Structure reactivity relationship in the accelerated formation of 2,3-diarylquinoxalines in the microdroplets of a nebuliser

Abstract

Competition experiments in which 1,2-phenylenediamine, C6H4(NH2)2, condenses with equimolar quantities of benzil, (C6H5CO)2, and a 3,3′- or 4,4′-disubstituted benzil (XC6H4CO)2 (X = F, Cl, Br, CH3 or CH3O) to form a mixture of 2,3-diphenylquinoxaline and the corresponding 2,3-diarylquinoxaline (Ar = XC6H4) in the microdroplets produced in a nebuliser allow a Hammett relationship with a ρ value of 1.85 to be developed for this accelerated condensation in the nebuliser. This structure reactivity relationship reveals that an appreciable amount of negative charge builds up on the carbon of the carbonyl group of the benzil during the rate-limiting step of the reaction, thus confirming that this process involves nucleophilic addition of the 1,2-phenylenediamine to the benzil. In general, the presence of an electron donating substituent, particularly in the 4 and 4′ positions, in the benzil retards the reaction, whereas an electron attracting substituent, especially in the 3 and 3′ position, accelerates it.

Hammett Correlation in the Accelerated Formation of 2,3-Diphenylquinoxalines in Nebulizer Microdroplets

“…Figure 1 is constructed on the basis of standard composite σ constants. The result is a good correlation, with a ρ value of −0.96 and an R 2 value of 0.96, which is comparable with that (0.89 or 0.90) obtained in the earlier competition experiments in which B and BY 2 competed to condense with P to form Q and QY 2 [ 7 ]. This good agreement suggests that using standard σ values generally may be appropriate in these analyses.…”

“…Thus, various reactions, particularly condensations, occur far more rapidly in the microdroplets of the nebulizer of a conventional electrospray mass spectrometer source, often at or near neutral pH and at ambient temperature, when either acid or base catalysis or heat would be required in classical alternative preparative methods [ 1 , 2 , 3 , 4 , 5 ]. The formation of C=N and C-N bonds, to produce heterocycles, in the microdroplets is especially effective, as exemplified by the Hantzsch synthesis of pyridine derivatives [ 4 ] and the facile formation of 2,3-diarylquinoxalines [ 6 , 7 ]. Many other scientific investigations covering a wide variety of topics have been made in microdroplets generated in a nebulizer [ 8 , 9 , 10 , 11 ].…”

“…The approach of applying competition experiments to obtain relative rate data was previously [ 7 ] exploited by measuring the quantities of 2,3-diphenylquinoxaline and the corresponding 2,3-diarylquinoxaline formed when phenylenediamine reacted with equimolar quantities of benzil and a 3,3′- or 4,4′-disubstituted benzil, Scheme 1 . The names of the reactants and products are abbreviated as follows: P , B and Q represent, respectively, 1,2-phenylenediamine, benzil and 2,3-diphenylquinoxaline; BY 2 and QY 2 represent the 3,3′- or 4,4′-disubstituted benzil and the derived 2,3-diarylquinoxaline containing substituents, Y, in the pendant aryl rings.…”

“…This disappointing outcome was attributed to the non-linear response of the detector to the [M+H] + ions and difficulties in accurately calibrating this response. However, when the ratio of Q and QY 2 obtained by transmission of starting materials through the nebulizer in “offline” competition experiments was measured by liquid chromatography using the UV detector, a good Hammett correlation, with a ρ constant of 1.87 and a correlation factor (“R 2 ” value) of 0.90 was obtained [ 7 ].…”

“…Closely similar results (a ρ value of 1.83 and an R 2 value of 0.89) were obtained when the quantities of Q and QY 2 were measured by the relative areas of the peaks in the total ion chromatogram, TIC, of signals in the gas chromatography mass spectrometry, GC-MS, analysis under electron ionization, EI, conditions of the product mixture. This protocol is especially attractive because it is possible to analyze a large number of mixtures by means of the auto-sampler on the GC-MS system [ 7 ].…”