US3189645A - N-hydroxycarbanilidies and their use as bactericides and fungicides - Google Patents

Description

United States latent O ice.

3,189,645 N-HYDROXYCARBANILIDES AND THEIR USE AS BACTERICIDES AND FUNGICIDES Peggy Pamela Hoffman, Somerviiie, and Wiiliam Baptist Hardy, Bound Brook, N.J., assignors to American Cyanamid Company, New York, N.Y., a corporation of Maine No Drawing. Filed Aug. 8, 1961, Ser. No. 129,999 4 Claims. (6]. 269-553) This invention relates to new germicides and to detergent compositions containing these germicides. More specifically this invention relates to N-hydroxycarbanilides having at least two substituents of the group consisting of halogen and trihalomethyl, and which may be further substituted by halogen, nitro, lower alkyl or lower alkoxy radicals; and to non-ionic and anionic detergent compositions containing them.

In recent years, increased attention has been given to the development of textile purifying finishes. These finishes inhibit the growth, and reduce the number of microorganisms on the material. These purifying finishes, when applied to articles of clothing worn close to the body, are also helpful in preventing the development of body odors.

A satisfactory purifying finish should be durable and active at low concentrations against a broad spectrum of microorganisms. It should be non-toxic and nonallergenic. It should not have the tendency to sensitize the wearer of the textile fabric to the material of the finish. It should not have the property of allowing strains of bacteria to develop which are resistant to the antibacterial agent of the finish. It should impart little or no color to the fabric and should be stable with respect to color and activity for many months under storage and shipping conditions. It should be resistant to the conditions used in laundering and dry cleaning. It should cause little or no modification of the hand of the textile. It should be substantive to the fiber. It should be compatible with dyes and resins with which it may be in contact on the textile. 1

Various textile purifying finishes containing anti-bacterial substances such as hexachlorophene, tetrachlorophene, quaternary ammonium compounds such as dimethyl benzyl ammonium chloride, organo-metallic complexes of mercury, copper and silver, and others have been used but are for the most part non-durable and unsatisfactory in other respects, especially in their inability to exhaust from a laundry bath.

substantivity on the fiber and durability of the antibacterial action are two of the most important desirable properties. Without substantivity on the fiber the germicide is merely a coating to be rubbed or washed oif by the first treatment to which it is subjected. substantivity for the fiber is, therefore, one of the main bases upon which durability rests. However, durability must also be a function of the stability of the compound itself to oxidation by air, degradation by light, heat and the like.

Especially important is the property of substantivity under laundering conditions and especially of exhaustion from such a laundry bath in the same way that a dye exhausts from a dye bath. If a germicide is to have the widest utility as a textile finish, the best place to use it is in the regular laundering, whether in the home or in a hospital or a commercial laundry. Such a germicidal finish builds up in concentration on the fiber with further Washing since new applications of germicide are made during such further washing.

This invention is based on the discovery of a new class of compounds, defined above, the members of which have high germicidal action and are substantive to fabrics. The

Fa -tented June 1 5, T955 new compounds may be represented by the structural Formula 1:

wherein the X X X X X Y Y Y Y and Y are individually either hydrogen, halogen (especially chlorine and bromine), nitro, lower alkyl, lower .alkoxy and trihalomethyl (e.g. trichloromethyl and especially trifluoromethyl), at least two of the X and Y radicals being halogen or trihalornethyl. Within the class of compounds constituting this invention those compounds which have halo and/ or trihalomethyl groups in both phenyl moieties are preferred since they generally show greater germicidal activity than the analogs which are substituted in only one phenyl moiety. It has also been found that those compounds having at least one 3,4-dichlorophenyl radical, 3,4,5-trichlorophenyl radical, and particularly a 3,5-dichlorophenyl radical or a S-trifluoromethylphenyl radical show higher activity than those in which the chloro radicals are in the 2- or the 6-positions of the phenyl moieties.

The new compounds of this invention may be prepared by reacting a phenyl isocyanate with an N-phenylhydroxylamine in the presence of a non-polar halogenated organic solvent (e.g. chloroform) or an aromatic monocyclic hydrocarbon (e.g. benzene, toluene and xylene) at ambient temperatures using approximately equimolar proportions of the reactants. The reaction may be represented by the following equation in which X X X X X Y Y Y Y and Y are as hereinbefore defined.

I I I I X -QNCO norm-@414 I I I X5 X5 Ya Ya X3 X2 Y2 Y3 I I I I I 0 X5 i I I As examples of suitable phenyl isocyanates which may be used, these may be named inter alia: phenyl isocyanate, 2-, 3- and 4-chlorophenyl isocyanate, 2,3, 25-, 3,4- and 3,5-dichlorophenyl isocyanate, 3-(trifiuoromethyl)phenyl isocyanate and 3,5-bis(trifluoromethyl)phenyl isocyanate, 2-, 3- and 4-bromophenyl isocyanate, 3,4 and 3,5-dioromophenyl isocyanate, 3,4,5-trichlorophenyl isocyanate, 3- and 4-nitrophenyl isocyanate, 2-, 3- and 4-methylphenyl isocyanate, 3-(trifiuoromethyl) 4 bromophenyl isocyanate, 3-(trifiuoromethyl)-4-chlorophenyl isocyanate and 4-methoxyphenyl isocyanate.

As examples of suitable N-phenylhydroxylamines which may be used, these may be named inter alia: N-phenylhydroxylamine, N-(Z-chlorophenyl)hydroxylamine, N-(4- chlorophenyl)hydroxylamine, N-(3-chlorophenyl)hydroxylamine, N- (4-iodophenyl) hydroxylamine, N- (2,5 -dichlorophenyl)hydroxylamine, N-(3,4-dichlorophenyl)hydroxylamine, N 3,5 dichlorophenyl)hydroxylamine, N 3- (trifiuoromethyDphenyl hydroxylamine, N-3 (trichloromethyl) phenyl hydroxylamine, N-(3,4,5-trichlorophenyl) hydroxylarnine, N-(2-methyl 3 chlorophenyl)hydroxylamine, N- Z-methyl-S-chlorophenyl) hydroxylarnine, and N 2-methyl-4,S-dichlorophenyl hydroxylamine.

The germicides of this invention when padded or exhaust dyed on cloth, show such germicidal activity that Staphylococcus aureus and E. cell, for example, are inhibited not only where in contact with the treated cloth, but in an area beyond. After many Washing cycles, the

a padded fabric still shows activity against Staphylococcus aureus and E. coli in contact with the cloth.

It is an important advantage of the germicides of this invention that they become attached to fibers when applied from an aqueous bath at only slightly elevated temperatures. They have notably strong afiinity for cotton and may be applied to cotton in temperatures as low as those used in laundry procedures. They may also be applied at.th e higher temperatures normally used in the dyeing of cotton, i.e. near the boil. These compounds are thus particularly suitable for hospital and home use, where it is more difficult to attain the temperatures close to the boil that are used in a dyeing mill. In addition to cotton, the germicides of this invention have afiinity for other fibers such as nylon, cellulose acetate and the like when applied from laundry bath. 7

The compounds of this invention are compatible with non-ionic and anionic detergents. This is a further :advantage of this invention since the germicide can be ap-1 plied from a detergent bath such'as is used in laundering in the home or in a hospital. Germicidal compositions including the compounds of this invention in admixture with alkyl aryl sulfonates (anionic detergents) are espe cially suitable compositions for the application for'durable finishes to cotton and other fibers especially during home or commercial laundering procedures. During the process of laundering, the germicide becomes attached to'the fiber and the fiber is thusrendered sterile for long periods. A detergent composition having from about 0.01 to 5.0% germicide on the weight of the detergent is an effective composition for this purpose.

The organic anionic detergents which may be used in the'compositions of this invention include alkali metal fatty acid soaps and, in addition, the well known surfaceactive alkali metal sulfonates and sulfates. The latter may be employed as the sole detergent base or in admixture with alkali metal fatty acid soaps, as for example, 1 part of fatty acid soap to 0.5 to '2 parts by weight of the surface-active alkali metal sulfonates or sulfates or mixtures thereof. A preferred group of this class is the long chain alkyl aryl sulfonates, i.e., those wherein the alkyl group is straight or branched in structure and contains from 8 to 22 carbon atoms, but preferably 10 to 16 carbon atoms, examples of which being octyl, decyl, dodecyl, pentadecyl, hexadecyl, octadecyl, mixed long chain alkyl' derived from long chain fatty acids such as the lauryl radical, cracked parrafin wax olefins, polymers of low mono-olefins such as propylene tetramer and the like, and wherein the aryl radical is derived from benzene, toluene, xylene, phenol, the cresols, naphthalene and the like. Specific examples of such comprise sodium decylbenzenesulfonate, sodium dodecylbenzenesulfonate,

sodium laurylbenzenesulfonate, and sodium hexadecylbenzenesulfonate. Other sulfonate surface active agents are contemplated also, as for example, the long chain :alkyl sulfonates such as sodium hexadecyl sulfonate and .and mixed alkyl sulfates, and higher sulfates such as sodium lauryl sulfate and sodium cetyl sulfate.

Additional .anionic surface active sulfonates and sulfates contemplated by this invention are the sulfonated and sulfated'alkyl acid amides such as Igepon T of the formula C H CONHCH CH SO N21 The sulfated and sulfonated esters such as Igepon AT of the formula Such detergents include sulfuric acid esters of din which R is an alkyl radical containing from 12-18 carbon atoms, the sodium salt of the sulfonic acid derivative of a dialkyl dicarboxylate, disodium sulfosuccinate monoamide such as and the like. ,j In addition to the. anionic surface active agents, nonionic surface active agents may be used as the base for germicidal compositions of our invention. Thenon-ionic surface active agents which may be used are viscous liquid, wax-like, water soluble surface active substances containing a polyglycol ether group of the strucmre Z1 Z2 in which Z and Z are hydrogen or a short chain alkyl,

p is an integer greater than three and Z is a residue of V typified by polyalkylene oxide derivatives (e.g. polyethylene oxide, polypropylene oxide, polybutylene oxide) of water-insoluble higher fatty acids, such as lauric, 'oleic, palmitic and stearic and the like, or'mixtures thereof such as the mixtures of fatty acids obtained from animal and vegetable fats and oils and by the oxidation of petroleum fractions such as parafin wax; They may also be exemplified by the polyalkylene oxide derivatives of such water-insoluble organic hydroxy compounds as higher aliphatic compounds (i.e. the alcohols corresponding to the fatty acids specified above or mixtures thereof) phenols, particularly alkyl phenols containing at.least six alkyl carbon atoms such as isooctyl, triisopropyl, nonyl, dodecyl, octadecyl phenols or naphthols, or of aralkyl alcohols such as benzyl alcohol, cinnamyl alcohol and the like. They may also be exemplified by the polyalkylene oxide derivatives of such amines as 'stearyl, lauryl, dicyclohexyl, dibutyl amine and the like. ticularly useful non-ionic detergent is that obtained by condensing one mole of tall oil with 5-15 moles of' Staphylococcus aureus, that they are effective against the other gram positive bacteria which break down perspiration into odoriferous products.

The germicides .of this invention may also be applied 7 to surfaces. This'can be done in the form of a solution in dimtehylformamide containing 0.01 to 1.0% on the Weight of the germicide. In addition, more concentrated solutions may be added to cleaning materials, floor waxes and the like to give a final concentration of 0.01 to 1.0%

germicide for application to a surface. Such an application produces a surface which is durably germicidali This invention can be illustrated by the following examples in which parts are by weight unless otherwise specified.

' EXAMPLE 1 3,3-dich[oro-N-hydroxycarbanilide To a solution of 3.59 parts' of N-(3-chlorophenyD- hydroxylamine in parts of chloroform are added 3.84 parts of 3-chlorophenyl isocyanate. is stirred for two hours at room temperature and their the precipitate is filtered off. After drying in vacuo, the; product is purified by crystallization from aqueous metharsuil. The almost white crystals melt at about 150 1 C. e r

These non-ionic detergents are well known 7 {c.g. US. 1,970,578 and US. 2,213,477) and may be A par- Thefresulting slurry" This compound shows more than .a three fold increase in activity by standard agar dilution procedures as compared with the non-N-hydroxylated analog, against Staph. aureus. It shows a correspondingly greater activity when padded from a dimethylformamide solution onto cotton against Staph. aureus and E. coli.

EXAMPLE 2 3',5'-dichloro-N-hydroxycarbanilide A solution of 9.40 g. of 3,5-dichlorophenyl isocyanate in 150 parts of chloroform is added to a solution of 5.46 parts of N-phenylhydroxylamine in 300 parts of chloroform. The resulting slurry is stirred at room temperature for two hours. The precipitate is filtered ofi, dried at room temperature and recrystallized from benzene to give a white product melting at about l51-152 C.

EXAMPLE 3 3-triflu0r0methyl- ',4'-dichl0r0N-hydroxycarbanilide C Fe To a solution of 14.23 parts of 3-(trifluoromethyl)- nitrobenzene in 65 parts of ethanol is added a solution of 1.6 parts of ammonium chloride in parts of water. While stirring at the reflux temperature, zinc dust is slowly added (about 28 parts) until the reaction mixture becomes colorless. After the reaction mixture has been cooled and the reaction vessel flushed with nitrogen, 90 parts of benzene are added, and the reaction mixture is well stirred. The benzene containing the reaction product, namely N-[3-(trifiuoromethyD-phenyl]hydroxylamine, is separated and dried with anhydrous sodium sulfate.

The above solution of N-[3-(trifluoromethyl)-phenyl] hydroxylamine in benzene is added to a solution of 6.6 parts of 3,4 dichlorophenyl isocyanate in parts of benzene. After stirring at room temperature for two hours, the benzene is removed by distillation in vacuo. The residue is slurried with chloroform and filtered to obtain the product which, after crystallization from aqueous methanol, appears as almost white crystals melting at about 148-l49 C.

The product shows high activity against Staph. aureas and E. coli when padded onto cotton (1% on the weight of the fabric) from a solution in dimethylformamide (DMF). The non-hydroxylated analog shows no sigriificant activity under the same conditions.

EXAMPLE 4 3,3',4,4 tetrachloro-N-hydroxycarbonilide The solution of N-(3,4-dichlorophenyl)hydroxylamine in benzene is added to a solution of 8.45 parts of 3,4- dichlorophenyl isocyanate in 40 parts of benzene. After stirring the reaction mixture at room temperature for two hours, the benzene is removed under vacuo and the a residue slurried with chloroform. The product obtained by filtration, and recrystallized from aqueous methanol, melts at about -141 C. with decomposition.

The above product prepared by the procedure of Ex ample 4 using the corresponding phenyl isocyanate and N-phenylhydr oxylamine and when tested by the conventional agar dilution method against Staph. aurea's shows more than seven times the activity of the non-hydroxylated derivative tested by the same method.

Example 6 The above product prepared by the procedure of Example 2 using the corresponding phenyl isocyanate and N-phenylhydroxylarnine and when tested by the conventional agar dilution method against Staph. aureus shows more than four times the activity of the non-hydroxylated derivative tested by the same method.

EXAMPLE 7 C F Cl I on Fab (a non-ionic detergent) on the weight of the fabric.

This compound is extremely active against S. aureas in the agar dilution test.

EXAMPLE 8 This product prepared by the reaction of 3-chlorophenyl isocyanate and N-(3,5 dichlorophenyl)hydroxylamine, prepared from 3,5-dichloronitrobenzene under the conditions of Example 4, having a melting point of about 179 C. when padded onto cotton (1% on the weight of the fabric) from a solution in DMF shows good activity against E. coli as compared to the non-N-hydroxylated analog which has negligible activity under the same conditions.

This product prepared by the reaction of p-chlorophenyl isocyanate and N-(3,4,5-trichlorophenyl)hydroxylamine, prepared from 3,4,5-trichloronitrobenzene under the conditions of Example 4, having a melting point of 198 C. shows good activity against Staph. am'eus in the 'agar dilution method and against Staph. aureus and E.

coli when applied to cotton by both the padding and exhaustion procedures as described hereinbefore.

EXAMPLE 10 This product prepared by the reaction of 3,4-dich1orophenyl isocyanate and N-'(p-chlorophenyl)hydroxylamine by the reaction shown in Example 2 has a melting point of about 150-151 C. and is active against Staph. aureus and E. coli when applied to textiles and against Staph. aureus in the agar dilution test.

EXAMPLE 11 C1 G1 (1711 I This product prepared by the reaction of 3,5-dichlorophenyl isocyanate and N-(3,5-dich1orophenyl)hydroxylamine having a melting point of 184 C. is highly active against Staph. aureus and E. coli.

EXAMPLE 12 EXAMPLE 13 7 0 H -r Q C1 This compound prepared by the reaction of S-(trifluorornethyDphenyl isocyanate with N-(p-chloropheny1)- hydroxylamine under the conditions of Example 2 having a melting point of about 125 C. when padded onto cotton (1% on the weight of the fabric) from a solution in DMF shows high activity against Staph. aureus as compared to the corresponding non-hydroxylated compound whichv shows a negligible activity under the same conditions.

EXAMPLE 14 C1 G1 I I V V A ,7 I 7 C1 Cl This product prepared by the reaction of 3,4,5-trich1orophenyl isocyanate with N-(3,4,5-trichlorophenyl)hydroxylamine prepared from 3,4,S-trichloronitrobenzene underthe conditions of Example 4, having a melting'point of about ZOO-210 C. is active against Staph. aureus when exhaust dyed onto cottonfrom both 0.1% and O.5% (on 8 weight of the fabric) aqueous solutions containing a nonionic detergent.

1 EXAMPLE 15 I .i 0 V V 01 This product prepared by the reaction of 3,4,5-trichlorophenyl isocyanate and N-[3-(trifiuoromethyl)phenyl]hydroxylamine, prepared from 3-(trifluoromethyl)nitrobenzene under the reaction conditions of Example 4, having a melting point of about 170172 C. shows good activity against Staph. aureus. 7'

EXAMPLE 16 I OH This product prepared by the reaction of p-bromophenyl isocyanate with N- (3,5-dich 1orophenyl)hydroxylamine, prepared from3,5-dichloronitrobenzene under the conditions of Example 4, having a melting point of 18ll82 7 C. is activeagainst Staph. aureau and E. coli in the cotton padding test hereinbefore described.

EXAMPLE 17 This product prepared by the reaction of 3-nitrophenyl V isocyanate and N (3 ,5 -dichlorophenyl) hydroxylamine,

' prepared from 3,5-dichloronitrobenzene underthe reaction conditions of Example4, having a melting point of about 189 C. shows activity. against Staph. aureus and E. coli when padded onto cotton fabric (1% on the.

weight of the fabric) from a-solution in DMF.

A corresponding p-nitro isomer having a melting point of l82l83 C. is highly active against Stap' h. aureus in the agar dilution test. 7

EXAMPLE 18 Cl OH This product prepared by the reaction of p-methoxyphenyl isocyanate and N-(3,5-dichlorophenyl)hydroxylamine, prepared from 3,5-dichloronitrobenzene by the procedure of Example 4, having a melting point of 170 171 C. is active against Staphaureus in the cotton padding test.

The product prepared from the corresponding p-methylphenyl isocyanate having a melting point of C. is

likewise an active germicide under the same test conditions.

EXAMPLE 19 0 F3 7 01 I (1311 l The carbanilide of the above formula from 3-(trifiuoromethyl)-4-bromophenyl isocyanate and N(3,4-dichlorophenyl)hydroxylamiue prepared from 3,4-dich1oronitrobenzene by the procedure of Example 4, having a melting point of about 167 C. shows greater activity than the corresponding non-hydroxylated analog against Staph. aureus when padded onto the fabric.

EXAMPLE 20 C F 3 C I I (l) H i Q I O C F a C1 This product prepared by the reaction of 3,5-bis(trifiuoromethyl)phenyl isocyanate and N-(3,5-dichlorophenyhhydroxylamine prepared from 3,5-dich1oronitrobenzene under the reaction conditions of Example 4, having a melting point of about 188-189 C. shows more than a 15 fold increase in activity against StapIh. aureus in the agar dilution test as compared to the corresponding nonhydroxylated analog.

EXAMPLE 21 This product obtained by the reaction of 3-(trifluoromethyl)-4-chlorophenyl isocyanate with N-[3-(trifluoromethyl)phenylJhydroxylamine prepared from 3-(trifluoromethy1)nitrobenzene by the reaction of Example 4, having a melting point of 147148 C. shows good activity against Staph. aureus and E. 0012' when padded onto cotton fabric (1% on the weight of the fabric) from a solution in DMF.

EXAMPLE 22 This product obtained by the reaction of 3-(trifluoromethyl)-4-chlorophenyl isocyanate with N-(3,4-dichloropheny1)hydroxylamine, prepared from 3,4-dichloronitrobenzene by the reaction in Example 4, having a melting point of 161162 C. shows very good activity against E. coli when padded on cotton fabric as compared with negligible activity by the corresponding compound without the hydroxyl group.

EXAMPLE 23 C F; G1

This product obtained by the reaction of 3-(trifluoromethyD-4-bromophenyl isocyan-ate with N-(3,4,5-trichlorophenyl)hydroxylamine, prepared from 3,4,5-trichloronitrobenzene by the reaction of Example 4, having a melting point of C. shows excellent activity in agar against Staph. aureus.

EXAMPLE 25 I OH HQ This product obtained by the reaction of 2,3-dichl'orophenyl isocyana-te with N(3-chlorophenyl)hydroxylamine underthe reaction conditions of Example 2 having a melting point of l61l62 C. is active against Staph. aureus when padded on cotton and in the agar dilution test as compared with insignificant activity against Staph. aureus of the non-hydroxylated analog.

EXAMPLE 26 C1 C1 I I This derivative obtained by the reaction of 2,5-dichlorophenyl isocyanate with N-(3-chl-orophenyl)hydroxylamine, having amelting point of 158-159 0., as compared with the non-hydroxylated analog shows good activity in the agar dilution test and when padded onto cotton fabric.

EXAMPLE 27 Cl OH:

I OH

This derivative obtained by the reaction under the conditions of Example 2 of 3,4-dichlorophenyl isocyanate with N-(2-methyl-3-chlorophenyl)hydroxylamine having a melting point of 179 C. shows good activity against Staph. aureus when padded :onto cotton fabric.

EXAMPLE 28 or 0 r (Ina !T his derivative prepared by the reaction of Z-(trifiuoromethyl)phenyl isocyanate with N-[3-(-trifiuoromethyl)- phenylJhydroxylamine prepared from 3-(trifluoromethyl) nitrobenzene by the procedure of Example 4, having a melting point of about 127 C. shows very good activity against E. coli when padded on cotton as compared to insignificant activity of non-hydroxylated analog. It also shows three times the activity of the non-hydroxylated derivative in the agar dilution test against Staph. aureus.

The product obtained by the reaction of 3,5-dichlorophenyl isocyanate with N-(4-iodop-henyl)hydroxylamine under the reaction conditions of Example 2 is active against Staph. aureus.

EXAMPLE 30 CCIa The product obtained by the reaction of 3,5-dichloro phenyl isocyan-ate with N-[3-(trichloromethy1)phenyl]- 1 1 hydr oxy-lamine by the reaction conditions of Example 4 is active against Staph. aureus.

EXAMPLE 31 Cl 7 Cl This derivative obtained by the reaction of 3,4-dichlorophenyl isocyanate with N-(3,5-diohlorophenyl)hydroxyl- "amine, prepared'from 3,5-dich1oronitrobenzene under the conditions of Example 4, shows good activity against Staph. aurezis when padded on cotton fabric.

EXAMPLE 32 This derivative obtained by the reaction of 3,4,5-trichlorophenyl isocyanate with N-(3,5-dichlorophenyl)- 'hydroXyla-mine, prepared from 3,5-dichloronitrobenzene under the conditions of Example 4, shows excellent activity against Staph. aureus in the agar dilution test.

EXAMPLE 3 3 F 3 C l I O H -Q This derivative obtained by the reactionof 3-(trifiuoromethyDphenyl :isocyanate with N-(-3,5-dich1oropheny1)- hydroxylam-ine, prepared from 3,5-dich1oronitrobenzene under the conditions of Example 4, shows very good activity against Staph. aureus when padded on cotton fabric.

We claim: V

' 1. An N-hydroxy carbanilide wherein the non-hy- V droxylated nitrogen atom is unsubstituted and the phenyl moieties of the carbanilide are substituted by m halo and n trihalomethyl groups wherein m is an integer less than eleven and n is an integer less than five and 1 2 the total of m than eleven wherein the halo groups have an atomic number less than 54 and the remaining valences of the phenyl moieties are satisfied by members selected from the group consisting of hydrogen, nit-r0,- lower alkyl and lower alkoxy.

2. The compound of the formula 3. The compound of the formula Cl 7 01 I I H 4. The compound of the vformula GFs C1 References Cited by the Examiner UNITED STATES PATENTS OTHER REFERENCES 7 Seheiber: J. Prakt. Chem., vol. 78, (1909), pages 74- 9.

NICHOLAS s. RIZZO, Primary Examiner. J. GREENWALD, WALTER A. MODANCE, Examiners,

and n is greater than one and less UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3,189,645 June 15, 1D65 Peggy Pamela Hoffman et al.

It is hereby certified that error appears in the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.

Column 4, line 52, for "dimtehylformamide" read dimethylformamide column 8, line 27, for "aureau", in italics, read aureus in italics; column 9 llnes 50 to 55, the formula should appear as shown below instead of as in the patent:

(1P im 1 BTQNH-fi-N same column 9,

lines 66 to 71, shown below ins the formula should appear as tead of as in th e patent:

CB5 w 1 OH BrQNII-fl-IL c1 column 10, lines 30 to 35,

the formula should appear as shown below instead of as in the patent:

column 12, lines 8 to 14, the formula should appear as shown below instead of as in the patent:

same column 12, lines 15 to 20, the formula should appear as shown below instead of as in the patent:

Signed and sealed this 16th day of November 1965.

(SEAL) attest:

ERNEST W. SWIDER EDWARD J. BRENNER Attesting Officer Commissioner of Patents

Claims (1)

1. AN N-HYDROXY CARBANILIDE WHEREIN THE NON-HYDROXYLATED NITROGEN ATOM IS UNSUBSTITUTED AND THE PHENYL MOIETIES OF THE CARBANILIDE ARE SUBSTITUTED BY "M" HALO AND "N" TRIHALOMETHYL GROUPS WHEREIN "M" IS AN INTEGER LESS THAN ELEVEN AND "N" IS AN INTEGER LESS THAN FIVE AND THE TOTAL OF "M" AND "N" IS GREATER THAN ONE AND LESS THAN ELEVEN WHEREIN THE HALO GROUPS HAVE AN ATOMIC NUMBER LESS THAN 54 AND THE REMAINING VALENCES OF THE PHENYL MOIETIES ARE SATISFIED BY MEMBERS SELECTED FROM THE GROUP CONSISTING OF HYDROGEN, NITRO, LOWER ALKYL AND LOWER ALKOXY.