10.1002/ejoc.201901553
European Journal of Organic Chemistry
COMMUNICATION
enriched by free amino acids (e.g.: food for particular medical
Author Contributions
uses or baked enriched foods).
G.B. Giovenzana and M. Arlorio designed and planned the
experiments. G.B. Giovenzana, M. Barbero and R. Negri
synthesized the compounds and carried out experiments to
elucidate the mechanism. V.A. Papillo, M. Bordiga, F. Travaglia
and M. Arlorio were responsible for analytical characterization. A.
Grolla and F. Condorelli performed the MTT tests. G.B.
Giovenzana, M. Arlorio, M. Barbero, F. Condorelli and F.
Travaglia wrote the manuscript and discussed the results with all
authors.
Preliminary toxicity tests were then undertaken in order to
evaluate the potential biological effect of 2,5-diamino-1,4-
benzoquinone, for which no literature data are available except
for the 2,5-diaziridino analogues, where cytotoxicity and
mutagenicity is well documented[27] but clearly related to the
presence of the strained aziridine heterocyclic three-membered
rings rather than to the benzoquinone moiety. Preliminary
investigations demonstrate that 2,5-diamino-1,4-benzoquinones
are not toxic even at 100 µM concentrations. In more details,
MTT-based assays were exploited in vitro to test the effect of our
compounds on viability of renal (HEK293T) and hepatocytic
(HepG2) human cell lines, showing negligible toxicity at
concentrations compatible with alimentary exposure. Thus,
although more detailed investigation are needed, our preliminary
observations exclude undesired biological activities for these
compounds.
Keywords: vanillin • amines • quinones • oxidation • colour
References
[1]
G. Banerjee, P. Chattopadhyay, J. Sci. Food Agric. 2019,
99, 499–506.
[2]
[3]
H. O. Mottern, J. Am. Chem. Soc. 1934, 56, 2107–2108.
W.-B. Huang, C.-Y. Du, J.-A. Jiang, Y.-F. Ji, Res. Chem.
Intermed. 2013, 39, 2849–2856.
B. Liu, L. Cheng, P. Hu, F. Xu, D. Li, W.-J. Gu, W. Han,
Chem. Commun. 2019, 55, 4817–4820.
D. F. Taber, S. Patel, T. M. Hambleton, E. E. Winkel, J.
Chem. Educ. 2007, 84, 1158.
B. Kaur, D. Chakraborty, Appl. Biochem. Biotechnol.
2013, 169, 1353–1372.
P. Chattopadhyay, G. Banerjee, S. K. Sen, J. Clean.
Prod. 2018, 182, 272–279.
“Vanillin Market | Growth Trends | Forecast| (2019-2024),”
can be found under
reports/vanillin-market, n.d.
D. L. J. Opdyke, Food Cosmet. Toxicol. 1977, 15, 633–
638.
The colouring properties of the 2,5-diaminoquinones potentially
formed from proline and other secondary amines are of great
interest regarding the evaluation of the sensorial properties of
some baked products (particularly surface colour of biscuits).
Colour is a fundamental attractive sensorial feature of baked
products, and e.g.: Maillard reaction are well known to contribute
to the development of brown colour in these foods. The wide
range of brilliant orange to brilliant dark red colours shown by the
2,5-diaminoquinones could be a possible contributor to the overall
perceived colour in bakery products. Moreover, the colouring
properties of these compounds can be evaluated in order to select
novel potential candidates as “new” colorant additives in foods,
following an in deep safety assessment.
[4]
[5]
[6]
[7]
[8]
[9]
[10] S. Rajasekar, T. P. A. Krishna, N. Tharmalingam, I.
Andivelu, E. Mylonakis, ChemistrySelect 2019, 4, 2281–
2287.
[11] H. P. V. Rupasinghe, J. Boulter-Bitzer, T. Ahn, J. A.
Odumeru, Food Res. Int. 2006, 39, 575–580.
[12] E. N. Carcamo-Noriega, S. Sathyamoorthi, S. Banerjee,
E. Gnanamani, M. Mendoza-Trujillo, D. Mata-Espinosa,
R. Hernández-Pando, J. I. Veytia-Bucheli, L. D. Possani,
R. N. Zare, Proc. Natl. Acad. Sci. 2019, 116, 12642–
12647.
[13] YūF. Sasaki, T. Ohta, H. Imanishi, M. Watanabe, K.
Matsumoto, T. Kato, Y. Shirasu, Mutat. Res. Lett. 1990,
243, 299–302.
[14] K. Ho, L. S. Yazan, N. Ismail, M. Ismail, Cancer
Epidemiol. 2009, 33, 155–160.
In conclusion, in this work we report the observation of an
unprecedented reaction of vanillin with secondary amines in
aerobic conditions, leading to the efficient formation of 2,5-
diamino-1,4-benzoquinones. The reaction involves several steps
and intermediates, as exemplified by the reaction mechanism,
proposed on the base of literature evidences and suitably
designed experiments. The importance of this reaction resides in
the possibility of this transformation to occur more frequently than
considered until now, due to the large use of vanillin (and
derivatives thereof, as ethylvanillin) and the occurrence of
secondary amines, either biogenic or thermally/chemically
generated in the experimental conditions encountered in food
processing. These outcomes open new findings both considering
the production of new coloured compounds (pigments for foods
or other colorants for pharmaceuticals products), as well as new
insights on the potential red-orange colour tone development in
baked foods, complementary to the browning correlated to the
well know Maillard reactions.
[15] A. Tai, T. Sawano, F. Yazama, H. Ito, Biochim. Biophys.
Acta BBA - Gen. Subj. 2011, 1810, 170–177.
[16] X. Chen, M. Wei, H. Zhang, C. Luo, Y. Chen, Y. Chen,
Food Chem. Toxicol. 2012, 50, 1897–1901.
[17] M. Hellwig, T. Henle, Angew. Chem. Int. Ed. 2014, 53,
10316–10329.
[18] M. Weerawatanakorn, J.-C. Wu, M.-H. Pan, C.-T. Ho, J.
Food Drug Anal. 2015, 23, 176–190.
[19] W. Chobpattana, I. J. Jeon, J. S. Smith, J. Agric. Food
Chem. 2000, 48, 3885–3889.
[20] A. H. Crosby, R. E. Lutz, J. Am. Chem. Soc. 1956, 78,
1233–1235.
Conflict of Interest
The authors declare no conflict of interest.
This article is protected by copyright. All rights reserved.