METAL-ORGANIC COMPOUNDS

---

Applications of Organotin Compounds

W. RICHARD LEWIS and ERNEST S. HEDGES

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Tin Research Institute, Perivale, Greenford, Middlesex, England

Organotin compounds were first studied in 1852 by Löwig (9), who prepared diethyltin by the action of a sodium-tin alloy upon ethyl iodide. In the following year Frankland (4) prepared tetraethyltin and in the next years a considerable number of both alkyl and aryl organotin compounds were synthesized and described. In the course of these studies more than one of the investigators became aware of the poisonous nature of some of these compounds and Frankland himself was made ill for several months, but happily recovered, and there are no reports that any of those affected actually succumbed. It was evident that certain organotin compounds, notably triethyltin hydroxide and triethyltin acetate, were highly toxic; this was confirmed in 1881 by White (22), who studied their effects upon dogs and other animals. A period of 70 years was to elapse before the significance of these preliminary observations was realized. In 1932 (13) a patent was taken out for the use of the tetraalkyltin compounds as stabilizers of chlorinated transformer oils. In 1940 and 1941 patents were taken out by Yngve (24) covering the use of various organotin compounds as stabilizers for poly (vinyl chloride). Dibutyltin dilaurate and other dibutyltin salts have since become widely used as stabilizers. The availability of dibutyltin dilaurate as a commercial material may have been a predisposing influence in the selection of this compound for experiments on the treatment of worms in chickens, for which it is now widely used. Methyltin triiodide was marketed in England over 20 years ago as a treatment for boils, but failed to gain wide acceptance. It has been known for centuries that even the rather insoluble dioxide, and the metal itself in powder form, often effected remarkable cures of worm infections both in human beings and in animals, and that tin and its salts had often given positive results in the treatment of staphylococcal infections such as boils. In view of the erratic results with the inorganic forms of tin, it seemed likely that the organotin compounds would be more potent. Modern Researches Linking of the tin atom directly to at least one carbon atom is adopted here as the criterion of an organotin compound. As tin, like carbon, is quadrivalent and as preparative chemistry has shown that tin atoms can be linked together in short chains, a considerable field of organic chemistry is possible in which one or more atoms of carbon are replaced by tin atoms. This concept differs somewhat from that of general organometallic chemistry, in view of chemical similarities between tin and carbon. The International Tin Research Council decided that the time was ripe for the systematic investigation of this new field of organotin chemistry. It was expected that among the vast number of possible new compounds a number would fill some industrial need, but it was necessary to develop methods of synthesis and to study 190

METAL-ORGANIC COMPOUNDS Advances in Chemistry; American Chemical Society: Washington, DC, 1959.

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LEWIS AND HEDGES—APPLICATIONS OF ORGANOTIN COMPOUNDS

r e a c t i o n m e c h a n i s m s a n d s t r u c t u r a l p r o b l e m s . I n t h i s field i t i s easy t o b e l e d a s t r a y b y t h e o r d i n a r y rules o f o r g a n i c c h e m i s t r y . T h e c o u n c i l was f o r t u n a t e i n e n l i s t i n g , 7 y e a r s ago, t h e e n t h u s i a s t i c c o l l a b o r a t i o n of v a n d e r K e r k , d i r e c t o r o f t h e I n s t i t u t e f o r O r g a n i c C h e m i s t r y , T . N . O . , U t r e c h t , w h o w i t h a t e a m of a s s i s t a n t s has b e e n i n c h a r g e o f t h e m a i n p r o g r a m o f r e s e a r c h e v e r since. H i s p e r s o n a l c o n t r i b u t i o n t o t h e success o f t h e w o r k i s e n o r m o u s . T h e c o u n c i l has also, d u r i n g t h e p a s t 7 y e a r s , s p o n s o r e d r e s e a r c h o n different a s p e c t s of o r g a n o t i n c h e m i s t r y i n t h e U n i v e r s i t y o f T o u l o u s e i n F r a n c e a n d i n t h e U n i v e r s i t i e s of L o n d o n a n d S o u t h a m p t o n i n E n g l a n d . I n recent y e a r s i n t e r e s t i n o r g a n o t i n chemistry has spread considerably and t h e council collaborates w i t h t h e research d e p a r t m e n t s o f u n i v e r s i t i e s a n d t e c h n i c a l i n s t i t u t e s a n d w i t h m a n u f a c t u r e r s a n d users of o r g a n o t i n c o m p o u n d s i n m a n y c o u n t r i e s .

Four Main Types of Organotin Compound T h e four types of c o m p o u n d m a y be characterized according t o the n u m b e r of carbon atoms directly linked t o t i n : RSn RsSnX R2S11X2 RSnXj

Tetraalkyltin Trialkyltin Dialkyltin Monoalkyltin

where R is an a l k y l radical a n d X is a n y radical not l i n k e d t h r o u g h a carbon a t o m . C o r r e s p o n d i n g series o f a r y l c o m p o u n d s e x i s t . Tetraalkyltin. T h e t e t r a a l k y l t i n c o m p o u n d s , s u c h a s t e t r a m e t h y l t i n a n d t e t r a e t h y l t i n , a r e a k i n t o h y d r o c a r b o n s , b u t less v o l a t i l e ; v o l a t i l i t y decreases a s t h e aggregate o f c a r b o n a t t a c h m e n t s increases t h r o u g h t h e series. W h i l e i t i s easiest t o p r e p a r e s y m m e t r i c a l t e t r a a l k y l t i n s i n w h i c h a l l t h e a l k y l g r o u p s are of i d e n t i c a l k i n d , i t i s n o w also possible t o p r e p a r e t h e m w i t h one, t w o , t h r e e , o r a l l t h e g r o u p s differing : R' Sn, 4

R"R' Sn, 3

R'"R"R' Sn, 2

R""R"'R"R'Sn

T h e l o w e r t i n t e t r a a l k y l s — e . g . , t e t r a e t h y l t i n — a r e colorless m o b i l e l i q u i d s , w i t h a w e a k o d o r w h e n p u r e . T h e y a r e i n s o l u b l e i n w a t e r b u t s o l u b l e i n o r g a n i c s o l v e n t s , es­ pecially i n hydrocarbons, chlorinated hydrocarbons, a n d ethers. T h e higher m e m b e r s — t e t r a - n - d o d e c y l t i n , e t c . — a r e solids w i t h l o w m e l t i n g p o i n t s . T i n t e t r a a r y l s are solids w i t h melting points above 200°C. T h e lower t i n tetraalkyls can be distilled under atmospheric pressure w i t h o u t decomposition. A l l t h e c o m p o u n d s are s t a b l e i n t h e presence o f a i r a n d w a t e r . Trialkyltin. T h e t r i a l k y l t i n compounds are formed from t h e tetraalkyl com­ pounds b y treatment w i t h a halogen: R4S11 + X -> R3S11X + R X 2

T h e t r i a l k y l t i n c h l o r i d e s , b r o m i d e s , a n d iodides are colorless l i q u i d s o r solids w i t h l o w m e l t i n g p o i n t s s h o w i n g t h e same t h e r m a l s t a b i l i t y as t i n t e t r a a l k y l s . T h e y a r e somewhat soluble i n water a n d miscible w i t h organic solvents. T h e e t h y l compounds i n p a r t i c u l a r possess a p e n e t r a t i n g a n d l a c h r y m a t o r y s m e l l . T h e f l u o r i d e s a r e solids w i t h h i g h m e l t i n g p o i n t s . A l l t h e t r i a l k y l t i n h a l i d e s are s o l i d s . O n s h a k i n g t h e h a l i d e s w i t h c a u s t i c p o t a s h s o l u t i o n t h e h y d r o x i d e s are f o r m e d . T h e s e a r e s o l i d s . D i a l k y l - and D i a r y l t i n . T h e d i a l k y l t i n a n d d i a r y l t i n c o m p o u n d s a r e f o r m e d b y reaction of the t e t r a a l k y l t i n w i t h two halogens: R S n + 2 X -> RaSnXa + 2 R X 4

2

T h e d i h a l i d e s are c r y s t a l l i n e substances w h i c h are r a t h e r m o r e s o l u b l e i n w a t e r t h a n t h e m o n o h a l i d e s . W i t h d i l u t e a l k a l i t h e y h y d r o l y z e , f o r m i n g t h e oxides, R S n O . T h e s e are w h i t e a m o r p h o u s i n f u s i b l e p o w d e r s w i t h w e a k l y b a s i c p r o p e r t i e s . With 2

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s t r o n g acids t h e y f o r m n o r m a l salts w h i c h a r e stable i n w a t e r . W i t h w e a k acids t h e n o r m a l salts c a n b e p r e p a r e d u n d e r s p e c i a l c o n d i t i o n s . T h e d i a l k y l t i n a n d d i a r y l t i n salts a r e m u c h less t o x i c t h a n t h e c o r r e s p o n d i n g t r i a l k y l o r a r y l t i n s a l t s ; some a r e nontoxic. T h e m o n o a l k y l a n d a r y l t i n c o m p o u n d s i n some respects resemble t h e i n o r g a n i c t i n t e t r a h a l i d e s . T h e t r i h y d r o x i d e s a r e u n k n o w n because t h e h y d r o l y s i s o f t h e halides produces either a l k y l o r arylstannonic acids, R S n 0 H . T h e s t a n n o n i c acids a r e w h i t e , a m o r p h o u s , i n f u s i b l e a n d i n s o l u b l e p o w d e r s , f o r m i n g salts w i t h b o t h s t r o n g a c i d s a n d bases.

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2

The

Distannanes

A n o t h e r t y p e of c o m p o u n d is t h e h e x a a l k y l o r h e x a a r y l d i s t a n n a n e , p r e p a r e d f r o m the corresponding t r i a l k y l o r a r y l t i n halides b y reduction w i t h sodium. 2 R S n X + 2 N a -> R S n 3

6

2

+ 2NaX

T h e h e x a a l k y l d i s t a n n a n e s a r e colorless l i q u i d s b o i l i n g a t f r o m 5 0 ° t o 1 0 0 ° C . h i g h e r t h a n t h e corresponding t i n tetraalkyls. T h e hexaaryl distannanes a r e crystalline solids.

Applications and Properties of Organotin Table I.

Compound CH SnCl 3

CH SnBr 3

CH SnI 3

Survey of Known Alkyltin Trihalides a n d Methods Used in Their Preparation (5)

Method of Preparation C H S n O O H + dry HC1 at 50°C. C H ( C H 6 ) S n + 3SnCl C H S n O O H + fuming H B r Sn + l ^ C H B r 50 hr. at 180°-220°C. CHsSnOOH + aq. H I S n l + 2CH I 4 hr. at 160°C. Snl + 4CH MgI K S n C l + C H I 48 hr. at 90°C. (C H ) Sn + 9SnCl 24 hr. reflux. K S n C h + C H E I 48 hr. at 110°C. KSnCls + C H I at 130°C.

3

3

6

3

4

3

2

3

2

5

2

6

3

2

3

7

3

3

3

7

3

3

4

4

3

3

7

6

2

Iso-C H SnCl Iso-C H SnBrs C HiSnI 4

3

3

3

2

3

4

2

Yield,

%

3

3

C H SnCl C H SnI C H Snl

Compounds

7

KSnCU + Iso-C H I at 110°C. Iso-C H SnOOH + coned, aq. H B r KSnCb + C H i I 72 hr. at 90°C. 3

3

7

4

7

65 53 90 65 50 15 43.7 15 37 40 25

Melting Point, °C. (53), 46 45-46 53 53 86.5 85 85 85

112

Boiling Point °C.

Mm.

210-211

746

196-198 181-184.5 200 (decomp.) 75

760 19 16

154

16 5

T h e Monoalkyltin Compounds. T h e o n l y one o f t h e c o m p o u n d s l i s t e d i n T a b l e I , w h i c h h a s so f a r h a d p r a c t i c a l a p p l i c a t i o n , is m e t h y l t i n t r i i o d i d e , w h i c h h a s been t r i e d i n medicine as a cure for boils, b u t n o t widely acclaimed f o r this purpose. Further re­ s e a r c h u p o n t h i s a n d o t h e r m o n o a l k y l o r a r y l t i n t r i h a l i d e s is essential before t h e y c a n b e safely recommended f o r a n y pharmacological purpose. F u r t h e r investigations upon m o n o a l k y l t i n c o m p o u n d s w i l l doubtless b r i n g t o l i g h t u s e f u l a p p l i c a t i o n s , so a t t h i s stage t h e y s h o u l d n o t b e d i s r e g a r d e d . Dialkyltin and D i a r y l t i n C o m p o u n d s . Plastics Stabilizers. A t present the plas­ t i c s i n d u s t r y consumes t h e largest t o n n a g e of o r g a n o t i n c o m p o u n d s . T h i s is due t o t h e o u t s t a n d i n g a b i l i t y of t h e d i b u t y l t i n salts t o s t a b i l i z e p o l y ( v i n y l c h l o r i d e ) . I n 1942, Y n g v e (25) specified t h e use of d i b u t y l t i n d i l a u r a t e as a v i n y l s t a b i l i z e r . S h o r t l y a f t e r w a r d s , Q u a t t l e b a u m a n d N o f f s i n g e r (16) d i s c o v e r e d t h a t d i b u t y l t i n m a l e a t e w a s m o r e effective f o r h i g h t e m p e r a t u r e p r o c e s s i n g o f t h e p o l y ( v i n y l c h l o r i d e ) because o f i t s d o u b l e b o n d , w h i c h enables i t t o r e a c t w i t h t h e c o l o r e d p o l y e n e s f o r m i n g i n h e a t - d e g r a d e d v i n y l p o l y m e r a n d so t o m a i n t a i n t h e w a t e r - c l e a r c o l o r o f t h e r e s i n . I n r e c e n t y e a r s t h e r e h a v e been m a n y v a r i a t i o n s m a d e i n t h e a c i d r a d i c a l s —

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f o r e x a m p l e , d i b u t y l t i n d i t h i o g l y c o l l a t e has been f o u n d e v e n m o r e effective. Syner­ gistic effects r e s u l t f r o m t h e use o f c o m b i n a t i o n s o f t h e v a r i o u s d i b u t y l t i n salts. M a c k a n d P a r k e r (14) describe the use o f o r g a n o t i n s u l f o n a m i d e s o f t h e g e n e r a l formula R.SnCR'NOsSR")*, w h e r e R , R ' , a n d R " a r e a l k y l o r a r y l r a d i c a l s a n d χ + y — 4. T h e s e substances are p l a s t i c i z e r s as w e l l as s t a b i l i z e r s a n d i n r e a c t i n g w i t h h y d r o c h l o r i c a c i d t h e y s p l i t off s u l f o n a m i d e s w h i c h are c o m p a t i b l e w i t h v i n y l resins. A n e x a m p l e o f t h i s c o m ­ p o u n d i s d i b u t y l t i n dibenzene s u l f o n a m i d e , ( C H ) S n ( H N 0 S · C H ) .

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4

9

2

2

6

5

2

M a n y v a r i a n t s of these a n d o t h e r d i b u t y l t i n c o m p o u n d s h a v e been i n v e s t i g a t e d as s t a b i l i z e r s b y B a n k s a n d his colleagues a t the R e s e a r c h L a b o r a t o r i e s of t h e M e t a l & T h e r m i t C o r p . , I L S Α . , w h e r e l a r g e scale m a n u f a c t u r i n g m e t h o d s h a v e b e e n d e ­ veloped. I n E n g l a n d B X Plastics, L t d . , P u r e Chemicals, and A l b r i g h t and Wilson are a l l a c t i v e l y i n t e r e s t e d i n t h i s field. T h e r e v i e w s b y S m i t h (17, 18) d e a l i n g r e a t d e t a i l w i t h t h e t h e o r y a n d p r a c t i c e of stabilizing poly ( v i n y l chloride), w i t h special emphasis o n the value of the d i b u t y l t i n compounds for this purpose. I t i s g e n e r a l l y a c k n o w l e d g e d t h a t t h e o r g a n o t i n s t a b i l i z e r s a r e i n a class b y t h e m s e l v e s i n t h e i r a b i l i t y t o p r e s e r v e t h e t r a n s p a r e n c y of p o l y ( v i n y l c h l o r i d e ) , e i t h e r w h e n b e i n g processed o r s u b s e q u e n t l y w h e n exposed t o t h e d e t e r i o r a t i n g a c t i o n of s u n l i g h t a n d heat. W h i l e t h e efficiency o f the d i b u t y l t i n d i t h i o g l y c o l l a t e s i s also a m a t t e r o f g e n e r a l a g r e e m e n t , t h e y suffer f r o m t h e serious d i s a d v a n t a g e t h a t t h e y h a v e a v e r y persistent c h a r a c t e r i s t i c a n d o b j e c t i o n a b l e s m e l l . M u c h effort i s s t i l l b e i n g e x p e n d e d i n the a t t e m p t t o f i n d a n i d e a l m e t h o d of c o m b i n i n g the d i a l k y l t i n r a d i c a l w h i c h w i l l be free f r o m t h i s o b j e c t i o n . T h e t o x i c i t y of the d i b u t y l t i n salts has l o n g been the subject o f some d o u b t , a n d p a r t i c u l a r l y t h e r e i s a n x i e t y as t o w h e t h e r o r not i t i s p e r m i s s i b l e t o use t h e m i n p l a s t i c s w h i c h w i l l come i n t o c o n t a c t w i t h foodstuffs o r w i t h the b o d y . T h e r e are t w o m a i n p o i n t s : the t o x i c i t y o f t h e s t a b i l i z e r itself a n d the e x t e n t t o w h i c h i t m a y be l e a c h e d d u r i n g the use of the p l a s t i c f o r its n o r m a l p u r p o s e s . T h e latter is of p a r a m o u n t i m p o r t a n c e , because i f l e a c h i n g were n o t possible t h e r e c o u l d b e n o r i s k , e v e n i f the s t a b i l i z e r were t o x i c . T h e l e a c h a b i l i t y i s v a r i a b l e , d e p e n d i n g u p o n t h e n a t u r e of t h e p l a s t i c a n d the p l a s t i c i z e r s used i n i t , so i t is n o t possible t o a v o i d the issue o f t o x i c i t y o n t h e score of n o n l e a c h a b i l i t y . T h e t o x i c i t y of d i b u t y l t i n c o m ­ p o u n d s i s d e e m e d i n m a n y c o u n t r i e s t o b e sufficiently h i g h t o w a r r a n t the d e n i a l o f t h e i r use i n c e r t a i n p o l y ( v i n y l c h l o r i d e ) p l a s t i c s w h e r e t h e r e m a y b e c o n t a c t w i t h foods o r w i t h the m o u t h , a n d these s t a b i l i z e r s are a v o i d e d so f a r as possible i n these applications. R e c e n t e x p e r i m e n t s c a r r i e d o u t i n H o l l a n d , F r a n c e , a n d G e r m a n y (20) s h o w e d t h a t the t o x i c i t y of the d i a l k y l t i n c o m p o u n d s declines f o r c h a i n l e n g t h s g r e a t e r t h a n b u t y l . E x p e r i m e n t s b y B a r n e s (19) a t t h e T o x i c o l o g y U n i t of t h e M e d i c a l R e s e a r c h C o u n c i l i n E n g l a n d have confirmed t h a t d i o c t y l t i n compounds are n o t toxic w h e n t a k e n b y m o u t h a n d t h a t v e r y l a r g e a m o u n t s of t h e m m a y be i n g e s t e d b y e x p e r i m e n t a l a n i m a l s w i t h o u t i l l effects. N o tests h a v e been c a r r i e d o u t u p o n h u m a n s u b j e c t s , b u t i t i s u n l i k e l y t h a t t h i s i s necessary. T h e w a y a p p e a r s t o b e o p e n n o w t o the use o f d i o c t y l t i n c o m p o u n d s , w h i c h w i l l o p e n e n t i r e l y n e w fields o f a p p l i c a t i o n s t o r e p l a c e d i b u t y l t i n salts. T h e s t a b i l i z i n g a c t i o n of t h e d i o c t y l t i n s a l t s has been s h o w n t o b e as g o o d as t h a t o f t h e d i b u t y l t i n salts a n d t h e i r c o m p a t i b i l i t y w i t h the p l a s t i c is b e y o n d q u e s t i o n . C h l o r i n a t e d R u b b e r S t a b i l i z e r (5). T h e s t a b i l i z i n g p r o p e r t y o f t h e d i a l k y l t i n salts has been s h o w n a t t h e T i n R e s e a r c h I n s t i t u t e t o e x t e n d t o c h l o r i n a t e d r u b b e r and to paints formulated w i t h it. D i b u t y l t i n dilaurate, i n amounts equal to only 0 . 1 % o f t h e w e i g h t o f t h e c h l o r i n a t e d r u b b e r , i s a n effective s t a b i l i z e r f o r c o m m e r c i a l

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chlorinated paints. stabilized paint.

A t least one w e l l - k n o w n f i r m i n E n g l a n d i s m a n u f a c t u r i n g a t i n -

Anthelmintic Property of Dialkyltin Salts (6). T i n a n d i t s salts h a v e b e e n u s e d i n m e d i c i n e s f o r t h e t r e a t m e n t o f w o r m i n f e c t i o n s i n h u m a n beings a n d a n i m a l s f o r a century o r more. T h e i n o r g a n i c t i n p r e p a r a t i o n s a r e safe a n d t h e y p r o d u c e n o u n p l e a s a n t effects i n t h e s u b j e c t , b u t t h e i r c u r a t i v e effect i s u n c e r t a i n . W h e n d i b u t y l ­ t i n d i l a u r a t e b e c a m e a v a i l a b l e i n d u s t r i a l l y a b o u t 10 y e a r s a g o i t w a s t h o u g h t t h a t t i n i n this f o r m m i g h t be more potent. T r i a l s s h o w e d t h a t t h i s w a s t h e case w i t h p o u l t r y a n d t h e r e h a s d e v e l o p e d a v e r y b i g o u t l e t f o r t h i s c o m p o u n d a n d i t s analogs as a w o r m c u r e a n d p r o p h y l a c t i c f o r p o u l t r y . T h e m a t e r i a l is f o r m u l a t e d as a p o w d e r , w h i c h is added t o the bird's daily mash. O r g a n o t i n c o m p o u n d s should not be used f o r the cure of w o r m s i n animals o r h u m a n b e i n g s w i t h o u t d u e care. F o w l s m a y b e e x c e p t i o n a l l y i m m u n e t o t h e a c t i o n of s u c h o r g a n o t i n c o m p o u n d s w h e n t a k e n b y m o u t h {23). O n e p r e p a r a t i o n o f d i e t h y l t i n d i i o d i d e , a d m i n i s t e r e d m e d i c i n a l l y , i s s u s p e c t e d o f h a v i n g b e e n r e s p o n s i b l e f o r deaths of h u m a n beings i n F r a n c e d u r i n g 1953 (19). A m e a s u r e o f success h a s b e e n r e p o r t e d i n t h e t r e a t m e n t o f w a r b l e fly i n f e s t a t i o n of c a t t l e (23) w i t h d i b u t y l t i n d i l a u r a t e b u t f u r t h e r c o n f i r m a t i o n o f i t s effectiveness is necessary. T h e possibility of a n active i m p u r i t y i n t h e material has t o be ex­ amined. I n g e n e r a l , t h e r e a p p e a r s t o b e a m a r k e d d i m i n u t i o n i n b i o c i d a l a c t i v i t y of d i a l k y l t i n c o m p o u n d s as t h e c h a i n l e n g t h s increase b e y o n d b u t y l . F o r e x a m p l e , d i o c t y l t i n d i l a u r a t e a n d o t h e r d i o c t y l t i n salts h a v e b e e n s h o w n t o b e n o n t o x i c (19). I n t h e case o f d i o c t y l t i n d i l a u r a t e , 4 0 0 m g . p e r k g . o f b o d y w e i g h t b y m o u t h i n a r a c h i s o i l p r o d u c e d n o loss o f w e i g h t n o r a n y signs o f p o i s o n i n g i n r a b b i t s , r a t s , m i c e , a n d guinea pigs. A t p o s t - m o r t e m t h e animals appeared healthy. A p p l i e d repeatedly t o the s k i n of rats, a solution of d i o c t y l t i n dilaurate i n d i m e t h y l phthalate produced n o l o c a l d a m a g e t o t h e s k i n a n d n o effects o f p o i s o n i n g . Diethyl, dimethyl, dipropyl, a n d d i b u t y l d i l a u r a t e t e s t e d o n t h e s k i n i n t h e same s o l v e n t caused i r r i t a t i o n . T h e d i m e t h y l a n d d i e t h y l salts p r o d u c e d s u p e r f i c i a l s k i n d a m a g e o n l y . T h e d i p r o p y l t i n , d i i s o p r o p y l t i n , a n d d i b u t y l t i n salts p r o d u c e d a deeper s e a t e d l e s i o n i n t h e s k i n a n d tissues b e l o w a n d a l l a t t a c k e d t h e b i l e d u c t . T h e d i p e n t y l t i n , d i h e x y l t i n , a n d d i o c t y l ­ t i n d i d n o t i n j u r e t h e s k i n o r d e e p e r tissues, b u t t h e first t w o caused severe loss of weight a n d t h e animals were i l l f o r a reason t h a t was n o t established. T h e dioctyltin dilaurate a n d dichloride h a d n o demonstrable toxicity when given t o f o u r species o f a n i m a l s i n r e p e a t e d doses o f m o d e r a t e l y l a r g e size. I t differs v e r y m a r k e d l y i n t h i s r e s p e c t f r o m t h e o t h e r d i a l k y l t i n salts. I t seems h i g h l y p r o b a b l e t h a t d i o c t y l t i n d i l a u r a t e a n d o t h e r salts s h o u l d c o n s t i t u t e n o h e a l t h h a z a r d i f u s e d as s t a b i l i z e r s i n p o l y ( v i n y l c h l o r i d e ) p l a s t i c s . Antidote. T h e effects of d i m e r c a p r o l ( B A L ) h a v e b e e n s t u d i e d b y B a r n e s (11) o n t h e s u r v i v a l t i m e s o f r a t s w h i c h h a d b e e n g i v e n 2 0 m g . p e r k g . of d i e t h y l t i n dichloride (intraperitoneally i n T w e e n 80) (Table I I ) .

Table II. Effect of Dimercaprol (BAL) (30 M g . per K g . I.M. in Oil) on Survival Time of Rats Given 2 0 M g . per K g . of Diethyltin Dichloride (LP. in Tween 80) ( U n t r e a t e d rats were g i v e n e q u i v a l e n t v o l u m e o f arachis o i l i . m . N u m b e r of rats shown i n parentheses) Survival Time Treatment B A L given 30 min. before and 6 hr. after injection of diethyltin B A L given at 2 and 6 hr. after injection of diethyl, tin

Treated, 3 7 >7 >7

days (1) (2) (1) (3)

Untreated, hr.

1000

>1000

SnCl -2H 0 2

2

compounds,

or no fungitoxicity.

as m e r c u r y , they

inorganic

compounds.

100

200

>1000

>1000

>1000

>1000

>1000

>1000

>1000

>1000

>1000

a n d stannic

however, the triethyltin

T h i s is s u r p r i s i n g because t h e f u n g i t o x i c i t y of o t h e r

copper,

structure

2 500

as w e l l as t h e s t a n n o u s

B y contrast,

Rhizopus nigricans 100

2

>1000

SnCh

fungitoxic.

>1000

0.5

III

Aspergillus niger 100

Pénicillium italicum

Botrylis allii 50

Type I

d i - , and monoethyltin

salts, have is

directly

T h e following

at Utrecht

Influence of Number of Alkyl Groups Directly Attached to Tin Atom on Antifungal Properties of Ethyltin Compounds ( Ï 9 )

Name Tetraethyltin Triethyltin chloride Diethyltin dichloride Ethyltin trichloride Stannic chloride Stannous chloride

3

of i n t e r e s t .

a n d his team

(11).

Compound

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them

investigations

cadmium,

are combined

with

a n d zinc a n d they

is n o t r e l a t e d t o t h e t y p e are fungitoxic

whether

of

chloride metals organic

as o r g a n i c

or

S t u d i e s of t h e f u n g i t o x i c i t y of t r i a l k y l t i n c o m p o u n d s were c a r r i e d o u t b y s y s t e m ­ atically v a r y i n g the attached

acidic or a l k y l

groups.

Table IV. Influence of Varying Group X on Antifungal Properties of Compounds with the General Formula (C2H ) SnX (7 7) 5

Compound

No. 8 3 19 22 21 9 10 11 12 13 15 14 16 17 4 5 6

18

Name Triethyltin hydroxide Triethyltin chloride Triethyltin bromide Triethyltin iodide Triethyltin sulfide Triethyltin sulfate Triethyltin acetate Triethyltin caproate Triethyltin laurate Triethyltin benzoate Triethyltin malonate Triethyltin maleate Triethyltin phenoxide Triethyltin p-nitrophenoxide p-Triethylstannylsulfonyltoluene Triethyltin toluene-psulfonamide Triethyltin methanesulfonamide N-Triethylstannylsaccharin

3

Concn. ( P . P . M . = M g . / L . ) Causing Complete Inhibition of Growth of FungiPenicillum italicum 5 2 2 1 1 0.2 2 5 0.2 10 5 5 1

Asper­ gillus niger 0.5 5 1 5 1 5 5 2 5 5 2 0.5 2

(C H ) SnOH (C H ) SnCl (C H )3SnBr (C H ) SnI [(C H ) Sn] S [(C H )3Sn] S04 (C H ) s S n O — C O — C H (C H ) sSnO—CO—CiHu (CVHshSnO—CO—C11H23 (CîHe) aSnO—CO—CeHe [ (C Hi) iSnO—CO—]îCHi [ (C2H6) sSnO—CO—CH=] j (C H ) SnO—C H

Botrytis allii 0.2 0.5 0.5 0.5 0.2 0.2 1 1 0.2 2 0.5 0.5 0.5

(C2H5) «SnO—CeHi—NOj (p)

0.5

2

2

(C H ) Sn-S0 —CeHi—CH«(p)

1

5

2

2

(CîH^sSnNH—SO^CeH —CH (p)

1

5

2

5

(C H ) SnNH—SO2—CH CO

0.5

5

2

2

1

10

2

2

0.2

5

1

2

Formula 2

2

2

6

3

6

3

6

2

5

3

2

2

6

3

6

2

6

2

6

2

2

3

2

2

6

2

8

6

6

3

6

2

4

2

6

3

(CIHOISIIN''

3

\) Η (ο) 6

3

Rhizopus nigricans 0.5 2 1 2 1 5 2 2 5 5 1 0.5 1 2

4

CO 7

iV-Triethylstannylphthalimide

(CtHiJaSnN^

^CeH^o)

CO

METAL-ORGANIC COMPOUNDS Advances in Chemistry; American Chemical Society: Washington, DC, 1959.

196

ADVANCES IN CHEMISTRY SERIES

T a b l e I V shows t h a t r e l a t i v e l y s l i g h t v a r i a t i o n s o c c u r i n t h e f u n g i t o x i c i t y of t r i e t h y l salts of a w i d e range o f i n o r g a n i c a n d o r g a n i c a c i d s . V a r y i n g t h e three a l k y l g r o u p s a t t a c h e d t o t h e t i n a t o m , b u t u s i n g a l w a y s t h e same s a l t — t h e a c e t a t e — r e v e a l e d t h a t t h e f u n g i t o x i c i t y w a s l i n k e d w i t h t h e c h a i n l e n g t h of a l k y l g r o u p s . T h e f u n g i t o x i c i t y of s y m m e t r i c a l t r i a l k y l t i n acetates,

Table V.

Influence of Varying

G r o u p R on Antifungal Properties

of Compounds R S n O — C O — C H

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H

10 25 26 28 29 30 31 32 33 49 50

Name Trimethyltin acetate Triethyltin acetate Tri-n-propyltin acetate Triisopropyltin acetate Tri-n-butyltin acetate Tri-n-pentyltin acetate Tri-w-hexyltin acetate Tri-n-octyltin acetate Tricyclohexyltin acetate Triphenyltin acetate Phenylmercuric bromide Phenylmercuric acetate

(7 7)

Concn. (P.P.M. = M g . / L . ) Causing Complete Inhibition of Growth of Fungi

Compound No. 1

A

Formula

Botrytis allii

Pénicillium italicum

Aspergillus niger

Rhizopus nigricans

20

20

200

200

(C H ) S n O — C O — C H s

1

2

5

2

(C3H7) 3SnO—CO—CH3

0.1

0.1

1

1

(C3H7) S n O — C O — C H s

0.1

0.1

1

0.5

(C4H9) S n O — C O — C H 3

0.1

0.1

0.5

(C5H11) S n O — C O — C H s

0.2

5

5

(CH ) SnO—CO—CHs 3

2

3

5

3

8

3

3

(CeHuhSnO—CO—CHe (Cslin) S n O — C O — C H s 3

1 >100

0.5 10

10

20

100

>100

MOO

>100

(CeHu) sSnO—CO—CHs

0.5

0.5

5

20

(C H ) SnO—CO—CHs

2

1

0.5

10

CeHôHgBr

0.1

0.1

0.1

2

C H HgO—CO—CHs

0.5

0.5

0.5

5

6

6

5

3

6

i n w h i c h a l l t h r e e a l k y l g r o u p s a r e t h e same, shows g r a d a t i o n t h r o u g h t h e series, being l o w w i t h t r i m e t h y l , m a x i m a l w i t h t r i - n - b u t y l , a n d declining t o almost negligible v a l u e s i n t h e t r i o c t y l s . T r i c y c l o h e x y l is a b o u t as t o x i c as t r i p e n t y l a n d t h e t r i p h e n y l is of a b o u t t h e same o r d e r of t o x i c i t y as t r i e t h y l . F o r c o m p a r i s o n , figures f o r p h e n y l m e r c u r i c b r o m i d e a n d acetate a r e i n c l u d e d . T h e i r f u n g i t o x i c i t y i s a b o u t t h e same as t h a t of t r i b u t y l t i n acetate. A n o t h e r v a r i a t i o n is s h o w n i n T a b l e V I , i n w h i c h t w o of t h e a l k y l s a r e a l w a y s e t h y l s a n d t h e t h i r d ranges f r o m e t h y l t o d o d e c y l . T h e m a x i m a l f u n g i t o x i c i t y i s possessed b y t h e d i e t h y l h e x y l t i n acetate.

Table VI.

Antifungal Activity of a Series of Diethylalkyltin Acetates (7 7) Concn. (P.P.M. = M g . / L . ) Causing Complete inhibition of Growth of Fungi

Compound No. 10 41 42 43 44

Name Triethyltin acetate Diethyl-nbutyltin acetate Diethyl-nhexyltin acetate Diethyl-noctyltin acetate Diethyl-ndodecyltin acetate

Formula

Botrytis allii

Pénicillium italicum

Aspergillus niger

Rhizopus nigricans

(C H )3SnO—CO—CHs

1

2

5

2

(C H ) 2 (C4H9) SnO—CO - CHs

0.1

1

0.5

0.5

(C H5MCeHi8)SnO—CO- - C H s

0.05

0.5

0.1

0.1

(C2H5) 2 (CsHn) S n O — C O - C H s

0.02

0.5

0.1

>5

(C H ) (Ci H 5)SnO—CO- - C H s

0.2

5

0.5

50

2

2

6

6

2

2

5

2

2

2

F o r c o m p a r i s o n , t h e f u n g i t o x i c i t y of some u n s y m m e t r i c a l t r i a l k y l t i n acetates i s given i n Table V I I .

METAL-ORGANIC COMPOUNDS Advances in Chemistry; American Chemical Society: Washington, DC, 1959.

LEWIS AND HEDGES-APPLICATIONS OF ORGANOTIN COMPOUNDS Table VII.

Antifungal

197

Activity of Some Further Unsymmetrical

Trialkyltin

Acetates (??) Concn. (P.P.M. = M g . / L . ) Causing Complete Inhibition of Growth of Fungi

Compound No. 45 46

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47 48

Name Dimethyl-nbutyltin acetate Dimethyl-noctyltin acetate Dimethyl-wdodecyltin acetate Ethyldi-r?pentyltin acetate

Botrytis allii

Formula (CH ) (C4lI )SnO—CO- - C H 3

2

9

3

(CH ) (C Hi7)SnO—CO- - C H 3

2

8

3

Pénicillium italicum

Aspergillus niger

1

2

5

5

0.5

0.5

0.2

2 10

(CHaMCuHaOSnO—CO-- C H (CHaMCuHaOSnO—CO-

3

0.2

1

0.2

(CiH )(C*Hii) SnO—CO- - C H

3

0.2

1

1

5

2

Rhizopus nigricans

0.5

W h e n t h e s u m t o t a l o f t h e c a r b o n a t o m s i n t h e t h r e e a l k y l c h a i n s ranges f r o m 10 t o 12, t h e f u n g i t o x i c i t y is a t a m a x i m u m . S o m e m i x e d a l i p h a t i c - a r o m a t i c c o m p o u n d s h a v e been m a d e a n d also some a r o ­ m a t i c c o m p o u n d s c o n t a i n i n g h a l o g e n i n t h e benzene n u c l e u s . T h e test r e s u l t s a r e s u m m a r i z e d i n T a b l e V I I I . I n t r o d u c t i o n of h a l o g e n i n t o t h e p h e n y l g r o u p s does n o t Table VIII.

Antifungal Activity of Some M i x e d Aliphatic-Aromatic a n d of HalogenSubstituted Aromatic Tin Compounds (??) Concn. (P.P.M. = M g . / L . ) Causing Complete Inhibition of Growth of Fungi

Compound No. 36 37 38 39 40 34

Name Diethylphenyltin acetate Ethyldiphenyltin acetate n-Octyldiphenyltin acetate Diethyl-pbromophenyltin acetate Diethyl-pchlorophenyltin acetate Tris-p-chlorophenyltin acetate

(C H ) (C6H )SnO—CO—CH 2

5

2

5

3

(C H ) ( C H ) 2 S n O — C O — C H 2

6

6

Pénicillium italicum

Aspergillus niger

Rhizopus nigricans

1

5

2

5

0.5

1

1

5

5

5

20

Botrytis allii

Formula

5

3

(CeHn) (CeHshSnO—CO—CH

3

10

(C II ) 2 (BrC H ) SnO—CO—CHs

0.2

0.5

1

1

(C2H5) (ClCelli) S n O — C O — C H s

0.1

1

1

2

20

50

2

6

6

4

2

20

(CICeHO sSnO—CO—CHs

>100

a l w a y s h a v e t h e effect o f i n c r e a s i n g t h e f u n g i t o x i c i t y . D i e t h y l - p - c h l o r o p h e n y l t i n i s somewhat more toxic t h a n d i e t h y l p h e n y l t i n , b u t t h e t r i s - p - c h l o r o p h e n y l t i n is of d i m i n i s h e d a n t i f u n g a l a c t i v i t y . I t is v e r y u n u s u a l t o f i n d a n e x a m p l e o f a b i o c i d a l c o m p o u n d i n w h i c h t h e r e p l a c e m e n t o f p h e n y l g r o u p s b y p - c h l o r o p h e n y l g r o u p s does n o t l e a d t o a n increase i n b i o c i d a l a c t i v i t y .

Toxicity to M a m m a l s T h e t o x i c i t y of t h e o r g a n o t i n c o m p o u n d s has b e e n s t u d i e d b y s e v e r a l i n v e s t i g a t o r s . Barnes a n d his collaborators have published a n u m b e r of papers dealing w i t h t h e p h y s i o l o g i c a l effects p r o d u c e d b y o r g a n o t i n c o m p o u n d s a n d t h e l e t h a l doses o f a l a r g e n u m b e r o f t h e a l k y l t i n s h a v e been d e t e r m i n e d . S o m e o f these results a r e e m b o d i e d i n T a b l e I X {19). T r i e t h y l t i n h y d r o x i d e is t h e m o s t t o x i c w h e t h e r a d m i n i s t e r e d b y i n j e c t i o n o r b y m o u t h . I n t r a p e r i t o n e a l i n j e c t i o n o f t r i - n - b u t y l t i n acetate shows t h i s m a t e r i a l t o b e n e a r l y as t o x i c b y t h i s route. O n the other h a n d , the oral L D is c o n s i d e r a b l y g r e a t e r t h a n f o r t r i e t h y l t i n h y d r o x i d e i n t h e case o f t h e r a t . L a t e r w o r k suggests t h a t t h e L D for rats f o r 5

0

5

0

METAL-ORGANIC COMPOUNDS Advances in Chemistry; American Chemical Society: Washington, DC, 1959.

ADVANCES IN CHEMISTRY SERIES

198 Table IX.

Certainly Lethal Doses (Mg. per K g . of Body Weight) of a Range of Organic Tin Compounds Rat

Rabbit

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Compound Trimethyl Triethyl Tri-n-propyl Tri-iso-propyl Tri-n-butyl Tri-n-hexyl Triphenyl Diethyl phenyl dichloride diiodide Dibutyl dichloride dilaurate Monoethyl trichloride

Oral

I.p.

10

10

60 >40

Oral 30 10 100 >150 50-100 >40 100 100

— —

I.p. 16 10 ( L D M 5-7)

— — 10 — — — 15 26

— 85

200

Guineapig Oral

—

5-10

— — 20 — 10 — — — — — —

t r i b u t y l t i n a c e t a t e g i v e n b y m o u t h is n e a r e r 4 0 0 m g . p e r k g . I n t h e case o f t r i o c t y l t i n a c e t a t e 4 0 0 m g . p e r k g . w a s w i t h o u t effect a n d i n t r a p e r i t o n e a l i n j e c t i o n o f 4 8 m g . p e r k g . w a s n o t fatal. I t appears, therefore, t h a t t h e m a m m a l i a n t o x i c i t y follows t h e same g e n e r a l course as t h e f u n g a l t o x i c i t y , d e c r e a s i n g as t h e c h a i n l e n g t h s o f t h e a l k y l s a t t a c h e d t o t h e t i n a t o m increase. T h e r e is n o e v i d e n c e i n t h i s w o r k t h a t t h e t i n i s c o n c e n t r a t e d i n a n y p a r t i c u l a r o r g a n b u t t h e r e a r e u s u a l l y s t r o n g effects o n t h e c e n t r a l n e r v o u s s y s t e m . I f t h e a n i m a l s d o n o t d i e a t once o r w i t h i n a v e r y f e w d a y s as a r e s u l t of t h e a d m i n i s t r a t i o n of t h e o r g a n o t i n c o m p o u n d , t h e y m a k e a c o m p l e t e recovery a n d t h e organs show n o permanent damage. I t i s r e a s s u r i n g t o n o t e t h a t L u i j t e n a n d v a n d e r K c r k state (12) : O r g a n o t i n c o m p o u n d s a r e also t o x i c t o w a r d s h u m a n s , t h e first s y m p t o m s o f p o i s o n ­ i n g resembling s y m p t o m s of concussion of t h e b r a i n . D u r i n g o u r w o r k , carried o u t f o r five y e a r s w i t h n o o t h e r p r e c a u t i o n s t h a n those n o r m a l i n c h e m i c a l l a b o r a t o r y p r a c t i c e , o n l y a f e w i s o l a t e d cases o f s t e r n u t a t o r y o r v e s i c a n t a c t i o n were n o t e d .

Biocidal Applications of Trialkyltin Compounds T h e a n t i f u n g a l p r o p e r t i e s o f t h e t r i a l k y l t i n c o m p o u n d s h a v e a r o u s e d t h e greatest i n t e r e s t , because t h e y a r e c l e a r l y o f a v e r y h i g h o r d e r , c o m p a r a b l e w i t h those o f o r g a n o m e r c u r i a l s . T h e r e i s o n e o b v i o u s a d v a n t a g e possessed b y t h e o r g a n o t i n s as c o m p a r e d w i t h o t h e r b i o c i d a l agents, i n t h a t t h e m o s t a c u t e t o x i c i t y i s s p e c i f i c a l l y a p r o p e r t y o f t h e t i n a t o m o n l y so l o n g as i t i s j o i n e d d i r e c t l y t o t h r e e c a r b o n a t o m s , a n d so soon as e v e n one o f these b o n d s w i t h c a r b o n h a s been b r o k e n t h e r e i s a g r e a t f a l l i n t o x i c i t y . B y successive b r e a k a g e s o f t h e t w o r e m a i n i n g c a r b o n b o n d s t h e t i n is t r a n s f o r m e d i n t o t h e n o r m a l l y h a r m l e s s i n o r g a n i c t i n . T h e r e i s , t h e r e f o r e , t h e a t t r a c t i v e p o s s i b i l i t y t h a t w h e n t r i a l k y l t i n c o m p o u n d s h a v e been u s e d as f u n g i c i d e s , t h e residues b e c o m e i n t h e course o f t i m e c h a n g e d i n t o a h a r m l e s s m a t e r i a l . I n v i e w o f t h e g e n e r a l b i o c i d a l a c t i v i t y o f t h e t r i a l k y l t i n c o m p o u n d s (10), t h e i r use so f a r h a s b e e n r e s t r i c t e d t o a p p l i c a t i o n s w h e r e t h e r e i s n o r i s k t o a n i m a l s o r h u m a n beings. T h e p r e s e r v a t i o n o f w o o d is a s u i t a b l e field o f a p p l i c a t i o n because there is n o risk of k i l l i n g l i v i n g m a t t e r other t h a n t h e fungus. S i m i l a r l y , paper, t e x t i l e s , p a i n t s , a n d o t h e r n o n l i v i n g m a t e r i a l s a r e s u i t a b l e f o r t r e a t m e n t . I t is a different m a t t e r , h o w e v e r , w h e n one considers t h e c o n t a c t of t r i a l k y l salts a n d l i v i n g m a t t e r w h i c h m u s t n o t be killed. F o r example, p h y t o t o x i c i t y has t o b e considered. A l t h o u g h i n t h e discussion of t h e fungitoxic character o f t r i a l k y l t i n compounds a c o n s i d e r a b l e n u m b e r o f substances were c o n s i d e r e d , n o t a l l o f these a r e c o m m e r c i a l l y a v a i l a b l e f o r p r a c t i c a l a p p l i c a t i o n . O n e d o m i n a t i n g f a c t o r i s t h a t t h e d i b u t y l t i n salts are b e i n g m a d e c o m m e r c i a l l y o n a large scale a n d i t i s f a i r l y easy t o v a r y t h e m e t h o d of m a n u f a c t u r e so as t o p r o d u c e t r i b u t y l t i n salts also. T h i s i s n o t t h e case w i t h a n y other organotin c o m p o u n d a n d i f others are required they have t o be made specially.

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H o w e v e r , w i t h a n increasing interest i n the antifungal a n d other biocidal qualities of organotin compounds i t is anticipated that a n u m b e r of t h e m m a y become available commercially.

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Wood

Preservation

Successful trials have been made i n the preservation of various woods against fungi a n d a g a i n s t w o o d - b o r i n g m a r i n e a n i m a l s (1). T r i a l s w i t h different w o o d s h a v e b e e n made i n mines i n C o r n w a l l a n d i n C u m b e r l a n d , where the conditions favored r a p i d d e s t r u c t i o n o f t h e t i m b e r b y f u n g a l g r o w t h . E x p o s u r e s o f 2 a n d 3 y e a r s h a v e so f a r f u l l y c o n f i r m e d t h e a n t i f u n g a l a c t i o n o f t h e t r i e t h y l t i n h y d r o x i d e w h i c h w a s used t o i m p r e g n a t e these t i m b e r s . T h e s o l u t i o n was o f 0 . 5 % s t r e n g t h a n d t h e t i m b e r s were i m p r e g n a t e d b y b e i n g v a c u u m i z e d w h i l e i m m e r s e d i n t h e h o t s o l u t i o n ; t h e t a n k was t h e n a l l o w e d t o c o o l d o w n o v e r n i g h t . T h i s m e t h o d i s n o t a p p l i c a b l e w i t h t h e t r i b u t y l o x i d e o r acetate because o f t h e i r l o w s o l u b i l i t i e s , a n d s o l v e n t i m p r e g n a t i o n of t h e t i m b e r is necessary i f e i t h e r o f these salts i s u s e d . W o o d b l o c k tests h a v e b e e n c a r r i e d o u t i n a n u m b e r o f r e s e a r c h l a b o r a t o r i e s w i t h f a v o r a b l e r e s u l t s . T h e resistance o f b o t h t r i e t h y l t i n h y d r o x i d e a n d t r i b u t y l t i n acetate t o l e a c h i n g i s p a r t i c u l a r l y g o o d . T h e v a l u e o f i m p r e g n a t i o n w i t h t r i e t h y l t i n o r t r i b u t y l t i n c o m p o u n d s a p p e a r s t o b e b e y o n d d i s p u t e , b u t t h e costs, as c o m p a r e d w i t h creosote a n d o t h e r w o o d p r e s e r v a t i v e s , h a v e n o t y e t been t h o r o u g h l y d e t e r m i n e d . P e r h a p s they m a y be used i n conjunction w i t h other wood preservatives w h i c h a r e more prone t o leaching. A n i m p o r t a n t feature i n favor of the organotin compounds is t h a t they i m p a r t neither color nor odor t o the treated wood. T h e y can, therefore, be used u p o n light c o l o r e d w o o d s s u c h a s a r e used f o r f u r n i t u r e . W o o d t r e a t e d w i t h o r g a n o t i n c o m ­ pounds c a n be p a i n t e d n o r m a l l y a n d there is n o risk of subsequent discoloration. T h e o r g a n o t i n c o m p o u n d s d o n o t increase t h e r i s k o f fire. I t i s also possible t o a p p l y t r i b u t y l t i n c o m p o u n d i n a s o l v e n t t o joists, floors, a n d s k i r t i n g s , etc., i n e x i s t i n g structures either b y b r u s h o r b y s p r a y , w i t h a v i e w t o p r e v e n t i n g t h e spread of m o l d s a n d d r y r o t . I t i s n o t y e t k n o w n w h e t h e r t r i b u t y l t i n acetate i s effective i n p r e v e n t i n g t h e a t t a c k o f t h e f u r n i t u r e beetle, b u t a p r o g r a m o f tests o n t h i s i s b e i n g c a r r i e d o u t i n B e r l i n b y B e c k e r . O t h e r tests w h i c h a r e i n p r o g r e s s i n c l u d e i t s r e ­ sistance t o t h e w h i t e a n t , b u t a g a i n t h e w o r k has n o t y e t been c o m p l e t e d . Much appears t o depend u p o n the d e p t h of the i m p r e g n a t i o n obtained a n d the concentration i n the surface layers. Teredo Tests o n W o o d . Tests carried o u t b y t h e T i n Research Institute a t Shoreham H a r b o u r i n E n g l a n d showed that impregnation w i t h t r i e t h y l and t r i b u t y l salts w a s as effective as creosote a g a i n s t t h e t e r e d o w o o d - b o r i n g w o r m . T h e t r i b u t y l ­ t i n a c e t a t e also r e d u c e d g r i b b l e a t t a c k t o t r i f l i n g a m o u n t s .

Ropes S o m e tests were c a r r i e d o u t i n S h o r e h a m H a r b o u r t o a s c e r t a i n t h e v a l u e o f t r i a l k y l t i n c o m p o u n d s f o r p r e s e r v i n g ropes. A s c o m p a r e d w i t h u n t r e a t e d r o p e s a n d ropes t r e a t e d b y i m p r e g n a t i o n w i t h t w o c o m m e r c i a l p r e s e r v a t i v e s , t h e t r i a l k y l t i n s o l u t i o n s w e r e v e r y effective. A l l t h e r o p e s w h i c h were i m p r e g n a t e d w i t h t r i a l k y l t i n c o m p o u n d s s u r v i v e d t h e test a n d were w i t h d r a w n w i t h o u t b r e a k a g e , whereas 13 o u t of 16 o f t h e o t h e r ropes b r o k e e i t h e r d u r i n g w i t h d r a w a l o r a t t h e first s l i g h t t e n s i o n p u t u p o n t h e m i n the laboratory.

Wood Pulp T r i a l s w h i c h h a v e n o w been g o i n g o n f o r o v e r a y e a r a t s o m e p a p e r m i l l s i n C a n a d a show t h a t a dispersion of t r i e t h y l t i n oxide is a complete p r e v e n t i v e of slime

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f o r m a t i o n d u r i n g t h e m a n u f a c t u r e o f w o o d p u l p . A m o u n t s of less t h a n 1 p . p . m . of t h e w a t e r u s e d are effective i n c o n t r o l l i n g t h e s l i m e . T h e effluent w a t e r i s free f r o m organotin c o m p o u n d i n significant a m o u n t , a n d the t r i b u t y l t i n oxide r e m a i n i n g i n the p a p e r is t o o s m a l l i n a m o u n t t o be a p p r e c i a b l e : D u r i n g c a l e n d e r i n g a n d exposure t o heat, light, a n d a i r there should be a f a i r l y complete b r e a k d o w n of t h e residual t r i b u t y l t i n c o m p o u n d i n t o h a r m l e s s i n o r g a n i c t i n ; t h i s m a y w e l l p r o v e t o b e a decisive a d v a n t a g e f o r t h e o r g a n o t i n c o m p o u n d s as c o m p a r e d w i t h o t h e r s l i m i c i d e s w h i c h a r e i n c o m m o n use a t p r e s e n t .

Paints E x c e l l e n t results h a v e b e e n r e p o r t e d w i t h s m a l l a m o u n t s of t r i b u t y l t i n acetate as a f u n g i s t a t i n p o l y ( v i n y l a c e t a t e ) p a i n t s ( 7 , 8). I n tests c a r r i e d o u t r e c e n t l y i n E n g l a n d i n w h i c h a l l the u s u a l f u n g i s t a t i c m a t e r i a l s f o r p a i n t s were i n c l u d e d , t r i b u t y l ­ t i n h y d r o x i d e w a s effective a t a c o n c e n t r a t i o n o f 1 p a r t i n 4000 u n d e r v e r y b a d c o n d i t i o n s i n w h i c h a l l t h e o t h e r f u n g i s t a t s were ineffective e v e n a t 16 t i m e s t h i s c o n ­ centration. P r a c t i c a l trials i n tropical a n d subtropical atmospheres have confirmed t h a t t r i b u t y l t i n oxide a t l o w c o n c e n t r a t i o n s p r e v e n t s t h e g r o w t h o f d i s f i g u r i n g f u n g i d u r i n g the whole life of the p a i n t .

Antifouling

Compositions

P r e l i m i n a r y l a b o r a t o r y w o r k i n E n g l a n d showed t h a t t r i e t h y l t i n h y d r o x i d e a t high dilution killed t h e larvae of barnacles a n d other organisms concerned w i t h m a r i n e fouling. T h i s w o r k w a s followed b y several years of testing of p a i n t e d w o o d e n p a n e l s w h i c h were i m m e r s e d i n sea w a t e r i n t h e T i n R e s e a r c h I n s t i t u t e ' s r a f t i n S h o r e h a m H a r b o u r . T r i e t h y l t i n c o m p o u n d s a g a i n s h o w e d t h e i r effectiveness, i n t h a t p a n e l s t r e a t e d w i t h a p a i n t c o n t a i n i n g t r i e t h y l t i n c o m p o u n d s were e n t i r e l y free f r o m f o u l i n g o r g a n i s m s o r weed f o r m a n y m o n t h s . T h e safe p e r i o d w a s f o l l o w e d b y r a t h e r s u d d e n b r e a k d o w n , associated u n d o u b t e d l y w i t h t h e h i g h r a t e of l e a c h i n g of these c o m p o u n d s . T h e r a t e of l e a c h i n g o f t r i b u t y l t i n c o m p o u n d s i n sea w a t e r is m u c h less a n d t h e t r i b u t y l t i n c o m p o u n d s i n f a c t p r e s e r v e t h e i r a n t i f o u l i n g effect f o r m u c h l o n g e r p e r i o d s . A s i s w e l l r e c o g n i z e d i n t h i s field, t h e w h o l e p r o b l e m is b o u n d u p w i t h c o m p a t i b i l i t y w i t h the p a r t i c u l a r paint m e d i u m . A l t h o u g h n o commercially acceptable antifouling c o m p o s i t i o n b a s e d o n o r g a n o t i n c o m p o u n d s is y e t a v a i l a b l e , t h e r i g h t k i n d of a c t i o n is t h e r e a n d p r a c t i c a l tests a r e b e i n g c o n t i n u e d i n c o l l a b o r a t i o n w i t h p a i n t m a n u ­ facturers.

Textiles W o o l i m p r e g n a t e d w i t h t r i b u t y l t i n acetate i s i m m u n e t o a t t a c k b y m o t h a n d b y c a r p e t beetle. I t i s a c o m p l e t e i m m u n i t y , i n t h a t t h e g r u b s d o n o t e v e n b e g i n t o feed u p o n t h e t r e a t e d s a m p l e s , so t h e r e m u s t b e a r e p e l l e n t a c t i o n . F o r f a b r i c s w h i c h h a v e t o b e w a s h e d f r e q u e n t l y i t w i l l b e necessary t o choose a n o r g a n o t i n c o m ­ p o u n d w i t h g r e a t e r resistance t o l e a c h i n g t h a n is possessed b y t h e t r i b u t y l t i n a c e t a t e . I n cases w h e r e t h e f a b r i c s w i l l c o m e i n t o c o n t a c t w i t h t h e s k i n , i t w i l l first b e necessary t o b e satisfied t h a t t h e r e i s n o a b s o r p t i o n o f t h e t i n c o m p o u n d t h r o u g h t h e s k i n . J u t e is o f t e n exposed t o m o i s t c o n d i t i o n s f a v o r i n g f u n g a l g r o w t h w h i c h r o t s t h e fiber. T e s t s w i t h b u r i e d s t r i p s o f j u t e i n a t r o p i c a l c l i m a t e s h o w e d t h a t t h e r e was v i r t u a l l y n o d e t e r i o r a t i o n o f t r e a t e d j u t e s a m p l e s a f t e r one m o n t h , b u t t h e u n t r e a t e d c o n t r o l s l o s t a l l t h e i r s t r e n g t h i n a few d a y s .

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LEWIS AND HEDGES-APPLICATIONS OF ORGANOTIN COMPOUNDS Crop Protection (3, 70)

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T h e u n i q u e p r o p e r t i e s of o r g a n o t i n c o m p o u n d s as b i o c i d a l agents m a k e t h e m w o r t h y o f v e r y serious s t u d y i n a g r i c u l t u r e , a l t h o u g h t h e r e a r e difficulties t o b e o v e r ­ come. O n t h e c r e d i t side a r e t h e a d m i t t e d l y h i g h f u n g i c i d a l a c t i o n a n d t h e t o x i c i t y t o insect pests. F o r e x a m p l e , t h e t r i e t h y l t i n a n d t r i b u t y l t i n c o m p o u n d s a r e t o x i c t o r e d s p i d e r . T h e n o n p e r m a n e n t c h a r a c t e r of t h e t o x i c i t y of t h e o r g a n o t i n c o m p o u n d s is o f great p o t e n t i a l i n t e r e s t f o r t w o reasons. F i r s t , these c o m p o u n d s u l t i m a t e l y decompose under the action of light a n d a i r into harmless inorganic t i n a n d there is therefore n o d a n g e r o f t h e l a n d ' s b e c o m i n g p o i s o n e d so t h a t c r o p s e i t h e r c a n ­ n o t g r o w o r , i f t h e y d o , c o n t a i n u n d e s i r a b l e a m o u n t s o f t o x i c substances. Ele­ m e n t a l t i n a p p e a r s t o b e e n t i r e l y w i t h o u t t r a c e effects u p o n l i v i n g m a t t e r . S e c o n d l y , i t m a y b e possible t o d e v e l o p o r g a n o t i n c o m p o u n d s w h i c h a r e t o x i c t o f u n g i a n d pests w h e n a p p l i e d b u t w h i c h d e c o m p o s e i n t o i n o r g a n i c t i n w i t h i n a f e w d a y s a n d leave o n l y h a r m l e s s residues o n t h e c r o p s w h e n h a r v e s t e d . O n t h e d e b i t side, t h e r a t h e r c r u d e t r i a l k y l t i n c o m p o u n d s , w h i c h a r e t h e o n l y ones so f a r t e s t e d , a r e t o x i c t o f u n g i a n d t o pests b u t a r e t o x i c also t o t h e p l a n t s w h i c h i t is t h e i r p u r p o s e t o p r o t e c t . I t i s essential t h a t n e w t y p e s of o r g a n o t i n c o m p o u n d s be f o u n d w h i c h a r e s e l e c t i v e l y t o x i c t o t h e pests a n d n o t t o t h e p l a n t s . M u c h w o r k r e m a i n s t o b e done here, b u t t h e w o r k o f v a n d e r K e r k a n d others h a s a l r e a d y demonstrated that fungitoxicity a n d phytotoxicity do n o t always r u n parallel. Indi­ c a t i o n s h a v e been o b t a i n e d t h a t h i g h l y f u n g i t o x i c o r g a n o t i n c o m p o u n d s m a y possess n o h i g h e r p h y t o t o x i c i t y t h a n c e r t a i n o r g a n o m e r c u r y c o m p o u n d s n o w i n c o m m o n use as seed d i s i n f e c t a n t s . M o r e o v e r , p h y t o t o x i c i t y c a n be r e d u c e d c o n s i d e r a b l y b y p r o p e r f o r m u l a t i o n . P e r h a p s m o r e p r o m i s i n g s t i l l is t h e p o s s i b i l i t y of p r e p a r i n g f u n c t i o n a l l y substituted organotin compounds.

Tetraalkyl- and Aryltin Compounds T a b l e X (11) shows some of t h e p r o p e r t i e s of t e t r a a l k y l t i n s , w h i c h a r e o f a d i f ­ ferent o r d e r o f t o x i c i t y f r o m t h e t r i a l k y l s (21).

Table X.

Melting a n d Boiling Points of Some Compounds of the Typa R Sn(?7) 4

Name of Compound Methylstannane Di methylstannane Tri methylstannane Tetramethyltin Tetraethyltin

Formula CH SnH (CH ) SnH (CH ) SnH (CH ) Sn (C H )4Sn

Tetra-n-propyltin Tetra-n-butyltin Tetra-n-dodecyltin

(C H ) Sn (C H ) Sn (C^H^Sn

3

3

3

2

M.P., °C.

2

3

3

3

4

5

3

7

4

4

9

4

2

-112

B.P. °C. 0 35 59 78 175 /222-225 \ 116 145

Mm. 760 760 760 760 760 760 13 10

T a b l e X I , based o n t h e w o r k of M e y n i e r (2, 15), shows t h e m a m m a l i a n t o x i c i t y of eight t e t r a a l k y l t i n c o m p o u n d s t o w a r d s m i c e . T h e first t w o c o l u m n s a r e i n t r a ­ p e r i t o n e a l doses, t h e n e x t t w o c o l u m n s a r e i n t r a v e n o u s doses, c o l u m n s 5 a n d 6 g i v e i n t r a m u s c u l a r doses, a n d t h e last t w o c o l u m n s a r e doses b y o r a l a d m i n i s t r a t i o n . T h e m a x i m u m t o x i c i t y i s associated w i t h t h e s m a l l e s t n u m b e r of c a r b o n a t o m s d i r e c t l y a t t a c h e d t o t h e t i n . A s t h e c h a i n l e n g t h s g r o w , u p t o o c t y l , t h e b i o c i d a l a c t i o n shows a consistent decline a n d t h e t e t r a o c t y l , f o r e x a m p l e , i s m a r k e d l y less t o x i c t h a n t e t r a h e x y l o r t e t r a h e p t y l . N o figures a r e as y e t p u b l i s h e d f o r m i x e d t e t r a a l k y l t i n s or t e t r a a r y l t i n s .

METAL-ORGANIC COMPOUNDS Advances in Chemistry; American Chemical Society: Washington, DC, 1959.

202

ADVANCES IN CHEMISTRY SERIES Table XI.

Toxicity of Tetraalkyltin Compounds to Mice (15) Maximum Never Fatal Dose, Mmoles/Kg.

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Alkyl Group Methyl Ethyl n-Propyl Isopropyl n-Butyl Isobutyl n-Amyl Isoamyl Hexyl Heptyl Octyl

Formula (CH ) Sn (C H )4Sn (CsH7)4Sn (C«H7)4Sn (C4H ) Sn (C4H ) Sn (C Hii) Sn (C Hn) Sn (C Hi ) Sn (C Hi )4Sn (C Hi )4Sn 8

2

I.p.* 0.01 0.005 0.2 0.05 0.5 0.1 0.25 0.05 1.0 0.75 40.0

4

6

8

4

9

4

5

4

6

4

fi

3

7

5

8

7

4

Ι.ν.· 0.4 0.4 0.2 0.005 0.5 0.01 0.25 0.05 1.0 2.0 20.0

a

0.· 0.1 0.1 0.1 0.1 2.0 0.5 1.0 0.25

— —

>20.0

Millemoles per kilogram of body weight. Intraperitoneal. « Intravenous. Intramuscular. « Oral.

β

6

d

I n g e n e r a l , t h e t o x i c effects o f t h e t e t r a a l k y l t i n s o r t e t r a a r y l t i n s a r e slower t o m a n i f e s t themselves t h a n t h e c o r r e s p o n d i n g t r i - c o m p o u n d s a n d i n some cases t h e a c t i o n m a y be d e l a y e d f o r 30 d a y s o r e v e n l o n g e r . W h e n t o x i c s y m p t o m s d o a p p e a r , t h e y a r e i d e n t i c a l i n c h a r a c t e r t o those c a u s e d b y t r i a l k y l t i n c o m p o u n d s a n d t h i s f a c t suggests t h a t t h e r e is first a b r e a k d o w n o f t h e t e t r a - c o m p o u n d i n t o t h e t r i - f o r m a n d t h a t t h i s is t h e effective t o x i c agent. A l m o s t t h e o n l y use of t h e t e t r a a l k y l t i n a n d t e t r a a r y l t i n c o m p o u n d s has b e e n as a d ­ ditives t o chlorinated hydrocarbons used as coolants f o r electrical transformers. A m o u n t s of t h e o r d e r o f 1 % of these t e t r a - c o m p o u n d s a r e effective i n a b s o r b i n g t h e h y d r o c h l o r i c a c i d w h i c h t e n d s t o b e s p l i t off a t e l e v a t e d t e m p e r a t u r e s a n d w h i c h , i f n o t n e u t r a l i z e d , acts as a n a u t o c a t a l y s t o f f u r t h e r d e c o m p o s i t i o n . T h e t e t r a a l k y l t i n s a r e n o t a b l y different f r o m t h e o t h e r categories of o r g a n o t i n compounds, i n t h a t a l l their four bonds are l i n k e d t o carbon atoms i n a n exactly analogous w a y t o t h e c a r b o n a t o m a t a t e r t i a r y j u n c t i o n i n a n o r g a n i c c o m p o u n d : R'"

R'"

I

I

R"—Sn—R""

R"—c—R""

I

I

R' R' A s hydrocarbons, compounds of this type w o u l d n o t appear t o have outstand­ i n g l y i n t e r e s t i n g features, b u t a t o t a l l y n e w field o f p o s s i b i l i t i e s h a s been o p e n e d u p b y t h e discovery of a m e t h o d b y w h i c h f u n c t i o n a l groups c a n be i n t r o d u c e d into one o r m o r e o f t h e c a r b o n c h a i n s a t t a c h e d t o t h e t i n a t o m . E v i d e n t l y i t i s n o w possible t o p r e p a r e c o m p o u n d s w h i c h a r e exact analogs o f o r g a n i c c o m p o u n d s o f t h e t e r t i a r y t y p e b u t w h i c h h a v e a t i n a t o m i n s t e a d of a c a r b o n a t t h e b r a n c h i n g p o i n t . S u c h o r g a n o t i n c o m p o u n d s as the f o l l o w i n g h a v e a l r e a d y been m a d e a n d , i n t h e o r y , a l m o s t a n y t y p e of functional group can n o w be i n t r o d u c e d into organotin compounds i n i m i t a t i o n of c a r b o n c o m p o u n d s , w i t h t h e l i m i t a t i o n o n l y t h a t a l l s u c h c o m p o u n d s a r e e s s e n t i a l l y of t h e t e r t i a r y t y p e . T h i s l i m i t a t i o n i s d u e t o t h e f a c t t h a t i f t h e t i n a t o m c a r r i e s o n e or more hydrogen atoms i t is, i n fact, a h y d r i d e a n d consequently v e r y reactive t o a n y source o f o x y g e n i n i t s v i c i n i t y . T h e p o s s i b i l i t y o f s t a b l e c o m p o u n d s b a s e d o n chains of m e t h y l e n i c - t i n units, — S n H — , i n simulation of o r d i n a r y methylenic groups, — C H — , i s e x c l u d e d i f r e d u c i b l e substances a r e p r e s e n t . T o s u m u p , t h e r e n o w exists t h e p o s s i b i l i t y o f p r e p a r i n g c o m p o u n d s o f t h e g e n e r a l type: 2

2

R' C H — (CH ) —Sn— (CH ) —X 3

2

n

2

n

R"

METAL-ORGANIC COMPOUNDS Advances in Chemistry; American Chemical Society: Washington, DC, 1959.

LEWIS AND HEDGES-APPLICATIONS OF ORGANOTIN COMPOUNDS

203

where X is the functional group, with the proviso that, for stability, R ' and R " shall be sufficiently large groups, either alkyl or aryl, to screen the tin atom from oxidation.

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Literature Cited (1) Britton, S. C., Tin and Its Uses 36, 10 (1956). Organotin compounds for timber. (2) Caujolle, F., Lesbre, M., Meynier, D., Compt. rend. 239, 556 (1954) ; 240, 1732, 1829 (1955). (3) Corke, A. T. K., J. Hort. Sci. 30 (3), 197 (1955). Laboratory tests on fungicides. (4) Frankland, Edward, Ann. 85, 329 (1853). (5) Gay, P. J., Tin and Its Uses 29, 6 (1953). Stabilizers for chlorinated rubber enamels. (6) Gras, G. C., "L'Etain. Etude expérimentale du pouvoir anthelminthique de quelques: composés minéraux et organiques," doctoral thesis, Montpellier University, 1956. (7) Hedges, E . S., Mfg. Chemist 28 (Jan. 16, 1957) ; Times Rev. Ind., 8 (May 1954). Tin compounds and alloys. Outlets recently developed in plastics, pestology, and metallurgy. (8) Hedges, E . S., Tin, 8 (August 1953). New use for tin in compounding special paints. (9) Löwig, C., Ann. 84, 320 (1852). (10) Luijten, J.G. Α., T. N. O. Nieuws 10 (110), 170 (May 1955). Biocidal properties of organic tin compounds. (11) Luijten, J. G. Α., Van der Kerk, G. J. M., "Investigations in the Field of Organotin Chemistry," pp. 7, 13, 14, 21, 29, 47, Tin Research Institute, London, 1955. (12) Ibid., p. 65. (13) McCabe, W. L., Mead, B. (to Standard Oil Dev. Co.), U . S. Patent 1,857,761 (May 10, 1932). (14) Mack, G. P., Parker, E. (to Advance Solvents and Chemical Corp.), Ibid., 2,618,625 (Nov. 18, 1952). (15) Meynier, Denise, "Recherches expérimentales sur la toxicité des tetraalcoylstannanes symétriques," doctoral thesis, Toulouse University, 1956. (16) Quattlebaum, W. M., Noffsinger, C. A. (to Carbide and Carbon Chemicals Corp.), U. S. Patent 2,307,157 (Jan. 5, 1942). (17) Smith, H . V., "Stabilization of Vinyl Chloride Polymers by Means of Organic Compounds of Tin," Plastternik Conference, Stockholm, 1954. (18) Smith, H. V., Tin and Its Uses 29, 7 (1953). (19) Stoner, H . B., Barnes, J. M., Duff, J. I., Brit. J. Pharmacol. 10 (1), 16 (1955). (20) Van der Kerk, G. J. M., Luijten, J. G. Α., Ind. chim. beige 2 (16), 567 (1956). Développements récents dans la recherche des composés organiques de l' étain. (21) Van der Kerk, G. J. M., Luijten, J. G. Α., J. Appl. Chem. (London), 4 (16), 301, 314 (1954) ; 6 (2), 49, (3), 93, (1956) ; 7, 363, 366 (1957). (22) White, T. P., Arch, exptl. Pathol. Pharmakol. 13, 53 (1881). (23) Worden, A. N., Vet. Record 65 (36), 586 (1953). (24) Yngve, Victor (to Carbide and Carbon Chemicals Corp.), U . S. Patents 2,219,463 (Oct. 29, 1940) ; 2,267,777, 2,267,779 (Dec. 30, 1941) ; 2,307,092 (Jan. 5, 1943). (25) Ibid., 2,307,092 (Jan. 5,1943). RECEIVED for review May 10, 1957 Accepted June 1, 1957.

METAL-ORGANIC COMPOUNDS Advances in Chemistry; American Chemical Society: Washington, DC, 1959.