Fig. 5: ‘Switchable’ hyperspace of the Hantzsch reaction network.
From: Robot-assisted mapping of chemical reaction hyperspaces and networks
a, Identification of reaction products by closed-loop repurification and refitting against four-dimensional hypercube UV-Vis spectra (see Supplementary Information Section 4.15). Within eight repurification rounds, 16 components (14 products plus unreacted 19a and 19c) were identified. The mismatch between fitted and experimental spectra (vertical axis) decreased to the median value of instrumental uncertainty (dashed green line; see Supplementary Information Section 4.9). The vertical axis shows the highest spectral mismatch per condition. Box plot elements indicate the first quartile, median and third quartile, whiskers show the 5th and 95th percentiles, with outliers as black diamonds. Blue scatter plot shows individual data points. b, UV-Vis ‘basis set’ of the 16 components. Their discovery follows the cycles in a: 3 components (19a, 19c, 19d), 7 components (+19k, 19r, 19o, 19m), 8 components (+EAB), 11 components (+19j, 19f, 19g), 12 components (+19e), 14 components (+19h, 19p), 15 components (+19i), 16 components (+19h). c, Reaction network: green, substrates; blue, isolated known products/intermediates; red, new products/intermediates. Network connectivity was verified by separate reactions (green arrows): (1) NH4OAc, AcOH, 80 °C, 18 h; (2) ethyl acetoacetate, EtOH, 80 °C, 18 h; (3) EAB, EtOH, 80 °C, 24 h. Note the presence of products of two separate ‘named reactions’, Hantzsch (19d) and Petrenko-Kritschenko (19e) (mechanisms are shown in Supplementary Information Schemes 2 and 3. d–f, Within the hyperspace, the reaction network at 80 °C can be switched between three main products observed in different corners of the space: Hantzsch ester 19d (maximum yield 63.5%, <3% 19p) (d); Petrenko-Kritschenko product 19e (maximum yield about 66%) (e); benzylidene-extended Hantzsch derivative 19k (maximum yield 61.7%) (f). These yields (after 48 h) were quantified by HPLC and are colour-coded according to the legend. Isosurfaces correspond to 20%, 30%, 40%, 50% and 60% yield. For full experimental details, see Supplementary Information Sections 4.7, 4.9 and 4.10.
