2- quinoxaline, with

B. Reaction of 2-Phenyl- and 2,3-Diphenyl-quinoxaline with Dimethyl Acetylenedicarboxylate.221... 

A careful study of the phenylation of quinoxaline with benzoyl peroxide, various benzenediazonium salts, and A -nitrosoacetanilide indicates that the 2-position is most reactive to phenyl radicals and that the 5-position is more reactive than the 6. The yields of 2-, 5-, and 6-phenylquinoxaline are in the ratio of 40 10 1, Benzoyl peroxide and A—nitrosoacetanilide are the most effective phenylating reagents. 

Quinoxalines undergo facile addition reactions with nucleophilic reagents. The reaction of quinoxaline with allylmagnesium bromide gives, after hydrolysis of the initial adduct, 86% of 2,3-diallyl-l,2,3,4-tetrahydroquinoxaline. Quinoxaline is more reactive to this nucleophile than related aza-heterocyclic compounds, and the observed order of reactivity is pyridine < quinoline isoquinoline < phenan-thridine acridine < quinoxaline. ... 

The formation of quinoxaline quaternary salts is often difficult. However, reaction of quinoxaline with ethyl iodide in boiling acetonitrile gives ethyl quinoxalinium iodide in 76% yield, and treatment of the parent base with methyl toluene-p-sulfonate at room temperature gives methyl quinoxalinium toluene-p-sulfonate in quantitative yield. ... 

Treatment of bis-lactim ether 420 with BuLi, then with cw-l,4-dichloro-2-butene in the presence of Nal afforded 3,4,9,9n-tetrahydro-6//-pyrido[l,2-fl]pyrazin-4-one (421) with 96% diastereomeric excess (97TA1855). Reaction of l,2-diphenyl-6-methyl-quinoxaline with 1,4-dichlorobutane in THF in the presence of Na at —78°C afforded a 3 1 mixture of 4a,5-diphenyl-9-methyl-l,2,3,4-tetrahydro-4a//-pyrido[l,2-n]quinoxaline and 4-(4-chlorobutyl)-2,3-diphenyl-6-methyl-1,4-dihydroquinoxaline (98JHC1349). 

Complexes. The structure of an n a charge-transfer complex between quinoxaline and two iodine atoms has been obtained by X-ray analysis and its thermal stability compared with those of related complexes. The hydrogen bond complex between quinoxaline and phenol has been studied by infrared spectroscopy and compared with many similar complexes. Adducts of quinoxaline with uranium salts and with a variety of copper(II) alkano-ates have been prepared, characterized, and studied with respect to IR spectra or magnetic properties, respectively. 

Quinoxaline with the carbanion of (chloromethyl)sulfonylbenzene (PI1SQ2 CH2CI) gave the diannulated adduct, l,8-bisphenylsulfonyl-l,8,8a, 8b-tetra-hydrobisazirino[l,2-a 2, l -c]quinoxaline (7) [KOH, Me2SO, 20°C, <5h... 

In a somewhat similar way, quinoxaline with A -benzylmethanesulfonamide gave a separable mixture of l-benzyl-l,3,3a,4,9,9a-hexahydroisothiazolo[3,4-bjquinoxaline 2.2-dioxide (9) and 2-(Af-benzylsulfamoylmethyl)-l,2-dihydro-quinoxaline (10) (MeS02NHPh, BuLi, THF, 20°C, 1 h then quinoxaline, 20°C, 2h 66% and 15%, respectively) the latter product was oxidized to 2-(Af-benzylsulfamoylmethyl)quinoxaline (11) by passing through a column of... 

Quinoxaline with allyltributyltin and 2,2,2-trichloroethyl chloroformate (CICO2-CH2CCI3) gave bis(2,2,2-trichloroethyl) 2,3-diallyl-l,2,3,4-tetrahydro-l,4-quinoxalinedicarboxylate (17) (CH2CI2, 0°C, 3 h 30%) and a separable byproduct, bis(2,2,2-trichloroethyl) 2-aUyl-3-hydroxy-l,2,3,4-tetrahydro-l,4-quinoxalinedicarboxylate (18) (18%). ... 

These major routes to quinoxalmecarbonitriles have been covered already by primary synthesis (Chapter 1), by cyanalysis of halogenoquinoxalines (Section 3.2.5), by deoxidative cyanation of quinoxaline N-oxides (Section 4.6.2.2), by cyanolysis of nitroquinoxalines (Section 6.1.2.2), from primary quinoxalina-mines by a Sandmeyer-type reaction (Section 6.3.2.3), from quaternary ammonio-quinoxalines with cyanide ion (Section 6.3.2.4), and by dehydration of quinoxalinecarboxamides (Section 7.4.2). Those remaining preparative routes that have been used recently are illustrated in the following examples. 

Quinoxalines with a cychc substituent other than an unsubstituted cycloalkyl, morpholino, phenyl, or piperidino group Quinoxalines bearing a substituent with more than six carbon atoms, except for an unsubstituted benzyl or benzoyl group Quinoxalines with two or more independent functional groups on a single substituent... 

The reaction of pyrazine and quinoxaline with methyl chloroformate and bis-silyl enol ethers gave fused tetrahydropyrazine lactones 88, in an extension of previous work. There was little consistency with the variation of R in the stereochemistry of the products <06T12084>. 

The Pd-mediated cross-coupling reactions on the pyrazine ring of quinoxaline with organometallic reagents are more cumbersome. In one example, the Stille reaction between 2-chloroquinoxaline 87 and benzylstannane 88, attainable from the SN2 displacement of... 

Aldakov D, Anzenbacher P Jr (2003) Dipyrrolyl quinoxalines with extended chromophores are efficient fluorimetric sensors for pyrophosphate. Chem Commun 12 1394—1395... 

Reaction of quinoxaline with the fluorine-iodine-triethylamine system gives 2-fluoroquinoxaline 40 and 2,3-difluoroquinoxaline 41, whose yields depend on the fluorine usage (Equation 6) <1999J(P1)803>. Using 6-chloro-quinoxaline or 6,7-dichloroquinoxaline as the substrate, the monofluoro product is predominantly formed regardless of the amount of fluorine used. It is suggested that the reaction proceeds via attack of the fluoride ion on the a-carbon of an intermediate A -iodo quinoxalinium species followed by elimination of hydrogen iodide with triethylamine. 

The flavazoles, an interesting type of pyrazoline derivative obtained by interacting sugar quinoxalines with phenylhydrazine, will be discussed in the next Section (see p. 398). 

B. 2,3-Pyrazinedicarboxylic acid. A 12-1. three-necked flask is provided with an efficient mechanical stirrer, a reflux condenser, and a 1-1. dropping funnel. In the flask are placed 4 1. of hot (about 90°) water and 145 g. (1.12 moles) of quinoxaline. With rapid stirring a saturated aqueous solution of 1050 g. (6.6 moles) of potassium permanganate (Note 4) is added through the dropping funnel in a thin stream. The rate of addition of the permanganate solution is adjusted so that the reaction mixture boils gently. The addition requires about 1.5 hours. 

The second synthetic route to PAE containing quinoxaline units involved the reaction of an aromatic dihydroxy quinoxaline or aromatic bis(hydroxy-quinoxaline) with activated aromatic difluoro compounds (Eq. (3)) [15]. The dihydroxy quinoxaline and bis(hydroxyquinoxaline) monomers were readily prepared from the condensation of 1,2-diaminobenzene with 4,4 -dihydroxyben-zil and aromatic bis(o-diamines) with 4-hydroxybenzil, respectively. The Tgs of a series of PAE containing quinoxaline units are presented in Tables 3 and 4. For these polymers, the trend for the Tg is sulfone > carbonyl > terephthaloyl-> isophthaloyl. This trend holds for most polymer families when polymers of similar molecular weights are compared. Several polyphenylquinoxalines of the same chemical structure as those in Table 3 were also prepared by the poly-... 

Comparison of the spectrum of a hydrocarbon analogue of the hetero-atomic molecule Formaldehyde with ethylene, pyridine with benzene, quinoxaline with naphthalene. If a long wavelength absorption band of weak intensity is observed, it may be an n -> it transition. 

Benzylquinoxaline (62) is the only product isolated from the homolytic benzylation of quinoxaline with dibenzyl mercury.73 Gardini and Minisci found that homolytic alkylation,74 acylation,75 cr-oxy-alkylation,76 carboxylation,77 and <5-aminoalkylation78 of quinoxaline always gave the 2-substituted product. When a mixture of quinoxaline and ferrous sulfate is treated with A-chlorodi-n-butylamine, exclusive 2-substitution occurs in 50% sulfuric acid, but in concentrated acid a... 

Reduction of quinoxaline with sodium in tetrahydrofuran (THF) at 20° yields 1,4-dihydroquinoxaline (26%).91 A 1,4-dihydroquinoxaline (75) is also the first product of reduction of 2-phenylquinoxaline (74), but 75 readily rearranges to the thermodynamically more stable 1,2-dihydro isomer (76).92... 

Peracetic acid oxidation of 2-carbamoylquinoxaline (94) at 20°-25° gives the monoxides 95 and 96, and at higher temperatures the 1,4-dioxide (97) is isolated in 50% yield, together with a small amount of the 1,4-dioxide of 2-amino-3-quinoxalinone.m However, Hayashi and co-workers report the isolation of only 96 from 94 using monoperphthalic acid in ether <10°.109 In their attempt to correlate the nature of 2-substitution with the formation of 1- versus 4-oxides, they examined the behavior of some 2-alkyl substituted quinoxalines 113,114 2-ethylquin-oxaline gives the 1- and 4-oxides and the 1,4-dioxide, 2-isopropylquin-oxaline yields the 4-oxide and the 1,4-dioxide however, 2-f-butylquin-oxaline only furnishes the 4-oxide because of steric hindrance.114 The N-oxidation of 2-phenyl- and 2-alkyl-3-phenyl-quinoxalines with monoperphthalic acid furnishes the products shown in Table 1.114... 

Quinoxaline and 2-methylquinoxaline form 1 1 adducts (111) with diphenylcyclopropenone,122 and an analogous pyrrolo[l,2-a]quin-oxaline has been isolated from the reaction of quinoxaline with di-phenylcyclopropenethione.123... 

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