester 66d is obtained from glycine derivative 65d in 75% yield by a one-step reaction. Various isoquinolone derivatives 66e-66i are also synthesized from cyclobutenyl amides... 

Iodophenethylamine derivatives were found to undergo palladium catalysed cyclization to indolines.45 Starting from the appropriate tetrahydro-isoquinoline derivative the reaction was extended by Buchwald to the preparation of tricyclic natural products (3.37.),46... 

Reissert chemistry has been employed for polymeric attachment of the isoquinoline heterocycle. Reissert compound (227) reacted with poly(vinylbenzyl chloride) (192) yielding the substitution product (228) in quantitative yield (Scheme 110) (76MI11111). Alkaline hydrolysis of (228) afforded the fully aromatized, polymer-bound isoquinoline derivative (229), again in quantitative yield. In a variation of this reaction (76MI11112), the Reissert... 

For steric reasons, the reaction of enamines with 1,4-diarylpyridazino-[4,5-d]pyridazines (260) takes place only with the unsubstituted pyridazine ring (91T3959). Numerous enamines were used in the reaction with 260. Among other products, a series of phthalazine derivatives was obtained. An efficient approach to isoquinoline derivatives is based on the reaction... 

Following their syntheses of ( )-pancracine and related alkaloids (vide supra), Hoshino et al [106] had described a different approach involving radical cyclisation of an isoquinoline derivative which permitted a rapid assembly of keto-5,11-methanomorphanthridine skeleton. The syntheses of 413, 414 and 415 commenced with the known 4-hydroxy-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoIine (439) (Scheme 62). Subsequent to protection of the amino group as the trifluoroacetyl derivative, the amide alcohol 440 was converted into the amide thioether 441, by reaction with phenylthiol in the presence of zinc iodide. Alkaline hydrolysis of 441,... 

Similarly, isoquinoline derivatives can be obtained by rhodium-catalyzed reaction of aromatic ketimines and alkynes [128] (Scheme 8.58). The authors suggested a... 

A 2-pyridone ring can be a building block for the synthesis of isoquinoline derivatives by acting as a dienophile in a Diels-Alder reaction. An electron-withdrawing group at C-4 is necessary for reaction with various substituted 1,3-butadienes (Equation 109) <2000CPB1814>. 

The same reaction has been developed that allows for in situ olefination in the synthesis of isoquinoline derivatives (Equation 11) <2003JOC980>. Although numerous examples were reported, it was found that the aryl methoxy substituent was necessary for the reaction to be successful. 

The reaction is prevented in the case of low-lying rot excited states, which are responsible for the lack of photocyclization of azobenzenes and benzylidene anilines. However, when the electronic configuration switches to a low-lying mt excited state upon complexation with Lewis acids, photocyclization takes place under these conditions [30]. Similarly, the presence of perchloric acid allows that, upon irradiation, (E)-4-benzyloxy-l,l,3,4-tetraphenyl-2-azabuta-l,3-diene is transformed in an isoquinoline derivative (Scheme 9.21) [31, 32]. 

Similar methodology was used in the synthesis of 3-methyl derivatives of the alkaloids thalactamine, doryanine, and 6,7-dimethoxy-A-methyl-l(2//)-isoquinolone652. The S l reaction between 0rr/20-halogenobenzylamines and enolates derived from a series of ketones and aldehydes affords 1,2-dihydroisoquinolines, from which the isoquinoline derivatives can be obtained by dehydrogenation and the 1,2,3,4-tetrahydroisoquinolines by reduction653. The products of the S l reactions of (2-halo-4,5-dimethoxyphenyl)acetic... 

The preparation and reaction of 1-alkylthioisoquinolinium salts with active methylene compounds was studied <02CPB225>. The selective N- and O-alkylation of 1-isoquinolones using Mitsunobu conditions was also studied <02JCS(P1)335>. Additionally, the oxidation of isoquinoline derivatives to the corresponding isoquinolones using iodosobenzene and catalytic tetrabuty(ammonium iodide was reported <02HCA1069>. 

Condensation reaction of an enaminone with 2-aminopropene-l,l,3-tricarbonitrile leads to a low yield of 2-dicyanomethylene-3-cyano-dihydropyridines, which are used as synthons for 1,6-naphthyridines63 (equation 45). Cyclic enaminones react similarly with malononitrile to give isoquinoline derivatives (equation 46). 

---