6-Chloroacridine

The first reported derivative of 1,2-oxazepine was dibenz[f,/][l,2]oxazepine-ll-carbonitrile (3 a). This, together with small amounts of compounds 4 and 5, is formed when acridine-9-carbonitrile 10-oxide (la) is irradiated with UV light,6,7 It is likely that the reaction proceeds by way of the oxaziridine valence tautomer 2a, which, however, was not detected.7 Photo-isomcrization of 9-chloroacridine 10-oxide (lb) yields the 11-chlorodibenzoxazepine 3b.6,7... 

Second only to sulfur-based systems, nitrogen complexes are relatively well represented in the structural literature with 41 complexes reported. Of these, 25 are with I2 as the electron acceptor, 11 are with the interhalogen IC1, three are with Br2, and two are with IBr. As expected, in every case the halogen bond forms between the nitrogen and the softest halogen atom, i.e., iodine, in all of the complexes except those with dibromine. Most N I2 complexes, and all N Br2, N IBr, and N IC1 complexes are simple adducts, mode A. Exceptions for the diiodine complexes include bridging mode (B) observed for diazines, such as pyrazine [86], tetramethylpyrazine [86], phenazine, and quinoxaline [87], and for 9-chloroacridine [89] and the 1 1 complex of diiodine with hexamethylenetetramine [144] and amphoteric bridging mode (BA) observed for 2,2 -bipyridine [85], acridine [89], 9-chloroacridine [89], and 2,3,5,6-tetra-2/-pyridylpyrazine [91]. The occurrence of both B and BA complexes with 9-chloroacridine, and of B and A complexes and an... 

Numerous examples of rearrangement in related systems have been reported. Oxazepines 77, for example, have been isolated as the major products of irradiation in benzene of 9-cyano- and 9-chloroacridine 10-oxides (78) and are again believed to arise via oxaziridines 7965 products arising by further irradiation have also been described.66 Diazine N-oxides... 

For example, in the instance of 9-chloroacridine, the attachment of the halogen (leaving group) at a suitably electrophilic carbon site allows the occurrence of a replacement reaction, presumably occurring via an addition-elimination procedure for phosphorus attachment, followed by the common nucleophilic displacement (ester cleavage) of the Michaelis-Arbuzov process (Figure 6.1).4... 

Figure 6.1 Reaction of 9-chloroacridine with triethyl phosphite.

Reaction of 9-chloroacridine with aryl sulfonyl hydrazides results in aminodechlo-rination to give the corresponding A-acridinylbenzenesulfonyl hydrazides kinetic studies in methanol and DMSO have been reported.44 Reaction of electron-deficient heteroaryl chlorides with tertiary amines may proceed by quaternization and dealkylation, as shown in Scheme 3. These reactions occur under mild conditions, e.g. acetonitrile solvent at room temperature, and in THF may be accelerated by the addition of lithium chloride.45... 

Anilinobenzoic acid 58 gives 9-chloroacridine 57 and acridone 59 under the conditions indicated in Scheme 29. 

Chloroacridine has been prepared by heating thioacridone,1 acridone,2 or iV-phenylanthranilic acid3 5 with phosphorus pentachloride, phosphorus oxychloride, or a mixture of the two phosphorus halides, with and without the addition of hydrocarbon solvents. The present method is essentially that of Magidson,3 but the troublesome filtration of the glutinous and easily hydrolyzed 9-chloroacridine has been avoided by the use of chloroform. 

Chloroacridine is readily hydrolyzed in neutral and acid solutions hence it must not be exposed to the air after removal of t lie phosphorus oxychloride and before treatment with ammonia. 

I f the drying is carried out at a higher temperature, loss results through sublimation. Care should be taken to keep 9-chloroacridine from entering the eyes, as it is distinctly irritating. 

The synthetic route to acridine-containing polymers is outlined in Scheme I. 9-Methyl acridine (II) was prepared via 9-ethyl-malonate acridine by the method of Campbell et al (14), from 9-chloroacridine (I, Kodak), (mp. 117-8°C from ligroin). 9-(3hydro-xyethyl) acridine (III) was synthesized via the condensation of formaldehyde with II (15) (mp. 154-6°C, from ethanol-water). Metha-cryloylchloride, freshly distilled, was reacted with III in dry THF with pyridine as base to give IV, 2-(9-acridyl) ethylmethacrylate, purified by chromatography with silica gel/toluene to give red gum (IR 5.85 ym ester carbonyl stretch). 

If pure 9-chloroacridine is desired, the crude product is dissolved in a little boiling alcohol, and 0.5 per cent ammonia is added until the solution becomes milky. About 0.5 g. of Norite is then added the solution is quickly filtered and at once cooled i n an ice bath. White crystals, melting at 119-120°, are obtained. The product keeps best in a desiccator over potassium carbonate, by warming 9-chloroacridine with various primary and secondary amines, many substituted 9-aminoacridines are readily obtained. 

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