Organotin Compounds: New Chemistry and Applications

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11

Organotins in Agriculture MELVIN H. GITLITZ

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M&T Chemicals Inc., P.O. Box 1104, Rahway, N.J. 07065

Although organotin compounds were suggested as having biological activity as early as 1929, it is only relatively recently that they have found a place in agriculture. The evolution of organotin compounds as commercially important agricultural fungicides and insecticides both here and abroad is discussed. Our limited knowledge of the relationship of structure to biological activity is considered and recent attempts to fill this void are described. Steric effects seem to be important. In vitro tests of fungicidal activity have limited value to the organotin pesticide chemist since they disregard phytotoxicity which is a problem with many organotins. General toxicological properties are described.

B

etween one-half and one-third of the world's agricultural food crops are lost annually to pests (I). W e continually battle against the competition from insects, fungi, bacteria, and weeds for our food. The most effective weapons that we have been able to devise thus far to assist us in this struggle are the chemical pesticides. Organotins are a relatively new class of compounds receiving increasing interest as agricultural pesticides. The use of organometallic compounds as pesticides and disease-control agents is not a recent phenomenon. Organoarsenic compounds, for example, have had a long and colorful history from Ehrlich's Salvarsan [4,4'-diarsenobis(2-aminophenol) dihydrochloride trimer] to the methylarsonic acid salts still used today as crabgrass herbicides and to control other grassy weeds. Another group of biologically active organometallics are the organomercurials which until recently were used widely as seed treatments to control seed-borne fungus diseases in many areas of the world and are still important as medicinals. There is at least one distinctive difference between tin and arsenic or mercury. Unlike these latter two elements, tin's inorganic compounds are orders of magnitude less toxic than its most toxic organometallic compounds. 167

Zuckerman; Organotin Compounds: New Chemistry and Applications Advances in Chemistry; American Chemical Society: Washington, DC, 1976.

168

ORGANOTIN COMPOUNDS:

NEW CHEMISTRY AND APPLICATIONS

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This property gives tin a unique place among the heavy metals and is an i m portant factor in its agricultural utility. Although there were reports of the biological activity of organotin compounds as early as 1929 (2), it was not until the early 1950s that van der Kerk and Luijten at T N O in Utrect systematically explored the in vitro fungicidal and antibacterial properties of organotin compounds (3,4). Their research laid the foundation for further studies which ultimately led to the commercial application of organotins as bio-control agents. Table I shows the diversity of biocidal applications for which organotins are being used or for which they have been suggested. Table I. B i o c i d a l A p p l i c a t i o n s of Organotin C o m p o u n d s Fungicidal Control of fungi on potatoes and sugar beets'* Control of scab on pecans and peanuts" Control of rice blast and pine needle blight Preservation of wood (from fungi and insects) Paint additive to prevent mold growth

(5)

0

Bacteriostatic Control of slime in paper and wood pulp production Fabric disinfectant Antimicrobial activity in synthetic fibers 0

Insecticidal Antifeedant against insect larvae Chemosterilant (preventing reproduction) Arachnidicide against phytophagous mites*

1

Other Tapeworm and helminthes eradication in poultry Protection of surfaces (ships, piers, etc.) from attack by marine organisms** Plankton control in reservoirs Molluscicide for bilharzia control 0

a

Commercially significant usage. Journal of Organometallic Chemistry

In the early 1960 s the first organotin agricultural fungicide, triphenyltin acetate, was introduced in Europe commercially by Farbwerke Hoechst A . G . as Brestan. Brestan was recommended for the control of Phytophthora (late blight) on potatoes and Cercospora on sugar beets at rates of a few ounces per acre (6). Shortly thereafter, triphenyltin hydroxide was introduced as Duter by Philips-Duphar N.V. with about the same spectrum of disease control as Brestan. Duter is presently registered in the United States as a fungicide for potatoes, sugar beets, pecans, and peanuts. Both materials are extremely effective protectant fungicides. Incidentally, both triphenyltin hydroxide and acetate exhibit the unusual and interesting property of deterring insects from feeding e

Zuckerman; Organotin Compounds: New Chemistry and Applications Advances in Chemistry; American Chemical Society: Washington, DC, 1976.

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11.

GITLITZ

Organotins in Agriculture

169

(7). This antifeedant effect is also shown by other triphenyltin compounds (8). Several triphenyltin compounds including the hydroxide have also been shown to be effective fly sterilants at sub-lethal concentrations (9). Although research on the biological activity and toxicology of organotins progressed at a rapid pace in the interim, it was not until 1968 that the next major agricultural application of organotins was realized. In that year, tricyclohexyltin hydroxide, the result of a joint research effort by M & T Chemicals and Dow Chemical Co., was introduced under the name Plictran (10). It was recommended for the control of phytophagous (plant-feeding) mites on apples and pears. It is now also registered for use on citrus, stone fruits, and hops. Plictran is very selective and gives good control of harmful arachnids with little toxicity towards other insects such as honeybees. The compound also shows antif eedant activity against some insect larvae (11). Tricyclohexyltin hydroxide can be prepared by the two routes shown in Figure 1. The first process, termed the butyl transfer route, involves two steps to prepare tricyclohexyltin chloride (12). In the first step, butyltin trichloride is allowed to react with 3 moles of cyclohexylmagnesium chloride to form butyl tricyclohexyltin which is then allowed to react with tin tetrachloride in an inert solvent to give tricyclohexyltin chloride and butyltin trichloride. The butyltin trichloride is extracted with water, distilled, and recycled into the process. BuSnCL + 3 C y M g C I — • BuCy Sn 3

V

SnCI 1:1 4

BuSnCI + Cy SnCI 3

3

OHCy SnOH 3

t

!

OH —

3 C y M g C I + SnCI -*Cy SnCI 4

3

Figure 1. Routes to tricyclohexyltin hydroxide. Data from Refs. 12 ana 13. An alternate route to tricyclohexyltin chloride involves the reaction of 3 moles of cyclohexyl Grignard and 1 mole of tin tetrachloride to form the organotin directly (13). Although this route seems economically more attractive, it requires very close control of reaction conditions to minimize byproducts. The commercial success of Plictran miticide stimulated research efforts on organotins in other companies. There are now three other organotin miticides which have been disclosed in the patent literature. The structures are shown in Figure 2.

Zuckerman; Organotin Compounds: New Chemistry and Applications Advances in Chemistry; American Chemical Society: Washington, DC, 1976.

170

ORGANOTIN COMPOUNDS:

NEW CHEMISTRY AND APPLICATIONS

SnOH

Plictran (Dow)

/

. N — .OR Sn—S—Ρ

Sn-N

OR

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'3

N

N

Tricyclazol (Bayer, Chemagro)

R-28627(Stauffer)

Figure 2. Organotin acaricides. clazol, Ref. 48; R-28627, Ref. 49.

Plictran, Ref. 21; Vendex, Ref. 26; Tricy­

The lower tri-n-alkyltins from trimethyl to tri-n-pentyl show high biological activity. The trimethyltins are highly insecticidal and the tripropyls, tributyls, and tripentyls have a high degree of fungicide and bactericide activity. The dialkyltin compounds are generally less active than the trialkyltin compounds. The typical relationship between chain length of di- and trisubstituted organotin

"Fungicides"

Figure 3. Influence of chain length of di- and trisubstituted tin com­ pounds on minimum concentration inhibitory to Mycobacterium phlei. Legend: Ο Ο, trialkyltin com­ pounds; · — ·, dialkyltin com­ pounds (14)

2

3

4

R = Me Ft

Pr

Bu Pen Hex Hep Oct

I

5 6 7 8

Zuckerman; Organotin Compounds: New Chemistry and Applications Advances in Chemistry; American Chemical Society: Washington, DC, 1976.

11.

GITLITZ

Organotins in Agriculture

171

compounds and their minimum inhibitory concentration for a particular bacteria, Mycobacterium phlei is shown in Figure 3. Note that diorganotins are less active than the analogous triorganotins. The response of fungi to triorganotins is generally similar to that exhibited by bacteria in the foregoing example and is typically illustrated in Figure 4 below for the fungus Aspergillus niger. Although the lower trialkyltins show high fungicide activity, they are unlikely candidates for agricultural fungicide use because of their high phytotoxicity. Over the years, various attempts have been made to moderate the phytotoxicity of the lower alkyltins by changes in the anion

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MIC n — ι — ι — ι — ι — ι — ι — ι

I

R-

Me

2 Et

3 Pr

4 5 6 7 8 Bu Pen Hex Hep Oct "Fungicides"

Figure 4. Influence of chain length of trialkyl-substituted tin acetates on minimum concentration inhibitory to Aspergillus niger (15) group. These have not been very successful since the nature of the anion group has little influence on the spectrum of biological activity provided that the anion is not biologically active in its own right and that it confers a sufficient minimal solubility on the compound. While the higher (Cg and above) trialkyltins are non-phytotoxic, they are neither fungicidal nor insecticidal. Tricyclohexyl and tricycloheptyltins are also essentially non-phytotoxic. Attempts to moderate the phytotoxicity of the trialkyltins by synthesizing asymmetric organotins of the form R C y S n X or RCy2SnX where R = lower alkyl group, C y = cyclohexyl, and X = chloride, 2

Zuckerman; Organotin Compounds: New Chemistry and Applications Advances in Chemistry; American Chemical Society: Washington, DC, 1976.

172

ORGANOTIN COMPOUNDS:

N E W CHEMISTRY AND APPLICATIONS

V V

1.

R Cy Sn + SnCI

2.

R CySn + SnCI RSnCI + R CySnCI R = Me, Et, n-Pr, η-Bu, n-Pent

2

2

3

4

H y d r o c a r b o n

H y d r o c a r b o n

4

so,ven

So,ven

RSnCI + RCy SnCI 3

3

2

2

Yields: 89-97% Purity: >95% as isolated (GLC) Reaction Time: 10-20 min. RSnCI removed by extraction with aqueous HCl 3

Figure 5. Process for asymmetric cyclohexyltin chlorides. from Ref. 16.

Data

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Table II. T y p i c a l A s y m m e t r i c C y c l o h e x y l t i n Chlorides^ Compound

Tetraorganotin Reagent

Melting Point, °C

Me CySnCF MeCy SnCl Pr CySnCl PrCy SnCl Bu CySnCl

Me CySn Me Cy Sn Pr CySn Pr Cy Sn Bu CySn

33-35 Ç2-54 d 33-35

2

3

2

2

2

2

3

2

2

2

2

3

e

Yield? %

Purity, %

89 97 97 95 92

99 98 99 97

b

Based o n tetraorganotin. b G L C area % . C y = c y c l o h e x y l . Sn and CI analyses satisfactory and agree with G L C results.