Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
  • C07D303/02—Compounds containing oxirane rings
  • C07D303/08—Compounds containing oxirane rings with hydrocarbon radicals, substituted by halogen atoms, nitro radicals or nitroso radicals
  • C07D303/10—Compounds containing oxirane rings with hydrocarbon radicals, substituted by halogen atoms, nitro radicals or nitroso radicals in which the oxirane rings are condensed with a carbocyclic ring system having three or more relevant rings

Definitions

• heptachlor that is, l,4,5,6,7,8,8-heptachloro-3a,4,7,7a-tetrahydro-4, 7-methanoindene
• epoxide that is, 2, 3 epoxy 1,4,5,6,7,8,8 heptachloro 2,3,3a,4,7,7ahexahydro-4,7-methanoindene
• That epoxide commonly known as metabolite heptachlor epoxide, has been found to be a potent insecticide, and to be about ten times as toxic with respect to the housefly as a heptachlor epoxide prepared synthetically.
• the synthetic heptachlor epoxide is prepared by the method set out in British Patent No. 714,869, Complete Specification published September 1, 1954. The method involves addition of the elements of hypochlorous or hypobromous acid to heptachlor, and then dehydrochlorinating or dehydrobrominating the product to give an epoxide (MP. 83-85 (3.).
• the metabolite and synthetic epoxides are spatial isomers, and that the diiference in spatial configuration causes the difference in biological activity of the two compounds. It is believed that the metabolite epoxide is the cis isomer that is, it is the isomer in which spatially the epoxide ring lies on the same side of the five-membered ring as do the hydrogen atoms at the 3a and 7a positionsand it is believed that the synthetic epoxide is the trans isomer. In terms of spatial configuration, it is therefore believed that the metabolite epoxide has the structure set out schematically in Formula I, While the synthetic epoxide has the structure set out schematically in Formula II.
• heptachlor epoxide has the planar formula 3,155,689 Patented Nov. 3., 1964 ice
• the chlorine atom in the 1-position is cis with respect to the angular hydrogen atoms-that is, the hydrogen atoms in the 3aand 7a-positions-and that both isomers have the endo configuration of the methano-bridged ring with respect to the fixe-membered ring.
• the epoxy bridge is cis with respect to the angular hydrogen atoms
• the epoxy bridge is trans with respect to the angular hydrogen atoms.
• the metabolite isomer is formed by the chromic acid oxidation of heptachlor at a temperature not exceeding about 100 C.
• the oxidation is carried out by any of the usual techniques for employing chromic acid (chromium trioxide) as a mild oxidizing agent.
• chromic acid chromium trioxide
• the chromic acid is slowly added to, or is gradually formed in the presence of, the heptachlor dissolved in a suitable liquid reaction medium to moderate the strength of the chromic acid as an oxidizing agent. That is to say, the preformed chromic acid can be used, or the acid can be formed in situ in the reaction mixture, as will be described in greater detail hereinafter.
• a lower carboxylic acid such as acetic acid
• the anhydride of such an acid such as acetic anhydride
• these materials desirably affect the oxidizing properties of the chromic acid.
• such materials as carbon tetrachloride or other halogenated lower alkane, carbon disulfide, or other solvents of like properties, are suitable.
• the amount of carboxylic acid or anhydride used should be at least sufiicient to dissolve the heptachlor and the heptachlor epoxide that is formed, thus maintaining a homogeneous organic liquid reaction phase, and it will usually be found desirable to employ a substantial excess of the acid or anhydride.
• acetic acid or acetic anhydride is employed, at least about seven parts by volume of the acid or anhydride should be used per part by weight (parts by volume bearing the same relation to parts by weight as does the liter to the kilogram) of hept-achlor used, and preferably somewhat moreeight to ten parts by volume, or even moreof the acid or anhydride is used.
• the epoxidation reaction is conducted at a temperature not exceeding about 100 C., and preferably temperatures not exceeding about C. are used, to minimize the possibility of such further oxidation. Any lower temperature which is suitable from the physical character of the reaction medium-it should remain homogeneous and liquid, of course-can be used. Ordinarily, temperatures below 10 C. will not be found of advantage. If desired, the addition of the chromic acid to the heptachlor solution can be conducted at a temperature within the upper end of the desirable range, and the further reaction also conducted at that temperature.
• reaction temperature it usually will be found more desirable, since control of the reaction temperature is more easily accomplished, to mix the chromic acid with the heptachlor solution at a low temperature, say from 10 C. to 25 C., allowing the heat evolved in the exothermic oxidation to heat the reaction mixture, then heat the reaction mixture, with stirring, at a higher temperature within the desirable range to insure completion of the oxidation.
• the reaction mixture should be maintained for the minimum time required to effect the oxidation.
• At least the stoichiometric amount of chromic acid is employed, but it will be desirable in many if not most cases to avoid use of more than a small-for example, a 5-10 percent-excess, to reduce the possibility of oxidation of the heptachlor epoxide.
• the chromic acid is formed in situ in the reaction mixture, this is most conveniently done by reacting an alkali metal chromate or dichromatefor example, sodium or potassium chromate or dichromate-with strong sulfuric acid.
• the reaction is essentially quantitative.
• the chromic acid can be formed by adding the sulfuric acid to the heptachlor solution and then adding the alkali metal chromate or dichromate, preferably, the reverse order of addition is employed. Still more preferably, to moderate the action of the chromic acid, the acid is formed gradually, by slow addition of one reactant to the other.
• the oxidation of heptachlor can be carried out to give high yields of the epoxide
• the concentration of the sulfuric acid used be at least 50 percent by weight.
• Commercial concentrated sulfuric acid-93-98 percent by weight H S is suitable and often most convenient.
• At least about 2 moles of such sulfuric acid (as H 50 should be provided per mole of chromic acid, and preferably there are used 'from about 5 to about or even more moles of sulfuric acid per mole of chromic acid used. Since the sulfuric acid need not be entirely present except in the latter stages of the oxidation, the oxidation can be conducted by mixing the heptachlor, liquid reaction medium and alkali metal chromate or dichromate, then adding strong sulfuric acid slowly to form the chromic acid and then also to provide the necessary sulfuric acid.
• the oxidation ordinarily is completed in a short timeof the order of minutes or lessafter all of the reactants have been mixed, which mixing ordinarily will require from about 15 minutes to about one hour.
• the reaction mixture then is quenched with water, preferably chilled water, such as ice water. A volume of water equal to that of the final reaction mixture ordinarily is sufficient, but more orless than this volume may be used in some cases.
• the epoxide then is recovered by the usual means, extraction of the mixture with ether being one satisfactory method.
• the epoxide then is purified by crystallization or other orthodox techniques.
• p.b.w. means parts by weight
• p.b.v. means parts by volume
• parts by weight bear the same relationship to parts by volume as does the kilogram to the liter.
• the bromohydrin then was converted back to the heptachlor epoxide: 84 milligrams of the heptachlor brornohydrin, 21 milligrams of potassium hydroxide, and 2 milliliters of ethanol were heated at reflux for 6 hours. Recrystallization from ethyl alcohol gave 75 milligrams of product, melting at 163 C., undepressed upon admixture with heptachlor epoxide prepared as set out hereinbefore. The infrared spectrum showed a peak at 11.68 microns.
• the product of the foregoing process was identified as the metabolite isomer by entomological evaluation, wherein it was found to possess the very high insecticidal activity which the art has shown that the metabolite isomer possesses.
• the chromic acid being formed in situ in the reaction mixture containing a member of the group consisting of alkali metal chromates and dichrom-ates by the gradual addition thereto of strong sulfuric acid.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
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• Agricultural Chemicals And Associated Chemicals (AREA)

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Cited By (2)

Citations (5)

• 0
  • NL NL271038D patent/NL271038A/xx unknown
  • BE BE609983D patent/BE609983A/xx unknown
• 1960
  • 1960-11-07 US US67501A patent/US3155689A/en not_active Expired - Lifetime
• 1961
  • 1961-11-06 CH CH1286361A patent/CH419079A/de unknown
  • 1961-11-06 DE DES76576A patent/DE1186851B/de active Pending
  • 1961-11-06 GB GB39626/61A patent/GB941130A/en not_active Expired
  • 1961-11-06 FR FR878063A patent/FR1306274A/fr not_active Expired

Patent Citations (5)

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