The Role of Ortho-Substitution in the Synthetic Auxins

The structure of molecules active as auxins has been investigated extensively, and presents one of the most attractive of all problems of the relation between a chemical structure and a biological activity. The structures are. relatively simple, the compounds generally stable and the tests reproducible and quantitative. The results and conclusions to date were reviewed in 1949 (13). The general rules for the structural requirements of active molecules which were given more than 14 years ago (5) have been slightly modified and restated to fit certain new cases (16, 17), but basically new departures in principle have not appeared until quite recently. There are now, however, two important new points to consider. One of these is the proposal of Muir and co-workers (3, 9, 10) that in order for a substance to liave auxin activity, at least one of. the positions on the aromatic ring ortho to the acidic side chain must be unsubstituted. This proposal stemmed from the inactivity (or very low activity) of 2,4,6-trimethylphenylbutyric acid, 4,7-dichloro-2-methylindoleacetic acid, and particularly the 2,4,6-trichloro-, tribromoand trimethyl-derivatives of phenoxyacetic acid. These authors used the elongation of Avena coleoptile sections as a test. It has been pointed out earlier (15) that the Avena coleoptile is more selective than the pea stem. However, the present paper shows that also in pea stems these latter three compounds are of very low activity. The second new principle is the activity of certain benzoic acid derivatives, reported (1) and confirmed (10) for growth of Avena sections, and which is also confirmed herein for the pea test. Earlier suggestions of activity in this series, based on different tests, had been made for 2-bromo-3nitrobenzoic acid and some other derivatives (19) ; but activity in the pea test had not been found (18). It was suggested that these compounds did not have true auxin activity (18). The fact that true auxin activity is present in benzoic acid derivatives means that the rule that the acid group must be separated from the ring by at least one atom (5), though valid in the large majority of cases (13), is subject to important exceptions. The same is true for the suggested explanation of this requirement, namely that the acid group must be held out of the plane of the ring (16). In the present study a number of other compounds relating to the above two points have been tested, and it is shown that the role of ortho-substitution is less simple than it appeared at first. Some of the facts are consistent