US3857838A - Organophosphate ester derivatives of heterocyclic compounds and process - Google Patents

Organophosphate ester derivatives of heterocyclic compounds and process Download PDF

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US3857838A
US3857838A US00288393A US28839372A US3857838A US 3857838 A US3857838 A US 3857838A US 00288393 A US00288393 A US 00288393A US 28839372 A US28839372 A US 28839372A US 3857838 A US3857838 A US 3857838A
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carbon atoms
dihydro
pyrimidine
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J Perronnet
A Poittevin
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Sanofi Aventis France
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings

Definitions

  • A represents a divalent radical selected from the group consisting of alkylene having three to five carbon atoms, aza substitued alkylene having atoms, alkoxy having one to four carbon atoms, alkoxyalkoxy having'one to four carbon atoms in each alk, and
  • R, and R are members selected from the group consisting of hydrogen and alkyl having one to three carbon atoms; as well as the process of producing said organophosphate esters.
  • the compounds have insecticidal and acaricidal properties 4 Claims, N0 Drawings ORGANOPIIOSPIIATE ESTER DERIVATIVES OF IIETEROCYCLIC COMPOUNDS AND PROCESS OBJECTS OF THE INVENTION T N A wherein A represents a divalent radical selected from the group consisting of alkylene having three to five carbon atoms, aza substituted alkylene having three to five carbon atoms in the chain and thia substituted alkylene having three to five carbon atoms in the chain,
  • Y represents a member selected from the group consisting of hydrogen, alkyl having one to six carbon atom, cyano, halo and alkylthio having one to six carbon atoms,
  • X represents a member selected from the group consisting of sulfur and oxygen
  • R represents an alkyl having one to four carbon atoms
  • R represents a member selected from the group consisting of alkyl having one to four carbon atoms, alkoxy having one to four carbon atoms, al-
  • R, and R are members selected from the group consisting of hydrogen and alkyl having one to wherein A represents a divalent radical selected from the group consisting of alkylene having three to five carbon atoms, aza substituted alkylene having three to five carbon atoms in the chain and thia substituted al kylene having three to five carbon atoms in the chain and Y represents a member selected from the group consiting of hydrogen, alkyl having from one to six carbon atoms, cyano, halo and alkylthio having from one to six carbon atoms.
  • halophosphate having the formula wherein Hal represents a member selected from the group consisting of chloro and bromo, X represents a member selected from the group consisting of sulfur and oxygen, R represents an alkyl having one to four carbon atoms and R represents a member selected from the group consisting of alkyl having one to four carbon atoms, alkoxy having one to four carbon atoms, alkoxyalkoxy having one to four carbon atoms in eac alk, and
  • R, and R are members selected from the group consisting of hydrogen and alkyl having one to three carbon atoms, and recovering said organophosphate ester.
  • a further object ofthe present invention is the development of insecticidal and/or acaricidal compositions containing from 10 percent to percent of the above organophosphate esters and the remainder inert excipients.
  • a yet further object of the present invention is the development of a method for combatting insects and/or acarids which comprises contacting 'them with the above organophosphate esters.
  • A represents an alkylene chain having from three to five carbon atoms, possibly interrupted by a beteroatom chosen from sulfur and nitrogen, and more particularly A represents a divalent radical selected from the group consisting of alkylene having three to five carbon atoms, aza substituted alkylene having three to five carbon atoms in the chain and thia substituted alkylene having three to five carbon atoms in the chain;
  • Y represents hydrogen, alkyl having one to six carbon atoms, linear or branched, cyano, halogen or alkylthio having one to six carbon atoms, and more praticularly Y represents a member selected from the group consisting of hydrogen, alkyl having from one to six carbon atoms, cyano, halo and alkylthio having from one to six carbon atoms;
  • X represents an atom of sulfur or oxygen
  • R represents an alkyl. linear or branched. having one to four carbon atoms
  • R represents an alkyl, linear or branched, having one to four carbon atoms, alkoxy having one to four carbon atoms and possibly substituted by alkoxy having one to four carbon atoms, or R represents an amino group in which R, and R the same or different, represent either hydrogen or an alkyl, linear or branched, having one to three carbon atoms, and more particularly R represents a member selected from the group consisting of alkyl having one to four carbon atoms, alkoxy having one to four carbon atoms, alkoxyalkoxy having one to four carbon atoms in each alk, and
  • R, and R are members selected from the group consisting of hydrogen and alkyl having one to three carbon atoms.
  • alkyl used here above designates particularly methyl, ethyl, propyl, isopropyl or n-butyl and the h. 2-diethoxythiophosphoryloxy-3-ethylthio-7 ,8-.
  • the compounds of formula I are endowed withpesti- I cidal properties particularly as insecticides and/or acaricides which make them suitable to control noxious organisms and particularly insects and acarids.
  • insecticidal properties of these compounds can be demonstrated particularly by tests on Prodenia lituru, Ceralin's capitata, Aphisfabl'ze, BIateIIa germanica or Musca domestica which are described later.
  • (III) such as acetone, acetonitrile, benzene, methanol or ethyl acetate, under, preferably, anhydrous conditions in the presence of a basic agent such as an alkali metal carbonate, an alkali metal lower alkanolate and/or a tertiary organic amine base such as triethylamine, trimethylamine or pyridine.
  • the basic agent may also be the alkali metal derivative of the compound of formula II as formed from the reaction of the compound of formula ll with an alkali metal lower alkanolate in a solvent such as a lower alkanol.
  • these compounds can be prepared by reacting a compound of the formula with a trialkyl phosphite. Preferably, this reaction is conducted with an excess of the trialkylphosphite and for example at temperatures of from 50C to 125C.
  • the invention also comprises the insecticidal and/or acaricidal compositions containing, as active material, at least one of the compounds of formula I.
  • These compositions can be presented in the form of powders, granules, suspensions, emulsions, solutions, containing the active principle, for example, in mixture with a vehicle and/or ananionic, cationic or nonionic surfaceactive agent assuring, among other things, a uniform dispersion of the substances of the composition.
  • the vehicle utilized can be a liquid such as water, alcohol, hydrocarbons or other organic solvents, mineral, vegetable or animal oil, or a powder such as talc, clays, silicates, Kieselguhr.
  • the insecticidal liquidsor powders for foliage applications contain preferably from 20 to percent by weight of the active material Formula I.
  • the acaricidal liquids or powders for foliage applications contain preferably from 20 percent to 80 percent by weight of the active material of formula I.
  • insects and/or acarids are contacted with the insects and/or acarids.
  • the compounds of formula 11. utilized as starting materials in the process of the invention. can be prepared accordingto a process analogous to that described by Le Berre et a1. Bull. Soc. Chim. 1969, 3137.
  • N OH 1 I A N Br can be prepared by the action ofN-bromo-succinimide on compounds of the formula
  • the following examples are illustrative of the practice ol the invention without being deemed limitative in any respect.
  • 1.6-dhydro-4-hydr0xy-5-isopropyl-azepino-[ 1 .2-a]- pyrimidine-6-one 45 gm of sodium ethylate were introduced into 450 cc of ethanol. 63 gm of ethyl isopropyl-malonate and 50 gm of the sulfate ofcaprolactamidine were added to the solution obtained. The reaction mixture was heated to reflux and maintained there for four hours. The solvent was then eliminated by distillation under reduced pressure. The residue was dissolved in water and acidified to a ph of 3 with an aqueous hydrochloric acid solution. The precipitate formed was isolated by vacuum filtration and dried.
  • EX/TMPILE 1 "M v 2-Diethoxytlfiophosfioryloxy g 'v 7 A -dihydro-6H-pyrrolo-[ l ,2-a]-pyrimidine-4-one 36 gm of 2-hydroxy-7,8-dihydro-6H-pyrrolo-[l,2-a]- pyrimidine-4-one were placed in suspension in 300 cc of acetone. After homogenization, 28 cc of triethylamine were added, then 35 cc of 0,0-diethy1 chlorothiophosphate were introduced drop by drop. The mixture was agitated at room temperature for forty-eight hours.
  • Step B 2-(o-ethyl NN dimethylthiophosphoramido-oxy)-7,8-dihydro-6H-pyrrolo- [l,2-a]-pyrimidine-4-one 88 gm of a sodium salt of 2-hydroxy-7,8-dihydro-6H- pyrrolo-[ l ,2al-pyrimidine-4-one and 63 cc of ethyl N- dimethyl-thiophosphoramido-chloridate were introduced into 700 cc of acetonitrile. The mixture was heated to reflux for 33 hours. The precipitate formed was eliminated by filtration. The filtrate evaporated to dryness and gm of red oil was obtained.
  • This oil was subjected to chromatography through silica eluting with a cyclohexane-acetone-chloroform mixture (1:1:1) in order to obtain some yellowish crystals which were purified by washing with essence G. 27.5 gm of 2-(O-ethyl-N,N-dimethyl-thiophosphoramido-0xy)- 7,8-dihydro-6H-pyrrolo-[1,2-a]-pyrimidine-4-one were thus obtained melting at 63 C.
  • Step A The sodium salt of 2-hydroxy3-methyl- 7 ,8-dihydro-6H-pyrrolo-[1 ,2-a]-pyrimidine-4-one.
  • Step B 2-Diethoxythiophosphoryloxy-3-methyl- 7,8-dihydro-6H-pyrrolo-[l ,2-a]-pyrimidine4-one.
  • EXAMPLE 8 l,6-Dihydro-4-dimethoxythiophosphoryloxy-azepino- [l,2-a]-pyrimidine-6-one
  • 35 gm of 1,6-dihydro*4-hydroxy-azepino-[l,2-a] pyrimidine-6-one and 27 gm of potassium carbonate were introduced into 350 cc of acetonitrile.
  • 32 gm of 0,0-dimethyl chloro-thiophosphate were then added, and the reaction mixture was agitated for 20 hours at room temperature.
  • the mineral salts were eliminated by filtration.
  • the filtrate was concentrated to dryness by distillation under reduced pressure.
  • EXAMPLE 9 l,6-Dihydro-4diethoxythiophosphoryloxy-azepinoll.2-al-pyrimidine-6-one
  • 35 gm of l,6-dihydro-4-hydroxy-azepino-l1.2-111- pyrimidine-6-one and 27 gm of potassium carbonate were introduced into 350 cc of acetonitrile.
  • 30 cc of .0,0-diethyl chloro-thiophosphate were added thereto.
  • the mixture was agitated for 56 hours at room temperature.
  • the mineral salts were eliminated by filtration.
  • the filtrate was concentrated to dryness by distillation under reduced pressure.
  • a]-pyrimidine-4-one and 27.6 gm of potassium carbonate were introduced into 300 cc of acetone. This mixture was heated to reflux and maintained there for 1 hour, then cooled to 20C. 34.8 gm of O-methyl-O- ethyl chlorothiophosphate were added. The reaction mixture was heated to 40C and maintained at this temperature for 4 hours. The insolubles formed were eliminated by filtration. The filtrate was concentrated to dryness under reduced pressure. The residue was subject to chromatography through silica gel with elution by a mixture of chloroform and acetone (111-). 6.5 gm of 2-(methoxy-ethoxythiophosphoryloxy)-7,8-dihydro- 6H-pyrrolo-[1,2-a]-pyrimidine-4-one were obtained having a melting point of 71C.
  • the first group ofplants was treated by Compound A, 1 ml of solution containing mg of Compound A 5 per liter was sprinkled on each leaf. Each leaf was infested with 20 plant lice and each leaf was encircled with gauze in order to hinder the departure ofthe plant lice.
  • a counting of living and dead insects as that of Carbaryl are expressed as a percentage of the a function of time was made. The results are expressed reduction of the number of living caterpillars. The re- 20 in a percentage of Abbott efficacy (taking into account sults are given in Table III below. the controlled test).
  • n represents an integer from 2 to 3
  • Y represents a member selected from the group consisting of hydrogen, alkyl having one to six carbon atoms, halo and alkylthio having one to six carbon atoms,
  • X represents a member selected from the group consisting of sulfur and oxygen
  • R represents an alkyl having one to four carbon atoms
  • R represents a member selected from the group consisting of alkoxy having one to four carbons atoms, alkoxyalkoxy having one to four carbon atoms alkoxyalkoxy having one to four carbon atoms in each alk, and

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Abstract

An organophosphate ester having the formula

WHEREIN A represents a divalent radical selected from the group consisting of alkylene having three to five carbon atoms, aza substitued alkylene having three to five carbon atoms in the chain and thia substituted alkylene having three to five carbon atoms in the chain, Y'' represents a member selected from the group consisting of hydrogen, alkyl having one to six carbon atoms, cyano, halo and alkylthio having one to six carbon atoms, X represents a member selected from the group consisting of sulfur and oxygen, R1'''' represents an alkyl having one to four carbon atoms, R2'''' represents a member selected from the group consisting of alkyl having one to four carbon atoms, alkoxy having one to four carbon atoms, alkoxyalkoxy having one to four carbon atoms in each alk, and

WHERE R1'' and R2'' are members selected from the group consisting of hydrogen and alkyl having one to three carbon atoms; as well as the process of producing said organophosphate esters. The compounds have insecticidal and acaricidal properties.

Description

United States Patent [1 1 Perronnet et al.
[ Dec. 31, 1974 ORGANOPHOSPHATE ESTER DERIVATIVES OF I-IETEROCYCLIC COMPOUNDS AND PROCESS [75] Inventors: Jacques Perronnet, Paris; Andre Poittevin, Vaires-sur-Marne, both of France [73] Assignee: Roussel Uclaf, Paris, France [22] Filed: Sept. 12, 1972 [21] Appl. No.:'288,393
[30] Foreign Application Priority Data Sept. 16, l97l France 71.33434 [52] US. Cl. 260/243 R, 260/25 A, 260/25 P,
260/256,4 E, 260/256.4 F, 260/256.5 R, 424/200 [51] Int. Cl C07d 51/46 [58] Field of Search 260/251 A, 251 P, 256.4 E, 260/243 R, 256.5 R
[56] References Cited UNITED STATES PATENTS 9/ 1 968' Schicke 260/256.4
Primary E.\'aminerRaymond V. Rush Attorney, Agent, or Firm--Hammond & Littell substituted wherein "A represents a divalent radical selected from the group consisting of alkylene having three to five carbon atoms, aza substitued alkylene having atoms, alkoxy having one to four carbon atoms, alkoxyalkoxy having'one to four carbon atoms in each alk, and
where R, and R are members selected from the group consisting of hydrogen and alkyl having one to three carbon atoms; as well as the process of producing said organophosphate esters. The compounds have insecticidal and acaricidal properties 4 Claims, N0 Drawings ORGANOPIIOSPIIATE ESTER DERIVATIVES OF IIETEROCYCLIC COMPOUNDS AND PROCESS OBJECTS OF THE INVENTION T N A wherein A represents a divalent radical selected from the group consisting of alkylene having three to five carbon atoms, aza substituted alkylene having three to five carbon atoms in the chain and thia substituted alkylene having three to five carbon atoms in the chain,
Y represents a member selected from the group consisting of hydrogen, alkyl having one to six carbon atom, cyano, halo and alkylthio having one to six carbon atoms,
X represents a member selected from the group consisting of sulfur and oxygen,
R," represents an alkyl having one to four carbon atoms,
R represents a member selected from the group consisting of alkyl having one to four carbon atoms, alkoxy having one to four carbon atoms, al-
koxyalkoxy havingl to 4 carbon atoms in each alk, and
where R, and R are members selected from the group consisting of hydrogen and alkyl having one to wherein A represents a divalent radical selected from the group consisting of alkylene having three to five carbon atoms, aza substituted alkylene having three to five carbon atoms in the chain and thia substituted al kylene having three to five carbon atoms in the chain and Y represents a member selected from the group consiting of hydrogen, alkyl having from one to six carbon atoms, cyano, halo and alkylthio having from one to six carbon atoms. with a halophosphate having the formula wherein Hal represents a member selected from the group consisting of chloro and bromo, X represents a member selected from the group consisting of sulfur and oxygen, R represents an alkyl having one to four carbon atoms and R represents a member selected from the group consisting of alkyl having one to four carbon atoms, alkoxy having one to four carbon atoms, alkoxyalkoxy having one to four carbon atoms in eac alk, and
where R, and R are members selected from the group consisting of hydrogen and alkyl having one to three carbon atoms, and recovering said organophosphate ester.
A further object ofthe present invention is the development of insecticidal and/or acaricidal compositions containing from 10 percent to percent of the above organophosphate esters and the remainder inert excipients.
A yet further object of the present invention is the development ofa method for combatting insects and/or acarids which comprises contacting 'them with the above organophosphate esters.
These and other objects of the invention will become more apparent as the description thereof proceeds.
DESCRIPTION OF THE INVENTION The above objects have been achieved by the discovery of novel insecticidal and/or acaricidal organophosphate ester derivatives of the general formula I in which A represents an alkylene chain having from three to five carbon atoms, possibly interrupted by a beteroatom chosen from sulfur and nitrogen, and more particularly A represents a divalent radical selected from the group consisting of alkylene having three to five carbon atoms, aza substituted alkylene having three to five carbon atoms in the chain and thia substituted alkylene having three to five carbon atoms in the chain;
Y represents hydrogen, alkyl having one to six carbon atoms, linear or branched, cyano, halogen or alkylthio having one to six carbon atoms, and more praticularly Y represents a member selected from the group consisting of hydrogen, alkyl having from one to six carbon atoms, cyano, halo and alkylthio having from one to six carbon atoms;
X represents an atom of sulfur or oxygen;
R," represents an alkyl. linear or branched. having one to four carbon atoms, and
R represents an alkyl, linear or branched, having one to four carbon atoms, alkoxy having one to four carbon atoms and possibly substituted by alkoxy having one to four carbon atoms, or R represents an amino group in which R, and R the same or different, represent either hydrogen or an alkyl, linear or branched, having one to three carbon atoms, and more particularly R represents a member selected from the group consisting of alkyl having one to four carbon atoms, alkoxy having one to four carbon atoms, alkoxyalkoxy having one to four carbon atoms in each alk, and
where R, and R are members selected from the group consisting of hydrogen and alkyl having one to three carbon atoms.
The term alkyl used here above designates particularly methyl, ethyl, propyl, isopropyl or n-butyl and the h. 2-diethoxythiophosphoryloxy-3-ethylthio-7 ,8-.
ih -py w tLZal-wrim M ne-1 :229-
The compounds of formula I are endowed withpesti- I cidal properties particularly as insecticides and/or acaricides which make them suitable to control noxious organisms and particularly insects and acarids.
The insecticidal properties of these compounds can be demonstrated particularly by tests on Prodenia lituru, Ceralin's capitata, Aphisfabl'ze, BIateIIa germanica or Musca domestica which are described later.
' The process of preparation of the organophosphate ester derivatives of formula I is characterized in that a compound of the formula ll:
wherein A and Y have the above-assigned values. is reacted with a halogenophosphate of the formula [I]:
(III) such as acetone, acetonitrile, benzene, methanol or ethyl acetate, under, preferably, anhydrous conditions in the presence of a basic agent such as an alkali metal carbonate, an alkali metal lower alkanolate and/or a tertiary organic amine base such as triethylamine, trimethylamine or pyridine. The basic agent may also be the alkali metal derivative of the compound of formula II as formed from the reaction of the compound of formula ll with an alkali metal lower alkanolate in a solvent such as a lower alkanol.
In the case where Y is hydrogen, R represents an alkyl and'R represents an alkoxy, for compounds of formula I, these compounds can be prepared by reacting a compound of the formula with a trialkyl phosphite. Preferably, this reaction is conducted with an excess of the trialkylphosphite and for example at temperatures of from 50C to 125C.
The invention also comprises the insecticidal and/or acaricidal compositions containing, as active material, at least one of the compounds of formula I. These compositions can be presented in the form of powders, granules, suspensions, emulsions, solutions, containing the active principle, for example, in mixture with a vehicle and/or ananionic, cationic or nonionic surfaceactive agent assuring, among other things, a uniform dispersion of the substances of the composition. The vehicle utilized can be a liquid such as water, alcohol, hydrocarbons or other organic solvents, mineral, vegetable or animal oil, or a powder such as talc, clays, silicates, Kieselguhr.
The insecticidal liquidsor powders for foliage applications contain preferably from 20 to percent by weight of the active material Formula I.
The acaricidal liquids or powders for foliage applications contain preferably from 20 percent to 80 percent by weight of the active material of formula I.
or several other pesticidal agents is contacted with the insects and/or acarids.
The compounds of formula 11. utilized as starting materials in the process of the invention. can be prepared accordingto a process analogous to that described by Le Berre et a1. Bull. Soc. Chim. 1969, 3137.
4-hydroxy-l,6-dihydro-azepino-[1,2-a]-pyrimidine- 6-one was described by Glushkov et a1, Zhur. Obsh- I chei. Khim. 31. 189 (1961). 2,3-dihydro-7-hydroxythiaz0lo-[3.2-a1-pyrimidine-5-one was described by Dashkevieh. Zhur. Obshchei, Khim. 31, 3723 (1961). Certain compounds of formula II are not described in the literature. These are 2-hydroxy-6.7.8,9-tetrahydropyrido-[ l .2-a]-pyrimidine-4-one, 2-hydroxy-3- ethylthio-7.8-dihydro-6H-pyrrolo-l1,2-al-pyrimidine- 4-one, 1,6-dihydro-4-hydroxy-5-bromo-azepino-l1,2- al-pyrimidine-o-one. and l,6-dihydro4-hydroxy-5- isopropyl-azepino-[l,2-al-pyrimidine-6 one, all of whose preparations are given as exemplary later in the examples.
The compounds of the formula N OH 1 I A N Br can be prepared by the action ofN-bromo-succinimide on compounds of the formula The following examples are illustrative of the practice ol the invention without being deemed limitative in any respect.
EXAM PLES Preparation A:
2-h yd roxy-6,7 ,8.9-tetrahydro-pyrido-l 1 .2a 1- pyrimidine-done 6.5 gm ofsodium were introduced into 300 cc ofethanol and. after the disappearance of the sodium. 19 gm of imino-pyridine hydrochloride and 22.5 gm of ethyl malonate were added thereto. The reaction mixture was heated to reflux and maintained there for sixteen hours. The insolubles formed were eliminated by filtration. The reaction mixture was concentrated to dryness and some water was added thereto. The aqueous mixture was acidified to a pH of 3 by the addition of an aqueous solution of hydrochloric acid. The precipitate formed was isolated by vacuum filtering and 13.8 gm of 2-hydroxy-6, 7,8,9-tetrahydro-pyrido- [1.2-alpyrimidine-4-one melting at 270C (with decomposition), was obtained.
1R. Spectra absorption at 1709 and 1606" corresponding to C=O, absorption at 1587"" corresponding to C=C. absorption at 1529" corresponding to C=N.
Preparation B 2-hydroxy3-ethylthio-7.8-dihydro-6H-pyrrolo-[ 1.241]- pyrimidine-4-one 19.5 gm of imino-pyrrolidine and 52 gm ofethyl ethylthio-malonate were mixed. This mixture was heated to 200C. maintained at this temperature'for fifteen minutes, and then cooled. The residue obtained was ground in the presence of ether. The resulting powder was isolated by vacuum filtering and 31 gm of 2- hydroxy-3-ethylthio-7,8-dihydro-6H-pyrrolo-l l .2-a pyrimidine-4-one was obtained.
[.R. Spectra absorption at 1720 ""f corresponding to C= O.
absorptions corresponding to C=C. C=N. OH.
Preparation C:
azepino-[1.2-al-pyrimidine-6-one 4-hydroxy-5-bromo- 1 .6-dihydro- 37 gm of 4-hydroxy-1.6-dihydro-azepino-l 1.2-alpyrimidine-6-one was introduced into 300 cc of methanol. 36.6 gm of N-bromo-succinimide were added progressively and then the reaction mixture was agitated for 16 hours at room temperature. The precipitate formed was isolated by vacuum filtering. washed and dried. 38 gm of 4-hydroxy-azepino-[ 1.2-al-pyrimidine- 6-one 5-brom0-l .-dihydro. melting at 265C (with de composition). was obtained.
1. R. Spectra absorption at 1694 cmfl. 1683cm corresponding to C= O. absorption at 1618 cm corresponding to C C. absorption at l569cmjand 1540cm corresponding to C N, absorption corresponding to OH.
Preparation D:
1.6-dhydro-4-hydr0xy-5-isopropyl-azepino-[ 1 .2-a]- pyrimidine-6-one 45 gm of sodium ethylate were introduced into 450 cc of ethanol. 63 gm of ethyl isopropyl-malonate and 50 gm of the sulfate ofcaprolactamidine were added to the solution obtained. The reaction mixture was heated to reflux and maintained there for four hours. The solvent was then eliminated by distillation under reduced pressure. The residue was dissolved in water and acidified to a ph of 3 with an aqueous hydrochloric acid solution. The precipitate formed was isolated by vacuum filtration and dried. 47 gm of 1,6-dihydro-4-hydroxy-5- isopropyl-azepino-l l,2-a]-pyrimidine-6-one was obtained, which was purified by dissolution in an aqueous sodium hydroxide solution, this solution being washed with ethyl acetate and acidified to a pH of 4. The purified product had a melting point of 246C. Analysis:
C H N O molecular weight 222.29 1 Calculated:
64.82% C 8.20% H 12.60% N Found:
EX/TMPILE 1 "M v 2-Diethoxytlfiophosfioryloxy g 'v 7 A -dihydro-6H-pyrrolo-[ l ,2-a]-pyrimidine-4-one 36 gm of 2-hydroxy-7,8-dihydro-6H-pyrrolo-[l,2-a]- pyrimidine-4-one were placed in suspension in 300 cc of acetone. After homogenization, 28 cc of triethylamine were added, then 35 cc of 0,0-diethy1 chlorothiophosphate were introduced drop by drop. The mixture was agitated at room temperature for forty-eight hours. Then the precipitate was eliminated by filtration and the filtrate was evaporated to dryness under reduced pressure. A raw oil was obtained which was subjected to chromatography through a column of silica eluting with a chloroform-acetone mixture (1:1). The
Rf 0.5 fraction was evaporated to dryness under reduced pressure. A yellow oil was obtained which crystallized giving 28 gm of yellow crystals of 2 diethoxythiophosphoryloxy-7,8-dihydro-6H-pyrrolo- [1,2-a1-pyrimidine-4-one melting at 56 C. Analysis:
C H N O PS; molecular weight 304.307
Calculated:
43.43% C 5.63% H 9.20% N 10.17% P 'Found:
EXAMPLE 2 2-(N -methyl-O-ethyl-thiophosphoramido-oxyi 7 ,8 i
dihydro-6H-pyrrolo-[1,2-a]-pyrimidine-4-one.
35 gm of 2-hydroxy-7,8-dihydro-6H-pyrrolo-[1,2-a]- pyrimidine-4-0ne were mixed with 400 cc of anhydrous acetonitrile, 32 gm of potassium carbonate and 50 gm of ethyl N-methyl-thiophosphoramido chloridate. The reaction mixture was agitated for 16 hours at room temperature and then the insolubles were eliminated by vacuum filtration. The filtrate was evaporated under reduced pressureand 55 gm of a red oil was obtained. This oil was purified by subjecting it to chromatography through a column of silica eluting with an acetonechloroform-cyclohexane mixture (1:111). The fraction of Rf 0.3 was separated. The solvents were eliminated under reduced pressure and 9 gm of Z-(N-methyl-O- ethyl-thiophosphoramido-oxy)-7,8-dihydro-6H- pyrrolo-[l,2-a]-pyrimidine-4-one were obtained, which crystallized slowly giving yellowish crystals melting at 85C.
weight 289.295
EXAMPLE 3 2-(O-ethylN ,N-dimethyl-thiophosphoramido-oxy)- 7,8-dihydro-6H -pyrrolo-[1,2-a]-pyrimidine-4-one 22 gm of sodium methylate were introduced therein. The mixture was maintained under agitation until the temperature returned to 20C. The precipitate formed was eliminated by filtration. The filtrate was evaporated to dryness. The residue was taken up in ether, triturated, and 88 gm of the sodium salt of 2-hydroxy- 7,8-dihydro-6H-pyrrolo-[l ,2-a]-pyrimidine-4-one was isolated by vacuum filtering.
Step B: 2-(o-ethyl NN dimethylthiophosphoramido-oxy)-7,8-dihydro-6H-pyrrolo- [l,2-a]-pyrimidine-4-one 88 gm of a sodium salt of 2-hydroxy-7,8-dihydro-6H- pyrrolo-[ l ,2al-pyrimidine-4-one and 63 cc of ethyl N- dimethyl-thiophosphoramido-chloridate were introduced into 700 cc of acetonitrile. The mixture was heated to reflux for 33 hours. The precipitate formed was eliminated by filtration. The filtrate evaporated to dryness and gm of red oil was obtained. This oil was subjected to chromatography through silica eluting with a cyclohexane-acetone-chloroform mixture (1:1:1) in order to obtain some yellowish crystals which were purified by washing with essence G. 27.5 gm of 2-(O-ethyl-N,N-dimethyl-thiophosphoramido-0xy)- 7,8-dihydro-6H-pyrrolo-[1,2-a]-pyrimidine-4-one were thus obtained melting at 63 C.
Analysis:
C H N O Ps; molecular weight 303.322 Calculated:
43.55% C 5.98% H 13.85% N 10.20% P 10.57% S Found:
EXAMPLE 4 34 gm of 2,3-dihydro-7-hydroxy-thiazolo-[3,2-a]- pyrimidine-S-one and 28 gm of potassium carbonate were introduced into a solution of 35 cc of 0,0-diethyl -chlorothiophosphate in 300 cc of acetonitrile. The solution thus obtained was heated to reflux for 16 hours. The precipitate formed was eliminated by filtration. The filtrate was evaporated to dryness. A red oil was obtained which was subject to chromatography through silica eluting with a cyclohexane-ethyl acetate mixture (2:8). 19 gm of 2,3-dihydro-7-(diethoxythiophosphoryloxy)-thiazo1o-[3,2-a]-pyrimidine-5-one was obtained having a refractive index n,, 1.5711. Analysis:
C H, N O.,PS molecular weight 322.344 Calculated:
37.26% C 4.69% H 8.69% N 9.62% P Found:
EXAMPLE 5 2-Diethoxythiophosphoryloxy-3-bromo-7,8-dihydro- 6H-pyrrolo-[ l,2-a]-pyrimidine-4-one 1.1 gm of 2-hydroxy-3-b'romo-7,8-dihydro-6H- pyrrolo-[1,2-a]-pyrimidine-4-one were introduced into a suspension containing 0.8 cc of 0,0-diethyl chlorothiophosphate and 0.7 gm of potassium carbonate in 10 cc of acetonitrile. The suspension obtained was agi tated for 48 hours. The insolubles were eliminated by E'XAMPLEG 2-Diethoxythiophosphoryloxy-3 -methyl-7 ,8-dihydro- 6H-pyrrolo-[l ,2-a]-pyrimidine4-one.
Step A: The sodium salt of 2-hydroxy3-methyl- 7 ,8-dihydro-6H-pyrrolo-[1 ,2-a]-pyrimidine-4-one.
44.5 gm of 2hydroxy-3-methyl-7,8-dihydro-6H- pyrrolo-[l,2-al-pyrimidine-4-one and 14.5 gm of sodium methylate were introduced at 40C into 400 cc of methanol. The solution obtained was agitated for minutes at room temperature and then evaporated to dryness. The crystals obtained were triturated in ether and isolated by vacuum filtration. 134 gm of the raw sodium salt of 2-hydroxy-3-methyl-7,8-dihydro-6H- pyrrolo-[l,2-a]-pyrimidine-4-one were thus obtained.
Step B: 2-Diethoxythiophosphoryloxy-3-methyl- 7,8-dihydro-6H-pyrrolo-[l ,2-a]-pyrimidine4-one.
134 gm of the raw salt obtained in Step A were introduced into a solution containing 42.5 cc of 0,0- diethyl chloro-thiophosphate in 500 cc of acetonitrile. The mixture was heated to reflux for 36 hours. The precipitate formed was eliminated by vacuum filtration and the filtrate was evaporated to dryness. A red oil was obtained which was subject to chromatography through silica eluting with a cyclohexa'neacetone-chloroform mixture (1:1:1). A yellow oil of Rf 0.35 was obtained which was subject to chromatography again through silica eluting with a cyclohexaneethyl acetate mixture (3:7). gm of 2-diethoxythiophosphoryloxy-3-methyl-7,8-dihydro-6H- pyrrolo-[l,2-a]-pyrimidine-4-one were thus obtained having a refractive index 1117 1.5335. Analysis:
C H19N2O PS: molecular weight 318.334 Calculated;
45.28% C 6.02% H 8.80% N 9.73% P Found:
EXAMPLE 7 2,3-Dihydro-8-diethoxythiophosphoryloxy-4H- pyrimido-[2,1-b]-[1,3]-thiazine-6-one (prepared according to the method of Schobert et al Ann. Chem. 742,91. 1970) 21 gm of potassium carbonate and 28.5 gm of 0,0- diethyl chloro-thio-phosphate were introduced into 250 cc of acetonitrile. The mixture was heated to reflux for 3 hours and then the precipitate formed was eliminated by filtration. The filtrate was evaporated to dryness, then crystallized by the addition of ether. Some yellow crystals were obtained which were subject to chromatography through silica with elution with a cyclohexane-chloroform-acetone mixture tlzlzl). 20.! gm of 2.3-dihydro-8-diethoxy-thio- 4 110 phosphoryloxy-4H-pyrimido-[2 l -b]-[1 ,3l-thiazine.
6-one were thus obtained melting at 80C.
Analysis: C H N O PS molecular weight 336.37 5 Calculated:
39.29% C 5.09% H 8.33% N 9.20% P Found:
EXAMPLE 8 l,6-Dihydro-4-dimethoxythiophosphoryloxy-azepino- [l,2-a]-pyrimidine-6-one 35 gm of 1,6-dihydro*4-hydroxy-azepino-[l,2-a] pyrimidine-6-one and 27 gm of potassium carbonate were introduced into 350 cc of acetonitrile. 32 gm of 0,0-dimethyl chloro-thiophosphate were then added, and the reaction mixture was agitated for 20 hours at room temperature. The mineral salts were eliminated by filtration. The filtrate was concentrated to dryness by distillation under reduced pressure. The residue was dissolved in a mixture of cyclohexane and ethyl acetate 1:1 The solution obtained was passed through florisil (activated magnesium silicate) and 27 gm of 1,6- dihydro-4-dirnethoxy-thiophosphoryloxy-azepino-[1,2- a]-pyrimidine-6-one were obtained having a melting point of 99C.
Analysis:
C H N O PS; molecular weight 304.31 Calculated:
43.42% C 5.63% H 9.20% N l0.l8% P Found:
EXAMPLE 9 l,6-Dihydro-4diethoxythiophosphoryloxy-azepinoll.2-al-pyrimidine-6-one 35 gm of l,6-dihydro-4-hydroxy-azepino-l1.2-111- pyrimidine-6-one and 27 gm of potassium carbonate were introduced into 350 cc of acetonitrile. 30 cc of .0,0-diethyl chloro-thiophosphate were added thereto. The mixture was agitated for 56 hours at room temperature. The mineral salts were eliminated by filtration. The filtrate was concentrated to dryness by distillation under reduced pressure. The residue was subject to chromatography through silica gel eluting with a mix- EXAMPLE 10 1.6-Dihydro-4-dietho xythiophosphoryloxy-S- isopropyl-azepino-[ l ,2-a]-pyrimidine-6-one 40 gm of l,6-dihydro-4-hydroxy-5-isopropyl- 9291991911 1-Py m ;Qa3liat tpq ssium carbonate and 29 cc of 0,0-diethyl chlorothiophosphate were introduced into 400 cc of acetoni trile. The reaction mixture was heated to reflux and maintained there for 6 hours. Thereafter the mixture was agitated for 60 hours at room temperature. The
was concentrated to dryness by distillation under reduced pressure. The residue was purified by chromatography through silica gel eluting with a mixture of cyclohexane and ethyl acetate (7:3). 50 gm of 1,6- dihydro-4-diethoxythiophosphoryloxy-S-isopropylazepino-[l,2-a]-pyrimidine-6-one were obtained having a melting point of 71C. Analysis:
C, H N O PS; molecular weight 374.44 Calculated:
51.33% C 7.27%H 7.48% N 8.27% P Found:
EXAMPLE 11 2-Dimethoxythiophosphoryloxy-7,8-dihydro-6l'lpyrro1o-[1,2-a]-pyrimidine- 4-one 41 gm of 2-hydroxy-7,8-dihydro-6l-1-pyrrole-[1,2-a]- pyrimidine-4-one, 400 mg of topanol, 36.5 gm of potassium carbonate were introduced into a mixture of 300 cc of acetone and 30 cc of methanol. 40 gm of 0,0- dimethyl chloro-thiophosphate were added thereto. The reaction mixture was heated to reflux and maintained there for a period of an hour and 45 minutes. Thereafter, the reaction mixture was concentrated to dryness by distillation under reduced pressure. Water was added to the residue and the mixture was extracted with ethyl acetate. The organic phase was dried and concentrated to dryness by distillation under reduced pressure. The residue was crystallized from ethyl ether and 23 gm of 2-dimethoxythi0phosphoryloxy-7,8- dihydro-6H-pyrrolo-[1.2-a1-pyrimidine-4-one were obtained having a melting point of 53C.
Analysis:
C H,;,N O,PS; molecular weight 276.25 Calculated:
39.13% C 4.75% H 10.14% N 11.20% P Found:
EXAMPLE-1.2-
2,3-Dihydro-7-dimethoxythiophosphoryloxythiazolo- [3,2-al-pyrimidine--one 12 gm of 2,3-dihydro-7-hydroxy-thiazolo-[3,2-a]- pyrimidine-S-one and 9.8 gm of potassium carbonate were introduced into 200 cc of acetonitrile. 8.5 cc of 0,0-dimethy1 chloro-thiophosphate were introduced therein. The mixture was agitated for s rnaur'sarreafi temperature. The mineral salts were eliminated by filtration. The filtrate was concentrated to dryness by distillation under reduced pressure. The residue was subject to chromatography through silica gel with elution by a mixture of cyclohexane and ethyl acetate (2:8). 8 gm of 2,3-dihydro-7-dimethoxythiophosphoryloxythiazolo-[3,2-a]-5-pyrimidine-5-one were obtained having a melting point of 84C.
Analysis:
C H N O PS molecular weight 294.29 Calculated:
32.65% C 3.77% H 9.52% N 10.53% P Found:
' mineral salts were eliminated by filtration. The filtrate- EXAMPLE 13 1,6-Dihydro-4-diethoxyphosphoryloxy-azepino-[1.2- al-pyrim idine-6-one 35 gm of 1,6-dihydro-4-hydroxy-azepino-[ l .2-alpyrimidine-6-one were introduced into 250 cc of triethyl phosphite. The reaction mixture was heated to C and maintained there for 16 hours. A slight insolubility was eliminated by filtration. The filtrate was concentrated to dryness by distillation under reduced pressure. The residue was subject to chromatography through silica gel eluting with a mixture of acetone, chloroform and cyclohexane (1:1:1), then subject to chromatography through florasil (activated magnesium silicate) eluting with a mixture of acetone and chloroform 1:1 and concentrated to dryness under reduced pressure. 21 gm of 1.6-dihydro-4- diethoxyphosphoryloxy-azepino-[1,2-a1-pyrimidine- 6-one were obtained containing about 10% of triethyl phosphite having a refractive index n 1.4994.
EXAMPLE 14 2-Diethoxythiophosphoryloxy-6,7,8,9- tetrahydropyrido-[1,2-a]-pyrimidine-4-one gel with elution by a mixture of cyclohexane and ethyl acetate (4:6). 7.96 gm of 2- diethoxythiophosphoryloxy-6.7,8,9-tetrahydro-pyrido- '[l.2-a]-pyrimidine-4-one were obtained having a refractive index of n 1.5410. Analysis:
C H N O PS; molecular weight 318.33 Calculated:
45.29% C 6.02% H 8.80% N 9.73% P Found: 45.6 6.2 8.6 9.7
EXAMPLE 15 2-Dimethoxythiophosphoryloxy-6,7,8,9- tetrahydropyrido-[1,2-a]-pyrimidine-4-one 17 gm of 2-hydroxy-6,7,8,9-tetrahydropyrido-[1,2- al-pyrimidine-4-one and 24 gm of potassium carbonate were introduced into 200 cc of acetonitrile. 12 cc of 0,0-dimethyl chloro-thiophosphate were added thereto. The mixture was agitated for 1 6 hours at room temperature and next the reaction mixture was heated to 60C and maintained at this temperature for one hour and thirty minutes. The mineral'salts were elimi- EXAMPLE l6 2-(Methoxy-ethoxy-thiophosphoryloxy)-7,8-dihydro- 6H-pyrro|o-[1,2-a]-pyrimidine-4-one 30.4 gm of 2-hydroxy-7,8-dihydro-6H-pyrrolo-[1,2-'
a]-pyrimidine-4-one and 27.6 gm of potassium carbonate were introduced into 300 cc of acetone. This mixture was heated to reflux and maintained there for 1 hour, then cooled to 20C. 34.8 gm of O-methyl-O- ethyl chlorothiophosphate were added. The reaction mixture was heated to 40C and maintained at this temperature for 4 hours. The insolubles formed were eliminated by filtration. The filtrate was concentrated to dryness under reduced pressure. The residue was subject to chromatography through silica gel with elution by a mixture of chloroform and acetone (111-). 6.5 gm of 2-(methoxy-ethoxythiophosphoryloxy)-7,8-dihydro- 6H-pyrrolo-[1,2-a]-pyrimidine-4-one were obtained having a melting point of 71C.
Analysis:
C H N O PS; molecular weight 290.28 Calculated:
41.37% C 5.21% H 9.65% N 10.67% P Found:
EXAMPLE l7 2-(O-ethyl-N-isopropylthiophosphoramido-oxy)-7,8- dihydro-6H-pyrrolo-[1,2-a]-pyrimidine-4-one 30.4 gm of 2-hydroxy-7,8-dihydro-6H-pyrrolo-[1,2- al-pyrimidine-4-one and 27.6 gm of potassium carbonate were introduced into 400 cc of acetone. The mixture was agitated for a period of 1 hour at room temperature. Then 40.3 gm of ethyl N-isopropyl-thiophos phoramidochloridate was added. The mixture was. agitated for 72 hours at room temperature. The insolubles formed were eliminated by filtration. The filtrate was concentrated to dryness by distillation under reduced pressure. The residue was subject to chromatography through silica gel with elution by a mixture of acetone, chloroform and cyclohexane (111:1). 17.5 gm of 2-(0- ethyl-N-isopropylthiophosphoramido-oxy)-7,8- clihydro-6H-pyrrolo-[1,2-a]-pyrimidine-4-one were obtained.
Analysis:
C, H N O PS; molecular weight 317.35 Calculated:
45.42% C 6.35% H 13.24% N 9.76% P Found:
EXAMPLE l8 2-[ Ethoxy-( 2-ethoxy -ethoxy-thiophosphoryloxy| 7,8-dihydro-6H-pyrrolo-[1,2-a]-pyrimidine-4-one 152 gm of 2-hydroxy-7.8-dihydro-6H-pyrrolo-[1,2- aI-pyrimidine-4-one and 13.8 gm of potassium carbonate were introduced into 400 cc of acetone. The mixture was agitated for one hour at room temperature. Then 23.2 gm of O-ethyl-O-(2-ethoxy-ethyl)chlorothiophosphate were added. The mixture was agitated for 72 hours at room temperature. The mineral salts were eliminated by filtration. The filtrate was concentrated to dryness. The residue was subject to chromatography through silica gel with elution by a mixture of acetone. chloroform and cyclohexane (1:1:1l). l1.7 gm
of Z-[ethoxy-(Z-ethoxy)-ethoxy-thiophosphoryloxyl1- 7,8-dihydro-6H-pyrrolo-[1.2-al pyrimidine-4-one were obtained having a refractive index n 1.5312. Analysis:
- C, H ,N O PS; molecular weight 348.36 Calculated:
44.82% C 6.08% H 8.04% N 8.89% P Found:
EXAMPLE 19 2-( Di-n-propyloxythiophosphoryloxy)-7,8-dihydro-6- 'PY -I 1 -a]-pyrimidine-4-on 9.2 gm of 2-hydroxy-7,8-dihydro-6H-pyrrolo-[1.2- al-pyrimidine-4-one and 8.5 gm of potassium carbonate were introduced into a mixture of cc of acetone and 20 cc of methanol. 13 gm of 0,0-di-n-propyl chloro-thiophosphate were added. The reaction mixture was heated to reflux and maintained there for five hours, and then cooled. The mixture was concentrated to dryness and water was added to the residue.
The aqueous material was extracted with ether. The ethereal phases were dried and concentrated to dryness. The residue was subject to chromatography through silica gel eluting with a mixture of cyclohexane, acetone and chloroform (1:1:1). 15 gm of 2-(di-npropyloxythiophosphoryloxy)-7,8-dihydro-6H-pyrrolo- [l,2-a]-pyrimidine-4-one were obtained having a refractive index n 1.5290. Analysis:
C H N O PS; molecular weight 332.36 Calculated:
47.00% C 6.37% H 8.42% N 9.32% P Found: j
EXAMPLE 20 2-Diisopropyloxythiophosphoryloxy-7.8-dihydro-6H- pyrrolo-[l ,2-al-pyrimidine-4-one pyrrolo-[l,2-a]-pyrimidine-4-one were obtained hav-- ing a melting point of 30C. Analysis:
C H N O PS: molecular weight 332.36 Calculated:
46.480/0 C 6.37% H. 8.43% N 9.32% P Found:
- EXAMPLE 21 7 ,8 dihydro 6l l pyrrolo l ,2-a]-pyrimjdine-4-'one 9.2- gm of2 hydroxy 7 ,8-dihydro-6H pyrrolo-[1,2- a]-pyrimidine-4-one and 8.5 gm of potassium carbonate were introduced into a mixture of 150 cc of acetone and 20 cc of methanol. 15 gm of 0,0-di-n-butyl chlorothiophosphate were added. The reaction mixture was heated to reflux, maintained there for 5 hours, then concentrated to dryness. Water was added to the residue and the aqueous phase was extracted with ether. The ethereal phase were dried and concentrated to dryness. The residue was subject to chromatography through silica gel eluting with a mixture of cyclohexane, chloroform and acetone 1:1 :1 11 gm of 2-(di-nbutyloxythiophosphoryloxy) 7,8-dihydro-6H-pyrrolo- [l,2-a]-pyrimidine-4-one were obtained having a refractive index n l.5 200. Analysis:
C H N O 'PS; 360.40 Calculated:
50.00% C 6.99%H 7.77% N 8.58% P Found:
50.3 6.9 7.6 8.8 were introduced into a mixture of 150 cc of acetone and 20 cc of methanol. 15 gm of O,O-di-n-butyl chlorothiophosphate Were dded.
' The reaction mixture was heated to reflux, maintained there for 5 hours, then concentrated to dryness. Water was added to the residue and the aqueous phase was extracted with ether. The ethereal phase were dried and concentrated to dryness. The
residue was subject to chromatography through silica gel eluting with a mixture of cyclohexane, chloroform and acetone (l:l:l ll gm of 2-(di-nbutyloxythiophosphonyloxy)7,8-dihydro-6H- pyrrolo-[l,2-a]-pyrimedine-4-one were obtained having a refractive index n 1.5200.
Analysis: CIH1Z5NQO4PS; Calculated:
50.00% C 6.99% H 7.77% N 8.58% P Found:
EXAMPLE 22 2-Diethoxythiophosphoryloxy-3-ethylthio-7,8-dihydro- 31 gm of Z-hydroxy-3-ethylithio-7,8-dihydro-6H- pyrrolo-ll,2-a]-pyrimidine-4-one, 205 gm of potasthiophosphate were introduced into 350 cc of ace tonitrile. The mixture was agitated for 60 hours at room EXAMPLE 23 Study of the insecticidal properties of 2-diethoxythio designated hereafter as Compound A.
A. Test on Aphis fabae Some bean plants were utilized which were divided into three groups:
a. The first group ofplants was treated by Compound A, 1 ml of solution containing mg of Compound A 5 per liter was sprinkled on each leaf. Each leaf was infested with 20 plant lice and each leaf was encircled with gauze in order to hinder the departure ofthe plant lice.
b. The second group of plants was treated in the same fashion as the group ofplants ofgroup a), but replacing TABLE I Concentration in mg/ 1 Activity 0 Product 24 hours i 2 hours 48 hours Compound A 5 0 Dimethoate 5 3 .6
f Conclusion: Compound A possesses a very good activity on Aphis a ae.
B. Test on Ceratitis capitata v In this test covered Petri dishes are utilized which are divided into three groups:
a. lnthe dishes of group a), 1 ml of acetonic solution of Compound A was inserted at concentrations oflOO, 10.7.5; 5, 2.5 and 1 mg of Compound A per liter.
b. In the dishes of group b), the corresponding solutions of Dimethoate were utilized in place of those of Compound A.
c. in the dishes of group c), no'solution was inserted and. itwas usedas the control group.
Twenty .Ceratitis capitataflies aged three days were placed in each Petri dish of group a), b) and c)-, and the lids were placed thereon. The living insects and those 'killed by Compound A and Dimethoate at different intervals of time were counted. The activity of compound and that of Dimethoate are expressed as a percentage of the reduction of the number of living insects. The results are given in Table II below:
TABLE ll Activity Concentration Product in mg/] 1 hour 24 hours Dimethoate .5 5
Conclusion: Compound A has a very good activity on Cerariris capirala.
C. Test on Prodenia litura (caterpillars) Salad leaves which were broken into bits of 8 mm in diameter were utilized. Each piece of leaf was placed in a box at a ratio of one piece of leaf per box, and the boxes were divided into three groups:
milk or water. The controls were effected one hour,
and then 24 hours after the treatment. The experimen- TABLE V a. The pieces of salad leaves of the boxes in group a) were treated with the Compound A at an amount of 4 1000RPM 2500 ppm 500 ppm p.14of aqueous solution ofCompound A on each piece, and with solutions containing 5,000, 2,500, 1,250 and 3 38 33 9 625 mg of Compound A per liter. 4
b. Operating in the same manner for group b), but 10 Compound A was replaced by Carbaryl (or l-N- 0 Test on Aphl-s fabae p y N' y This test was effected by contact-ingestion on beans. Nothmg was Placed on the bits of left g p After pulverization of the solution of the product 7 In each box of groups i caterpillar was tested, the infestation rate of individual aphids per inserted. The caterpillars remaining alive and those l t of b ns was made. The bean plants were killed by the two insecticides at different intervals of wrapped in gauze in order to hinder the departure of time were counted. The activity of Compound A and the plant lice. A counting of living and dead insects as that of Carbaryl are expressed as a percentage of the a function of time was made. The results are expressed reduction of the number of living caterpillars. The re- 20 in a percentage of Abbott efficacy (taking into account sults are given in Table III below. the controlled test).
' TABLE n Concen- Amount of active Activity Prodtration product absorbed uct in mg/l in pg 1 hour 24 hours 48 hours 5000 20 100 100 100 2500 i0 100 r00 r00 Com- 1250 5 90 I00 I00 pound A 625 2.5 80 I00 I00 5000 20 100 I00 100 2500 I0 100 100 100 Cttr- 1250 5 100 100 100 haryl Conclusion: Compound A possesses a very good activity on Pmdenia lilura, superior to that of carbaryl.
7 EXAMPLE 24 The resuhs obtained are given in Table VI below:
Study of the insecticidal activity of x 2-dimethoxythio-phosphoryloxy-7,8-dihydro-6H- pyrrolo-[ l,2-a]-pyrimidine-4-one 100 ppm ppm A. Test on Blatella germanica: I hour 60 0 This test was. effected by micro-contact. Larvae of 24 hours ()0 39 the cockroaches chosen according to their length re- 48 hours 100 l 00 ceived a micro-drop of an acetonic solution of the th econd and third air product to be tested between e S t. n p D. Test on Prodema lztura of legs. After the treatment, the test insects were o This test was effected on the caterpillars of Prodenia held in semi-darkness at 20 C, and were nourished. The
t l m de 24 hours 48 hours and then 5 d3 5 htura. It IS a test by ingestion. An acetonrc solution of a S g t X riniemal reslms ex ressed i 50 the product to be tested was deposited on bits of salad l. ..l i .llll .p;l-.. 39.2? leaves of 8 mm in diameter which were disposed in a Percentage of mortallty are g'ven m a e e closed plastic boxes of 5 cm in diameter. Fifteen caterpillars were utilized per treatment (caterpillars aged 10 TABLE IV days in average). The caterpillars were held at 20C and 50% relative humidity, and were fed. The controls 5,000 ppm. 1.250 p.p.m. 625 ppm. were effected 1 hour, 24 hours and 48 hours after treat- 90 75 ment. The experimental results obtained expressed as 24 h I00 i 48 mo 95 35 a percentage of mortality are given in Table VI] below.
5 days 100 100 90 B. Test on Musca domestica TABLE Vll This test was effected by micro-contact. The flies received a micro-drop of acetonic solution of the product 500 p.p.m. 250 ppm. 125 ppm. 62.5 being tested on the dorsal thorax, after having been put P-P- to sleep with ether. The insects were maintained at [ham 0 0 0 0 O I 24 h 100 so so 20 C and 50% relative humidity. They were fed with 48 mo 00 I00 E. Test on larvae ofdomestic flies (Musca domestica) This test was effected by contact-ingestion. It consists of depositing 2 ml of an acetonic solution of the compound to be tested on 1 gm of bran, placed in a watch glass. The solvent was allowed to evaporate. Then the treated bran was deposited in a plastic box. Two ml of milk was added and after having been mixed the material was contaminated with larvae of domestic flies aged 3 to 4'days. There were 3 tests by concentration. The larvae were maintained at 20C and 50% relative humidity. The controls were effected 48 hours and 8 days after the treatment. The experimental results obtained expressed as a percentage of mortality are given in Table Vlll below:
TABLE Vlll 5,60 dp.p. rn. 500 ppm.
48 hours 37 28 8 days 97 87 Conclusion:
i (out). j
wherein n represents an integer from 2 to 3,
Y represents a member selected from the group consisting of hydrogen, alkyl having one to six carbon atoms, halo and alkylthio having one to six carbon atoms,
X represents a member selected from the group consisting of sulfur and oxygen,
R, represents an alkyl having one to four carbon atoms,
R represents a member selected from the group consisting of alkoxy having one to four carbons atoms, alkoxyalkoxy having one to four carbon atoms alkoxyalkoxy having one to four carbon atoms in each alk, and
aI-pyrimidine-S-one.
UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION patent 3. 857 ,838 Dated December 31, 1-974 Inventor) Jacques Perronnet et al Page 1 of 2 It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:
' Column 5, line 4 omitted in 11,2 a]
Column 5 line 4 and 5 "pyrrdo-A-pyrimidone" should have been omitted.
Column 6 lines 41 and 42 "4zhydrojcy-wazepinofll ,2a] myrimidine- 6-one 5.bromo-.l,6edihydro" should read we 4ehydroxy-5 bromo-l,6- dihydro azepino-ILZ-a]pyrimidine 6one Column 8, line 5-8, insert Step A: The sodium salt of 2- hydroxy-J,8-dihydro+6H+pyrroloIl,Z a]-pyrimidine4-one. 60 gm of 2hydroxy-7',8-dihydro6H pyrrolo-[1,Z a]-pyrimidine-4- one were introduced into 400 cc on methanol. Next Column 9, line 3, insert with an ethyl acetatecyclohexane mixture (9:1) 406 mg after the word "eluting" Column 9, line 56, Before "pyrimido" insert 24.6 gm of 2 ,Zmdihy-dro 8-hydroxy4H= Column 13, line 68, (111211)" should be (121:1)
Column 14, line 60, "0/0" should he Column 14, line 66, Before "7',8- dihyd-ro"' insert e- 2- (Di:nebutyloxwthiophophorloxy)e Column 15, lines 19 38 all material after "50 .3 6 .9 7.6 8 8" should be cancelled as duplicate of lines l-l9 Column 15, line. 58, "c" in formula should be C UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patmm No. 3,857,838 Datai December 31 1974 Invmworhfl Jacques Perronnet et al. Page 2 f 2 It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:
Column 17, line 7, the "4" in after ,ul should be omitted.
Column 19, line 24, "testz" should be tests Signed and Scaled this seventeenth Day Of February 1976 [SEAL] Attest:
C. MARSHALL DANN A I testing Officer (or

Claims (4)

1. AN ORGANO PHOSPHATE ESTER HAVING THE FORMULA
2. An organophosphate ester of claim 1 wherein Y'' is hydrogen.
3. An organophosphate ester of claim 1 being 2,3-dihydro-8-diethoxythiophosphoryloxy-4H-pyrimido-(2,1-b)-(1,3)-thiazine-6-one.
4. An organophosphate ester of claim 1 being 2,3-dihydro-7-dimethoxythiophosphoryloxy-thiazolo-( 3,2-a)-pyrimidine-5-one.
US00288393A 1971-09-16 1972-09-12 Organophosphate ester derivatives of heterocyclic compounds and process Expired - Lifetime US3857838A (en)

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3973009A (en) * 1974-05-06 1976-08-03 Stauffer Chemical Company Insecticidal and miticidal method
US4152427A (en) * 1977-01-29 1979-05-01 Bayer Aktiengesellschaft Combating pests with substituted pyrimidinone [(di)-thio]-phosphoric(phosphonic) acid esters and ester-amides
US4472389A (en) * 1981-12-10 1984-09-18 Uniroyal, Inc. Substituted pyrimidinyl organophosphorus insecticides
US4634690A (en) * 1981-12-10 1987-01-06 Uniroyal Chemical Company, Inc. Substituted pyrimidinyl organophosphorus insecticides
US5366969A (en) * 1989-09-09 1994-11-22 Boehringer Mannheim Gmbh Amidine group containing monocycloheteracyclic or bicycloheterocyclic diphosphonic acid derivatives and medicaments containing these compounds
US6228553B1 (en) * 1998-07-14 2001-05-08 Fuji Photo Film Co., Ltd. Pyrrolo [1,2-A] pyrimidine compound and heat-sensitive recording material using the same
US10562663B2 (en) * 2017-02-15 2020-02-18 Creative Impact Inc. Apparatus for housing and revealing a plurality of children's toys

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4000267A (en) * 1972-09-11 1976-12-28 Roussel-Uclaf Insecticidal and acaricidal compositions employing pyrido[1,2a]pyrimidinone thiophosphates
FR2198697B1 (en) * 1972-09-11 1975-09-12 Roussel Uclaf
US4395551A (en) * 1981-12-10 1983-07-26 Uniroyal, Inc. Pyridopyrimidinone compounds

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3402176A (en) * 1964-12-24 1968-09-17 Bayer Ag O-pyrazolo-(1, 5-a)-pyrimidyl phosphorus-containing esters

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3402176A (en) * 1964-12-24 1968-09-17 Bayer Ag O-pyrazolo-(1, 5-a)-pyrimidyl phosphorus-containing esters

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3973009A (en) * 1974-05-06 1976-08-03 Stauffer Chemical Company Insecticidal and miticidal method
US4152427A (en) * 1977-01-29 1979-05-01 Bayer Aktiengesellschaft Combating pests with substituted pyrimidinone [(di)-thio]-phosphoric(phosphonic) acid esters and ester-amides
US4472389A (en) * 1981-12-10 1984-09-18 Uniroyal, Inc. Substituted pyrimidinyl organophosphorus insecticides
US4634690A (en) * 1981-12-10 1987-01-06 Uniroyal Chemical Company, Inc. Substituted pyrimidinyl organophosphorus insecticides
US5366969A (en) * 1989-09-09 1994-11-22 Boehringer Mannheim Gmbh Amidine group containing monocycloheteracyclic or bicycloheterocyclic diphosphonic acid derivatives and medicaments containing these compounds
US6228553B1 (en) * 1998-07-14 2001-05-08 Fuji Photo Film Co., Ltd. Pyrrolo [1,2-A] pyrimidine compound and heat-sensitive recording material using the same
US10562663B2 (en) * 2017-02-15 2020-02-18 Creative Impact Inc. Apparatus for housing and revealing a plurality of children's toys
US11192682B2 (en) 2017-02-15 2021-12-07 Zuru (Singapore) Pte. Ltd. Apparatus for housing and revealing a plurality of children's toys

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ES406728A1 (en) 1975-10-01
CA981671A (en) 1976-01-13
FR2152469B1 (en) 1974-03-29
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IT965384B (en) 1974-01-31
AU466846B2 (en) 1975-11-13
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GB1396169A (en) 1975-06-04
IL40323A0 (en) 1972-11-28

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