Elliott et al. : The Pyrethrins and Related Compounds. X 49

THE PYRETHRINS AND RELATED COMPOUNDS X.*-The methylbenzyl chrysanthemates

By M. ELLIOTT, N. F. JANES and K. A. JEFFS

New or improved routes are used to prepare all the nineteen methylbenzyl chrysanthemates, including 2,4,6-trimethylbenzyI (+) and (-)-trans-chrysanthemates, 2,3,4,6-tetramethyl- and 2,3,4,5,6-pentamethyI- benzyl chrysanthemates, and the chrysanthemates of the new alcohols, 2,3,5- and 3,4,5-trirnethyfbenzyl alcohols.

Introduction

2,4-DimethylbenzyI chrysanthemate (dimethrin) and related benzyl esters without aromatic alkenyl substituents have useful insecticidal activity and low mammalian toxicity;' however, Barthell?, observed that only 2,4- and 3,4-dimethylbenzyl chrysanthemates had been much in- vestigated. In connexion with other work on synthetic compounds related to the ~yrethrins,3-~ information was needed on the variation of insecticidal action with structure of the chrysanthemates of simpler alcohols, such as the methylbenzyl alcohols, in which physical properties and chemical reactivity could be more easily determined than in more complex esters, such as those of alkenylcyclo- pentenolonesl and of furfuryl and furylmethyl alcohol^.^ Moreover, indications of useful species specificity between chrysanthemates of alkylated and non-alkylated alkenyl- benzyl chrysanthematess prompted further examination of this series.

Therefore, all nineteen methylbenzyl chrysanthemates were prepared. The benzoic acids corresponding to all the methylbenzyl alcohols were known' and the benzyl alcohols needed could therefore have been obtained from them by reduction. However, this procedure was not always most convenient, and the best methods for the present work are described here.

Experimental

The general observations under this heading in Part IX3 apply also to this work. In addition, nuclear magnetic resonance (n.m.r.) spectra were recorded on a Perkin- Elmer R10 spectrometer for dilute solutions in carbon tetrachloride with tetramethylsilane as internal standard.

When appropriate, purity of products was also assessed by gas-liquid chromatography on a Pye argon apparatus using a 4 ft column of 10% polypropylene sebacate on Chromosorb at 100-170".

General procedures Chrysanthemates fvorn benzyl alcohols

Esters of chrysanthemic acid with various alcohols were made using the acid ~h lo r ide .~ Any anhydrides detected in the crude esters by absorption at 1780 cm-l near the ester band at 1730 cm-l in the infra-red (i.r.) spectrum, or any unchanged alcohol, were removed by passing the crude ester (1.5 g) through neutral alumina (Woelm, 25 g) in 1 : 1 by vol. hexane-ether.

Chrysanthemates from benzyl halides Triethylammonium ( ~t)-cis-trans-chrysanthemate~~~ or

silver ( &)-cis-trans-chrysanthemates were used as described.

Reduction of benzoic acids and esters with lithium aluminium h ydride

The acid or ester as a 10% solution in tetrahydrofuran * Part IX: J. Sci. Fd

was added to excess lithium aluminium hydride in tetra- hydrofuran. When reaction was complete (after refluxing if necessary) drops of saturated ammonium chloride were added to the cooled solution with vigorous stirring until the inorganic sludge coagulated and the solution cleared. The tetrahydrofuran solution was concentrated, the residue was dissolved in ether, and the ether solution was washed with saturated potassium hydrogen carbonate, then satura- ted sodium chloride and dried with Na,SO,. The ether was evaporated and the residue was distilled.

Benzyl alcohols from benzyl halides via acetates The procedure used previously3 to convert 2-bromo-4,6-

dimethylbenzyl chloride to the corresponding alcohol was followed.

Benzyl alcohols from bromobenzenes The Grignard derivative, prepared from the bromo-

benzene in tetrahydrofuran, was treated with gaseous formaldehyde, as described previ~usly.~

Bromobenzenes from anilines The procedure used to synthesise 4-allyl-2,6-dimethyl

bromobenzenelO by the Sandmeyer reaction was followed.

Examination of (&)-cis-trans-chrysanthemates by n.m.r. Esterification shifted the position of resonance of the

benzylic CH2 from 4 . 5 7 (benzyl alcohols and halides) to -5.07, directly indicating whether the product contained unesterified benzyl derivative. Further, peaks correspond- ing to the benzylic CH, in the cis- and trans-esters appear separately, about 0-05 ppm apart, so the cisltrans ratio followed directly from a measurement of the relative areas of the two peaks. The ratio could be confirmed from the olefinic protons, which also resonate at different posi- tions in cis- and trans-chrysanthemates (4.6 and 5-17 respectively).ll?l'- The cisltrans ratio determined by this method is given for each of the esters described.

As in the natural pyrethrins,12 the spectra of the esters are all a direct summation of the spectra of the constituent alcohols and acids (except for the shift in the benzylic CHz position noted above). The spectra of the esters synthesised here all agreed with predictions on this basis, confirming their structures and the absence of benzylic impurities.

Individual compounds 2-Methyfbenzyl( &)-cis-trans-chrysanthemate

Redistilled 2-methylbenzyl bromide (b.p. 108" at 16 mm, n.m.r. peaks at 2.8-3.0~ (m, 4H, aromatic Hs) 5.6, (s, 2H, CHz) 7.6 (s, 3H, CH,) ) and triethylammonium (&)-cis- trans-chrysanthemate formed a product that was purified (chromatography) and distilled to give the ester (b.p. 120-122" at 0.1 mm, nLo 15194; Barthel13 b.p. 134-155" at047 mm, ng 1-5157). Found: C, 79-7;H, 9.0%.CIsH,,0z requires C, 79.4; H, 8.9%. The cisltrans ratio was 45/55.

Agric., 1967, 18, 325

Pestic. Sci., 1970, Vol. 1, March-April

50 Ellioff et al.: Pyrethrins and Related Compounds. X

3-Methylbenzyl ( i)-cis-trans-chrysanthemate 3-Methylbenzyl alcohol (b.p. 77-78' at 0.2 mm, ntz

13317) (Shoesmith14 b.p. 108-11 1 at 10 mm) (n.m.r. peaks at 2.9-3.27 (m, 4H, aromatic H's), 5.6 (s, 2H, CHz) 6.9 (s, lH, OH) and 7.7 (s, 3H, CH,) ) prepared by lithium aluminium hydride reduction of m-toluic acid, was treated with ( &)-cis-trans-chrysanthemoyl chloride, chromato- graphed and distilled to give the ester (b.p. 130" at 0.1 mm, ng 15172). (Barthel13 b.p. 133-139" at 0.6mm, n z 1.5135.) Found: C, 79-2; H, 9-3 %. The cisltruns ratio was 25/75.

4-MethyIbenzyl( i)-cis-trans-chrysunthemate 4-Methylbenzyl bromide (n.m.r. peaks at 2.7-3.17 (m,

4H, aromatic H's) 5.6 (s, 2H, CHJ 7.6 (s, 3H, CH,) ) and triethylammonium ( -+)-cis-trans-chrysanthemate gave 4- methylbenzyl (i)-cis-trans-chrysanthemate (b.p. 132" at 0.1 mm, n? 1.5181). Found: C, 79.2; H, 8.6%; cisltruns ratio : 45/55.

2,3- Dimethylbenzyl ( 5)-cis-trans-chrysunthemute 2,3-Dimethylbenzyl alcohol, obtained by general pro-

cedures from 2,3-xylidine via 2,3-dimethylbromobenzene, was recrystallised from pentane and then melted at 65-5 " (Smithx5 m.p. 65-66.5") (n.m.r. peaks at 3.07 (s, 3H, aromatic Hs), 5.6 (s, 2H, CHz) 7.4 (s, lH, OH), 7.8 (s, 3H) and 7.9 (s, 3H) (2 x CH3) ). 2,3-Dimethylbenzyl (&)-cis- trans-chrysanthemate, made from the recrystallised alcohol, had b.p. 139" at 0.002mm, n? 1.5228. Found: C, 79.4; H, 9.0%. ClBHg608 requires C, 79.7; H, 9.2%; &/trans ratio : 40160.

2,4- Dimethylbenzyl ( f )-cis-trans-chrysunthemate (dimeth- rin)

A commercial sample13 examined by n.m.r. had a cis/ trans ratio 25/75.

2,5- Dimethylbenzyl ( &)-cis-trans-chrysanthernate 2,5-Dimethylbenzyl alcohol, made by general procedures

from 2,5-dimethylaniline via 2,5-dimethylbromobenzene, was esterified to give 2,5-dimethylbenzyl ( f)-cis-trans- chrysanthemate (b.p. 124" at 0.003mm, n y 1.5194; Barthel13 b.p. 145-146" at 0.6 mm, n g 1.5163). Found: C, 79.7; H, 9.1 %.

2,6-Dimethylbenzyl( f )-cis-trans-chrysanthemute 2,6-Dimethylbenzyl alcohol, made from 2,6-xylidine via

2,6-dimethylbromobenzene, was distilled at 117-120" at 16 mm when it solidified. Recrystallisation from hexane gave a sample (m.p. 83"; Lofgrenlg 82.5-835" for a sample made by the same method). The n.m.r. spectrum showed peaks at 3.0-3.27 (m, 3H, aromatic H's) 5.6 (s, ZH, CH,), 7.4 (s, lH, OH) and 7.7 (s, 6H, 2xCH3. Esterification gave 2,6-dimethylbenzyl ( 5)-cis-trans-chry- santhemate (b.p. 124" at 0.002mm, n: 1.5210). Found: C, 79.3; H, 9.0%; cisltruns ratio: 25/75.

3,4- Dimethylbenzyl ( &)-cis-trans-chrysunthemute A commercial sample of 3,4-dimethylbenzyl chloride

contained -30:/, of the 2,3-dimethyl isomer, so the mix- ture was converted, via the acetates, to a mixture of alcohols, from which 3,4-dimethylbenzyI alcohol (m.p. 60"; Sommelet17 63") could be recrystallised. The n.m.r. spectrum had peaks at 3-0-3.27 (m, 3H, aromatic H's),

Esterification gave the (&)-cis-trans-chrysanthemate (b.y. 128" at 0.002 mm, ng 1-5181; Barthel13 b.p. 151-172" at 0.6 mm, ng 15172). Found: C, 79.7; H, 9.1 %; cis/ trans ratio : 30170.

5.6 (s, 2H, CHt) 6.8 (s, lH, OH), 7.8 (s, 6H, 2XCH3).

3,5- Dimethylbenzyl ( &)-cis-trans-chrysunthemate 3,5-Dimethylbenzyl alcohol (b.p. 118-120" at 15 mm,

n! 1-5300, n.m.r. peaks at 3.27 (m, 3H, aromatic Hs),5.6 (s, 2H, CH2),7.2(s, lH,OH), 7.8 (s, 6H, 2 x CH,)), obtained by lithium aluminium hydride reduction of 3,5-dimethyl- benzoic acid, was esterified to give 3,5-dimethylbenzyl (*)-cis-trans-chrysanthemate, b.p. 130" at 0.002 mm, nt: 15203. Found: C, 79.6, H, 8.6 %; cisltruns ratio: 25/75.

2,3,4-TrimethyIbenzyl ( 5)-cis-trans-chrysanthemate Chloromethylation of hemimellitene18 gave the best

yield of 2,3,4-trimethylbenzyI chloride (b.p. 119-123" at 12 mm, n g 15515) when the reaction was kept at 65-70" for 12 h. This product, with triethylammonium (*)-cis- trans-chrysanthemate, gave 2,3,4-trimethylbenzyI (&)-cis- trans-chrysanthemate (b.p. 153" at 0.01 mm, n"," 1.5260). Found: C, 79.9; H, 9.3%. C,,H,,O, requires C, 80.0, H, 9-4 %; cisltruns ratio: 35/65. The chloromethylation pro- duct of hemimellitene was as suggested, and not 3,4,5- trimethylbenzyl chloride because the aromatic region of the n.m.r. spectrum of the derived chrysanthemate appeared as an AB quartet with J 8 Hz, characteristic of 2 ortho- protons, and the chloromethylation product was con- verted by the normal route to an alcohol (m.p. 45" after recrystallisation from hexane), identified as 2,3,4-trimethyl- benzyl alcohol (Kantor18 m.p. 49-50') from its n.m.r. spectrum: peaks at 3.17 (s, 2H, aromatic Hs), 5.5 (s, 2H, CH2), 7.75, 7.8, 7.85 (3s, 9H, 3 non-equivalent CH,'s), 8.1 (s, lH, OH). The two aromatic protons do not differ sufficiently in chemical shift to show the expected AB quartet structure.

2,3,5-Trimethylbenzyl( &)-cis-trans-chrysunthemate 2,3,5-Trimethylbenzoic acid, made by the action of

phosgene on the Grignard reagent from freshly distilled 2,4-dimethylbenzyl chloride,20 had m.p. 126-128" (Jacot- Guillarmod20 m.p. 126-127'). Diazomethane gave methyl 2,3,5-trimethyibenzoate (b.p. 85" at 0.6 mm, n g 1.5230, n.m.r. peaks at 2.67 (s, lH), 3.0 (s, 1H) 6.2 (s, 3H, OMe) 6.6 (s, 3H), 7.7 (s, 6H) (3 x CH3) ). The two aromatic peaks were both broad, consistent with the expected meta (-2 Hz) coupling. Lithium aluminium hydride reduction of this ester gave 2,3,5-trimethylbenzyl alcohol (b.p. 88-94" at 0.6 mm, m.p. (after recrystallisation from hexane) 49"). Found: C, 79.8, H, 9.4%. C,,Hl, 0 requires C, 80.0, H, 9-4%, n.m.r. peaks at 3-27 (m, 2H, aromatic Hs), 5.7 (s,

Esterification gave 2,3,54rimethyIbenzyl (rt)-cis-trans- chrysanthemate (b.p. 138" at 0.2 mm, n2: 1.5210). Found: C, 79.6, H, 9.2 %; cisltrans ratio: 30170.

2,3,6-Trimethylbenzyl( f)-cis-trans-chrysa~zthemu~e 2,3,6-Trimethylbromobenzene, made' from y-cumene

(n.m.r. peaks at 3.27 (s, 2H, aromatic Hs) 7.6 (s, 6H) and 7.7 (s, 3H) (3 x CH,) ) was converted by the usual method to 2,3,6-trimethylbenzyl alcohol (m.p. 81.5"; Sommeletl' 83.5-8S0), n.m.r. peaks at 3-27 (s, 2H, aromatic Hs), 5.5 (s, 2H, CHz) 7.7 (s, 3H) and 7.8 (s, 6H)(3xCH3), 8.2 (s, 1 H, OH). Esterification of the alcohol gave 2,3,6-trimethyl- benzyl (&)-cis-trans-chrysanthemate (b.p. 128" at 0-001 mm, n z 1.5208). Found: C, 79.4, H, 9.3 %; cisltrans ratio: 25/75.

2,4,5-Trimethylbenzyl( i)-cis-trans-chrysunthemute Chloromethylation of y-cumene is knownzz to give a

mixture in which 2,4,5-trimethylbenzy1 chloride pre- dominates. The chloromethylation mixture (b.p. 115-1 18' at 25 mm, n z 1.5451) showed 2 n.m.r. peaks in the benzylic region, at 5.4 and 5.57 in the ratio 20180, but conversion to the alcohol by the usual procedure and recrystallisation

2H, CHz) 6.6 (s, lH, OH) 7.9 (8, 6H) 8.0 (s, 3H) (3 X CH8).

Pestic. Sci., 1970, Vol. 1, March-April

Elliott et al. : Pyrethrins and Related Compounds. X 51

removed the unwanted isomer, giving 2,4,5-trirnethylbenzyl alcohol (m.p. 81"; Lakea2 82-83-5"), n.m.r. peaks at 3.17 (s, lH), 3.2 (s, 1H) (aromatic H s ) 5.6 (s, 2H, CH1. Peak at 5.5 from other isomer absent) 7.6 (s, lH, OH) 7.8 (s, 9H, 3 x CH,). Esterification of the recrystallised alcohol gave 2,4,5-trimethylbenzy1 (f)-cis-trans-chrysan- themate (b.p. 137-140" at 0-02 mm, ny 1-5190). Found: C, 80.4, H, 9.5%; cisltrans ratio: 25/75.

2,4,6-Trimethylbenzyl ( 5)-cis-trans-chrysanthemate and individual isomers

Chloromethylation of mesitylene,, gives a mixture from which 2,4,6-trimethylbenzyl chloride (m.p. 37") and di(chloromethy1) mesitylene (m.p. 105 ", recrystallised from pentane), can be separated by distillation.

The monochloro derivative with silver ( f)-cis-trans- chrysanthemate gave 2,4,6-trimethylbenzy1 ( +)-cis-trans- chrysanthemate (b.p. 155-157" at 0.2 mm, n: 1.5202, m.p. 34-36'). Found: C, 795, H, 9.2%, cisltrans ratio: 30170. Recrystallation from pentane (8 times) gave 2,4,6-trimethyl- benzyl (f)-trans-chrysanthemate (m.p. 51 O ; n.m.r. spec- trum had no peaks due to cis-isomer).

The silver salt of (-)-trans-chrysanthemic acidz4 gave 2,4,6-trimethylbenzyI (-)-trans-chrysanthemate (b.p. 130- 133" at 0.003mm, n z 15182, [u]2,0+20.1" (c, 3.2 in EtOH)). Found: C, 79.3, H, 9.6%. Similarly the silver salt of (+)-trans-chrysanthemic acidas gave 2,4,6-trimethyl- benzyl (+)-trans-chrysanthemate (b.p. 134-1 35" at 0.01 mm, n: 1.5165, [u]?,0-22.8" (c, 2.3 in EtOH)). Found: C, 79.8, H, 9.9%.

3,4,5-TrimethylbenzyI ( &)-cis-trans-chrysanthemate 3,4,5-Trimethylbenzoic acid (m.p. 216"; Pearson2$

2203-221 5 ") made from acetomesitylene via 3,4,5-tri- methylacetophenoneZ6 was converted to its methyl ester (b.p. 94-98' at 0.1 mm, m.p. 35-36"; Porowska2' m.p. 40-5-41.5") n.m.r. peaks at 3-57 (s, 2H, aromatic H's), 6.2 (s, 3H, OMe), 7.7 (s, 6H) and 7.8 (s, 3H) (~xCH,) , then reduced with lithium aluminium hydride to 3,4,5- trimethylbenzyl alcohol (b.p. 98" at 0.1 mm, m.p. 68.5"). Found: C, 79.3, H, 9.2%; n.m.r. peaks at 3-27 (s, 2H, aromatic H's), 5.7 (s, 2H, CHJ 7-3 (s, lH, OH) 7-8 (s, 6H), 7.9 (s, 3H) (3 x CH,). Esterification gave 3,4,5-trimethyl- benzyl (f)-cis-trans-chrysanthemate (b.p. 143-145" at 0*004mrn, n: 1.5234). Found: C, 79.6, H, 9.2%; cisltrans ratio : 30170.

2,3,4,5-Tetramethylbenzyl( f )-cis-trans-chrysanthemate Prehnitine (b.p. 84-87" at lOmm, n? 1-5175; Bircha8

b.p. 115" at 49 mm, n v 1.5203) was obtained by reduc- tion as usual with lithium aluminium hydride of 2,3,4- trimethylbenzyl chloride (see above), then chloromethyla- tedee to give 2,3,4,5-tetramethylbenzyl chloride (b.p. 144" at 10 mm; Beningt~n,~ b.p. 140-150" at 7-10 mm) n.m.r. peaks at 3.27 (s, lH, aromatic) 5.6 (s, 2H, CH,) 7.8, 7.8, 7-9, 7.9 (4s, 12H, 4xCH3). Reaction with the triethyl- ammonium salt gave 2,3,4,5-tetramethylbenzyl (&)-cis- trans-chrysanthemate (b.p. 140" at 0.005 mm, n2: 1.5290). Found: C, 79.7, H, 9.3 %; C2,H,,02 requires C, 80.2, H, 9-6 %; cislfrans ratio: 40160.

2,3,4,6-Tetramethylbenzyl( 5)-cis-trans-chrysanthemate Di(chloromethy1)mesitylene (22 g, from above) in

tetrahydrofuran (50 ml) was treated with vigorous stirring for 1 h with lithium aluminium hydride (0.9 g) in tetra- hydrofuran (27 ml) and then boiled under reflux for 1 h. Processing as usual gave 2,3,4,6-tetramethylbenzyl chloride (7.6 g) which after redistillation had b.p. 137-145" at 12 mm, n r 1-5504 ( B e n i n g t ~ n ~ ~ b.p. 133-137" at 10 mm), n.m.r. peaks at 3.27 (s, IH, aromatic H), 5.4 (s, 2H, CHJ,

Pestic. Sci., 1970, Vol. 1, March-April

7.7, 7.7, 7.8, 7-9 (4s, 12H, 4xCH3) which was further characterised by conversion to 2,3,4,6-tetramethylbenzyl alcohol (m.p. 95"; Summers30 m.p. 93-94') n.m.r. peaks at 3.37 (s, lH, aromatic H) 5.5 (s, 2H, CH,) 7.7, 7-7, 7.8, 7.9 (4s, 12H, 4xCH3), 8.5 (s, lH, OH)). The chloride, reacted with triethylammonium ( &)-cis-trans-chrysanthe- mate, gave 2,3,4,6-tetramethylbenzyl (+)-cis-trans-chry- santhemate (b.p. 154" at 0.01 mm, n"$ 1.5269). Found: C, 80.2, H, 9.2 %; cisltrans ratio : 40160.

2,3,5,6-Tetramethylbenzyl( f )-cis-trans-chrysanthemate 2,3,5,6-Tetramethylbenzyl chloride, made by chloro-

methylation of d ~ r e n e , ~ ~ had m.p. 67", b.p. 144-147" at 25 mm (Benington2s m.p. 70-71", b.p. 122-125" at 5 mm) n.m.r. peaks at 3-27 (s, lH, aromatic H) 5.4 (s, 2H, C H 3 7.7 (s, 6H) and 7.8 (s, 6H) (4 x CH,). It was converted by the triethylamine route to 2,3,5,6-tetramethylbenzyl (5)- cis-trans-chrysanthemate (b.p. 150" at O W 4 mm, n'," 1.5220). Found: C, 79.9, H, 9.6%; cisltrans ratio: 45/55.

2,3,4,5,6-Pentamethylbenzyl ( &)-cis-trans-chrysathemafe 2,3,4,5,6-Pentamethylbenzyl chloride, made by the

method of Benington et aLaS from di(chloromethy1)- mesitylene via pentamethylbenzene, had b.p. 155-161 " at 20 mm, m.p. 83-84" (Beningt~n,~ m.p. 81-82') and was converted by the silver salt route to 2,3,4,5,6-pentamethyI- benzyl (f)-cis-trans-chrysanthemate (b.p. 186" at 0.4 mm, m.p. 75"). Found: C, 80.1, H, 9.9%; C,,H,,O, requires C, 80.4, H, 9.8 %; cisltrans ratio: 30170.

As an alternative synthesis, halogenation of hexamethyl- benzene was tried. Hexamethylbenzene with N-bromo- succinimide gave a product containing substantial amounts of dibromo-compound (Volhard estimation), but reaction was smoother with sulphuryl chloride. Hexamethylbenzene (40-5 g) in boiling carbon tetrachloride (220 ml) was treated with sulphuryl chloride (33.8 g) in carbon tetra- chloride (130 ml) for 7 h. Evaporation left a residue, which was treated with silver acetate (37.5 g) in carbon tetra- chloride (250 mi) to give crude 2,3,4,5,6-pentamethylbenzyl acetate (33 g). Saponification gave 2,3,4,5,6-pentamethyI- benzyl alcohol (26.7 g), m.p. 164-165" (Newmans' m.p. 159-160') n.m.r. peaks at 5-47 (s, 2H, CH,) 7.7 (s, 6H) 7.8 (s, 9H)(5xCH3) 9.3 (s, lH, OH).

2,4,6,-Triethylbenzyl( f )-cis-trans-chrysunthemute Chloromethylation of 1,3,54riethylbenzene as des-

cribed,, gave 2,4,6-triethylbenzyl chloride (b.p. 145-156" at 12 mm, ng 1.5290 (Bost et al.32 b.p. 115-125" at 4 mm, ng 1,5263) ). Reaction with silver (+)-cis-trans-chrysan- themate made 2,4,6-triethylbenzyl ( f )-cis-trans-chrysan- themate (b.p. 154-158" at 0003 mm, n z 1-5117). Found: C, 79.8, H, 10.5 %; C13H3402 requires C, 80.6, H, 10.0%; cisltrans ratio : 35/65.

Di( ( 5 )-cis-trans-chrysanthemoxymethy1)mesitylene Treating di(chloromethy1)mesitylene (see above) with 2

molar proportions of triethylammonium ( f )-cis-trans- chrysanthemate gave di( ( f )-cis-trans-chrysanthemoxy- methy1)mesitylene (b.p. 215-225" at 0.004 mm, n: 1.5230). Found: C, 77.4, H, 9.3 %; C,,H,,O, requires C, 77.5, H, 9.2 %; cisltrans ratio : 35/65.

2,4,6-TrimethylbenzyI 2,2-dimethyl-3-pkenylcyclopropane curboxylate

The silver salt of 2,2-dimethyl-3-phenylcyclopropane carboxylic acids3 was reacted with 2,4,6-trimethylbenzyI chloride to give 2,4,6-trimethylbenzy1-2,2-dimethyl-3- phenylcyclopropane carboxylate (b.p. 155-157" at 0.002 mm, n? 1-5505). Found: C, 82.0, H, 8.2%; Ca2Hz602 requires C, 82.0, H, 8.1 %.

52 Elliott et al. ; Pyrethrins and Related Compounds. X

Results and Discussion

Most of the benzylic compounds were made by one of the following methods: (i) reduction of benzoic acids and esters to benzyl alcohols; (ii) chloromethylation of a hydro- carbon to form a benzyl chloride; or (iii) conversion of a bromobenzene, often obtainable from the corresponding aniline by Sandmeyer reaction, to a Grignard derivative and then, with formaldehyde, to the benzyl alcohol. Method (i) was chosen when the pure benzoic acid was easily obtainable (the 3-; 33-; 2,3,5-; 3,4,5- compounds). Method (ii) was widely applicable; when mixtures of benzyl chlorides were obtained (3,4- and 2,4,5- compounds), con- version to the solid alcohol and recrystallisation gave the pure isomer required. Others (2,3,4-; 2,4,6-; 2,3,4,5-; 2,3,5,6-) were free from isomers, so the convenient one-step conversion of the benzyl chloride to the chrysanthemate, using either silver or triethylammonium chrysanthemate, could be used. Method (iii) is attractive because many methylanilines and thence the corresponding bromo- benzenes are obtainable. It was used for the 2,3-; 2,5-; 2,6-; 2,3,6- compounds. 2- and 4-methylbenzyl bromides were obtained commercially, as was 2,4-dimethylbenzyl chrysanthemate (dimethrin). Reduction of a -CH2Cl group to a -CH3 group provided the relatively inaccessible prehnitene for the 2,3,4,5-tetramethylbenzyl chloride synthesis, and, with limited reducing agent, converted di- (chloromethyl) mesitylene directly to 2,3,4,6-tetramethyl- benzyl chloride. Excess reducing agent gave pentamethyl- benzene, used in the synthesis of pentamethylbenzyl chloride. This last compound could also be made by mono- chlorination of hexamethylbenzene, using sulphuryl chloride.

Detailed insecticidal results will be published later. Briefly, against Phaedon cochleariae and Musca domestica, the relative order of toxicity of the compounds differed little. The most toxic and easily prepared compound to both species was 2,4,6-trimethylbenzyl chrysanthemate; thus, in addition to the (&)-&/trans mixture, the (&)-trans, (+)-trans and (-)-trans-isomers were made and examined individually for insecticidal activity. Also, three compounds with structures closely related to this one, viz. the 2,4,6- triethyl analogue, di-(chrysanthemoxymethyl)mesitylene, and the 2,4,6-trimethylbenzyl ester of 2,2-dimethyl-3- phenylcyclopropane carboxylic acid were synthesised.

Estimation by n.m.r. of the &/trans ratio of synthesised esters revealed an interesting trend. When commercial ethyl chrysanthemate (cisltrans ratio 38/6211) was saponi- fied, and the acid obtained was converted to the chloride, esters obtained were richer in trans-isomer (25/75), but the route using triethylammonium chrysanthemate gave esters with no loss of cis-isomer (ratio 40/60). In agreement with the first observation, (&)-cis-chrysanthemoyl chloride is partly converted, by heat, to the trans-isomer (Smejkal & FarkaSS4 and Elliott et al., unpublished work).

Department of Insecticides and Fungicides, Rothamsted Experimental Station,

Harpenden, Herts.

Received 8 December, 1969

References

Barthel, W. F., 'Advances in Pest Control Research', 1961, Vol. IV, p. 33 (New York & London: Interscience)

Barthel, W. F., Wld Rev. Pest Control, 1964, 3, 97 Elliott, M., Janes, N. F., & Pearson, B. C., J. Sci. Fd Agric.,

1967, 18, 325 Elliott, M., Farnhani, A. W., Janes, N. F.,Needham, P. H.,

& Pearson, B. C., Nature, Lond., 1967, 213, 493 Elliott, M., Chemy Ind.. 1969, p. 776 Elliott, M., Janes, N. F., Jeffs, K. A., Needham, P. H., &

Sawicki, R. M., Nafure, Lond., 1965, 207, 938 Smith, H. A,, & Stanfield, J. A., f. A m . chem. Soc., 1949,71,

81 ; and Liining, B., Acta. chenz. scand., 1959, 13, 1623 * Mills, R. H., Farrar, M. W., SC Weinkauff, 0. J. , Chemy I d . ,

1962, p. 2144 Corral, C., & Elliott, M., J. Sci. Fd Agric., 1965, 16, 514

'"Elliott, M., & Janes, N. F., J. chem. Soc. (C) , 1967, p. 1780 l1 Hutton, H. M., & Schaefer, T., Can. J. Chem., 1962,40,875 l2 Bramwell, A. F., Crombie, L., Hemesley, P., Pattenden, G.,

Elliott, M., & Janes, N. F., Tetrahedron, 1969, p. 1727 j3 Barthel, W. F., Alexander, B. H., & Brown, R. T., U.S. Dept.

Agric. ARS-33-51, April 1959 l4 Shoesmith, J. B., & Slater, R. H., J. chem. Soc., 1924, p. 2280 l 5 Smith, L. I . , & Spillane, L. J., J. Am. chem. Soc., 1940, 62,

2639 Ih Lofgren, N., Ragnarsson, U., & Sjoberg, K., Acfa. cheni.

scand., 1963, 17,1252 Sommelet, M., C.r. hebd. Se'aanc. Acad. Sci., Paris, 1913, 157,

1445 Shacklett, C. D., & Smith, H. A., J. Am. chem. Soc., 1951,

73,766

Is Kantor, S. W., & Hauser, C . R., J. Am. chern. Soc., 1951,

z o Jacot-Guillarmod, A., Helv. chem. Acta., 1958, 41,474 21 Smith, L. I., & Agre, C. L., J. Am. chem. Soc., 1938, 60, 652 22 Lake, R. D., & Corson, B. B., J. org. Chem., 1959,24,1823 z3 Fuson, R. C., & Rabjohn, N., 'Organic Syntheses', 1955,

24 Campbell, I . G. M., & Harper, S. H., J. Sci. Fd Agric., 1952,

25 LaForge, F. B., Gersdorff, W. F., Green, N., & Schechter,

z6 Pearson, D. E., & Bruton, J. D., 1. org. Chem., 1954, 19, 957 27Porowska, N., Roczn. Chem., 1957, 31, 677; Chem. Abstr.,

2 8 Birch, S . F., Dean, R. A., Fidler, F. A., & Lowry, R. A.,

29Benington, F., Morin, R. D., & Clark, L. C., jun., J. org.

3o Summers, L., f. Am. chem. Soc., 1954, 76, 3481 31 Newman, M. S., & Deno, N. C., J. Am. chem. Soc., 1951,

32 Bost. J. J.. KeDner. R. E., & Webb, A. D., J. org. Chem.,

73,4122

Vol. 111, p. 557 (New York: John Wiley & Sons)

4, 189

M. S., J . org. Chem., 1952, 17, 381

1958, 52, 5334

J. Am. chem. Soc., 1949, 71, 1362

Chem., 1958,23,2034

73,3644 ~,

1957,22; 51

52, 695; Chem. Abstr., 1958, 52, 13651

1963, 28,481

FarkaS, J., Koufim, P., & Sorrn, F., Chemicke' Lisfy., 1958,

31 Smejkal, J., & FarkaS, J., Cofln Czech. Chem. comnrrm.,

Pestic. Sci., 1970, Vol. 1, March-April