Quinolines acylating agents

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). 

The ring nitrogen of quinoline reacts with a wide variety of alkylating and acylating agents to produce useful intermediates, for example, N-benzoylquinolinium chloride (4). 

Clay den et al. [115] have reported the synthesis of spirocyclic p-lactams 176 (Scheme 41) by exo-cyclization of lithiated pyridine and quinoline carboxamides. The reaction of isonicotinamide or chlorinated isonicotinamide 175 with LDA at -40°C with addition of methyl chloroformate led to the formation of spirocyclic p-lactams 176 in good yields. Benzyl chloroformate, benzoyl chloride, methyl triflate can also be used as the effective acylating agents. In these type of reactions, lithiation of /V-benzyl pyridine and quinoline carboxamides to nitrogen provided... 

A particularly interesting nucleophilic substitution occurs when quinoline N-oxide is treated with acylating agents in the presence of nucleophiles. These two examples show that nucleophilic substitution occurs in the 2-position and you may compare these reactions with those of pyridine Af-oxide. The mechanism is similar. 

Acylating agents derived from pyridine or quinoline 1.132.82 Carboxymethyleniminium salts... 

Dimethoxyphenyl)-5AI (90KGS914) and 4-(cyclo(aza)alkenyl)-5-AI (84S1052) were condensed with acylating agents to give isoxazolo[5,4-Z>]quinolines 71 and 72 (Scheme 30). 

Quinoline adds cyanide [as KCN or (CH3)3SiCN] in the 2-position in the presence of acylating agents, usually C6H5COCI or CICOOR, producing A-acyl-2-cyano-l,2-dihydroquinolines 23 Reissert reaction) ... 

Scheme 51 Amination of l//-imidazo[4,5-c]quinoline 5-oxides in the presence of acylating agent...

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). 

Dialkyl phosphites such as 49 (Scheme 9) have been reacted as nucleophiles with activated pyridines [69, 70]. The first examples of this chemistry involved either 77-alkyl-pyridinium salts in the presence of DDQ, or pyridine and terminal alkynes as activating agents in a one-step protocol. The reaction proceeds under mild conditions that include AI2O3 catalysis. Quinolines 1 and chloroformates afford the expected adducts 68. The latter structures can be easily oxidized with O3 to provide the substituted indoles 69 (Scheme 12a). Isoquinolinephosphonates obtained this way have been used in Wittig-Homer chemistry. The whole sequence offers ready access to alkyl substituted isoquinolines [71]. Analogously, sUyl substituents have been introduced into A-acylated pyridines by using silylcuprates [72]. 

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