Reissert compounds, with

Reissert compounds (l-acyl-l,2-dihydro-2-quinolinecarbonitriles) have been prepared on cross-linked polystyrene and C-alkylated in the presence of strong bases (Entry 8, Table 15.25). Treatment of polystyrene-bound C-alkylated Reissert compounds with KOH leads to the release of isoquinolines into solution (Entry 9, Table 15.25). The reaction of support-bound quinoline- and isoquinoline /Y-oxides with acy-lating agents followed by treatment with electron-rich heteroarenes and enamines has been used to prepare alkylated and arylated derivatives of these heterocycles (Entry 10, Table 15.25 see also Table 15.26). 

The alkylation of 20, obtained by the action of phenyllithium on the Reissert compound, with a number of alkyl halides to give 21 which can... 

A new synthesis of aporphines has appeared. The key step in this synthesis involves the generation of l-(o-nitrobenzyl)isoquinoline by reaction of a Reissert compound with o-nitrobenzyl chloride in dimethylformamide in the presence of sodium hydride. 

The anion 10, generated from the reaction of 3-benzoyl-3,4-dihydro-2-methylquinazoline-4-carbonitrile (a 2-methylquinazoline Reissert compound) with sodium hydride, undergoes both rearrangement and aromatization (cf. p 84), resulting in the formation of 4-benzoyl-2-methylquinazoline (32%), and 2-methylquinazoline-4-carbonitrile (20%). ... 

The cation isolated from treatment of Reissert compounds with acid has generally been written as 18. A detailed study using a combination ... 

Treatment of the compounds 78 with various alkyl halides in the presence of sodium hydride results in 1-alkylation as with normal Reissert com-pounds. ° Acylation has also been reported under these conditions. Under a variety of conditions, however, 78 does not react with benzaldehyde. Acid hydrolysis of 80 gave tetrahydroquinaldic acid, while acid hydrolysis of the alkylated dihydroisoquinoline-Reissert compounds gave the amino acids 81. By first complexing the alkylated dihydroisoquinoline-Reissert compound with zinc chloride in ether and then hydrolyzing the complex, the nitrile was hydrolyzed to an acid, but the amide group was left intact. The perchlorate salts of dihydroisoquinoline-Reissert compounds have also been prepared, and sodium borohydride reduction proceeds in the same manner as reduction of the Reissert salt to... 

New reactions of isoquinoline derivatives include the following 3,4-di-hydroisoquinoline N-oxide with 2-acetylcycloalkane-l,3-diones, Reissert compounds with stilbene and tolan derivatives, isoquinoline with pyrrole derivatives and with 2-methylfuran " (both in the presence of benzyl chloride), and the chromium trioxide oxidation of the benzo[a]quinolizidine (49) to give (50). Compound (49) was prepared by the condensation of 3,4-dihydroiso-quinoline with the 5-lactone (51). Further examples of a classical benzo[a]-... 

Reissert reaction. The alkylation of Reissert compounds with bcnzylic halides was originally conducted with NaH as base in DMF. Skiles and Cava have examined three more modern systems LDA and HMPT in THF, KOH and a crown ether, and phase-transfer conditions. Of these, the two last systems are clearly superior to the first the phase-transfer system is somewhat superior to the crown ether system, both in yields and economic use of reagents. Cetyltrimethyl-ammonium bromide served as catalyst. 

A series of bisbenzylisoquinolines has been prepared through alkylation of 6,7-disubstituted isoquinoline Reissert compounds with diaryl ethers such as 8, 9, and 10. ... 

Qu tern iy S Its. The ring nitrogen of quinoline reacts with a wide variety of alkylating and acylating agents to produce useful intermediates like A/-benzoylquinolinium chloride [4903-36-0] (8). The quinoline 1,2-adducts, eg, A/-benzyl-2-cyano-l,2-dihydroquinoline [13721 -17-0] (9), or Reissert compounds (28), formed with potassium cyanide can produce 2-carboxyquinoline [93-10-7] (10) or 2-cyanoquinoline [11436-43-7] (11). 

Excellent yields of the former product are also obtained with quinoline N-oxide. Improved yields of Reissert compounds are found under phase-transfer conditions (29). The regiochemistry of the method changes dramatically with /V-alkyl quin olinium salts, eg, /V-methy1quino1inium iodide [3947-76-0] (12), which form 4-cyanoquinoline [23395-72-4] (13) (30), through the intermediary in this example of A[-methyl-4-cyano-l,4-dihydroquinoline... 

Isoquinoline also forms Reissert compounds when treated with benzoyl chloride and alkyl cyanide (28), especially under phase-transfer conditions (29). The W-phenylsulfonyl Reissert has been converted to 1-cyanoisoquinoline with sodium borohydride under mild conditions (154). When the AJ-benzoyl-l-alkyl derivative is used, reductive fission occurs and the 1-alkyLisoquinoline is obtained. 

Methylpyridazine gives the pyridazine Reissert compound (105) with trimethylsilyl cyanide and freshly distilled benzoyl chloride. On the other hand, when pyridazine or 3-methylpyridazine reacts with undistilled benzoyl chloride the bicyclic compounds (106) are formed and these react with dimethyl acetylenedicarboxylate in anhydrous DMF to give pyrrolopyridazine derivatives (107 Scheme 30) (81JHC443). 

The Reissert compound obtained from phthalazine and potassium cyanide in the presence of benzoyl chloride can be converted with methyl iodide and sodium hydride in DMF into... 

Heterocyclic structures analogous to the intermediate complex result from azinium derivatives and amines, hydroxide or alkoxides, or Grignard reagents from quinazoline and orgahometallics, cyanide, bisulfite, etc. from various heterocycles with amide ion, metal hydrides,or lithium alkyls from A-acylazinium compounds and cyanide ion (Reissert compounds) many other examples are known. Factors favorable to nucleophilic addition rather than substitution reactions have been discussed by Albert, who has studied examples of easy covalent hydration of heterocycles. 

This reaction is illustrative of a general procedure for the alkylation of active methylene functions in the presence of concentrated aqueous alkali catalyzed by tetraalkylammonium salts. This catalytic method has been used to alkylate arylacetonitriles with monohaloalkanes,2 dihaloalkanes,3 a-chloroethers,4 chloronitriles,.5 haloacetic acid esters,6 and halonitro aromatic compounds.7 It has also been used to alkylate ketones,8 lf/ indene,9 9i/-fluorene,ll) and the Reissert compound.11 The reaction is inhibited by alcohols and by iodide ion.2... 

Reissert compounds (116) are prepared from the acyl halide by treatment with quinoline and cyanide ion. Treatment of 116 with sulfuric acid gives the... 

Several syntheses of secoquettamines have been performed. Seco compounds 234 and 235 were semisynthesized from quettamine (236) by Hofmann and Emde degradations, respectively (179). Chattopadhyay and Shamma (184) conducted a total synthesis of these bases with the intermediacy of quettamine (236) (Scheme 36). In this approach Reissert compound 237 served as substrate. On reaction with 4-benzyloxybenzaldehyde 237 supplied the addition product 238, which after N-methylation and sodium borohydride reduction afforded amino carbinol 239. Compound 239 was cyclized to... 

Apart from isolated reports summarized in Scheme 47, the chemistry of the fully conjugated ring systems has not been especially developed since CHEC-II(1996). In 1999, Monnier et al. reported the 1,3-dipolar cycloaddition of Reissert compound 160 with acrylates. Addition of triethylamine traps hydrofluoroboric acid and increases the proportion of milnchnone imine 160B the reaction therefore predominantly yields 1,3-adduct 161 which rearranges to 162 (Scheme 47) <1996BSB777, 1999EJ0297>. 

Reissert compounds (>70%), derived from benzimidazole, phthalazine, quinoline and isoquinoline, have been prepared by a simple catalysed one-pot N-acylation of the appropriate heterocycle, followed by reaction with cyanide ion [e.g. 101-103],... 

Sonication [130, 131] aids the standard phase-transfer catalysed [e.g. 132, 133] C-alkylation of Reissert compounds. As much as twofold increases in yield are observed with shortened reaction times. No alkylation is observed when sonication is used alone. 

Method A (normal conditions) The Reissert compound (8.6 mmol), alkylating agent (9 mmol) and quaternary ammonium salt (1 mmol) in PhH (20 ml) is stirred with aqueous NaOH (50%, 5 ml) for 13 h at room temperature. The mixture is adjusted to pH 6 with aqueous H,S04 (5%) and the organic phase is separated, dried (MgS04), and evaporated to yield the alkylated Reissert compound. 

Method B (with sonication) Sonication of the Reissert compound (4.6 mmol), haloalkane (6.6 mmol), and TEBA-C1 (34 mg, 0.15 mmol) in CH,C1, (2.5 ml) and aqueous NaOH (50%, 1.8 ml) is conducted for 20 min. Work-up at this stage, as described in 6.2.30.A, yields the alkylated Reissert compound. Addition of EtOH (6 ml) and sonication for a further 30 min with subsequent work-up by addition of the mixture to 11,0 (20 ml) and extraction with CH,C1, (3 x 10 ml) produces the C-alkylated heteroarene, which is isolated as the hydrochloride salt (70-90%) by saturation of the dried organic extracts with HC1 gas. 

The Reissert compound (5.7 mmol), an aryl aldehyde and TEBA-C1 (14 mg, 0.06 mmol) in CH,C1, (3 ml) are sonicated with aqueous NaOH (50%, 2.5 ml) for 5 min. EtOH (8 ml) and CH,C1, (15 ml) are added and sonication is continued for a further 85 min and the mixture is then poured into H,0 (20 ml). The aqueous phase is separated and extracted with CH2C1, (3x10 ml). The combined organic solutions are dried (MgS04), concentrated to 20 ml, and saturated with HCI gas to yield the hydroxymethylheteroarene hydrochloride (80-99% ). 

Bischler-Napieralski cyclization of pyridazin-6-one 134 with POCI3, and subsequent hydrogenation of the cyclized product 135 over Pt02, gave rise to 2,3,4,6,7,llZ -hexahydro-l//-pyridazino[6,l-fl]isoquinoline (51) (75CPB3056). Treatment of Reissert compound 136 with NaH gave 116-cyano-l, 2,3,116-tetrahydro-4//-pyrido[2,l-fl]phthalazin-4-one (137) (80JHC433). 

Cyclizing ca-chloro Reissert compound 136 gives rise to tricyclic lactam 137 (72JHC541). In a study of the cobalt-mediated reaction of pyridones with alkynes, in the case of the N-hexynyl compound, C-H activation with... 

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