ITEM No. 24 FILE No. XXVII—4 COPY No.. INSECTICIDES AND FUNGICIDES AT THE LG. FARBENINDUSTRIE PLANT, HOCHST COMBINED INTELLIGENCE OBJECTIVES SUB-COMMITTEE INSECTICIDES AND FUNGICIDES AT THE I. G. PARBENINDUSTRIE PLANT, HOCHST Reported by Stanley A. HALL, Ph.D. U. 3, Civilian, Hq.USFET CIOS Target Number 2k/k • Medical COMBINED INTELLIGENCE OBJECTIVES SUB-COMMITTEE 6-2 Division, SHAEF 'Rear) APO 4-13 TA3LS OP CONTENTS Subject No» I* INTRODUCTION 3 II• INSECTICIDES 4 !• H6 2474 or "Gix" 4 a. Composition 4 b* Manufacture 4 c* "Gix" vs* DDT Against Insects 6 d* Pharmacological Testing of "GixM 11 2* Use of nGix* and DDT Preparations Against the Ox garble 13 3» "Nirosan" 13 a. Composition 13 b* Preparation of Active Ingredient 14 c* Use 14 4* *Dizantt 14 a* Composition 14 b* Preparation of Active Ingredient 14 c* Use 14 5. "RaupedLeim" (Caterpillar glue) 14 a* Composition 14 b# Use 14 III* FUNGICIDES 14 1* "2317W" 14 2* "Brassicol" and "Tritisan-5" 15 3. "Bulbosan" 15 4. "srassisan" 15 I* INTRODUCTION A* Outline of trip: The undersigned, an investigator attached to the Isfedical Intelligence Branch, Office of the Chief Surgeon, Hq* USFET, was ordered on 30 June 1945 to proceed by aircraft to Frankfurt a/M and thence to HOchst (Target 24/4), Germany, for the purpose of investigating the I* G* Farbenindustrie plant at that location# The subjects covered in this investigation comprise insecticides and fungicides* No rodenticides were found at this target* Upon arrival at Frankfurt on 5 July, the undersigned joined a CIOS team composed of Drs* KLeiderer, Conquest and Williams, who were investigating pharmaceutical products of thja HOchst plant* The team was joined by Dr* Hie© on 9 July* Investigation of the target was completed 13 July 1945* Q« Summary of Investigation: The insecticide knoim as "Six" containing as the active ingredient 60# of 1-trlchloro- 2*2-bis (p-fluorophenyli ethane % was investigated in con- detail as to its composition, method of manufac- ture* action against several insect species, modes of application against houseflies, alleged advantages over DDT, and pharmacological action on warm-blooded animals and also on frogs# The biological testing methods at the HSchst laboratories were generally poor, so that the results obtained are not at all conclusive* In discussions with Drs* Pfaff, Wagner and Lanz of the HBchst staff there was a tendency on their part to interpret-their testing results as unduly favorable to the performance of "Gix" as compared to that of DDT* Their testing methods and procedures were definitely inferior to those employed by the U* S* Department of Agriculture, Bureau of Entomology and Plant Quarantine* Dr* Wagner carried out a few preliminary tests against the ox warble (Hypo derma line at urn) using applications of "Gix* or DDT preparations on cattle to prevent the flies from.laying their eggs* No results could be obtained, in field trials of his preparations, because of disruption caused by the war# The formulae of the preparations that he used are reported for what they may be worth* Other insecticides investigated are as follows; "Mrosan* containing IjSiSsQ-tetranitrocarbazole es the active ingredient# "Dizan" containing N-(phenyldiazo) piperidine as the active ingredient# An adhesive caterpillar bait known as "Raupenleim", for use on the* bark of fruit trees to trap the larvae of the winter moth, was developed at the HBchst labora- tories* Castor oil and resins unobtainable by Germany during the war were substituted largely by a mixture of chlorinated aliphatic hydrocarbons in the formulation of this caterpillar glue* The following fungicides were investigated: Nam Active Ingredient *2317 vr 1-Thio cyano-8,4-dinitrobenzene *3rassicoln ) and "Tritisan 5*) *Bulbosan* Pent achloronitrobenzene 1,3,5-Trichloro-2,4,6-trinitrobenzene *Brassiaan 1,2,4-Trichloro-3f3-clinit robe nzene XI* BBSEOTICIPBS !• H8 2474 or wGlx" a* Composition"* The active ingredient is 60$ l-trichloro-2,2- his (p-fluorophenyl) ethane, 20% nLohauer Gas8lw (a petro- leum fraction with initial boiling-point 240°C end 93% distilling up to 360°C) plus 20$ of an emulsifying agent of the polyhydroxyethylated iso-octylphenol type* The l-trichloro-2,2-bis (p-fluorophenyl) ethane is a liquid boiling at 160-180°C under 8 mm pressure* It is made by condensing chloral acetal with fluorobenzene in the presence of chlorosulfonic acid* The chloral acetal is made by chlorinating diethyl acetal* The fluorobenzene is made by diazotizing aniline hydrochloride in anhydrous hydrogen fluoride* b* Manufacture [1] FluofoBenzene Into a reaction vessel of 5 cu. m* capacity containing 3000 kg of hydrogen fluoride (97-100$) 1250 kg of aniline hydrochloride are introduced* Diazo- tizetion is accomplished by the addition of 720 kg of solid sodium nitrite, keeping the reaction mixture cooled to 10°C* The diazotized solution is then transferred to 34*5 cu* m* reaction vessel equipped with a reflux condenser where slow decomposition is allowed to take place at 40°• After nitrogen has ceasedto evolve the upper layer of fluorobenzene is drawn off into a 2 cu* m* vessel where it is washed with alkali until neutral and then distilled* The excess EF in the reaction vessel is recovered by distillation from oleum (100$ for use in the next batch reaction* Yield of fluorobenzene: 700-750 kg (77-82$ of theory) (2) Chloral acetal Into a 2 cu. m* enamel vessel containing 590 kg of diethyl acetal chlorine is added as fast as it is absorbed at a temperature of 20-50°C during the addition of the first 1000 kg of chlorine. The reaction mixture is then transferred to a ceramic reaction vessel when a second 1000 kg of chlorine are added while 270 kg of water are run in at the same time. The reaction temperature is held at 50-85°• A third 1000 kg of chlorine is added at a temperature of 90-95°* The finished reaction product solidifies at 12-15°* This is distilled into a cast-iron reaction vessel* 1150 kg of sulfuric acid (100$) are added and the mixture distilled at 90° a condenser made of lead coils* The inside temperature of the vessel is raised to 130° at the end of the distillation* Yield*1380-1450 kg (62-65$ of theory) (3) Condensation of Fluorobenzene with Chloral Acetal Into a 2 cu* m* cast iron vessel there is added 485 kg chloral acetal and 690 kg fluorobenzene* With stirring and good outside cooling 415 kg chlorosulfonic acid are introduced during 5 to 7 hours so that the reaction temperature does not exceed 12°* After the reaction has ended, it is stirred for an additional 12 hours. The reaction mixture is then run into a 7 cu. m. ceramic vessel containing 3000 kg water* It is heated to 100° by blowing in steam. On standing, an aqueous acid layer separates, Which is drawn off and disposed of* The reaction product is washed twice with water and finally neutralized with 33$ alkali* The product is then dried by applying a vacuum and heating to 60°. Yield of clear anhydrous oil; 900 kg (85$ theory) (4) Formulation of nGlxw The condensation product (900 kg) is mixed with 300 kg of wetting agent ("Igepal" or poly- hydroxyethylated iso-octyl phenol) and 300 kg of "Lobauer Gas8ln (petroleum boiling at 240-360°c) to give 1500 kg of "Gix"• (5) Modifications in Manufacturing Procedure (a) FlUQrobenze~ne To prevent corrosion of the steel reaction vessels and condenser coils Dr. Lanz has proposed that instead of using aniline hydrochloride, aniline base and hydrofluoric acid be used to eliminate the HC1 which is more corrosive to iron than HF* The use of condensers made from Vj&A steel (Krupp) has also been proposed, as well as coating the condenser surfaces with carbon# (b) Chloral Acetal - Hie diethyl acetal produced in the acetone-acetic acid Division was not of uniform quality. Instead, Dr# Lanz has proposed using as a starting material the half-acetal which is more easily prepared from acetal- dehyde and ethanol# (c) Condensation Dr# Lanz has found- that chlorosulfonic acid gives somewhat better yields (80-82$) of condensation product than vhen sulfuric acid is used. -There is also a saving in the sulfuric acid consumed by this modification of the Bayer condensation# o# *Glx* vs# DDT against Insects til Terminology and boncentrations The following terminology has been used at tne HOchst laboratories; (a) Gix -Containing 60$ active ipgra- (b) Fluorgesarol- » 5$ « dignt (o) Bromgesarol « 5$ " w (d) Gesarol « 5$ DDE The concentration of a preparation referred to in their entomological data means the concentration of the preparation used and not the concentration of active ingredient, unless other wise noted# Thus 1$ Fluorgesarol is equivalent to 0,05$ active ingredient; 0#1$ Gix is equivalent to 0#06$ active ingredient; Gesarol is equivalent to 0*06$ active ingredient (DDE)# (2) Contact Poison Experiments Against the Q^psy fopth ±n general the effects of Flurogesarol and Gesarol as resulting in final kill after several days, was about the same for both preparations# The initidl symptoms of loss of ability to crawl and climb were exhibited by fourth-instar larvae of the gipsy moth sooner when Fluorgesarol was used than with Gesarol at the same concentrations# The onset of symptoms was observed after several minutes when Fluorgesarol preparations were used while it required one or more hours using Gesarol# Two chambers were dusted respectively with Fluorgesarol diluted with talc 1;1 and with Gesarol also diluted with talc 1;1# The effect on fourth-instar larvae of the gipsy moth is given in the following table: Preparation;Q,uantity:$Kill(in parenthesis after: : ;24 Hours*2 Days:3 Days;4 Days;5 Days 50(50) ;60{40) : —- ;90(0) ;90(0) ♦talo(ljl) 20(30 i50130 :60(20); --- :80(0) Gesarol ♦ :2.5te/ha: 10(905 ;50(5P ; — : 70 (0) :90(0) talc (1 ;1J 0(01 :lQ(lo! :20(0) ; :20(0) *ha«hectare«10,000 sq« coeters In another experiment the larvae were dustad respectively with Fluorgesarol and Gesarol: Preparation; ♦ Concn* parenthesis : 24 hours : 2 Days ; $af fe cted)after; 5 Days : 5 Days; Fluor gesarcii W . : 100 .0 • I — • mm m» • mmMm s lOO (oi * ——— # —— Gesarol : s5 nHien — ; 90(0) • B f Hsicn s so to) ; 96 (6;■ ilOoioS '3) Stomach Poison Experiments Against the Brown Tail koth Gesarol and Fluorgesarol respectively were sprayed on larvae of the brown tail moth and also on their food in parallel experiments. The following results were obtained; Reparation;Concn. : %Kill (Affected) : ; 2 Days : 3 Days After; 5 Days; 10 Days FluoraesaroU \% : 5 95 : 45 55) f—* o 0 • • 1 1 1 Gesarol : 1$ t 0 : 25 25) 100 : Fluorgesarol Mixed ; 70 k30] : 90 o 1—1 • 100 : Gesarol ;with fxd; 10 [Oj : so 20 J Won 86(0] . (4) Against the Grain Weevil Fluorgesarol is faster-acting than Gesarol# After 10 days Gesarol gave 74$ kill and 6$ of the insects were unaffected# Fluorgesarol gave 100$ kill in the same period# A Fluorgesarol preparation containing 3$ active ingredient is as effective as Gesarol (5$ active ingredient) according to a report received from the Biologische Reichsanstalt in Berlin, (5) Against Cockroaches The 3$ active ingredient Fluorgesarol was just as effective as the 5$ active ingredient Gesarol against Phyllodromia germanica and Periplaneta americana# There was no difference in the speed of action of Fluor- gesarol and Gesarol at the seme concentration. (6) Against Sohildl&use (Aspiodotus duplex) Gesarol is ineffective against SchildlRuse# Using a preparation containing 40$- l-trichloro-2,2-hia (p-fluorophenyl) ethane, 25$ acetone and 35$ emulsifier an emulsion was made up containing 2$ active ingredient and sprayed on over-wintered ZwetschenschildlBuse# The spray was completely effective"! A similar spray con- taining DDT (Gesarol) in the same concentration was ineffective# Control experiments using acetone and emulsifier only were likewise ineffective against this insect# (7) Stomach Poison Experiments Against Houseflies Curds (Quark) were sprayed with Fluorgesarol and Gesarol respectively* Houseflies were allowed to feed on the material thus treated# The results are given in the following table; Preparation ; • . - ♦ Concn. ; $ Kill : 1 Day : after 2 Days ; 4 Days nuorpesarol; 0.25$ : 66 ; 95 ! l&J • * o.08%‘ 5S ; TOO Gesarol : 0.£5* ; 30 ; “W” ; IT • 0*05% ; 4 ; 6& 5 96 (0) Contact Sprays Against Houseflies Houseflies confined in chambers were sprayed with petroleum solutions of Fluorgesarol and with Gesarol respectively* Hesuits were as follows; Preparation; • quantity Used Knockdown after : 15 Minutes 5% Gesarol j 1 cc/cu. meter ! 66.1 in petroleum; 2 cc/cu. meter f 69.9 5
Composition . (1} Srassicol contains 20$ pentachlor©nitro- benzene plus 80$ talc. (2) Tritisan-5 contains 15$ pentachloronitro- - benzene plus 83$ talc plus 2$ maschine oil. b. Preparation of Active Ingredient Nitrobenzene is chlorinated in chiorosulfonic acid using iron and iodine as catalysts. c. Use TTT Brassicol is used as a soil disinfectant and against Salatflule (a disease of lettuce). i2J 'tritisan-5 is used as a dry-seed dressing against stinking smut of Wheat (Weizenstelnbrand). 3. "Bulbosan" a. Composition 1, S,5-trichloro-2, 4, 6-trinitrobenzene 92.5$ talc b. Preparation of Active Ingredient The triciiloro-trinitrobenzene, because of its explosive properties, has been made only in limited quan- tities by nitration of 1, 3, 5-trichlorobenzene» c. Use It is reported to be extremely effective in controlling tomato leaf mold (Cladosporium fulouml. 4. "Brassiaan* lu Composition 20$ 1,2,4-Tri ch1or o-3,5-dinit robe nzene 3$ Maschine oil 77$ Talc b. Preparation of Active Ingredient 1,2,4-1^1chloro-3,5-d in itr obe nze ne is prepared by nitration of 1,2,4-trichlorobenzene• c. Use claimed to be very effective in controlling finger and toe club root (Kohlhernie) of cabbage plants.