Reissert

One route to o-nitrobenzyl ketones is by acylation of carbon nucleophiles by o-nitrophenylacetyl chloride. This reaction has been applied to such nucleophiles as diethyl malonatc[l], methyl acetoacetate[2], Meldrum s acid[3] and enamines[4]. The procedure given below for ethyl indole-2-acetate is a good example of this methodology. Acylation of u-nitrobenzyl anions, as illustrated by the reaction with diethyl oxalate in the classic Reissert procedure for preparing indolc-2-carboxylate esters[5], is another route to o-nitrobenzyl ketones. The o-nitrophenyl enamines generated in the first step of the Leimgruber-Batcho synthesis (see Section 2.1) are also potential substrates for C-acylation[6,7], Deformylation and reduction leads to 2-sub-stituted indoles. 

A modification of the Reissert-Hen2e reaction employing ben2oyl chloride and (CH2)3SiCN gives good yields of 2-cyano pyridine (14) from pyridine... 

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). 

A very useful procedure for introducing a cyano group into a pyridazine ring is the Reissert-type reaction of the A/-oxide with cyanide ion in the presence of an acyl halide or dimethyl sulfate. The cyano group is introduced into the a-position with respect to the A-oxide function of the starting compound. The yields are, however, generally poor. In this way, 6-cyanopyridazines (111) can be obtained from the corresponding pyridazine 1-oxides (Scheme 33). 

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... 

IsothiazoIe-5-carboxyIic acid, 3-methyI-bromination, S, 58 Isothiazolecarboxylic acid chlorides Amdt-Eistert reaction, 6, 157 Reissert reactions, 6, 157 Isothiazolecarboxylic acids esters... 

Reissert type reaction, 3, 25 Phthalazine, tetrahydro-synthesis, 3, 44 Phthalazinediones in synthesis of (3S,5S)-5-... 

The Reissert procedure involves base-catalyzed condensation of an o-nitrotoluene derivative 1 with an ethyl oxalate (2) which is followed by reductive cyclization to an indole-2-carboxylic acid derivative 4, as illustrated below . ... 

In 1897, Reissert reported the synthesis of a variety of substituted indoles from o-nitrotoluene derivatives. Condensation of o-nitrotoluene (5) with diethyl oxalate (2) in the presense of sodium ethoxide afforded ethyl o-nitrophenylpyruvate (6). After hydrolysis of the ester, the free acid, o-nitrophenylpyruvic acid (7), was reduced with zinc in acetic acid to the intermediate, o-aminophenylpyruvic acid (8), which underwent cyclization with loss of water under the conditions of reduction to furnish the indole-2-carboxylic acid (9). When the indole-2-carboxylic acid (9) was heated above its melting point, carbon dioxide was evolved with concomitant formation of the indole (10). 

Butin et al. reported that the indole derivative 29 was prepared by treatment of 2-tosylaminobenzylfuran 25 with ethanolic HCl in 78% yield. The furan ring served as the origin of a carbonyl group in this modification of the Reissert procedure. ... 

The Reissert-Henze reaction offers a method to prepare cyanopyridines and extends the Reissert and Kaufmann reactions in the quinoline and isoquinoline series. 

One can extend the strategy employed in the Reissert-Henze reaction to nucleophiles other than cyanide. Phosphorus-based systems were employed in the... 

Formyl-3-methylisothiazole is prepared by hydrolysis of the appropriate Reissert compound and, as the thiosemicarbazone, in poor yield by the McFadyen-Stevens reaction. 4-Formylisothiazole has been obtained by oxidation of 4-methylisothiazole although no details of the preparation have been reported. 

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