US3707477A - 1,1,1-trichloro-2-amido-2-amino-ethanes - Google Patents

Abstract

COMPOUNDS OF THE FORMULA

R1-CO-NH-CH(-R2)-CCL3

WHEREIN

R1 IS HYDROGEN; ALKYL OF 1 TO 17 CARBON ATOMS; MONO-, DI- OR TRI-HALO-SUBSTITUTED ALKYL OF 1 TO 17 CARBON ATOMS; ALKENYL OF 2 TO 17 CARBON ATOMS; ALKOXY OF 1 TO 2 CARBON ATOMS; PHENYL; 2,4-DICHLOROPHENOXYMETHYL; OR A-(2,4-DICHLOROPHENOXY)-ETHYL; AND R2 IS DISUBSTITUTED ACYCLIC AMINO OR OPTIONALLY SUBSTITUTED MONOCYCLIC OR BICYCLIC HETEROCYCLIC AMINO;

THE COMPOUNDS ARE USEFUL AS CONTACT OR SYSTEMIC BIOCIDAL OR BIOSTATIC AGENTS, ESPECIALLY AGAINST MILDEW AND VARIOUS OTHER FUNGI.

Description

United States Patent 3,707,477 1,1,l-TRICHLORO-Z-AMIDO-2-AMlN0-ETHANES Walter 0st, Klaus Thomas, and Dietrich Jerchel, Ingelheim am Rhein, Germany, assignors to C. H. Boeh- 5 ringer Sohn, Ingelheim am Rhein, Germany No Drawing. Filed Sept. 10, 1970, Ser. No. 71,262 Claims priority, application Germany, Sept. 11, 1969, P 19 46 112.2 Int. Cl. C07d 49/18, 49/36 US. Cl. 260309 2 Claims 10 ABSTRACT OF THE DISCLOSURE Compounds of the formula 0 Rr lNHCH-Rz wh re'n R is hydrogen; alkyl of 1 to 17 carbon atoms; mono-, dior tri-halo-substituted alkyl of 1 to 17 carbon atoms; alkenyl of 2 to 17 carbon atoms; alkoxy of 1 to 2 carbon atoms; phenyl; 2,4-dichlorophenoxymethyl; or a-(2,4-dichlorophenoxy)-ethyl; and

R is disubstituted acyclic amino or optionally substituted monocyclic or bicyclic heterocyclic amino;

the compounds are useful as contact or systemic biocidal or biostatic agents, especially against mildew and various other fungi.

This invention relates to novel 1,1,1-trichloro-2-amido- 2-amino-ethanes, as well as to methods of preparing these compounds.

More particularly, the present invention relates to compounds of the formula wherein R is hydrogen; alkyl of 1 to 17 carbon atoms; mono-, dior tri-halo-substituted alkyl of I to 17 carbon atoms; alkenyl of 2 to 17 carbon atoms; alkoxy of 1 to 2 carbon atoms; phenyl; 2,4-dichlorophenoxy-methyl; or a-(2,4-dichlorophenoxy)-ethyl; and

R2 is where R is allyl, cyclohexyl, 2-propinyl, l-methyl-Z-propinyl or 2-cyano-ethyl, and

R is alkyl of 1 to 4 carbon atoms, allyl or 2-cyanoethyl;

where R is where R, is hydrogen, halogen, thiocyano, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms,

Patented Dec. 26. 1972 "ice alkylthio of 1 to 4 carbon atoms, alkylsulfoxide of 1 to 4 carbon atoms, alkylsulfonyl of l to 4 carbon atoms or COOR where R is hydrogen or alkyl of 1 to 4 carbon atoms;

R is hydrogen, halogen, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms; and

R is hydrogen, halogen or alkyl of 1 to 4 carbon atoms,

and R is alkyl of 1 to 4 carbon atoms, hydroxy-alkyl of 1 to 4 carbon atoms, cyano-alkyl of 1 to 4 carbon atoms, allyl, 2-propinyl, benzyl or cyano;

(c) -N l)n where n is 2, 4 or 6; a CHE-0H (llz cHl CH: H! CH2'CH where R is methyl or phenyl;

where R14, R and R16 which may be identical to or different from each other, are each hydrogen or alkyl of 1 to 3 carbon atoms;

where R is hydrogen or alkyl of 1 to 17 carbon atoms;

where R is hydrogen, methyl, phenyl, monochlorophenyl, pentachloro-phenyl, nitroso, cyano, p-hydroxy-ethyl,

R is hydrogen; phenyl; monohalo-phenyl, dihalophenyl, allyl, alkyl of 1 to 4 carbon atoms, or benzyl;

R is hydrogen, methyl or ethyl;

R and R are methyl or ethyl, and

nis2or3;

The compounds embraced by Formula I above may be prepared by various methods involving well known chemical principles, among which the following are particularly preferred.

By reacting a 1,I,1-trichloro-2-amido-ethane of the formula wherein R; has the same meanings as in Formula I and R is a substituent which can be readily split off as an anion, preferably bromine or chlorine, with a secondary amine of the formula Rg-H (HI) wherein R, has the same meanings as in Formula I. The reaction is advantageously performed in the presence of an acid acceptor, preferably a tertiary aliphatic amine, such as triethylamine. If the amine of the Formula III is a relatively strong base, a commensurate excess over the stoichiometric amount required for reaction with compound II may serve as the acid acceptor. The reaction is advantageously also performed in the presence of an inert organic solvent, such as acetone, ether, tetrahydrofuran, methylene chloride, dimethylformamide or a lower alkanol.

A compound of the Formula I wherein R is a piperazino substituent of the formula shown under (1) above, may also be prepared by reacting a piperazine of the formula (I wherein R has the same meanings as in Formula I, with a 1,1,1-trichloro-2-amido-ethane of the Formula II as previously described, or also by converting a 1,1,l-trichloro-2-amido-2-piperazino-ethane of the formula 001: wherein R has the same meanings as in Formula I, into a 1,1,l-trichloro-2-amido-2-(N'-substituted piperazino)-ethane of the formula ll R1-C-NHOHN 4701; by reaction with the desired reaction partner, such as HN0 acylating agent, isocyanate, etc.

The starting compounds of the Formula V or their salts may be prepared by reacting a 1,1,1-trichloro-2- amide-ethane of the Formula II with piperazine within a very definite pH-range. If the reaction is carried out at a pH above the optimum value, symmetrical di-substitution products of the formula 0 o Rr-ii-NH-CH-N N-CH-HN-ii-Rr are formed. On the other hand, at a pH below the optimum value no reaction at all takes place. Thus, the compounds of the Formula V and their salts may be used as starting materials for a variety of asymmetrically substituted piperazine derivatives and are therefore useful as intermediates for the preparation of biocidal and biostatic agents.

Compounds of the Formula I wherein R is a morpholino substituent of the formula shown under (e) may be prepared by reacting a morpholine of the formula u (VII) wherein R has the same meanings as in Formula I, with a compound of the Formula II in the presence of an acid acceptor; or also by reacting a bis-(fl-chloro-ethyD-ether of the formula l n Cl-GHr-CE 0 (ll-CHs-Cfi 11 (VIII) wherein R has the same meanings as in Formula I, with a 1,1,1-trichloro-2-amido-2-amino ethane of the formula Rr-(ii-NH-OH-NH:

wherein R; has the same meanings as in Formula I.

The following examples further illustrate the present invention and will enable others skilled in the art to undertsand it more completely. It should be understood, however, that the invention is not limited solely to the particular examples given below.

EXAMPLE 1 A solution of 2.5 gm. of N-(1,2,2,2-tetrachloroethyl)- methacrylamide in tetrahydrofuran was added dropwise to a mixture of 1.13 gm. of N-methyl-cyclohexylamine, 1.2 gm. of triethylamine and 25 ml. of tetrahydrofuran,

accompanied by stirring. Thereafter, the reaction mixture was stirred for one hour at room temperature, and then the precipitated triethylamine hydrochloride was separated by vacuum filtration, the filtrate was evaporated in vacuo, and the liquid residue was dissolved in hexane. The resulting solution was treated with activated charcoal, filtered and evaporated in vacuo. The oily, slightly yellow product was dried at 50 C. and 0.5 mm. Hg, yielding the compound of the formula H2O=o-i'JHNoH-N t... to.

Analysis Calculated (percent): C, 47.7; H65; N, 8.6. Found (percent): C, 47.5; H, 6.5; N, 8.3.

EXAMPLE 2 A solution of 6.7 gm. of N-(1,2,2,2-tetrachloroethyl)- pivalic acid amide in tetrahydrofuran was added dropwise at room temperature to a solution of 3 gm. of N-phenylcyanamide in 50 ml. of tetrahyrdrofuran, and then 3 gm. of triethylamine were added while stirring. The resulting mixture was stirred for one hour at room temperature, the precipitated triethylamine hydrochloride was separated by vacuum filtration, the filtrate was evaporated in vacuo, and the semi-solid residue extracted three times with warm hexane. The residual colorless, crystalline substance, M.P. 121-124 C., was identified to be the compound of the formula A solution of 8.4 gm. of N-(1,2,2,2-tetrachloroethyl)- formamide in 40 ml. of tetrahydrofuran was added dropwise to a solution of 7.44 gm. of N-methyl-4-bromo-aniline and 4.2 gm. of triethylamine in 60 ml. of tetrahydrofuran, while stirring. The resulting mixture was stirred for two hours at room temperature, and then the precipitated triethylamine hydrochloride was separated by vacuum filtration, the filtrate was evaporated in vacuo, and the residue was crystallized by digestion with hexane. The crystalline raw product was recrystallized from methanol, yielding the compound, M.P. 130-131 C., of the formula A solution of 5 gm. of N-propargyl-3,4-dichloroaniline and 2.6 gm. of triethylamine in 30 ml. of tetrahydrofuran was added dropwise at room temperature to a solution of 7.2 gm. of N-(1,2,2,(Z-tetrachloro-ethyl)-benzamide in 50 ml. of tetrahydrofuran, accompanied by stirirng. The resulting mixture was stirred at room temperature for one hour more, the tetrahydrofuran was then distilled off in vacuo, and the solid residue was recrystallized from benzene, yielding the colorless crystalline compound, M.P. 122-124 C., of the formula 0 CHz-CECH (a) A solution of 10.5 gm. of N-.(1,2,2,2-tetrachloroethyl)-formamide in 30 ml. of ethylacetate was added dropwise to a mixture of 3.4 gm. of imidazole, 5 gm. of triethylamine and 50 ml. of ethylacetate, accompanied by stirring. The resulting mixture was stirred for two hours 6 at room temperature, and then the precipitated triethylamine hydrochloride was filtered off, and the filtrate was evaporated in vacuo. The oily residue was caused to crystallize by treatment with warm benzene, and the crystalline raw product was recrystallized from benzene, yielding the compound, M.P. 101-103" C., of the formula (b) A solution of 10.5 gm. of N-(l,2,2,2-tetrachloroethyl)-formamide in 50 ml. of methyl ethyl ketone was added dropwise to a solution of 3.4 gm. of imidazole in 50 ml. of methyl ethyl ketone, whereby a crystalline precipitate was immediately formed which was collected by vacuum filtration, extracted with warm acetonitrile, and dried at 40 C. A finely crystalline, colorless, readily watersoluble substance, M.P. 210 C. (decomp.), was obtained which was identified to be N [(1 formamido-2,2,2-trichloro)-ethyl]-imidazole hydrochloride.

EXAMPLE 6 A solution of 6.5 gm. of N-(l,2,2,2-tetrachloroethyl)- chlorocetamide in 25 ml. of tetrahydrofuran was added dropwise at room temperature to a mixture of 3 gm. of

benzotriazole, 2.6 gm. of triethylamine and 25 ml. of

ll C1-CHa-C-HN-CH-N EXAMPLE 7 A solution of 34.4 gm. of piperazine in 220 ml. of water was adjusted to a pH of 4.0 by addition of 2 N hydrochloric acid (about 500 ml. of HCl were required). While vigorously stirring the acidic solution, a solution of 84 gm. of N-(1,2,2,2-tetrachloro-ethyl)formamide in 200 ml. of acetone and an aqueous concentrated solution of gm. of sodium acetate were simultaneously added; the rate of addition of the sodium acetate solution was metered in such a way that the pH of the mixture remained at 40:0.1. Thereafter, the mixture was stirred for fifteen minutes more at room temperature, then the small amount of precipitated N,N bis (l formamido- 2,2,2-trichloro-ethyl)piperazine was filtered off, and the filtrate was admixed with 200 ml. of aqueous 20% sodium hydroxide while cooling to 50 C. Subsequently, 200 ml. of methylene chloride were added, and the aqueous phase was separated and saturated with potassium carbonate. A colorless, crystalline precipitate was formed which was collected by vacuum filtration and recrystallized from acetone, yielding the water-soluble free base, M.P. 122-123 C., of the formula 0 H--HN-CH-N 7 EXAMPLE 8 5.6 gm. of powdered N-(o-chloro-phenyl)-piperazine monohydrochloride monohydrate were suspended in a mixture of 50 ml. of tetrahydrofuran and 5.1 gm. of triethylamine, and then, while stirring, a solution of 5.3 gm. of N-( l,2,2,2 tetrachloro-ethyl) formamide was added dropwise at room temperature. The resulting mixture was stirred at room temperature for two hours more and then for one hour at 65 C., the precipitated triethylamine hydrochloride was separated by vacuum filtration, the filtrate was evaporated in vacuo, and the residue was made to crystallize by treatment with ethanol. The crystalline raw product was recrystallized from ethanol/ water, yielding the compound, M.P. 153-155 C., of the formula EXAMPLE 9 A solution of 1.4 gm. of potassium cyanide in 15 ml. of water was added'dropwise to a vigorously stirred mixture of 3.2 gm. of bromine and 40 ml. of water. After disappearance of the bromine color, 5.2 gm. of N-(lformamido-Z,2,2-trichloro-ethyl)-piperazine were added in several small portions to the bromocyan solution. Thereafter, 2.06 gm. of sodium carbonate were added, and the mixture was stirred for two hours at room temperature. The precipitate formed thereby was collected by vacuum filtration, dried at room temperature and dissolved in chloroform, and the solution was admixed dropwise with ether, yielding the colorless crystalline compound, M.P. 109-110 C. of the formula While vigorously stirring a solution of 2.6 gm. of N-( 1- formamido-Z,2,2-trichloro-ethyl)-piperazine in 20 ml. of tetrahydrofuran at 50 C., first a solution of 0.76 gm. of carbon disulfide in 10 ml. of tetrahydrofuran and then ml. of 2 N sodium hydroxide were added dropwise thereto, and the mixture was stirred for one hour at room temperature. Thereafter, the tetrahydrofuran was distilled off in vacuo on a water bath at 40 C., the residue was stirred with isopropyl ether, the mixture was vacuum-filtered, and the filter cake was dried at room temperature, yielding the yellowish crystalline sodium dithiocarbamate of the formula EXAMPLE 11 A solution of 3.2 gm. of triethylamine in 25 ml. of tetrahydrofuran was added dropwise to a solution of 3.4 gm. of N-formyl-piperazine and 6.3 gm. of N-(1,2,2,2- tetrachloroethyl)-formamide in 75 ml. of tetrahydrofuran, while stirring. The resulting mixture was stirred for 8 two hours more at room temperature, the precipitated triethylamine hydrochloride was vacuum-filtered off, and the tetrahydrofuran was distilled out of the filtrate in vacuo. The residual raw product was recrystallized from ethanol, yielding the compound, M.P. 98-101 C., of the formula 0 o rr-tLrm-cn-N N(UJH EXAMPLE 12 1.22 gm. of acetic acid anhydride were added to a solution of 3.9 gm. of N-(1-formamido-2,2,2-trichloro-ethyl)- piperazine in 10 ml. of tetrahydrofuran, and the mixture was heated at its boiling point for two hours. Thereafter, the reaction mixture was allowed to cool, poured over ice, and the precipitated semi-solid product was extracted with five l5 mL-portions of methylene chloride. The combined extract solutions were dried over sodium sulfate and then evaporated, and the residue was recrystallized from isopropanol/hexane, yielding the compound, M.P. 149-150" C., of the formula 0 H--HN-CH-N N-iIL-CH;

EXAMPLE 13 17.2 gm. of piperazine were dissolved in water, and pH of the resulting solution was adjusted to 2.0 by addition of 2 N hydrochloric acid. While vigorously stirring the acidic solution, 42 gm. of powdered N-(1,2,2,2-tetrachloro-ethyl)-formamide were added in small portions, and simultaneously a concentrated aqueous sodium acetate solution was added at a rate such that the pH was maintained at 201-01. Thereafter, the acidic reaction solution was carefully saturated with potassium carbonate. The oil precipitated thereby was taken up in ethanol, and the resulting solution was allowed to stand for 12 hours at room temperature. The small amount of precipitated N,N'-bis-(1-formamido 2,2,2 trichloro ethyl)-piperazine was filtered off, the ethanol was distilled out of the filtrate, and the semisolid residue was recrystallized from ethanol/water, yielding the compound, M.P. 7780 C.,

of the formula 0 H HN CHN NCOOH 001, The product was insoluble in dilute alkalis.

EXAMPLE 14 A solution of 1.6 gm. of tetrahydrofurfuryl chloroformate in 20 ml. of methyl ethyl ketone was added dropwise to a solution of 2.6 gm. of N-(l-formamido- 2,2,2-trichloroethyl)-piperazine and 1.1 gm. of triethylamine in. 30 ml. of methyl ethyl ketone, while stirring. The resulting mixture was heated at its boiling point for ten minutes, then cooled and poured into ice water. The oil which precipitated out was extracted with benzene, and the extract solution was washed with water, dried with sodium sulfate and evaporated in vacuo. The oily residue crystallized upon stirring with hexane, yielding the compound, M.P. 72-75 C., of the formula c or,

EXAMPLE 15 2.6 gm. of N-(1-formamido-2,2,2-trichloro-ethyl)-piperazine were dissolved in 5 ml. of 2 N hydrochloric acid, the solution was cooled to 5 C., and then a solution of 0.97 gm. of potassium cyanate in 20 ml. of water was 0.71 ml. of methyl isocyanate were added to a solution of 2.6 gm. of N-(1-formamido-2,2,2-trichloro-ethyl)- piperazine in 10 ml. of absolute tetrahydrofuran, and the TABLE I 10 resulting mixture was allowed to stand at room temperature for 18 hours. Thereafter, the tetrahydrofuran was distilled off in vacuo, and the solid residue was recrystallized from isopropanol/hexane, yielding the compound, M.P. 166-167 C. (decomp.), of the formula Using procedures analogous to those described in Examples 1-16 and correspondingly substituted starting compounds, the compounds listed in the following tables were also prepared:

Example Melting point in 0. Number R2 (recrystallized from) Remarks 17 (CHz=CH-CH2)2N- Brownish, viscous oil.

18 (i311; 105 (hexane) 19 CH3 CH3 Yellowish wax.

H=CCH-N 20 CH3 85417 (benzene) NC-CHz-CHz-lh- 21 (NCCH2CH2)2N 125-127 (ethanol/water) 22 CH3 87-88 (ethylacetate/hexane) CeHlN 23 01H; 118-119 (lsopropanol) (kHz- 24 CH(CH;); 165-167 (ethanol) Decomposition.

CaHsN- 25 D-ClHo 84-85 (methanol/water) Calls- 26 CHr-CHz-OH Colorless oil. Analysis (percent)- CM. 27 cm-onz-cN 154-155 (methanol) CH5N 28 CHz-CsHs 108-109 (benzene) CQ 5N' Ca s- 31 CH; 129-132 (lsopropyl ether) 32 OH; 124-126 (benzene/hexane) 33 CH: Approx, (isopropanol) Crystallizes as a solvate with 1 mol 0! 1; lsopropanol.

C O 0 H 34 CaHl TABLE I-Continuecl O H- -HNCHR2 Example Melting point in 0. Number R: (recrystallized from) Remarks ?Hr-CH(CH3): 173-174 (lsopropanol) 38 (FE-Clzh-CN 158-159 (isopropanol) 37 (I3H-CH1CN 135-136 (isopropanol) 38 (|3H|CH=CH; 117-119 (methanol/water) 39 (IIHr-CECH -93 (benzene/hexane) 40 CE\I 104-108 (diethylether) 41 f' 1 1 Light-brown wax.

42 /CH--CH -107 (hexane) 7 7 CE: /CH| 4 CHC z 43 CH: 95-97 (isopropylether) 45 T 142-144 (ethylacetatelhexane) (12 46 Ii -142 (methylenechloride/hexane)-- n-CaH1 47 i 183 [decomposition] (lsopropanol) 48 -189 IdecompJ l CIHI 49.-. CH; 148[decomp.1

TABLE II CH3-C NH(I)HR,

C Cl:

Me lting point Ex. (recrystallized N o. R; from) Remarks I (ethanol/ Brwater).

85-.." CH2 CH(CH3)2 140-143 I (benzene). Cl N- C1 N- (methanol! I water C 2 Cl (6H I C I 87.." HC C-CH2N 163-165 (benzene) I Cl (ethylace- /N tote/hexane CH /Cg-CH2 1123 119 exane 7 7 N Cg: CH2/ 0 HCH:

90.... CH: 139-141 After boiling With 7 N- ether.

I (ethanol/ water).

I (ethanol! water).

I OH;

93--.. CH;;- 150 After boillng with 180- N N- p wl ether.

I CH:

I! (ethanol/ N N water).

I n-CnHza 96- N\ 214-216 (130)- propanol CHa-N N- ON-N N- TABLE III F CH;C ONH-CHR,

C Cla Melting Point in C. (recrys- Ex. tallized N o. R: from) Remarks 99.... CH;=CHCH1 Light yellow oil, Analysis (percent)Calc.

N- 0,139.6; H, 4.7; N, 9.3. Found: C, 38.4; H, 4.7; CHz=CH-CH; N, 9.

(isopro- N panol).

v101... Slightly yellow, viscous oil. Analysis (percent)- N 02110.: C 37.9; H, 4.2;

N, l3.3. ound: C, 38 2, H, 4.4; N, 13 5 n-CaH1 I (isopto- N panel).

103.- N 117 After boiling with hexane. I

TABLE IV ClCH;C O-NH-CHR Melting point in Ex. C. (recrystal- N o. R; lized from) Remarks 104-. CH;=CHCH= Slightly greenish /N oil. CHz=CHCHg 105..- CHg-CH3OH Almost l colorless oil.

I CN 107-.- I 136-138 (benzene)! NC S N I CH3 I 108 HCEC-CH2N- 112-114 (benzene! hexane).

I C1 109 CH 144-145 (ethylacetate/hexane) 110.. 108-185 [decomp.]

I ldimethydl I ormaml e ethanol).

111 169-170 (ethanol! I water N\/N- CH3 112 186-188 After CH;4N N- ldecomp.] boiling with hexane.

TABLE V ClCHC O-NH(I3H-R Melting point in Ex. C. (recrystallized No. R; from) Remarks 113-- N 126-128 (benzene).

I CH3 114-. 101-102 (methanol/ (31- Ifwater CH, G1 I i111 CH,

115.. 123-126 (benzene/ I hexane f5 CH3 CH3 117.... Colorless oil,

1(1nalysits') pereen N N Cale; N

8.7, Found: N, 8.5, 11-011 TABLE VI CCh-CO-NH-CH-Rz Melting point in Ex. C. (recrystallized N 0. R: from) Remarks 118... CH1=CHCH 64-56 (methanol! 7,

\ water).

CH|=CH 0Q:

119- CH1 Yellowish oil.

. Analysis HCEC-OH-N- (percent)- calm: 01, OH: 56.8; N, 7.5.

Found: 01, 56.0; 7.4.

120- (OHmOH 170-173 I (isopropanol).

121. 155-158 [decomp.]

N G S If- (ethanol/benzene). CH3

TABLE VII CsHsC O-NHCHR Ex. Melting point in C. N o. R; (recrystallized from) Remarks 123- \N 99-100 (methanol/water)...

124. 1 137-139 (ethanol/water) 125. :1 157-158 (methanol/ water)--- 126. {:1 209-211 (methanollwater)...

127- 107-109 After boiling with hexane.

TABLE VIII s)sCC ONHCHR C Clz Ex. Melting point in C. No. R; (recrystallized from) Remarks 128 0 H C H- 032 53-55 (hexane) C H] C H- 0 H3 (3H 102-103 (ethanol/water).

130- HCEC-OHz-N- 111-113 (benzene) -1 131- 0 Hz 99-100 (hexane) 132... CH; 86-88 (hexane) 134.. GHr-izl 162-164 (benzene) Melting point in Remarks TABLE XI CHz=CH-C O-NH-CH-Rz C. (recrystala lized from) OH; 141-142 (ethanol/ I water). Br-

EC-CH1-N 148-149 (benzene).-

TABLE VIII-Continued Melting point in C. (recrystallized R; from) Remarks 124-126 (hexane). CH3N N0.

148-150. After ONN boiling with hexane.

Ex. No.

S w a m e R G.) m m ma hmm H MM S 1m E e m Mm O A 1 n 0 .H

m Lo EN 105-108 (hexane) 139-141 (ethanol! water) Analysis (percent)-Cale.: CI, 25.0; N, 9.9. Found: Cl, 25.8 N, 9.5.

viscous oil.

I C C13 Melting point in C. (recrystallized) from) Remarks (ethanol/ water).

(benzene).

(banzene).

(ethanol! water).

155-157 (ethanol/ water).

.-...--... Colorless oil.

Light-yellow,

TABLE XII CHz=(i7COCH-CHRa CH-Cfig CHr-CH(CH3)2 126-128 Ex. No.

156-.. CH =OHCHz Remarks viscous oil. Analysis (percent)- Calc: 01, 20.1; N, 5.3. Found: Cl, 19.7; N, 5.2.

111-114 (isopropylether).

TABLE X -C11 :sC 0NH(JHR Melting point in C. (recrystallized from) 65-67 (methanol)- 109-111 (ethylacetate/hexane).

-.-- Light-brown,

148-151 (isopropanol).

Ex. No.

90-91 (hexane) 160..-

\l/ CH TABLE XIV-Continued Melting point in Ex. C, (recrystal N o. R: lized from) Remarks 187-. Colorless oil ONN N Analysis (percent)- Gale: 0, 32.5; H, 4.6; N, 16.9. Found: C, 32.3; H, 4.6; N, 16.6.

188-.- 95-97 (benzene! OHC-N N hexane).

EXAMPLE 189 In like manner, the compound of the formula CH2=CH-CH O a light-yellow oil, was prepared.

Analysis.Calculated (percent): C, 44.5; H, 3.5; N, 6.1; Cl, 38.6. Found (percent): C, 44.2; H, 3.9; N, 6.0; Cl, 38.4.

The compounds according to the present invention, that is, those embraced by Formula I and their acid addition salts, have useful biocidal and biostatic properties. More particularly, the compounds according to the present invention are useful for combatting a broad spectrum of pathogenic fungi and bacteria, such as mildew, Asperfillus, Xanthomonas, Pseudomonas and Fusarium, and for combatting insects and acarids, such as aphids and spider mites.

Especially effective against genuine mildew fungi are those compounds of the Formula I wherein R is hydrogen, and R is a substituents defined under (b), where R-; and R are hydrogen and R is chlorine or bromine, or R is hydrogen and R and R are chlorine or bromine; a substituent defined under (f); the substituent defined under (g); or a substituent defined under (1), where R is preferably hydrogen, methyl, nitroso, cyano, fi-hydroxy-ethyl,

where R R R and R have the meanings previously defined.

Thus, for example, the compounds of Examples 3, 30, 31, 34, 37, 38, 39, 40, 43, 64, 67, 74 and 75 are especially effective as contact fungicides against genuine mildew fungi on plants; the compounds of Examples 12, 44, 49 and 55 are especially effective systemic fungicides against mildew fungi on plants; the compounds of Examples 5, 13, 53, 65, 66 and 72 are effective contact and systemic fungicides against mildew fungi on plants.

The growth of Aspergillus niger is effectively inhibited, for example, by the compounds of Examples 11, 19, 23, 24, 25, 28, 37, 42, 43, 48, 57, 61, 74, 76, 77, 79, 110, 141 and 169.

Effective against F usarium oxysp. are, for example, the compounds of Examples 10, 37, 74, 75, 76, 77 and 79.

Very eeifctive bacteriocides against Pseua'amonas morspruncrum are, for example, the compounds of Examples 57, 71, 74, 77 and 79; against Xanthomonas malv. the compounds of Examples 10, 42, 57, 74, 76, 77 and 79; against Pythz'um ultim. the compounds of Examples 9, 10, 57, 74, 76 and 79; and against Rhizoctonia solani the compounds of Examples 9 and 10.

For the purpose of controlling or combatting the growth of the various microorganisms set forth above, the compounds according to the present invention are applied to areas infested with such microorganisms as active ingredients in conventional liquid or solid compositions, such as dusting powders, suspensions, emulsions, solutions, aerosols and the like. Such compositions may additionally comprise conventional inert auxiliary ingredients, such as emulsifiers, diluents and adhesion-enhancing agents, as well as other biocidal or biostatic ingredients. The effect tive concentration range of the compounds of the instant invention in such compositions is from 0.00001 to 1% by weight, preferably 0.01 to 0.5% by weight, based on the total weight of the composition. Dusting powders and socalled ultra-low-volume (ULV) compositions may have a higher concentration of active ingredient.

The following examples illustrate a few compositions comprising a compound according to the present invention as an active ingredient and represent the best modes contemplated of putting the invention into practical use. The parts are parts by weight unless otherwise specified.

EXAMPLE Dusting powder The powder was compounded from the following ingredients:

Parts 1,1,1-trichloro 2 foramido 2 (N-methyl-N-pbromophenyl-amino)-ethane 1 Talcum 98 Methyl cellulose 1 The ingredients were admixed with each other, and the mixture was milled into a homogeneous powder. The resulting dusting powder was an effective contact fungicide for use on plants infested with genuine mildew.

EXAMPLE 191 Wettable powder The powder was compounded from the following ingredients:

Parts 1,1,1 trichloro 2 formamido 2 (N'-acetylpiperazino)-ethane Kaolin 55 Colloidal silicic acid 10 Lignin sulfonate (dispersing agent) 9 Sodium tetrapropylene-benzene-sulfonate (wetting agent) Emulsion concentrate (a) The concentrate was compounded from the following ingredients:

Parts 1,1,1 trichloro 2 formamido 2 imidazolinoethane Sodium tetrapropylene-benzene-sulfonate (anionic emulsifier) 5 Nonylphenol polyglycol ether (nonionic emulsifier) 20 Propylene glycol 32.5 N-methyl-pyrrolidone 32.5

The ingredients were admixed with each other in conventional fashion to make an emulsion concentrate which, prior to use, was emulsified in a sufiicient amount of water to make the active ingredient conventration in the aqueous emulsion between 0.0001 and 0.5% by weight, based on the total weight. The resulting sprayable aqueous was Parts 1,1,1 trichloro 2 formamido 2 (N-ethoxycarbonylpiperazinoethane 80 Calcium lignin sulfonate 8 Colloidal silicic acid Sodium sulfate 5 Diisobutyl-naphthalene sodium sulfonate 2 EXAMPLE 193 Aerosol spray The aerosol composition was compounded from the following ingredientsz Parts 1,1,1 trichloro 2 formamido 2 (N'-formylpiperazino)-ethane 0.05 Sesame oil 0.10 N-Methyl-pyrrolidone 10.00 Mixture of Frigen 11 and 12 89.85

The trichloroethane compound, the sesame oil and the N- rnethyl-pyrrolidone were admixed with each other, and the mixture'was charged into an aerosol can equipped with an aerosol spray valve. The cans were then pressurized with the propellant gas mixture in conventional manner. The aerosol spray discharged from the pressurized can was an effective fungistatic contact composition for use in inhibiting the growth of Aspergillus niger.

While the present invention has been illustrated with the aid of certain specific embodiments thereof, it will be readily apparent to others skilled in the art that the invention isnot limited to these particular embodiments, and that various changes and modifications may be made without departing from the spirit of the invention or the scope of the appended claims.

We claim:

1. A compound of the formula wherein R is hydrogen; lower alkyl; or monoor di-halo-substituted lower alkyl; R is hydrogen; alkyl of 1 to 3 carbon atoms; nitro; or phenyl; and R is hydrogen; alkyl of l to 3 carbon atoms; or

phenyl. 2. The compound of the formula (:I) HCNHCH--N References Cited UNITED STATES PATENTS 2,888,462 5/1959 Cannon 260310 R 3,140,290 7/1964 Lafon 260309-7 3,253,030 5/1966 Buc 260561 R 3,280,139 10/1966 Klosa 260309 3,520,927 7/1970 Malz et al 260562 R 3,531,494 9/1970 Adolphi et a1. 260309 3,595,916 7/1971 0st et a1. 260--268 R FOREIGN PATENTS 1,006,334 9/ 1965 Great Britain 260309 1,026,631 4/ 1966 Great Britain 260309 1,067,387 5/1967 Great Britain 260309 26,847 11/1969 Japan 260562 R 392,067 3/ 1924 Germany 260309 OTHER REFERENCES 0st et al., 11 Chem. Abst. vol. 72, No. 3053s (1970). Shaffer et al., Chem. Abst. vol. 67, No. 54074d (1967). Shaps et al., Chem. Abst. vol. 70, N0. 3942q (1969). Watanabe et al., Chem. Abst. vol. 72, N0. 31467y (1970).

US. Cl. X.R.

260239 A, 239 B, 239 BA, 242, 247.2 A, 268 R, 268 N, 268 C, 268 'PH, 268 ON, 287 R, 285 AM, 308 B, 308 A, 309.6, 310 R, 310 D, 326.3, 404, 404.5, 454, 465 D, 465.4, 518 R, 558 R, 559 B, 561 R, 561 N, 561 HL, 562 B, 562 R, 562 A; 424245, 248, 250, 258, 263, 269, 273, 274, 302, 304, 309, 320, 324

NATALIE TROUSOF, Primary Examiner