KENNETH V. THIMANN 31 



pal requirement for activity then a compound like aV-cinnamic acid, in 

 which this position is fixed, should be much more active than, say, indole- 

 acetic acid, in which this is only one of many positions attainable by free 

 rotation. 



The effect of ring substitution can be considered in this connection. 

 Introduction of a methoxy group into the benzene ring of indole- 

 propionic acid, in any one of 3 positions, 4, 5, or 6,* inactivates it com- 

 pletely (3). On the other hand introduction of halogens into the ring of 

 phenyl derivatives greatly increases activity. The phenoxyacctic acids 

 show the following primary activities (10) (relative to that of indole- 

 acetic as 100): 



Phenoxyacctic ca. 



o-chlorophenoxyacetic 4 



/7-chlorophenoxyacetic 200 



2,4-dichlorophenoxyacetic 1000 



2,4,5-trichlorophenoxyacetic 500 



Similarly, 2,4-dichlorophenylacetic acid has very high activity. A strik- 

 ing case is that of phenylbutyric acid whose activity is virtually zero; 

 f-bromination raises it to about 15 per cent of that of Indoleacetic acid 

 (see Table i). Methyl groups In the o- and p- position apparently 

 increase the activity in the phenoxyacctic series about as much as 

 chlorine atoms (7).! Many similar examples can be drawn from the work 

 of Norman and his colleagues at Camp Detrick, though they used 

 different tests. 



It Is difficult to see how substitution In the remote para- position could 

 twist the carboxyl out of the plane of the ring, or how in Indoleacetic 

 acid substitution of a methoxyl In the remote 5-posItion could have 

 the opposite effect. According to Veldstra the influence of the halogens 

 may be exerted on the lipophilic properties of the molecule, which 

 are increased thereby; however, if the molecule becomes too lipophilic 

 the balance between this and its hydrophihc properties is disturbed 



*On the other hand, S. P. Findlay and G. Dougherty [/. Biol. Chem., 183:361 

 (1950)] have recently reported, but without quantitative data, that 5- 6-, and 

 7-methoxyindoleacedc acids are active. The activity is probably rather low. Their 

 data also confirm the inactivity of A'-cyclopenteneaceric acid. (See page 25). 



fR. M. Muir, C. H. Hansch, and A. H. Gallup [Plant Physiol, 24:359-366 

 (1949)] have recently reported in some detail on the halogenated phenoxy 

 compounds. 



