VIII. Amines and salts of quaternary ammonium bases

One of the most important groups of physiologically active compounds, having great significance for the vitality of living organisms, is the amines. The pesticidal properties of various amines and their salts with organic and inorganic acids have been studied.

The maximum activity as a contact insecticide against larvae of the house fly is shown by di-n-octylamine; amines of the aliphatic series with a higher or lower molecular weight have less insecticidal activity. Triamyl­amine, di-(4-ethylnonyl)amine, and di-(3-methylamyl)amine are relatively toxic to lice.

Going from the amines of the aliphatic series to the aromatic ones the toxicity increases. Aniline, for example, is more toxic than hexylamine. Introduction into the aromatic nucleus of halogen atoms or some other substituents does not affect the insecticidal activity of the compound, while the nitro group increases the general toxicity of the compound both to insects and to animals. It has been reported that o-iodoaniline is toxic for caterpillars, and 2,5-dichloroaniline is also toxic for lice.

The diarylamines as a rule have a higher insecticidal activity. Diphenyl­amine was used as an agent to control pediculosis during the Second World War and gave completely satisfactory results as a 20-25% dust. The triaryl­amines also are relatively toxic to insects. In Table XXI the insecticidal activity of primary, secondary, and tertiary amines toward the pea aphid is shown.

Table XXI. Toxicity of aromatic amines to the pea aphid

Amine

Aniline Diphenylamine Triphenylamine

I (,:a~~/I.) I Amine

0.53-1 I Benzylamine 0.03 Dibenzylamine 0.04 , Tribenzylamine

I Leoo • (moles/I.)

0.19 0.Q25 0.07

Amines have not been used to control plant pests because of their phytotoxicity for most plants. Some aromatic amines are so phytocidal that they find use as herbicides. For the control of annual weeds the following amines have been recommended; 2,6-dinitro-4-trifluoromethyl-N,N-dipro­pylaniline (trifluralin), 2,6-dinitro-4-trifluoromethyl-N-butyl-N-ethylani-

83

N. N. Melnikov, Chemistry of Pesticides© Springer-Verlag New York Inc. 1971

84 Chemistry of Pesticides

line (benefin), and 2,6-dinitro-4-methylsulfonyl-N,N-dipropylaniline (ni­tralin).

2,6-Dinitro-4-trifluoromethyl-N,N-dipropylaniline (trifluralin) is a crystalline substance, m.p. 48.5°-49° c., vapor pressure at 29.5° C. 1.99 x 10-4 mm. of Hg; solubility in water 40 p.p.m., acetone 40 g./100 mI., and xylene 58 g./100 ml. Its LDso is 10,000 mg./kg. It is used to control weeds in cotton at dosages of 0.5 to 2 kg./ha. in soil. It is produced in the following way:

C~ C~ C~ ¢I HNOJ. ~ (CJ H7hNH• ~ ::::,... YN02 02NY N02

CI CI H7C3-N-C3H7

2,6-Dinitro-4-trifluoromethyl-N-butyl-N-ethylaniline (benefin) is a crystalline substance, m.p. 65°-66.5° c., vapor pressure 4 x 10-7 mm. of Hg at 25° c.; solubility in water 70 p.p.m., readily soluble in most organic solvents, but having a lower solubility in ethanol. Its LDso is 10,000 mg./kg. Benefin is produced in a similar way to trifluralin.

2,6-Dinitro-4-methylsul/onyl-N,N-dipropylaniline (nitralin) is a crys­talline substance, m.p. 150°-151 ° c., vapor pressure 1.5 x 10-6 mm. of Hg at 25° c.; solubility in water 0.6 p.p.m., acetone 36 g./100 mI., dimethyl­sulfoxide 33 g./100 ml. at 22° C. Its LDso is 2,000 mg./kg. It is prepared in the following way:

¢SCH3 -¢:O'::::-S~~H3 -¢:O'::::-S~~H3 r' I HNOJ• r' I (C3H7h NH.. r' I ::::,... ~N::::,... N02 02N::::,... N02

CI CI H7C3-N-C3H7

Derivatives of 2-phenoxyethylamine, derivatives of benzyl amine, and their salts also show herbicidal activity. Since the derivatives of phenoxy­ethyl amine are more active toward dicotyledonous plants, it has been suggested that they are converted in the plants or in the soil to derivatives of phenoxyacetic acid.

The fungicidal and bactericidal activity of the amines is relatively low, but it increases going from the free amines to their salts with various organic and inorganic acids. The salts of amines containing aliphatic hydro­carbon radicals with not fewer than eight carbon atoms have significant microbiological activity.

The germicidal quaternary ammonium salts also have an insecticidal effect which appears when insects are fed baits treated with such com­pounds. Recently the quaternary ammonium salts have been proposed as systemic insecticides, but because of their phytocidal effect have received

Amines and salts of quaternary ammonium bases 85

little use. The ammonium salts are used for disinfection in the home and in animal husbandry. Positive properties of the substituted ammonium salts are their high solubility in water (which permits their use in aqueous solutions), absence of odor, and comparatively low toxicity to animals and man. This last property permits their use not only as disinfectants and fungicides, but also as detergents.

Table XXII. Bactericidal effect of tetraalkylammonium and trialkylbenzylammonium salts at 37° C.

Compound

[C,H'5(CH3)3N+] Br-[CsH,,(CH3),N+] Br­[C12H25(CH3)3N+] Br­[C14H29(CH3)3N+] Br­[C,.H33(CH3)3N+] Br­[C'8H ,,(CH3)3N +]Br­[C,.Ha3(C4H.)3N+] Br­[ClZH25(CH3)2N+CH2C.H5] Br­[C15HS' (CH3),N+CH2C.H5] Br­[C,.H33(CH3).N+CH2C.H5] Br­[2-CIC.H4CH2N+(CH3),CH,C.H5]Br-

Bactericidal dilution

Staphylococcus au reus

Not active 1:30 1: 4,000 1: 38,000 1: 80,000 1: 64,000 1: 48,000 1: 32,000 1: 52,000 1: 76,000 1: 52,000

Escherichia typhi

1: 15 1: 75 1: 9,000, 1: 36,000 1: 40,000 1: 8,000 1: 16,000 1: 30,000 1: 36,000 1: 32,000 1: 8,000

Tabelle XXIII. Bactericidal effect of ammOnium salts with ether groups in the cation at 20° C.

Compound

[C4H.C.H40C2H40C2H4 (CH3)2N+CH2C.H5] CI-[( CH3),CCH2C.H.OC2H.OC2H. (CHa)2N+CH2C.H5] CI-[ 4-C.H5C.H.OC2H.OC2H. (CH3)2N+CH2C.H5] Cl [ 4-C.H5CH2C.H.OC2H.OC2H. (CHs),N+CH2C.H5] Cl

Bactericidal dilution

Staphylococcus Escherichia aureus typhi

1: 1,200 1: 2,500

1: 12,000 1: 25,000

1: 6,000 1: 2,000

1 : 2,800 1: 2,800

In Table XXII the bactericidal actlvmes of the simplest tetra alkyl­ammonium and trialkylbenzylammonium salts are given. Compounds con­taining radicals with ether groups also have high activity. The bactericidal activity of compounds of this type is shown in Table XXIII.

The microbiological activity of substituted ammonium salts is affected not only by the structure of the radicals entering into the composition of

86 Chemistry of Pesticides

the cation, but also by the structure of the anion. Thus, the salts obtained by the reaction of esters of phosphoric, thio- and dithiophosphoric acids with dimethyloctadecylamine are several times as active as trimethylocta­decylammonium iodide and chloride. The bactericidal activities of these salts are given in Table XXIV.

Table XXIV. Bactericidal effect of substituted ammonium salts with organophosphorus anions at 37° C.

Compound

[C,sH37N+(CHa)a] lOr(S)OCH2CH2SC2H 5 j-OCHa

[C,sH37N+(CHa)a] [Or(S)OC6H 2Cla-2,4,5 j-OC2H 5

[C,sH a7N + (CHa) a] l °r(S)SC2H 5 r OCHa

[C,sHa7N+(CHa)a] [Or(S)SCH.CONHCHa r OCHa

[C,sHa7N+(CHala] 2 r °r(S)S~(S)O r-l H 5C20 OC2H 5

Bactericidal dilution

Staphylococcus au reus

1: 25,000

1: 12,000

1: 50,000

1: 25,000

1: 50,000

Escherichia coli

1: 25,000

1: 6,000

1: 12,000

1: 400

The substituted ammonium salts are prepared by the reaction of tertiary amines with halogen derivatives at an elevated temperature. The reaction goes most rapidly with compounds containing labile halogen. The iodine derivatives react the most easily, and the chlorine derivatives with some­what more difficulty. However, with such compounds as benzyl chloride, esters of monochloroacetic acid, chloromethyl alkyl ethers, and other effec­tive alkylating agents the reaction takes place rapidly.

The substituted ammonium salts are colorless crystalline substances, highly soluble in water, but not in hydrophobic organic solvents of the hydrocarbon type. Some of them are so hygroscopic that they deliquesce on standing in the air. The solubility of the substituted ammonium salts in water decreases as the amine molecule becomes more complex: e. g., 1,3-di­alkylbenzotriazolium salts are hardly soluble in water.

All the salts of quaternary ammonium bases form complexes with platinic chloride that are barely soluble in water. This reaction can be used for their identification and quantitative determination. At an elevated temperature the substituted ammonium salts decompose with the formation of the tertiary amine and an unsaturated compound:

[RCH2CH2NR~]Cl- -+ RCH = CH2 + R~NHCl-

Amines and salts of quaternary ammonium bases 87

Many salts of quaternary ammonium bases are toxic and have a curare­like effect.

Mixtures of various salts of quaternary ammonium bases, which are marketed in the form of 10-50% aqueous solutions, are used as fungicides and disinfectants. An alkyldimethylethylammonium bromide consisting of a mixture of compounds containing alkyls with 9-18 carbon atoms is used for seed disinfection. Preparations based on alkyldimethylbenzylammonium chloride (where the alkyl is C 12H 25 to C16H33)' which is prepared by the reaction of benzyl chloride with alkyl dimethyl amine, are used for dis­infection.

Preparations are also known that have as the active ingredient a mixture of salts formed by the reaction of trimethylamine with alkyl benzyl chloride. These compounds can be synthesized by the following route:

C6H6 + RCH = CH2 --+ C6H 5CH2CH2R

RCH2CH2C6H 5 -T- CH20 + HCI--+ RCH2CH2C6H4CH2CI + H 20

(CH3)3N + RCH2CH2C6H4CH2CI--+ [RCH2CH2C6H4CH2N(CH3)3JCl-

The aliphatic hydrocarbon radical in these compounds contains 9-15 carbon atoms.

Instead of benzyl chloride sometimes 3,4-dichlorobenzyl chloride is used, which is easily synthesized by the chlorination of benzyl chloride at a low temperature in the presence of catalysts for substitutive chlorination of the benzene nucleus. These compounds are distinguished from preparations that do not contain halogen in the benzene nucleus by their lower activity. Because of the additional step in their production, they are more expensive.

In spite of numerous investigations, the mechanism of action of the substituted ammonium salts still has not been established. There is also a question as to whether the action of these compounds is bactericidal or bacteriostatic. In the opinion of some investigators such compounds do not kill bacteria and fungi, but only inhibit their growth; however, there still is no definite proof for this point of view.

Of the free amines, only 2,6-dichloro-4-nitroaniline has been used as a fungicide; it is effective in controlling Botrytis and Sclerotinia on various crops.

2,6-Dichloro-4-nitroaniline (dichloran, dicloran) melts at 192° to 194° c., vapor pressure at 20° C. 1.2 X 10-6 mm. of Hg. Its LD50 for warm-blooded animals lies within the limits 1,500-4,000 mg./kg. It is used mainly in the form of a 50% wettable powder, but also can be used in dusts (4-8%). It is produced by direct chlorination of p-nitroaniline:

CI

H2N -o-No, + 2CI2 - o,N-Q-NH2 + 2HCI

CI

88 Chemistry of Pesticides

An interesting physiologically active amine derivative is chlorocholine chloride (Ccq which is a white crystalline, hygroscopic substanct. It is highly soluble in water and hydrophilic organic solvents and poorly soluble in hydrophobic organic solvents. It can be prepared by several methods:

1. By the action of chlorides of phosphorus, thionyl chloride, and aro­matic sulfonyl chlorides on choline hydrochloride:

HOCH2CH2N+(CHahCl- + SOCl2 --+- ClCH2CH2N+(CHa)aCl- + +HCl+S02

2. By the reaction of an excess of dichloroethane with trimethylamine:

(CHa)aN + ClCH2CH2Cl--+- ClCH2CH2N+(CHa)aCl­

Chlorocholine chloride is used as an agent to stimulate growth of the root system and thickening of the stem of cereal grains, making it possible to prevent breakage in rainy weather and under other circumstances.

General references

BROWN, A.: Insect control by chemicals. New York-London: Wiley (1951). CCC Symposium 14. 12. 1965 auf der Landwirrschaftlichen Versuchsstation Limburgerhof.

BASF, Ludwigshafen (1966). CLARK, N.: Chern. & Ind. 1960,572. Guso, L.: Proc. S. Weed Control Conf., p. 121 (1966); U. S. Patent 3257190. lUNG, J.: Naturwissenschaft 54, 346 (1967). MEL'NIKOV, N. N., and Yu. A. BASKAKOV: Khimiya gerbitsidov i regulyatorov rosta

rastenii [Chemistry of herbicides and plant growth regulators]. State Scientific and Technical Publishing House of Chemical Literature [USSR] (1962).

-, B. A. KHASKIN, G. N. PERSHIN, and S. N. MlLOVANOVA: Khim. v Sel'skom Khozyaistve No.7, 59 (1965).

- -, and K. D. SHVETSOVA-SHILOVSKAYA: Khim. v. Sel'skom Khozyaistve No.3, 60 (1965).

-, N. D. SUKHAREVA, and O. P. ARKHIPOVA: Zhur. Priklad. Khim. 20, 643 (1947). - - - Zhur. Priklad. Khim. 21, 306 (1948). - - - Zhur. Priklad. Khim. 22,1122 (1949). - - - Trudy Tsentral. Dezinfekt. Nauch. Issledovatel. Inst. 5, 88 (1949). SCHIEFERSTEIN, R. H., and W. J. HUGHES: Proc. 8th Brit. Weed Control Conf., p.377

(1966). SOLOWAY, S. B., and K. D. ZWAHLER: French Patent 1453170. TATTERSFIELD, F.: Ann. Applied BioI. 17, 181 (1927). VOROZHTSOV, N. N.: Osnovy sinteza poluproduktov i krasitelei [Principles of synthesis of

intermediates and dyes]. State Scientific and Technical Publishing House of Chemical Literature [USSR] (1955).