31(I JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS serial dilutions were made in sterile tap water and aliquots of the dilution series added to A.O.A.C. agar. Plates were streaked with $. aureus as previously mentioned, incubated at 37øC., and results recorded at the end of forty-eight hours. Controls demonstrating lack of inhibition due to the soap were employed. All bacteriostatic tests in the presence of soap were conducted at a soap/compound ratio of 50/1. The values listed in Tables 1 to 5 are the higher numerical figures (•g./ mi.) demonstrating inhibition in the twofold serial dilution series. If, e.g., one test showed inhibition at 3.12 ug./ml. and a second one at 6.25 ug./ml., the latter figure was chosen. TABLE 2--ANTIMICROBIAl. ACTIVITY OF 2•2'-ETHYLIDENE AND 2•2t-BENzYLIDENEBIS-PHENOLS, AND OF 2•2/-STILBENEDIOLS No. Compound r--Minimum Inhibitory I,evel, og./ml.---- S. aureus T. S. (in Presence E. menta- aureus of Soap) coli grophytes 2,2'-Ethylidenebis (... phenol) Substituent 15 4-Chloro 3.12 12.5 50 3.12 16 6-Bromo-4. chloro 3.12 6.25 50 3.12 17 4-Methyl 12.5 12.5 50 50 18 2,2'-(2,2,2-Trichloroethylidene)-bis(4- chlorophenol) 0.78 12.5 50 3.12 19 2,2'-(2,2,2-Trichloroethylidene)-bis!6- bromo-4-chlorophenol) 0.78 12.5 50 3.12 20 5,5'-Dichloro-2,2'-stilbenediol 3.12 12.5 50 3.12 21 3,5,3',5'-Tetrachloro. 2,2'-stilbenediol 0.39 3,12 50 6.25 22 2,2'-Benzylidenebis(4. chlorophenol) 3.12 12.5 50 50 23 2,2'-Benzylidenebis(6- bromo-4-chloro- phenol) 6.25 12.5 50 50 24 2,2'-Benzylidenebis(4,6-dimethylphenol) 6.25 12.5 50 50 25 4,4qBenzylidenedithymol 1.56 12.5 50 50 26 4,4'-(2-Chlorobenzylidene)dithymol 0.78 6.25 50 50 27 4,4'-(4-Chlorobenzylidene)dithymol 0.78 6.25 50 50 28 4,4'-(4-Hydroxy-3-me thoxybenzyl- idene)-dithymol 3.12 6.25 50 50 The relationship of the antimicrobial activity of Ns-phenols to their structure had been studied previously. Bechhold and Ehrlich (9) were the first ones to demonstrate that halogenation of o,o'-diphenol enhanced its antibacterial potency. From the figures presented in our tables, it may be seen that halogen substitution in the rings is essential. Marsh and Butler (5) and Marsh, Butler and Clark (6), in their investigations on the fungicidal properties of bis-phenols, have discussed the dependence on certain structural features for high activity. Corey and Shirk (10) reported on the influences of chemical structure of a number of Ns-phenols with an unsubstituted methylene bridge upon antifungal potency. From these and other papers, it is apparent that there is no correlation between bacteriostatic and fungistatic properties. Pfieger and his associates (11)

ELEVENTH MEDAL AWARD TABLE 3--ANTIMICROBIAL ACTIVITY OF 2,2'-THIOBIS-PHENOLS 311 No. Compound ----Minimum Inhibitory Level, ug./ml.----, S. aureus T. S. (in Presence E. menta- aureus of Soap) coli grophytes Substltuents 29 5O 5O 25 30 4-(•/•ioro 3.12 13_i • 25 3.12 3l 4-Bromo 3.12 12.5 25 3.12 32 4,6-Dichloro,(bithionol) 1.56 3• 12 50 0.78 33 6-Bromo-4-chloro 1.56 3.12 50 1.56 34 3,4,6-Trichloro 0.78 6.25 50 50 35 Tetrachloro 0.78 12.5 50 50 36 4-Chloro-6-isopropyl-3-methyl 3.12 12.5 50 50 37 4-Chloro-3,5-dimethyl 6.25 12.5 50 50 38 2_Hydroxy-2-methoxy-5,5'-dichloro. diphenylsulfide 6.25 12.5 50 12.5 TABLE 4--ANTIMICROBIAL ACTIVITY OF RELATED BIs-PHENOLS No. Compound -Minimum Inhibitory I.evel, ug./ml.- --. S. aureus T. S. (in Presence E. menta- aureus of Soap) coli grophytes 39 1,1'-Methylenebis(2-naphthol) 6.25 12.5 50 6.25 40 3,3'-Methylenebis (2,4,6= trichloro- ,p, henol) 6.25 12.5 50 3.12 41 3,3 -Methylenebls(4-bromo-2,6- ,d, ichlorophenol) 12.5 12.5 50 12.5 42 4,4 -Methylenebls(2,3,6-trichloro- phenol) 12.5 12.5 50 3.12 43 2,2'-Oxybis(tetrachlorophenol) 0.78 1.56 50 50 44 4,4'-Thiodiphenol 50 50 25 45 2,2'-Sulfinylbis(3,4,6-trichlorophenol) 12.5 1•i• 50 25 46 o,oLDiphenol 5(} 70 50 47 4,4',6,6'-Tetrabromo-o,o'-diphenol 1.56 •i i2 50 6.25 48 Salicil(2,2'-dihydroxybenzil) 50 50 50 49 5,5'-Dichlorosalicil 3.12 151• 50 1.56 TABLE 5--BIs-PHENOLS SHOWING INHIBITORY LEVELS OF 50 btC./ML. AGAINST THE THREE TEST ORGANISMS No. Compound 50 2,2'-Me th¾1enediphen(•l 51 2,2'-Meth3lenebis(4,6-dim ethylphenoB 52 2,2'-Methylenebis(6-bromo-4-methylphencl) 53 2,2'-Methylenebis(4-nltrophenol) 54 2,2'-Methylenebis(4,6-dichlororesorcinol) 55 2,2'-Methylenebis(3,5,6-trichloroanisole) 56 4,4'-Methylenebis(2,6-dibromophenol) 57 2,2'-Thiobis (4-chloroanisole) 58 2,2'-Sulfinylbis (4-chlorophenol) 59 2,2'-Sulfonylbis(4-chlorophenol) 60 2,2'-Dihydroxy-5,5'-dichlorobenzophenone 61 1,1'-Methylenebis(6-bromo-2-naphthol) 62 1,1'-Methvlenebis(3,6-dibromo-2-naphthol) 63 4,4'-(3,4-Dimethoxybenzylidene) dithymol 64 Bis(3,5-dichloro-2-hydroxybenzyl)amine