Quantitative Reaction Cascades of Ninhydrin in the Solid State

Organic synthesis by Twin Screw Extrusion (TSE): continuous, scalable and solvent-free

“…Kaupp et al reported the reaction between ninhydrin and dimedone by ball milling, to produce a substituted 1,3 indandione (6) (Scheme 6). 28 We were able to reproduce this result by ball milling and therefore subsequently investigated it by twin screw extrusion. Initial results showed that the reaction would not go to completion without the presence of Na2CO3 (0.1 mol.…”

Temperature progression in a mixer ball mill

“…One option is the integration of milling pauses to the milling cycle that allow a cooling down of the milling beakers, but also increase the total reaction time [10,17,18]. Technical solutions for a temperature-controlled milling are: cryogenic milling, where the beakers are cooled with liquid nitrogen [19]; water cooling of the vessels [5] and of the milling beaker holder [20]; (forced) air cooling [21]; use of heating tapes [22]; the application of double-walled milling beakers, which are equipped with an inlet and outlet for a circulating liquid that can be tempered by a thermostat [23][24][25].…”

Ninhydrin as a building block in scaffold-linked chromophoric dyad construction

“…Indeed, reaction with CE-1 proceeded smoothly to produce a single, red-coloured 1:1-adduct 22a (Scheme 5). That reaction had occurred at the CO-group rather that at the imine was supported by the presence of a single 13 C ketone resonance at δ 182.8 and an imine 13 C resonance at δ 163.1. In all cases to date (ninhydrin, indenopyridazines), the phenylene component had been preferentially positioned in the exo-site and this stereo-preference was retained in this reaction as no NOE correlation was observed between the either phenylene protons and the aryl protons of the N-substituents and the endo-protons Ha, Hb.…”

“…The structure was assigned on the basis of mass spectrometry, NMR spectroscopy and chemical reactions. In particular, the 13 C-NMR showed two closely spaced CO-resonances at δ 193.7 and δ 193.9 typical of aryl ketones as well as two up-field CO-resonances for the ester groups (δ 163.6, 165.3). The lack of colour in this adduct supported the absence of α-dione chromophore which was consistent with the fact that no evidence for a quinoxaline derivative was observed on treating it with o-phenylenediamine 15a (see later for contrasting behaviour of the minor 1:1-adduct 13).…”

“…The minor product 13 isolated from this reaction was yellow-coloured and shown to be a 1:1-adduct by mass spectroscopy. 13 C-NMR displayed four carbonyl resonances corresponding to the ester COs (δ 164.2, 165.1) and two well-separated resonances indicative of an aryl carbonyl (δ 194.1) and an aliphatic α-dione carbonyl (δ 184.6; note that those in the reference α-dione 18 resonated at δ 187.1). The presence of the α-dione functionality was confirmed by reaction of 13 with o-phenylenediamine 15a to form the quinoxaline 16a.…”