Sovember lSAG
SOMEHERBICIDAL SILICOX Conr~our;ns
30 mg/kg of body weight caused only 37, inhibition, but the tiimor growth could be inhibited t o S5% by increasing the dosc 10 120 nig/kg.
Discussion The Structure of Picrates.-The elemental analyses of the picrates prepared from 4'-aminobutyrophenone hydrochlorides indicate that the products have been dehydrated. Perhaps dehydration occurred during the process of converting the hydrochlorides into the picrates. Since all the picrates were subjected to prolonged heating in absolute alcohol during recrystallization, it seemed reasonable to suspect that the heating caused dehydration. I n order to test this premise, the at tempted picrate of 4'-chloro-4-aminobutyrophenone mas also prepared by adding an aqueous solution of picric acid to the aqueous solution of 4'-chloro-4-aminobutyrophenone hydrochloride. The precipitate was thoroughly wished with water and dried at 40". The infrared spectruni and the melting point of this product proved that the compound was identical with a sample of 2-(4-chlorophenyl)-A1-pyrrolinepicrate. This experiment indicated that dehydration and cyclization took place a t room temperature arid was not due to the influence of heat during recrystallization. The detailed structures of these pyrroline picrates will be discufsed in a subsequent paper. Structure-Activity Relationships.-The in vivo antitumor screening of 4-aniinobutyrophenone hydrochloride indicated that this compound possessed a weak carcinostatic activity, but the effect was not significant from a practical view point. The in vitro cytotoxicity tests against protozoa, bacteria, and mammalian cells disclosed three interesting generalities for structureactivity relationships. I n general the growth-inhibitory activity of the pyrimidinylhydrazones of 4-aminobutyrophenone hydrochlorides are twice as great as that of the parent 4-aminobutyrophenone hydrochlorides.
9.29
The second generality points out that the growthiiiliihitory nc*tdviticsarc greater for !hc Ii,svdroc~hlorides with an rhtroiicgativc halogcn atom a t the para position of the benzene nucleus than for those carrying an electropositive moiety such as hydrogen, methyl, or methoxyl at the same position of the phenyl ring. The third generality indicates that the growth-inhibitory activities of the 4'-halogeno-4-aminobutyrophenonehydrochlorides and their pyrimidinylhydrazones vary with the sizes of the halogen atonis. Thus the activity of the bromo derivative is greater than that of the chloro derivative, which, in turn, i.: greater than that of the Auoro derivative (Tables IV and VII). Consequently, it seems that both inductive and mesomeric effects play a role in determining the magnitudes of the growthinhibitory activities of the compoundq being t r s t d . TABLE1-11 REL.YrIVE GROWTH-ISHIBITORY L~CTIVITIES OF 4-hINOBCTYROPHENOXE HYDROCHLORIDES LSD 2-AMINO.iCETOPHENOSE Organism E . coli K . pneumoniae P. vulgaris P. aeruginosa S. aureus T.pyriformis KB cell culture L cell culture Q
HYDROCHLORIDES
Order of activity'" 13>10>11>14>15> 8>17>12>16>
7 >
9
16>13>17>10>14>11>16>12> 8> 9 > 13> l 6 > 17> l o > 1 4 > 11> 9 > 121 8 > l5>
7
15>13> 8>16>17>12>14>10> 1 6 > 17> 13> l o > 1 1 > 1 4 > l5> 8 >
13>10>11>14> 17 > 10
>
16
>
9
>
8>16>15>
i
7 > Q>ll 9 > 12> i
9>1;>12>
i
11
17 > 16 > 10 > 11 > 9
The numbers correspond to the compounds listed in Tables
11-111.
Among five species of bacteria and one speries of protozoa tested, the P. aeruginosa test system seemed to show more irregularities in adhering to theabove generalities than other test systems.
Some Herbicidal Silicon Compounds J. K. LEASURE AKD J. L. SPEIER~ Rioproducts Department, The Dow Chemical Company, and Organic Research, Dow Corning Corporation, Midland, Michigan Received M a y $1, 1966
A large niimber of organofunctional silicon compounds were examined for biological activity. -4 small, closely related group of (haloalky1)silicon compounds wm found to have strong herbicidal activity in both preemergence and postemergence screening tests, and to act in some cases as defoliants. The active compounds are leachable in moist soil but seem t o become fixed upon drying. These compounds seem to be the first organosilicon compounds that have been found to have herbicidal activity,
,4 program of screening silicon compounds for biological activity revealed a small group of closely related structures that have strong herbicidal activity. Although there exists extensive literature concerned with the herbicidal properties of thousands of chemical compounds, no reference could be found for such activity in an organosilicon compound. Therefore, these results were especially interesting as the first of their kind. (1) Communications concerning this paper may be addresspd t o J. I,. jpeier, no\\ Corning Corp
Active compounds had RCHXSiAleY2 for their structure with R = H or CH3; X = C1, Br, or I; and Y being C1, F, or an alkoxy group. Variations of this structure such as RCX2SillleY2 or RCHXSiMeY or RCHXSiY, showed no activity. (Trichloromethy1)methyldimethoxysilane [C13CMeSi(OAIe)s]was active and an exception to the above generalizations. Hydrolysis of Y and the formation of siloxane polymers would be expected during the testing of all of the active compounds. Therefore the rorresponding polymer [CICHJIeSiO], was prcpnrcrl. I1 had very little
\'Ill. ! I
100 Ill0 1,
I! I
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IO0
71, I,!\
',Ill I1
(1 I!
!!
!I
I! I1
I1 S.i
I1 I1
I1
I1 I! IJ
(1
I! I1
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act ivo
Sovcnihe~IO66
S O M E H E R B I C I D A L SILTCOS COMPOUSIB
T l B L E 111 POSTEMERGEICE TESTS"OF CICHAIeSi(0Ct)~
-__ Concn of spray, ppm--Feet plants
0
10,000
5000
2000
100 100 Pigweed Pinto bean 100 90 100 1larigold 100 Cucumber 98 80 German millet 98 40 95 80 Large crabgrass 20 Japanese millet 40 Kild oats 40 30 40 20 Radish Corn 30 20 20 Sudan grass 30 Meadow fescue 20 20 Ratings are on a scale of 100 = kill, 0 = no effect.
80 90 50 60 20 30 20 0 10 0 20 0
The ease with which chloromet hylmet hyldiet hoxysilane was leached through soil was measured in columns 45.7 c n ~deep and 7.6 cm in diameter. The compound was applied to the top of the column at a rate of 2.24 g/m2 and leached with water. 111 one series of tests the water was applied immediately. I n a second series, the soil was permitted to stand dry for 1week before the leaching. I n the first series, the active chemical mas detected at a depth of 20.3 cm in the column when water to a depth of 15-30 cm was used for leaching. In the second series, the penetration was only 5 em. The distribution of the chemical in the soil was measured by c'omparing the growth of seeds planted in soil taken from different levels in each column. The data indicate that the silicon compound is fairly mobile in wet soil, but that once it dries on the particles of soil, it becomes resistant to the leaching effects of water. In order to determine persistence, the herbicide was applied at 2.24 g/m2 as a preemergent treatment to soil in 20.3-cm glazed crocks. The soil was watered as required for good growth of plants but not enough to cause leaching through the bottom of the pots. Plant growth was observed during 4 weeks, after which the plants were carefully removed from the soil. A second planting was made in the same soil and the cycle was repeated with no further application of the chemical until herbicidal effects were no longer observed. Results of these tests shown in Table I V indicate that the effect of the chemical disappears during the fourth month. TABLE Is' RIONTHLY PLASTISGS IN SOILTREATED ONCE WITH ClCHAIeSi(0Et)p Planting no.
Japanese millet
Radish
Wild oats
40 90 0 20 0 70 0 0 4 0 0 0 Rating on a scale of 100 = kill, 0 = no effect. 1 2
95
no
Cranberry bean
100 70 30 0
Experimental Section Reagents.-Methyltrichlorosilane, dimethyldichlorosilane, methyltrimethoxysilane, and n-propyltrimethoxysilane were redistilled commercial materials sold 11.vDow Corning Corp.
9.51
Chlorination of trimethylchlorosilane was carried out as described by Speier.2 The chlorinated products were separated by distillation. Chloromethyldimethyluhlorosilane, lip 115' (T84 mm), and dichloromethyldimethylchlorosilane~ bp 14s" (734 mm), were isolated. Dimethyldichlorosilane was similarly chlorinated. Distillation then gave the compounds previoiisly described: chloromethylmethyldichlorosilane,3 bp 122' ; dichloromethylniethyldichlorosilane, bp 149';4 and trichlorometliylmethyldichlorosilane, mp 99-9TO.3 Chloromethyldimethylethoxysilane was prepared from the corresponding chlorosilane as previously described,5 bp 132'. Dichloromethyldimethylmethoxysilane was prepared by addiirg anhydrous methanol (3.8 moles) to a solution of dirhloromethyldimethylchlorosilane (3.4 moles) in 500 ml of petroleum ether (Skelly F). The mixture was heated to reflux briefly to drive out most of the HCI that formed. The solution was then cooled to room temperature, saturated with anhydrous IL",,filtered free of SH,Cl, and distilled to give 470 g (797, yield), bp 66" (35 mm), n z 51.4392, ~ d2j4 1.1260, R D 0.2333, calcd R D 0.2336.6 Chloromethylmethyldimethoxysilane was prepared in the preceding manner from chloromethylmethyldichlorosilane, bp 138", n Z 51.4094, ~ dZ541.058, RD 0.2343, calcd RD 0.2368. Chloromethylmethyldiethoxysilanewas prepared from chloromethylmethyldichlorodarie (481 g, 3 moles) and ethyl orthoformate (1,000 g, 7 moles) by the procedure of Shorr7 in 8SCG yield, bp 74' (30 mm), n Z 5 1.4123, ~ d254 0.9952, Ru 0.2502, calcd RD 0.2515. Anal. Calcd for CtHljC102Si: Si, 15.39. Found: Si, 15.43, 15.44. Chloromethylmethyldiisopropoxysilane was prepared from chloromethylmet~hyldichlorosilane and isopropyl alcohol in petroleum ether, bp 91" (40 mm), n Z 51.4114, ~ d254 0.951, RD 0.2613, calcd RD0.2617. Dichloromethylmethyldimethoxysilane was prepared from dichloromethylmethyldichlorosilane (3.6 moles) and anhydrous methanol (7.5 moles) in 500 ml of petroleum ether. Distilla~ cP4 tion gave 588 g (Sic; yield), bp 88" (50 mm), n Z j 1.4332, 1.1917, RD0.2381, calcd RD 0.2131. Trichloromethylmethyldimethoxysilane was prepared in the same manner from trichloromethylmethpldichlorosilane (465 g) ) in unusually low yield (137 g), bp 80" (25 mm), n Z 5 ~1.441, d254 1.2521, RD 0.2122, calcd RD 0.2118.
Iodomethylmethyldiethoxysilane.-Chloromethylmethyldiethoxysilane (320 g, 1.75 moles) and XaI (300 g, 2 moles) in acetone (750 ml) %-ere stirred and refluxed intermittently for 6 days. At the end of this time, a vapor phase chromatogram ( y e ) indicated that the metathesis was greater thstn 99yG complete. The mixture was then filtered and distilled to give 374 g (1.37 moles, 78% yield) of purity greater than 99% by ~ dZ641.414, I ~ 0.1959, D calcd vpc, bp 101" (30 mm), n Z 51.4660, R D 0.1972. Anal. Calcd for CGHJ02Si: Si, 10.23. Found: Si, 10.37, 10.31. Bromomethylmethyldimethoxysilane was prepared from the corresponding dichlorosilane, which was made by brominating dimethyldichlorosilane with BrCl by the method of Speier.8 The bromomethylmethyldichlorosilane had bp 50" (25 mm), nZ5D1.4758. Anal. Calcd for BrCH2MeSiC12: neut equiv, 103.9. Foiind: neut equiv, 104.1, 104.7. This product was heated t o reflux 3 hr with a slight excess of methyl orthoformate and stripped free of volatiles under vaciiiini to give bromomethylmethyldimethoxysilane,nZ% 1.4352, d * j 4 1.324, RD 0.197, calcd RD 0.197. Chlorination of ethylmethyldichlorosilane (3375 g, 25 moles) was performed by the photocatalpzed reaction with chlorine in an apparatus designed to favor the formation of monochlorinated
(2) J. L. Speier, J . A m . Chem. Soc.. 73, 824 (1951). (3) R . H. Krieble and I. R . Elliott, ibid.. 67, 1810 (1945). (4) 8. D. Petrov, V. F. Mironov, and N. A . Pogankina, Dokl. A k n d . Nauk. S S S R , 81, 100 (1955). ( 5 ) H. Freiser, hl. V. Eagle, and J. L. Speier, J. A m . Chem. Soc.. 75, 2824 (1953). (6) Specific refractions, R D , were calculated using t h e values for bond refractions published by E . L. Warrick, i b i d . , 68, 2455 (19461, and revised by t h e use of C-C and C-H values of A. I. Vogel, TV. T. Creswell, and J. Leicester, J . Phys. Chem., 53, 174 (1954). (7) L. M . Shorr, J . A m . Chem. Soc., 76, 1390 ilO51). ( 8 ) J . I,. Speier, i f l i d , , 73, 8261 (19.51).