Synthesis Of Pyrazine And Quinoline Derivatives And Their Pyrolysis Research

In recent years,C-H bond activation and catalytic coupling reactions have played an important role in the field of organic synthesis due to their advantages of high efficiency and atomic economy.Therefore,the synthesis of novel pyrazine and quinoline derivatives have been investigated based on C-H bond activation or catalytic coupling reactions.To develop the new flavor precursor of nitrogen-containing heterocyclic compounds,the thermogravimetry,pyrolysis,and sensory evaluation in cigarette flavoring of the representative compounds have been studied.These studies will provide theoretical support for the application of nitrogen-containing heterocyclic compounds in the food and cigarette industry.1.Olefination reactions of pyrazine N-oxides through Pd-catalyzed C-H bond activation.This new methodology has been demonstrated to be suitable for the cross-coupling of aza-heteroaromatic N-oxides with olefins via palladium catalysis,which afforded a broad range of alkenyl substituted aza-heteroaromatic N-oxides in up to 93%yields(Scheme 1).The method has the advantages of readily available substrates,straightforward and atom-economy.The pyrolysis of representative product 3a indicates that the characteristic aromas of pyrazines,such as aromas of nutty,roasty,earthy and sweet,are obtained.The pyrolysis of 3f and 3g shows that except for the characteristic aromas of pyrazines,there are also almond flavor of benzyl alcohol and floral of 2-methyl-thiophene,respectively.The pyrolysis atmospheres of 9%oxygen in nitrogen and inertness have effects on the types and relative contents of pyrolysis products,while the oxygen atmosphere has beneficial effects on the formation of flavors.2.Alkylation reaction of pyrazine N-oxides under transition-metal free conditions.A series of alkyl compounds in moderate to good yields with broad substrates scopes were obtained through the reaction of aza-heteroaromatic N-oxides and cyclic ethers in the presence of TBHP(Scheme 2).Mechanistic studies indicated that a radical process was involved in this reaction.The method has the features of simple,efficient,step economy and environment-friendly.The pyrolysis analysis of representative products 6a and 6i shows that the characteristic aromas of pyrazines,such as aromas of nutty,roasty,earthy and sweet,are obtained.The pyrolysis atmospheres have a great influence on the types of pyrolysis products of 6a and 6i,and the 9%oxygen in nitrogen condition is more conductive to the release of aromatic compounds.3.Direct thiolation of quinoline N-oxides via copper-catalyzed C-H bond activation.A series of 2-ArS-substituted aza-heteroaromatic N-oxides were prepared via the reaction of aza-heteroaromatic N-oxides with disulfides in up to 90%yields(Scheme 3).The possible reaction mechanism was also proposed.This method is simple and efficient,and provides a significant way to selective activated aza-heteroaromatic N-oxides.Pyrolysis analysis of representative products shows that 9f could produce the pyrolysis products with aromas of spice,almond and caramel.The pyrolysis products of 9h possess aromas of boiled beef,earthy and sweet.The pyrolysis products of 9o have the aromas of boiled beef,almond and sweet.Pyrolysis atmospheres have effects on the relative contents of flavors,and the existence of oxygen can promote the generation of aromatic compounds.4.Cross-coupling reactions of aza-heteroaromatic bromides with tetraalkylthiuram disulfides via copper catalysis.A broad range of the aza-heteroaromatic dithiocarbamates were synthesized in up to 98%yields(Scheme 4),and the possible reaction mechanism was also speculated.This method is efficient and simple,which provides a meaningful way to obtain aza-heteroaromatic dithiocarbamates with bio-activity.The aromas of phenolic,syrupy and radish could be produced by the pyrolysis of representative compound 13i,while the pyrolysis of 13q can generate the characteristic aromas of nutty and bell pepper.Pyrolysis atmospheres have little effect on the types of pyrolysis products of 13i and 13q,but have a slight effect on their relative contents.It is indicated that the existence of oxygen can promote the formation of aromatic compounds.5.The sensory evaluation in cigarette flavoring of compounds 3f and 6a.The sensory evaluation results show that the best additive concentrations of compounds 3f and 6a in cigarette of single grade tobacco are 2 mg/kg and 4 mg/kg,respectively,and the aroma features,smoke features and taste characteristics of cigarette are significantly improved compared with the control group.The optimal additive concentrations of compounds 3f and 6a in cigarette blend are 2 mg/kg.The obtained results proves that the addition of these two compounds could make a contribution to increasing quantity of aroma,improving harmonicity,reducing offensive odor,minimizing irritation,and making aftertaste clean and comfortable.