6-Chloro-2 -quinoxalinone 4-oxide

Only one procedure has been reported recently within this category. Thus 7-chloro-l-methyl-5-phenyl-2,3-dihydro-lH-benzodiazepin-2-one 4-oxide (437) with dimethyl acetylenedicarboxylate in methylene chloride at 20° C for 3 days gave a separable mixmre of the primary tricyclic adduct, dimethyl lO-chloro-6-oxo-llb-phenyl-5,6,7, 1 lb-tetrahydroisoxazolo[2,3-t/] [ l,4]benzodiazepine-1,2-dicarboxylate (438), and its rearrangement product, 6-chloro-4-(2-methoxalyl-2-methoxycarbonyl-l-phenylvinyl)-l-methyl-3,4-dihydro-2(lT0-quinoxalinone (439) each product afforded 6-chloro-l-methyl-2(l//)-quinoxalinone (440) on refluxing in ethanol (see also Section 1.7.13). However, the final quinoxaline (440) was best obtained in 75% yield) by simply heating the initial substrate (437) and dimethyl... 

Azido-6-chloroquinoxaline 4-oxide (22, R = N3) gave 3-azido-7-chloro-2(lT0-quinoxalinone (23, R = N3) (AC2O, AcOH, reflux, 4 h 46%) " ° 6-chloro-2-piperidinoquinoxaline 4-oxide [22, R = N(CH2)s] gave 7-chloro-3-piperidino-2(177)-quinoxalinone [23, R = N(CH2)5](likewise 58%)." °... 

Chloro-2/3-pheny lquinoxaline 1,4-dioxide 2-Chloro-3-phenylquinoxaline 4-oxide 6-Chloro-2-phenylquinoxaline 4-oxide 6-Chloro-3-phenylquinoxaline 1 -oxide 6-Chloro-3-phenyl-2( 17/)-quinoxalinone 6-Chloro-3-phenyl-2(17/)-quinoxalinone 4-oxide 2-Chloro-3-piperidinoquinoxaline... 

Chloro-2( 1 //(-quinoxalinone 6-Chloro-2( 1 //(-quinoxalinone 4-oxide 2-Chloro-2-styrylquinoxaline... 

Malz, Jr. et al. found platinum sulfide supported on carbon to be superior to any of other nonsulfided and sulfided catalysts in the selective hydrogenation of 6-chloro-2(l//)-quinoxalinone-4-oxide to 6-chloro-2(l//)-quinoxalinone.230 The hydrogenation was performed in an aqueous potassium hydroxide solution at 60°C and 0.69-1.38 MPa H2 to give the product containing 92% of the desired compound in 90% isolated yield (eq. 9.79). 

The major reactions in this section are those involving an V-oxide oxygen. Deoxygenation of 2,3-disubstituted quinoxaline 1,4-dioxides is achieved under mild conditions by treating with hexa-chlorodisilane, TMS-1, TFAA-sodium iodide, or titanium tetrachloride-zinc dust <81H(i6)4ii>. Quinoxaline and phenazine V,A( -dioxides are also deoxygenated under mild conditions by sodium hypophosphite catalyzed by Pd/C or by treatment with sodium iodide in the presence of pyri-dine/sulfur trioxide complex <83JHC1735>. Deoxygenation of 6-chloro-2(l//)-quinoxalinone 4-oxide is effected particularly by sodium borohydride or sodium hydrosulfite <85H(23)143>. 

The most convenient synthesis of halogenopyrazines and -quinoxalines is by halogenation of pyrazinones and quinoxalinones with phosphoryl or other acid halides. A methoxy group is also displaced with phosphoryl chloride to yield chloropyrazine when the period of reaction is prolonged or the reaction is carried out at higher temperatures <78JHC665>. Chloro- and bromopyrazine N-oxides are obtained by diazotization of aminopyrazine A-oxides in concentrated hydrochloric acid and hydrobromic acid, respectively (see Section 6.03.5.4.2). 

We selectively hydrogenated 6-chloro-2(IH)-hydroxyquinoxaline-4-oxides to 6-chloro-2(IH)-quinoxalinone, using sulfided and non-sulfided catalysts. The catalyst of choice is platinum sulfide. Our catalyst studies included sulfided and non-sulfided platinum, palladium, rhodium, ruthenium, sulfided nickel, Raney nickel, and cobalt. 

One can produce 6-ohloro-2(IH)-quinoxalinone, via the N-oxide by, a multi-step method by condensing 4-chloro-2-nitroaniline, (111), and diketene,(IV), to produce 4-ohloro-2 -nitroacetoacet-anilide, (V). Patents and literature - reveal the reaction is carried out in the presence of a nucleophillic amine (Figure 3). 

Another unique example of the use of sulfided catalysts is in the production of 6-chloro-2(lH)-quinoxalinone (5) from 6-chloro-2(lH)-quinoxaline-4-oxide (4) on platinum sulfide (Malz et al., 1993). 

We have utilized this reaction path with some modifications (scheme 3). The diketene addition to 4-chloro-2-nitroaniline occurred spontaneously at room temperature with traces of 4-dimethylaminopyridine. Cyclisation and reduction were then completed in a one-pot procedure in a mixture of isopropanol and water. This allow the use of only 2.2 equivalents of sodium hydroxide instead of 5 to 6 in water and to control the temperature of the cyclisation at "65 C. Various catalysts, particularly Raney nickel or palladium on charcoal (8) were known to be efficient for the hydrogenation of the N-oxide. Eventual overreduction to the 3,4-dihydro-2(lH)-quinoxalinone could be smoothly compensated by reoxidising with hydrogen peroxide or air (9). 

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