EP0271550A1 - Benzopyran and benzothiopyran derivatives and compositions containing them - Google Patents

Benzopyran and benzothiopyran derivatives and compositions containing them

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Publication number
EP0271550A1
EP0271550A1 EP19870904090 EP87904090A EP0271550A1 EP 0271550 A1 EP0271550 A1 EP 0271550A1 EP 19870904090 EP19870904090 EP 19870904090 EP 87904090 A EP87904090 A EP 87904090A EP 0271550 A1 EP0271550 A1 EP 0271550A1
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EP
European Patent Office
Prior art keywords
benzopyran
dimethyl
selenadiazolo
general formula
group
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP19870904090
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German (de)
French (fr)
Inventor
Rezsö BOGNAR
Csaba Jaszberenyi
Sándor MAKLEIT
András FODOR
Péter DEAK
Tibor Timar
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Alkaloida Chemical Co Zrt
Original Assignee
Alkaloida Chemical Co Zrt
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Publication date
Application filed by Alkaloida Chemical Co Zrt filed Critical Alkaloida Chemical Co Zrt
Publication of EP0271550A1 publication Critical patent/EP0271550A1/en
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N55/00—Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D517/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having selenium, tellurium, or halogen atoms as ring hetero atoms
    • C07D517/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having selenium, tellurium, or halogen atoms as ring hetero atoms in which the condensed system contains two hetero rings
    • C07D517/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D517/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having selenium, tellurium, or halogen atoms as ring hetero atoms
    • C07D517/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having selenium, tellurium, or halogen atoms as ring hetero atoms in which the condensed system contains three hetero rings
    • C07D517/14—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
    • C07F9/6596—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having atoms other than oxygen, sulfur, selenium, tellurium, nitrogen or phosphorus as ring hetero atoms

Definitions

  • the inven t ion relates to novel benzopyran, and benzothiopyran derivatives, to their intermediates and to compositions containing the novel benzopyran and benzothiopyran derivatives.
  • the invention also relates to the preparation of these compounds, their intermediates and of the compositions containing the novel benzopyran and benzothiopyran derivatives; furthermore, the invention relates to the use of these compositions against nematodes, insects, worms and the like.
  • novel benzopyran and benzothiopyran derivatives of the present invention have the general formula (I),
  • R 1 and R 2 are independently from each other hydrogen, an unsubstituted or optionally suitably substituted alkyl or aryl group; or
  • R 1 and R 2 together may be a cycloalkyl group
  • R 3 is hydrogen; an optionally protected hydroxyl group; an alkyl, alkoxy, O-trialkyltin group; a phosphoric acid, thiophosphoric acid or phosphorous acid alkyl or aryl ester group connected through the oxygen atom; an acyloxy, acyloxyalkoxy, O-trialkylsilyl, aryloxy, alkenyloxy, alkynyloxy, cycloalkyloxy, cyclo- alkenyloxy, cycloalkylalkoxy group; an acyloxy or alkoxy group substituted by phosphoric acid, phosphonic acid or their esters; or two adjacent R 3 groups together may represent: an -O-(CH 2 ) m -O-group, wherein m is 1, 2, 3 or 4; or a condensed aromatic ring; or an -O-(CH 2 ) m -(O) z - group, wherein m is as defined above and z is 0 or
  • the compounds of the general formula (I) are new; simultaneously, they contain each structural moieties of the original precocene 1 and precocene 2 molecules which are essential for the biological activity.
  • the biotransformation-sensitive double bond is preferably in a protected form.
  • R 4 means hydrogen, CO-alkyl, CO-aryl, COO-alkyl, COO-aryl, CONH 2 , CSNH 2 , CONHNH 2 , CSNHNH 2 , CNHNH 2 , CNHNHNHNH 2 , SO 2 -alkyl or SO 2 -aryl group, and reacting the thus-obtained compound of the general formula (IV), ( IV )
  • R 1 , R 2 , R 3 , R 4 , Q 1 and n are as defined above, with selenium dioxide in order to obtain a compound of the general formula (I), wherein
  • Q 2 is selenium (as shown in scheme a);
  • R 1 , R 2 , R 3 , R 4 and n are as defined above, with an acid and then with selenium dioxide to obtain a compound of the general formula (I), wherein Q 1 is oxygen and Q 2 is selenium (as shown in scheme b);
  • R 1 , R 2 , R 3 , Q 1 , Q 2 and n are as defined above, with a diazo-transfer reagent in the presence of a base (as shown in scheme c);
  • R 1 , R 2 , R 3 , Q 2 and n are as defined above, with acetic acid in order to obtain a compound of the general formula (I), wherein Q 1 is oxygen (as shown in scheme d);
  • R 1 , R 2 , R 3 , Q 1 , Q 2 and n are as defined above and R 5 means an alkyl, aryl, alkylamino or arylamino group, with a base (as shown in scheme e);
  • R 1 MgX and/or R 2 MgX wherein R 1 and R 2 are as defined above and X is halogen, or with a metal alkyl compound (as shown in scheme f) ( f )
  • selenous acid or selenous acid derivatives e.g. salts
  • selenium oxychloride are used in the presence of C 1- 6 aliphatic carboxylic acids or their mixtures or the mixtures of these acids with suitable selected solvents or in suspensions prepared therefrom.
  • an equimolar amount of 1.1 to 1.3 equivalents of the selenium compound are used for oxidation.
  • the reaction is usually carried out at a temperature of 0 to 120 °C, preferably at 30 to 80 °C.
  • the product is obtained by evaporation, whereby the solvent used for the reaction can be recyclized into the process.
  • the cyclizing reaction is accomplished by using selenium dioxide, selenous acid or selenium oxychloride.
  • the selenium- containing reagent is preferably used in an amount of 1.0 to 1.5 equivalents and optionally given in several portions to the compound to be cyclized. This reaction is usually carried out at 0 to 120 oC, preferably between 20 °C and 80 °C.
  • the product is separated by evaporating or pouring the reaction mixture into water optionally followed by extraction.
  • a compound of the general formula (VII) is cyclized according to the first step of process b), i.e. by using an aliphatic carboxylic acid or an inorg anic acid , opt ion ally in a miscible solvent under heating.
  • the cyclization is carried out by treating a compound of the general formula (VIII) with a base.
  • the ring closure proceeds through a non- -isolated intermediate.
  • a compound of the general formula (IX) is reacted with an R 1 MgX or R 2 MgX Grignard reagent.
  • This method is well known in the chemistry of coumarins [J. Houben: Chem. Ber. 37, 489 (1904)] which has been investigated in detail [H. Decker and T. Fellenberg: Liebigs Ann. Chem. 356, 281 (1907); R. L. Shriner and A. G. Sharp.: 3 . Org. Chem. 4, 575 (1939); L. I. Smith and P. M. Rouff: 3 . Amer. Chem. Soc. 62, 145 (1940)] and is also being used today [H. P. Pommier et al.: Can. J. Chem. 51, 1377 (1979); M. V. Naidu and G. S. Krishna-Rao: Proc. Ind. Acad. Sci. 88, 197 (1979)].
  • a particularly preferred but not exclusive use of the above substituents is as follows: 4-Phenyl-4H-selenadiazolo[5,4-c][1]benzopyran, 4-phenyl-4H-selenadiazolo[5,4-c][1]benzothiopyran, 4-phenyl-4H-selenadiazolo[5,4-c][1]bentzhoiopyran-5-oxide, 4-phenyl-4H-selenadiazolo[5,4-c][1]bentzhoiopyran-5,5-dioxide, 4-phenyl-4H-thiadiazolo[5,4-c][1]benzopyran, 4-phenyl-4H-thiadiazolo[5,4-c][1]benzothiopyran,
  • the invention is illustrated in detail by the aid of the following non-limiting Examples.
  • the compounds prepared were characterized also by their IR, 1 H-NMR and mass spectra.
  • the working-up may be carried out in such a way that the thus-obtained product is dissolved in ethyl acetate, the organic phase is washed with alkali, dried and evaporated to give the title compound in a yield of 88 % , m.p.: 63- -65 oC after recrystallization from a mixture of benzene and ethyl acetate).
  • Example 81 Preparation of 4,4-dimethyl-7-methoxy-4H- selenadiazolo[5,4-c][1]benzopyran A solution of 2.81 g (10 mmoles) of 3-hydroxy- -1-(2'-hydroxy-4-methoxyphenyl)-3-methylbutanon-1-one semicarbazone in 25 ml of glacial acetic acid is boiled for one hour, then 1.11 g (10 mmoles) of selenium dioxide are portionwise added under continuous heating and stirring. The stirring and heating are continued until the gas evolution ceases and the starting substance disappears (as detected by TLC).
  • N-nitroso-N-(thiaflavanon-3-selenon-4-yl)urea 50 ml of tetrahydrofuran and 10 ml of 10 % potassium hydroxide solution is stirred at 25 °C for 2 hours, then the solvent is evaporated under vacuum and the residue is purified by chromatography on a Kieselgel column to give the title compound, m.p.: 55-58 °C.
  • the locusts were bred and kept according to the international standards, in rooms thermostated at 29 °C under a stable moisture content, with a day- -part change of the temperature.
  • the LC 50 value of this compound is at a dose of 25 to 50 ⁇ g/animal. Survival was observed even at a dose of 100 ⁇ g/animal.
  • the sheets also contained E. coli OP 50 bacterial nutriment. After 48 hours, the number of the living, normally developed animals was determined. The percentage ratio of this number related to the control represents the percentage of the survival. In the majority of the cases, this ratio was useful for the approximately accurate calculation of the LD 50 and LD 95 values.
  • Table 2 The results of the nematocide test are summarized in Table 2.
  • the numbering of the compounds in Table 2 is the same as shown in Table 1. Further substances are as follows: 15: 4,4-dimethyl-7-ethoxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, 16: KSeCN, 17: 7-allyloxy-4,4-dimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran, and 18: 4,4-dimethyl-4H-[1,3]-dioxolo[4,5-h]selenadiazolo- [5,4-c][1]benzopyran.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Environmental Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Plant Pathology (AREA)
  • Pest Control & Pesticides (AREA)
  • Dentistry (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

Sont décrits des composés de formule générale (I) dans laquelle R1, R2, R3, n, Q1 et Q2 ont la même notation que dans la revendication 1, ainsi que leurs sels biologiquement actifs. Sont également décrits des compositions fongicides, nématocides, acaricides, bactéricides et insecticides contenant comme principes actifs les composés de formule générale (I), ainsi que le procédé pour la préparation de ces composés et compositions.Compounds of general formula (I) are described in which R1, R2, R3, n, Q1 and Q2 have the same notation as in claim 1, as well as their biologically active salts. Also described are fungicidal, nematocidal, acaricidal, bactericidal and insecticidal compositions containing as active principles the compounds of general formula (I), as well as the process for the preparation of these compounds and compositions.

Description

Benzopyran and benzothiopyran derivatives and compositions containing them
The inven t ion relates to novel benzopyran, and benzothiopyran derivatives, to their intermediates and to compositions containing the novel benzopyran and benzothiopyran derivatives. The invention also relates to the preparation of these compounds, their intermediates and of the compositions containing the novel benzopyran and benzothiopyran derivatives; furthermore, the invention relates to the use of these compositions against nematodes, insects, worms and the like.
In 1976, Bowers et al. [Science 193, 542 (1976)] reported on the isolation of the anti-juvenile hormones of plant origin which were active against insects. After this publication, an intense resea rch was worldwide started in order to obtain compounds surpassing the activity of the two original precocenes, i.e. precocene 1 of formula (A) and precocone 2 of formula (B). During the study on the action mechanism and structure-activity relations, several recognitions arose which promoted the further synthetic work (e.g. G. T. Brooks: Gen. Pharmac. 8, 221 (1977); K. Slama: Acta Entomol. Bohemoslov. 75, 65 (1978), etc.].
The novel benzopyran and benzothiopyran derivatives of the present invention have the general formula (I),
(I) where in
R1 and R2 are independently from each other hydrogen, an unsubstituted or optionally suitably substituted alkyl or aryl group; or
R1 and R2 together may be a cycloalkyl group;
R3 is hydrogen; an optionally protected hydroxyl group; an alkyl, alkoxy, O-trialkyltin group; a phosphoric acid, thiophosphoric acid or phosphorous acid alkyl or aryl ester group connected through the oxygen atom; an acyloxy, acyloxyalkoxy, O-trialkylsilyl, aryloxy, alkenyloxy, alkynyloxy, cycloalkyloxy, cyclo- alkenyloxy, cycloalkylalkoxy group; an acyloxy or alkoxy group substituted by phosphoric acid, phosphonic acid or their esters; or two adjacent R3 groups together may represent: an -O-(CH2)m-O-group, wherein m is 1, 2, 3 or 4; or a condensed aromatic ring; or an -O-(CH2)m-(O)z- group, wherein m is as defined above and z is 0 or 1; or an -O-P(Cl)-O-, -O-P(OC2H5)-O-, -O-P=O(OC2H5)-O-, -O-P=S(OC2H5)-O-, -O-(C=O)-O-, -O-(C=S)-O-, -O-P=O(SC2H5)-O-, -O-P=S(SC2H5)-O- or an -O-(S=O)-O- group; or a halogen or a haloalkyl, nitro, amino or suitably substituted amino group; an alkoxy group substituted by an alkylamino or a dial- kylamino group; or a nitrile, mercapto, optionally substituted alkylthio group; an optionally ring-substituted aralkyloxy group; an acyl group; or two adjacent R groups together may also represent a -C=C-C(=O)-O- and -C=C-C=(CH3)2-O- group; n is 0, 1, 2, 3 or 4, and these R3 groups may have, independdntly from each other, any meaning defined for the R3 groups, Q1 is oxygen, sulfur, SO or SO2; Q2 is sulfur or selenium.
The compounds of the general formula (I) are new; simultaneously, they contain each structural moieties of the original precocene 1 and precocene 2 molecules which are essential for the biological activity. However, the biotransformation-sensitive double bond is preferably in a protected form.
According to an other aspect of the invention, there is provided a process for the preparation of the novel compounds of the general formula (I) and salts thereof, which comprises a) reacting a compound of the general formula (II),
(II)
wherein Q1 R1, R2, R3 and n are as defined above, with a compound of the general formula (III),
H2N-NH-R4 (III)
wherein R4 means hydrogen, CO-alkyl, CO-aryl, COO-alkyl, COO-aryl, CONH2, CSNH2, CONHNH2, CSNHNH2, CNHNH2, CNHNHNH2, SO2-alkyl or SO2-aryl group, and reacting the thus-obtained compound of the general formula (IV), ( IV )
wherein R1, R2 , R3, R4, Q1 and n are as defined above, with selenium dioxide in order to obtain a compound of the general formula (I), wherein
Q2 is selenium (as shown in scheme a);
U
or b) reacting a compound of the general formula (V)
(V)
wherein R1, R2 , R3, R4 and n are as defined above, with an acid and then with selenium dioxide to obtain a compound of the general formula (I), wherein Q1 is oxygen and Q2 is selenium (as shown in scheme b);
(b)
or c) reacting a compound of the general formula (VI)
(VI)
wherein R1, R2 , R3, Q1, Q2 and n are as defined above, with a diazo-transfer reagent in the presence of a base (as shown in scheme c);
(c)
or d) reacting a compound of the general formula (VII) (VII)
wherein R1, R2 , R3, Q2 and n are as defined above, with acetic acid in order to obtain a compound of the general formula (I), wherein Q1 is oxygen (as shown in scheme d);
(d) VII
or e) treating a compound of the general formula (VIII)
(VIII)
wherein R1, R2 , R3, Q1, Q2 and n are as defined above and R5 means an alkyl, aryl, alkylamino or arylamino group, with a base (as shown in scheme e);
(e)
or f) reacting a compound of the general formula (IX),
(IX)
wherein R3, Q1, Q2 and n are as defined above, with a Grignard reagent of the general formula
R1MgX and/or R2MgX, wherein R1 and R2 are as defined above and X is halogen, or with a metal alkyl compound (as shown in scheme f) ( f )
IX
and, if desired, oxidizing a thus-obtained compound of the general formula (I), wherein Q1 is sulfur, to a compound of the general formula (I) wherein Q1 is an SO or SO2 group and/or, if desired, converting a compound of the general formula (I) to the salt thereof.
The cyclization of the semicarbazones according to the process a) is known [I. Lalezari, A. Shafiee: Tetrahedron Lett. 5105 (1969); I. Lalezari, A. et al.: Angew. Chem. 82 , 484 (1970); I. Lalezari et al.: J . Org. Chem. 36, 2836 (1971)]. However, these reactions were not extended to the preparation of systems involving more fused heterocycles. The ring systems of the compounds of the invention are new.
A part of semicarbazones having the general formula (II) used as starting substances are also novel compounds.
For carrying out the cyclization selenium dioxide, selenous acid or selenous acid derivatives (e.g. salts) or selenium oxychloride are used in the presence of C1- 6 aliphatic carboxylic acids or their mixtures or the mixtures of these acids with suitable selected solvents or in suspensions prepared therefrom. In the most cases, an equimolar amount of 1.1 to 1.3 equivalents of the selenium compound are used for oxidation. The reaction is usually carried out at a temperature of 0 to 120 °C, preferably at 30 to 80 °C.
At the end of the mostly unidirectional reaction, the product is obtained by evaporation, whereby the solvent used for the reaction can be recyclized into the process.
An important part of the substituted or unsubstituted hydrazones, thiosemicarbazones, guanylhydrazones, bis-carbohydrazones or bis-thiocarbohydrazones used as starting substances in process b) are also novel compounds. Thus, the invention also relates to the compounds of the general formulae (V), (X)
(X) and (XI)
(XI)
as well as to the preparation of these compounds. Similarly to the process a), the cyclizing reaction is accomplished by using selenium dioxide, selenous acid or selenium oxychloride. The selenium- containing reagent is preferably used in an amount of 1.0 to 1.5 equivalents and optionally given in several portions to the compound to be cyclized. This reaction is usually carried out at 0 to 120 ºC, preferably between 20 °C and 80 °C. The product is separated by evaporating or pouring the reaction mixture into water optionally followed by extraction.
According to process c) , a compound o f the general formula ( VI ) i s reacted with a suitably selected diazo-transfer reagent [M. Regitz: Recent Synthetic Methods in Diazo Chemistry, Synthesis 1972, 351].
In the process d), a compound of the general formula (VII) is cyclized according to the first step of process b), i.e. by using an aliphatic carboxylic acid or an inorg anic acid , opt ion ally in a miscible solvent under heating.
In process e), the cyclization is carried out by treating a compound of the general formula (VIII) with a base. The ring closure proceeds through a non- -isolated intermediate.
According to process f) of the invention, a compound of the general formula (IX) is reacted with an R1MgX or R2MgX Grignard reagent. This method is well known in the chemistry of coumarins [J. Houben: Chem. Ber. 37, 489 (1904)] which has been investigated in detail [H. Decker and T. Fellenberg: Liebigs Ann. Chem. 356, 281 (1907); R. L. Shriner and A. G. Sharp.: 3 . Org. Chem. 4, 575 (1939); L. I. Smith and P. M. Rouff: 3 . Amer. Chem. Soc. 62, 145 (1940)] and is also being used today [H. P. Pommier et al.: Can. J. Chem. 51, 1377 (1979); M. V. Naidu and G. S. Krishna-Rao: Proc. Ind. Acad. Sci. 88, 197 (1979)].
A particularly preferred but not exclusive use of the above substituents is as follows: 4-Phenyl-4H-selenadiazolo[5,4-c][1]benzopyran, 4-phenyl-4H-selenadiazolo[5,4-c][1]benzothiopyran, 4-phenyl-4H-selenadiazolo[5,4-c][1]bentzhoiopyran-5-oxide, 4-phenyl-4H-selenadiazolo[5,4-c][1]bentzhoiopyran-5,5-dioxide, 4-phenyl-4H-thiadiazolo[5,4-c][1]benzopyran, 4-phenyl-4H-thiadiazolo[5,4-c][1]benzothiopyran,
4-phenyl-4H-thiadiazolo[5,4-c][1]benzothiopyran-5-oxide, 4-phenyl-4H-thiadiazolo[5,4-c][1]benzothiopyran-5,5- -dioxide, 4H-selenadiazolo[5,4-c][1]benzopyran, 4H-selenadiazolo[5,4-c][1]benzothiopyran,
4H-selenadiazolo[5,4-c][1]benzothiopyran-5-oxide, 4H-selenadiazolo[5,4-c][1]benzothiopyran-5,5-dioxide, 4,4-dimethyl-7-methoxy-4H-selenadiazolo[5,4-c][1]benzo- pyran, 4,4-dimethyl-7-methoxy-4H-selenadiazolo[5,4-c][1]benzo- thiopyran,
4,4-dimethyl-7-methoxy-4H-selenadiazolo[5,4-c][1]benzo- thiopyran-5-oxide, 4,4-dimethyl-7-methoxy-4H-selenadiazolo[5,4-c][1]benzo- thiopyran-5,5-dioxide,
4H-thiadiazolo[5,4-c][1]benzopyran, 4H-thiadiazolo[5,4-c][1]benzothiopyran, 4H-thiadiazolo[5,4-c][1]benzothiopyran-5-oxide, 4H-thiadiazolo[5,4-c][1]benzothiopyran-5,5-dioxide, 4,4-dimethyl-7-methoxy-4H-thiadiazolo[5,4-c][1]benzo- pyran,
4,4-dimethyl-7-methoxy-4H-thiadiazolo[5,4-c][1]benzo- thiopyran, 4,4-dimethyl-7-methoxy-4H-thiadiazolo[5,4-c][1]benzo- thiopyran-5-oxide,
4,4-dimethyl-7-methoxy-4H-thiadiazolo[5,4-c][1]benzo- thiopyran-5,5-dioxide,
7,8-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]-benzopyran, 7,8-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzothiopyran, 7,8-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]-benzothiopyran-5-oxide, 7,8-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]-benzothiopyran-5,5-dioxide, 7,8-dimethoxy-4,4-dimethyl-4H-thiadiazolo[ 5 , 4 -c ][ 1]b en zo-pyran, 7,8-dimethoxy-4,4-dimethyl-4H-thiadiazolo[ 5 , 4 -c ][ 1]b en zo-thiopyran, 7,8-dimethoxy-4,4-dimethyl-4H-thiadiazolo[5,4-c][1]benzo-thIopyran-5-oxide, 7,8-dimethoxy-4,4-dimethyl-4H-thiadiazolo[5,4-c][1]benzo-thiopyran-5,5-dioxide, 4,4-dimethyl-7-ethoxy-8-methoxy-4H-selenadiazolo[5,4-c]-[1]benzopyran, 4,4-dimethyl-7-ethoxy-8-methoxy-4H-selenadiazolo[5,4-c]-[1]benzothiopyran, 4,4-dimethyl-7-ethoxy-8-methoxy-4H-selenadiazolo[5,4-c]-[1]benzothiopyran-5-oxide, 4,4-dimethyl-7-ethoxy-8-methoxy-4H-selenadiazolo[5,4-c]-[1]benzothiopyran-5,5-dioxide, 4,4-dimethyl-7-ethoxy-8-methoxy-4H-thiadiazolo[5,4-c]-[1]benzopyran, 4,4-dimethyl-7-ethoxy-8-methoxy-4H-thiadiazolo[5,4-c]-[1]benzothiopyran, 4,4-dimethyl-7-ethoxy-8-methoxy-4H-thiadiazolo[5,4-c]-[1]benzothiopyran-5-oxide, 4,4-dimethyl-7-ethoxy-8-methoxy-4H-thiadiazolo[5,4-c]-[1]benzothiopyran-5,5-dioxide, 4,4-dimethyl-8-ethoxy-7-methoxy-4H-selenadiazolo[5,4-c]-[1]benzopyran, 4,4-dimethyl-8-ethoxy-7-methoxy-4H-selenadiazolo[5,4-c]-[1]benzothiopyran, 4,4-dimethyl-8-ethoxy-7-methoxy-4H-selenadiazolo[5,4-c]-[1]benzothiopyran-5-oxide, 4,4-dimethyl-8-ethoxy-7-methoxy-4H-selenadiazolo[5,4-c]-[1]benzothIopyran-5,5-dioxide, 4,4-dimethyl-8-ethoxy-7-methoxy-4H-thiadiazolo[5,4-c]- [1]benzopyran, 4,4-dimethyl-8-ethoxy-7-methoxy-4H-thiadiazolo[5,4-c][1]- benzothiopyran, 4,4-dimethyl-8-ethoxy-7-methoxy-4H-thiadiazolo[5,4-c]- [1]benzothiopyran-5-oxide, 4,4-dimethyl-8-ethoxy-7-methoxy-4H-thiadiazolo[5,4-c][1]- benzothiopyran-5,5-dioxide, 4,4-dimethyl-7-(2',2',2'-trifluoroethoxy)-4H-selena- diazolo[5,4-c][1]benzopyran, 4,4-dimethyl-7-(2',2',2'-trifluoroethoxy)-4H-selena- diazolo[5,4-c][1]benzothiopyran, 4,4-dimethyl-7-(2',2',2'-trifluoroethoxy)-4H-selena- diazolo[5,4-c][1]benzothiopyran-5-oxide, 4,4-dimethyl-7-(2',2',2'-trifluoroethoxy)-4H-selena- diazolo[5,4-c][1]benzothiopyran-5,5-dioxide, 7,8-diethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, 4,4-dimethyl-7-ethoxy-4H-selenadiazolo[5,4-c][1]benzo-pyran, 4,4-dimethyl-7-propoxy-4H-selenadiazolo[5,4-c][1]benzo¬pyran, 4,4-dimethyl-7-isopropoxy-4H-selenadiazolo[5,4-c][1]-benzopyran, 7-n-butoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]benzo¬pyran, 7-sec.-butoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]-benzopyran, 4,4-dimethyl-7-isobutoxy-4H-selenadiazolo[5,4-c][1]-benzopyran, 7-amyloxy-4,4-dimethyl-4--selenadiazolo[5,4-c][1]benzo-pyran, 4,4-dimethyl-7-n-octyloxy-4H-selenadiazolo[5,4-c][1]-benzopyran, 4,4-dimethyl-7-n-dodecyloxy-4H-selenadiazolo[5,4-c][1]-benzopyran, 4,4-dimethyl-7-n-octadecyloxy-4H-selenadiazolo[5,4-c]-[1]benzopyran, 4,4-dimethyl-7-(methoxy)methoxy-4H-selenadiazolo[5,4-c]-[1]benzopyran, 7-cyclopropyloxy-4,4-dimethyl-4H-selenadiazolo[5,4-c]-[1]benzopyran, 7-cyclobutyloxy-4,4-dimethyl-4H-selenadiazolo[5,4-c]-[1]benzopyran, 7-cyclopentyloxy-4,4-dimethyl-4H-selenadiazolo[5,4-c]-[1]benzopyran, 7-cyclohexyloxy-4,4-dimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran, 7-benzyloxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]ben-zopyran, 7-(2-chlorobenzyloxy)-4,4-dimethyl-4H-selenadiazolo[5,4-c]-[1]benzopyran, 7-benzyloxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]-benzothiopyran, 7-(3-chlorobenzyloxy)-4,4-dimethyl-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-(4-chlorobenzyloxy)-4,4-dimethyl-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-(l-naphthylmethoxy)-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-(2,3-dichlorobenzyloxy)-4,4-dimethyl-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-(2,4-dichlorobenzyloxy)-4,4-dimethyl-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-(2-naphthylmethoxy)-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-(l-tetralinyloxy)-4H-selenadiazolo[5,4-c]-[1]benzopyran, 4,4-dimethyl-7-(2-tetralinyloxy)-4H-selenadiazolo[5,4-c]-[1]benzopyran, 4,4-dimethyl-7-hydroxy-4H-seIenadiazolo[5,4-c][1]benzo¬pyran, 7,8-dihydroxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, 4,4-dimethyl-7-hydroxy-4H-selenadiazolo[5,4-c][1]- benzopyran, 7,8-dihydroxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzothiopyran, 7,9-dihydroxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, 6,7-dihydroxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, 4,4-dimethyl-7-hydroxy-6-methoxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, 6,7-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran 7,9-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, 7-allyloxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, 4,4-dimethyl-7-prenyloxy-4H-selenadiazolo[5,4-c][1]- benzopyran, 7-(3-cyclopentenyloxy)-4,4-dimethyl-4H-selenadiazolo- [5,4-c][1]-benzopyran, 7-(3-cyclohexenyloxy)-4,4-dimethyl-4H-selenadiazolo-[5,4-c][1]-benzopyran, 4,4-dimethyl-7-propargyloxy-4H-selenadiazolo[5,4-c][1]-benzopyran, 7-chloro-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]benzo¬pyran, 7-bromo-4,4-dimethyl-4H-selenadiazolo[5,4-c][1[benzo-pyran, 4,4-dimethyl-7-trifluoromethylthio-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-methylthio-4H-selenadiazolo[5,4-c][1]-benzopyran, 4,4-dimethyl-7-ethylthio-4H-selenadiazolo[5,4-c][1]benzo-pyran, 4,4-dimethyl-7-(2',2',2'-trifluoroethylthio)-4H-selena¬diazolo[5,4-c][1]benzopyran, 7-allylthio-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]benzo¬pyran, 4,4-dimethyl-7-propargylthio-4H-selenadiazolo[5,4-c][1]-benzopyran, 4,4-dimethyl-7-prenylthio-4H-selenadiazolo[5,4-c][1]-benzopyran, 4,4-dimethyl-7-propylthio-4H-selenadiazolo[5,4-c][1]-benzopyran, 4,4-dimethyl-7-isopropylthio-4H-selenadiazolo[5,4-c][1]-benzopyran, 7-butylthio-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]-benzopyran, 4,4-dimethyl-7-isobutylthio-4H-selenadiazolo[5,4-c][1]-benzopyran, 7-sec.-butylthio-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]-benzopyran, 4,4-dimethyl-7-(2-dimethylaminoethoxy)-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-(2-dimethylaminoethylthio)-4H-selena-diazolo[5,4-c][1]benzopyran, 7-(2-diethylamInoethylthio)-4,4-dimethyl-4H-selena-diazolo[5,4-c][1]benzopyran, 7-(2-diethylaminoethooy)-4,4-dimethyl-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-(2-pyrrolidInoethoxy)-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-(2-piperidinoethoxy)-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-(2-morpholinoethoxy)-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-(N-methylpiperazinoethoxy)-4H-selena-diazolo[5,4-c][1]benzopyran, 4,4-dimethyl-7-(N-ethylpiperazinoethoxy)-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-(N-benzylpiperazinoethoxy)-4,4-dimethyl-4H-seIenadiazolo[5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-(2',2',2'-trifluoroethoxy)- -4H-selenadiazolo[5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-propoxy-4H-selenadiazolo[5,4-c]- [1]benzcpyran, 4,4-dimethyl-7-isopropoxy-8-methoxy-4H-selenadiazolo- [5,4-c][1]benzopyran, 7-n-butoxy-4,4-dimethyl-8-methoxy-4H-selenadiazolo- [5,4-c][1]benzopyran, 7-sec.-butoxy-4,4-dimethyl-8-methoxy-4H-selenadiazolo- [5,4-c][1]benzopyran, 4,4-dimethyl-7-isobutoxy-8-methoxy-4H-selenadiazolo- [5,4-c][1]benzopyran, 4,4-dimethyl-7-isobutoxy-8-methoxy-4H-selenadiazolo- [5,4-c][1]benzothiopyran. 7-amyloxy-4,4-dimethyl-8-methoxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, 4,4-dimethyl-8-methoxy-7-n-octyloxy-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-n-dodecyloxy-8-methoxy-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-n-octadecyloxy-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-(methoxy)methoxy-4H-selenadiazolo[5,4-c][1]benzothiopyran, 4,4-dimethyl-8-methoxy-7-methoxyethoxy-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-cyclopropyloxy-4,4-dimethyl-8-methoxy-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-cyclopropylmethoxy-4,4-dimethyl-8-methoxy-4H-selena-diazolo[5,4-c][1]benzopyran, 7-cyclobutyloxy-4,4-dimεthyl-8-methoxy-4H-selenadiazolo-[5,4-c][1]benzcpyran, 7-cyclopentyloxy-4,4-dimethyl-8-methoxy-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-cyclohexyloxy-4,4-dimethyl-8-methoxy-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-benzyloxy-4,4-dimethyl-8-methoxy-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-(2-chlorobenzyloxy)-4,4-dimethyl-8-methoxy-4H-selena-diazolc[5,4-c][1]benzopyran, 7-(3-chlorobenzyloxy)-4,4-dimethyl-8-methoxy-4H-selena-diazolo[5,4-c][1]benzopyran, 7-(4-chlorobenzyloxy)-4,4-dimethyI-8-methoxy-4H-selena-diazolo[5,4-c][1]benzopyran, 7-(2,3-dichlorobenzyloxy)-4,4-dimethyl-8-methoxy-4H-selenadiazolo[5,4-c][1]benzopyran, 7-(2,4-dichlorobenzyloxy)-4,4-dimethyl-8-methoxy-4H-selenadiazolo[5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-(1-naphthylmethoxy)-4H-selena-diazolo[5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-(2-naphthylmethoxy)-4H-selena-diazolo[5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-(1-tetralinyloxy)-4H-selena-diazolo[5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-(2-tetralinyloxy)-4H-selena-diazolo[5,4-c][1]benzopyran, 4,4-dimethyl-7-hydroxy-8-methoxy-4H-selenadiazolo[5,4-c]-[1]benzopyran, 4,4-dimethyl-7-hydroxy-9-methoxy-4H-selenadiazolo[5,4-c]-[1]benzopyran, 4,4-dimethyl-7-hydroxy-6-methoxy-4H-selenadiazolo[5,4-c]-[1]benzopyran, 7-methoxy-4,4,6-trimethyl-4H-selenadiazolo[5,4-c][1]benzo-pyran, 7-methoxy-4,4,9-trimethyl-4H-selenadiazolo[5,4-c][1]benzo-pyran, 7-ethoxy-4,4,6-trimethyl-4H-selenadiazolo[5,4-c][1]benzo-pyran, 7-propargyloxy-4,4,6-trimethyl-4H-seIenadiazolo[5,4-c][1]-benzopyran, 7-ethoxy-4,4,9-trimethyl-4H-selenadiazolo[5,4-c][1]benzo¬pyran, 7-propargyloxy-4,4,9-trimethyl-4H-selenadiazolo[5,4-c]- [1]-benzopyran, 7-allyloxy-4,4-dimethyl-8-methoxy-4H-selenadiazolo- [5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-prenyloxy-4H-selenadiazolo- [5,4-c][1]benzopyran, 7-(3-cyclopentenyloxy)-4,4-dimethyl-8-methoxy-4H-selena- diazolo[5,4-c][1]benzopyran, 7-(3-cyclohexenyloxy)-4,4-dimethyl-8-methoxy-4H-selena- diazolo[5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-propargyloxy-4H-selenadiazolo- [5,4-c][1]benzopyran, 7-chloro-4,4-dimethyl-8-methoxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, 7-bromo-4,4-dimethyl-8-methoxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, 4,4-dimethyl-8-methoxy-7-trifluoromethoxy-4H-selena-diazolo[5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-trifluoromethylthio-4H-selena-diazolo[5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-methylthio-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-ethylthio-8-methoxy-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-methylthio-8-(2',2',2'-trifluoroethylthio)- -4H-selenadiazolo[5,4-c7[1]benzopyran, 7-allylthio-4,4-dimethyl-8-methoxy-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-propargylthio-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-prenylthio-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-propylthio-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-isopropylthio-8-methoxy-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-butylthio-4,4-dimethyl-8-methoxy-4H-selenadIazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-isobutylthio-8-methoxy-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-sec.-butylthio-4,4-dirnethyl-8-methoxy-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-(2-diethylaminoethylthio)-4,4-dimethyl-8-methoxy- -4H-selenadiazolo[5,4-c][1]benzopyran, 4,4-dimethyl-7-tributylstannyloxy-4H-selenadiazolo[5,4-c]-[1]benzopyran, 4,4-dimethyl-8-methoxy-7-tributylstannyloxy-4H-selena-diazolo[5,4-c][1]benzopyran, 7-diethoxyphosphoroyloxy-4,4-dimethyl-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-diethoxyphosphoroyloxy-4,4-dimethyl-8-methoxy-4H-selenadiazolo[5,4-c][1]benzopyran, 4,4-dimethyl-4H-dioxolo[4,5-h]selenadiazolo[5,4-c][1]ben¬zopyran, 4,4-dimethyl-4H-[1,4]-dioxano[2,3-h]selenadiazolo[5,4-c]-[1]benzopyran, 4,4-dimethyl-4H-[1,3[-dioxolo[4,5-g]selenadiazolo[5,4-c]-[1]benzopyran, 4,4-dimethyl-4H-[1,4]-dioxano[2,3-g]seIenadiazolo[5,4-c]-[1]benzopyran, 7-methoxy-5-spirocyclopropyl-4H-selenadiazolo[5,4-c]-[1]benzopyran, 7,8-dimethoxy-4-spirocyclopropyl-4H-selenadiazolo[5,4-c]-[1]benzopyran, 8-ethoxy-7-methoxy-4-spirocyclopropyl-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-ethoxy-8-methoxy-4-spirocyclopropyl-4H-selenadiazolo-[5,4-c][1]benzopyran, 7'-methoxy-spiro[cycloproane-1,4'-(4'H-selenadiazolo-[5,4-c][1]benzopyran)[ spiro[cyclopropane-1,4'-(4'H-[I,3[-dioxolo[4,5-g[selena-diazolo[5,4-c][1]benzopyran)[ spiro[cyclobutane-1,4'-(4'H-[1,3]-dioxolo[4,5-g]selena- diazolo[5,4-c][1]benzopyran], spiro[cyclopropane-1,4'-(4'H-[1,4]-dioxano[2,3-g]selena- diazolo[5,4-c][1]benzopyran)], spiro[cyclopentane-1,4'-(4'H-[1,4]-dioxano[2,3-h]selena- diazolo[5,4-c][1]benzopyran)], spiro[cyclohexan-1,4'-(4'H-[1,3]-dioxoln[4,5-g]selena- diazolo[5,4-c][1]benzopyran, spiro[cyclooctane-1,4'-(4'H-[1,3]-dioxolo[4,5-h]selena- diazolo[5,4-c][1]benzopyran.
The invention is illustrated in detail by the aid of the following non-limiting Examples. The compounds prepared were characterized also by their IR, 1H-NMR and mass spectra.
Example 1
Preparation of 2,2-dimethyl-7-methoxy-4- -chromanone semicarbazone This compound was prepared or referred to, respectively (W. Bridge et al.: J . Chem. Soc. 1937, 1530)
A mixture containing 8.24 g (40 mmoles) of 2,2-dimethyl-7-methoxy-4-chromanone , 4.8 g of semicarbazide hydrochloride and 5 g of ammonium acetate in 100 ml of ethanol is refluxed for 12 hours, then evaporated and the solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p..: 224-226 °C (literature m.p.: 226 °C). Rf: 0.12 (benzene/ethyl acetate 1:1)
0.41 (toluene /ethyl acetate/formic acid 7:3:1) 0.36 (chloroform/ethanol 9:1) Analysis: Calculated for C13H17N3O3 (molecular weight 263) C % = 61,71; H % = 6,77; N % = 16,61; Found: C % = 61,9 ; H % = 6,65; N % = 16,8 ;
Example 2 Preparation of 2,2-dimethyl-6,7-dimethoxy- -4-chromanone semicarbazone A mixture containing 9.44 g (40 mmoles) of 2,2-dimethyI-6,7-dimethoxy-4-chromanone , 4.8 g of semicarbazide hydrochloride and 5 g of ammonium acetate in 100 ml of ethanol are refluxed until the most part of the starting substance has been transformed [as detected by thin layer chromatography (TLC)]. Then, the mixture is evaporated, the solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 208ºC which is useful for the next step without any purification. Rf: 0,07 (benzene/ethyl acetate 1:1)
0,28 (toluene/ethyl acetate/formic acid 7:3:1) 0.35 (chloroform/ethanol 9:1) Analysis:
Calculated for C14H19N3O4 (molecular weight: 293) C % = 57.38; H % = 6.53; N % = 14.34;
Found: C % = 57.7 ; H % = 6.4 ; N % = 14.5 ;
Example 3 Preparation of 7-methoxy-2,2,8-trimethyl- -4-chromanone semicarbazone
8.8 g (40 mmoles) of 7-methoxy-2,2,8-trimethyl--4-chromanone , 4.8 g of semicarbazide hydrochloride and 5 g of ammonium acetate are refluxed In 100 ml of ethanol till the transformation of the most part of the starting substance (as detected by TLC). Then, the mixture is evaporated, the solid residue is washed with water and with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 186-188 °C, which is useful for the next step without any purification. Rf = 0.14 (benzene/ethyl acetate = 1:1) 0.47 (toluene/ethyl acetate/formic acid 7:3:1) 0.37 (chloroform/ethyl acetate = 9:1) Analysis:
Calculated for C14H19N3O3 (molecular weight: 277) C % = 60.7 ; H % = 6.91; N % = 15.17; Found: C % = 60.9 ; H % = 6.9 ; N % = 15.3 ;
Example 4
Preparation of 7-methoxy-2,2,5-trimethyl- -4-chromanone semicarbazone The process and working up described in
Example 3 are followed, except that 8.8 g (40 mmoles) of 7-methoxy-2,2,5-trimethyl-4-chromanone are used as starting material to give the title compound, m.p.: 220-222 °C. Rf = 0.13 (benzene/ethyl acetate = 1:1)
0.47 (toluene/ethyl acetate/formic acid = 7:3:1) 0.38 (chloroform/ethanol = 9:1) Analysis:
Calculated for C14H19N3O3 (molecular weight: 277) C % = 60.7 ; H % = 6.91; N % = 15.17;
Found: C % = 60.8 ; H % = 6.9 ; N % = 15.2 ;
Example 5
Preparation of 7,8-dimethoxy-2,2-dimethyl- -4-chromanone semicarbazone
9.44 g (40 mmoles) of 7,8-dimethoxy-2,2- -dimethyl-4-chromanone , 4.8 g of semicarbazidehydrochloride and 4 g of ammonium formiate are refluxed in 100 ml of methanol till the transformation of the most part of the starting substance (as detected by TLC). Then, the mixture is evaporated and the solid residue is washed with water to give the title compound, m.p.: 183-185 °C, which is useful for the next step without any purification. Rf = 0.10 (benzene/ethyl acetate = 1:1)
0.30 (toluene/ethyl acetate:formic acid = 7:3:1)
0.35 (chloroform:ethanol = 9:1)
Analysis:
Calculated for C14H19N3O4 (molecular weight: 293)
C % = 57.38; H % = 6.53; N % = 14.34; Found: C % = 57.5 ; H % = 6.5 ; N % = 14.5 ;
Example 6
Preparation of 5,7-dimethoxy-2,2-dimethyl- -4-chromanone semicarbazone 9.44 g (40 mmoles) of 5,7-dimethoxy-2,2- dimethyl-4-chromanone are refluxed with 4.8 g of semicarbazide hydrochloride and 5 g of ammonium acetate in 100 ml of n-propanol till the transformation of the most part of the starting substance (as detected by TLC). Then, the mixture is evaporated, the solid residue is washed with water and with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 181-182 °C, which is useful for the next step without any purification. Rf = 0.09 (benzene/ethyl acetate = 1:1) 0.43 (chloroform/ethanol = 9:1)
0.39 (toluene/ethyl acetate/formic acid = 7:3:1) Analysis:
Calculated for C14H19N3O4 (molecular weight: 293) C % = 57.38; H % = 6.53; N % = 14.34;
Found: C % = 57.6 ; H % = 6.5 ; N % = 14.4 ;
Example 7
Preparation of 2 ,2-dimethyl-7-ethoxy-4-chroma- none semicarbazone
2.2 g (10 mmoles) of 2,2-dimethyl-7-ethoxy- -4-chromanone are refluxed with 1.2 g of semicarbazide hydrochloride and 1.25 g of ammonium propionate in 25 ml of isopropanol up to the transformation of the most part of the starting substance (as detected by TLC), then the mixture is evaporated, the solid residue is washed with water and dried to give the title compound, m.p.: 183-185 °C, which is useful for cyclization or as intermediate for other reactions, too. Rf = 0.13 (benzene/ethyl acetate 1:1)
0.52 (benzene/ethyl acetate/acetic acid 7:3:1) 0.42 (chloroform/ethanol 9:1) Analysis : Calculated for C14H19N3O3 (molecular weight: 277) C % = 60.7 ; H % = 6.91; N % = 15.17;
Found: C % = 60.9 ; H % = 6.8 ; N % = 15.3 ;
Example 8
Preparation of 2,2-dimethyl-7-ethoxy-6-methoxy- -4-chromanone semicarbazone
5.0 g (20 mmoles) of 2,2-dimethyl-7-ethoxy- -6-methoxy-4-chromanone are refluxed with 2.4 g of semicarbazide hydrochloride and 2.5 g of ammonium acetate in 50 ml of ethanol till the transformation of the most part of the starting substance (as detected by TLC), then evaporated and the solid residue is washed with water and with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 205-207 °C, which is useful for the next step without any purification.
Rf = 0.07 (benzene/ethyl acetate 1:1)
0.54 (benzene: ethyl acetate/glacial acetic acid 7:3:1) 0.49 (chloroform:ethanol 9:1) Analysis: Calculated for C15H21N3O4 (molecular weight: 307) C % = 58.68; H % = 6.89; N % = 13.69; Found: C % = 58.5 ; H % = 6.7 ; N % = 13.8 ;
Example 9 Preparation of 2,2-dimethyl-7-isopropoχy-
-6-methoxy-4-chromanone semicarbazone 2.64 g (10 mmoles) of 2,2-dimethyl-7-iso- propoxy-6-methoxy-4-chromanone are refluxed with 1.2 g of semicarbazide hydrochloride and 1.25 g of ammonium acetate In 25 ml of ethanol till the transformation of the most part of the starting substance (as detected by TLC), then the mixture is evaporated, the solid residue is washed with water and with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 158-160 ºC, which is useful for the next step without any purification. Rf = 0.12 (benzene/ethyl acetate 1:1)
0.49 (benzene/ethyl acetate/glacial acetic acid 7:3:1) 0.48 (chloroform/ethanol 9:1) Analysis: Calculated for C16H23N3O4 (molecular weight: 321)
C % = 59.86; H % = 7.22; N % = 13.09; Found: C % = 60.1 ; H % = 7.3 ; N % = 13.1 ;
Example 10
Preparation of 2,2-dimethyl-7-propargyloxy- -4-chromanone semicarbazone
9.2 g (40 mmoles) of 2,2-dimethyl-7-propargyl- oxy-4-chromanone are refluxed with 4.8 g of semicarbazide hydrochloride and 5 g of ammonium acetate in 100 ml of ethanol up to the transformation of the most part of the starting substance (as detected by TLC). Then, the mixture is evaporated, the solid residue is washed with water and with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 174-176 ºC which is useful for the next step without any purification. Rf = 0.12 (benzene/ethyl acetate 1:1)
0.54 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)
0.44 (chloroform/ethanol = 9:1) Analysis:
Calculated for C15H17N3O3 (molecular weight: 287) C % = 62.77; H % = 5.97; N % = 14.64; Found: C % = 63.1 ; H % = 6.05; N % = 14.8 ;
Example 11
Preparation of 7-n-butoxy-2,2-dimethyl-4- -chromanone semicarbazone 9.92 g (40 mmoles) of 7-n-butoxy-2,2-dimethyl-
-4-chromanone are refluxed with 4.8 g of semicarbazide hydrochloride and 5 g of ammonium acetate in 80 ml of ethanol up to the transformation of the most part of the starting substances (as detected by TLC). Then, the mixture is evaporated, the solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 148-151 °C, which is useful for the next step or as intermediate for other reactions without any purification.
Rf = 0.14 (benzene/ethyl acetate = 1:1)
0.51 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.49 (chloroform/ethanol = 9:1) Analysis:
Calculated for C16H23N3O3 (molecular weight: 305)
C % = 63 ; H % = 7.6 ; N % = 13.78; Found: C % = 63.2 ; H % = 1.6 ; N % = 13.9 ; E x a mp l e 12
Preparation of 2.2-dimethyl-7-n-propoxy-4- -chromanone semicarbazone
2.34 g (10 mmoles) of 2,2-dimethyl-7-n-propoxy- -4-chromanone are refluxed with 1.2 g of semicarbazide hydrochloride and 1.25 g of ammonium acetate In 25 ml of ethanol up to the transformation of the most part of the starting substance (as detected by TLC). Then, the mixture is evaporated, the solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 194-196 °C, which is useful for cyclization without any purification. Rf = 0.12 (benzene/ethyl acetate = 1:1) 0.52 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.45 (chloroform/ethanol = 9:1) Analysis:
Calculated for C15H21N3O3 (molecular weight: 291) C % = 61.9 ; H % = 7.27; N % = 14.44;
Found: C % = 61.9 ; H % = 7.3 ; N % = 14.5 ;
Example 13
Preparation of 2 ,2-dimethyl-4-chromanone semicarbazone
1.76 g (10 mmoles) of 2,2-dimethyl-4-chromanone are refluxed with 1.2 g of semicarbazide hydrochloride and 1.25 g of ammonium acetate in 20 ml of ethanol up to the transformation of the most part of the starting substance (as detected by TLC). Then, the mixture is evaporated, the solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound m.p.: 193- 195 °C, which is useful for further transformations without any purification Rf = 0.19 (benzene/ethyl acetate = 1:1)
0.58 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.49 (chloroform/ethanol = 9:1) Analysis:
Calculated for C12H15N3O2 (molecular weight: 233)
C % = 61.85; H % = 6.49; N % = 18.03; Found: C % = 61.6 ; H % = 6.6 ; N % = 18.2 ;
Example 14
Preparation of 4-chromanone semicarbazone 2.5 g (16.9 mmoles) of 4-chromanone are refluxed with 1.88 g (17 mmoles) of semicarbazide hydrochloride and 2.12 g of ammonium acetate in 42 ml of ethanol till the transformation of the most part of the starting substance (as detected by TLC). Then, the mixture is evaporated and the solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound in a yield of 86.7 %, m.p.: 205-208 ºC, which is useful for the cyclization without recrystallization or other purification. Rf = 0.08 (benzene/ethyl acetate = 1:1)
0.51 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)
0.37 (chloroform/ethanol = 9:1) Analysis:
Calculated for C10H11N3O2 (molecular weight: 205) C % = 58.58; H % = 5.41; N % = 20.5 ; Found: C % = 58.4 ; H % = 5.32; N % = 20.7 ;
Example 15
Preparation of 7-allyloxy-2,2-dimethyl-4- -chromanone semicarbazone 18.56 g (80 mmoles) of 7-allyloxy-2,2-dimethyl-
-4-chromanone are refluxed with 9.6 g of semi- carbazide hydrochloride and 10 g of ammonium acetate in 200 ml of ethanol till the transformation of the most part of the starting substance (as detected by TLC). Then, the mixture is evaporated and the solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 173-175 ºC, which is chromatographically uniform and useful for cycllzations with any further purification. Rf = 0.08 (benzene/ethyl acetate = 1:1)
0.54 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.49 (chloroform/ethanol = 9:1) Analysis: Calculated for C15H19N3O3 (molecular weight: 289) C % = 62.27; H % = 6.62; N % = 14.52; Found: C % = 62.1 ; H % = 6.5 ; N % = 14.6 ;
Example 16 Preparation of 7-propargyloxy-2,2,5-trimethyl-
-4-chromanone semicarbazone
2.44 g (10 mmoles) of 7-propargyloxy-2,2,5-
-trimethyl-4-chromanone are refluxed with 1.2 g of semicarbazide hydrochloride and 1.2 g of ammonium acetate in 25 ml of ethanol till the transformation of the most part of the starting substance (as detected by TLC), thenthe mixture is evaporated. The solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 195-198 °C, which is useful for further transformations without any purification. Rf = 0.11 (benzene/ethyl acetate = 1:1)
0.51 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1) 0.44 (chloroform/ethanol = 9:1) Analysis :
Calculated for C16H19N3O3 (molecular weight: 301) C % = 63.84; H % = 6.36; N % = 13.96;
Found C% = 64.1 ; H%= 6.5 N% = 14.1 ;
Example 17
Preparation of 7-propargyloxy-2,2,8-trimethyl- -4-chromanone semicarbazone 9.77 g (40 mmoles) of 7-propargyloxy-2,2,8- -trimethyl-4-chromanone are refluxed with 4.8 g of semicarbazide hydrochloride and 5 g of ammonium acetate in 100 ml of ethanol till the transformation of the most part of the starting substance (as detected by TLC) and evaporated. The solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 193-196 °C, which is useful as intermediate for further reactions without any purification. Rf = 0.15 (benzene/ethyl acetate = 1:1) 0.56 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.46 (chloroform/ethanol = 9:1) Analysis:
Calculated for C16H19N3O3 (molecular weight: 301) C % = 63.84; H % = 6.36; N % = 13.96;
Found: C % = 64 ; H % = 6.5 ; N % = 13.9 ;
Example 18
Preparation of 2,2-dirnethyl-6,7-ethylenedioxy-
-4-chromanone semicarbazone
2.34 g (10 mmoles) of 2,2-dimethyl-6,7-ethylene- dioxy-4-chromanone . are refluxed with 1.2 g of semicarbazide hydrochloride and 1.2 g of ammonium acetate in 20 ml of ethanol till the transformation of the most part of the starting substance (as detected by TLC), then evaporated. The solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate to give the title compound, m.p.: 203-206 ºC, which is useful for cyclization reactions without any purification. Rf = 0.12 (benzene/ethyl acetate = 1:1)
0.53 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)
0.44 (chloroform/ethanol = 1:1) Analysis: Calculated for C14H17N3O4 (molecular weight: 291
C % = 57.78; H % = 5.89; N % = 14.44 found: C % = 57.6 ; H % = 5.9 ; N % = 14.3
Example 19
Preparation of 2,2-dimethyl-6,7-methylenedioxy-
-4-chromanone semicarbazone
8.8 g (40 mmoles) of 2 ,2-dimethyl-6,7-methylene- dioxy-4-chromanone are refluxed with 4.8 g of semicarbazide hydrochloride and 5 g of ammonium acetate in 100 ml of ethanol till the transformation of the most part of the starting substance (as detected by
TLC), then evaporated. The solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 188-191 °C, which is useful for further reactions without any purification.
Rf = 0.08 (benzene/ethyl acetate = 1:1)
0.70 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.41 (chloroform/ethanol = 9:1)
Analysis:
Calculated for C13H15N2O4 (molecular weight: 277)
C % = 56.36; H % = 5.46; N % = 15.17; found: C % = 56.5 ; H % = 5.6 ; N % = 15.3 . Ex a mp le 20
Preparation of 2,2-dimethyl-7,8-ethylenedioxy- -4-chromanone semicarbazone
2.34 g (10 mmoles) of 2,2-dimethyl-7,8-ethylene dioxy-4-chromanon are refluxed with 1.2 g of semicarbazide hydrochloride and 1.25 g of ammonium acetate in 25 ml of isopropanol till the transformation of the most part of the starting substance (as detected by TLC), then evaporated. The solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 236-238 °C, which can be used without any purification.
Rf = 0.07 (benzene/ethyl acetate = 1:1) 0.50 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1) 0.43 (chloroform/ethanol = 9:1) Analysis:
Calculated for C14H17N3O4 (molecular weight: 291) C % = 57.78; H % =.5.89; N % = 14.44; found: C % = 57.6 ; H % = 5.7 ; N % = 14.4 .
Example 21
Preparation of 2 ,2-dimethyl-7,8-methylenedioxy- -4-chromanone semicarbazone
2.2 g (10 mmoles) of 2,2-dimethyl-7,8-methylene- dioxy-4-chromanone are refluxed with 1 . 2 g o f semicarbazi de hydrochloride and 1 . 25 g o f ammonium acetate in 25 ml of ethanol till the transformation of the most part of the starting substance (as detected by TLC), then evaporated. The solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate an dried to give the title compound, m.p.: 194-197 ºC, which is chromatographically uniform and useful for further transformations without any purification. Rf = 0.07 (benzene/ethyl acetate = 1:1)
0.52 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.61 (chloroform/ethanol = 9:1) Analysis:
Calculated for C13H15N3O4 (molecular weight: 277)
C % = 56.36; H % = 5.46; N % = 15.17; found: C % = 56.2 ; H % = 5.4 ; N % = 15.3 . IR (KBr): 3490, 3150, 3050, 2980, 1679, 1643, 1458, 1408, 1357, 1059 cm-1.
MS (El, 70 eV): 277 (M+, 70 %), 219 (91 %), 189 (38 %),
161 (16 %), 77 (21 %), 36 (100 %). 1H-NMR (200 MHz, DMSO-d6, δ PPm as related to DSS): 1.25 (s, 6H, gem. dimethyl); 2.8 (s, C-3 CH2, 2H); 6.0 (s, 2H, -O-CH2-O-); 6.5 (d,
1H, aromatic); 7.3 (2H, NH2); 7.8 (d, 1H, aromatic); 9.3 (s, 1H, NH). 13C-NMR (50.3 (MHz, DMSO-d6, δ ppm): 26.3, 35.2, 76.2.
101.8, 115.7, 118 139, 149, 157.
Example 22
Preparation of 2-phenyl-4-chromanone semicarbazone
A solution of 60 g of sodium acetate and 11.4 g (0.1 mole) of semicarbazide hydrochloride in 150 ml of water is added to a solution of 22.4 g (0.1 mole) of 4-flavanone in 500 ml of ethanol, then the mixture is refluxed till the complete transformation of the starting substance and then evaporated. The residue is diluted with water, the product is filtered, washed with water and dried to give the title compound in a yield of 19.5 g + 5.1 g (i.e. in a total yield of 87.2 %) which may be recrystallized from ethanol, however, it Is useful for cyclization without purification, m.p.: 192-194 °C. Analysis:
Calculated for C16H15N3O2 (molecular weight: 281)
C % = 68.3 ; H % = 5.37; N % = 14.94; found: C % = 68.3 ; H % = 5.5 ; N % = 15.0 .
Example 23
Preparation of 2,2-dimethyl-6,7-dipropargyl- oxy-4-chromanone semicarbazone 11.36 g (40 mmoles) of 2,2-dimethyl-6,7-di- propargyloxy-4-chromanone are refluxed with 4.8 g of semicarbazide hydrochloride and 5 g of ammonium acetate in 100 ml of ethanol for 12 hours, then evaporated. The solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 190-193 °C. Rf = 0.16 (benzene/ethyl acetate = 1:1)
0.46 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.4 (chloroform/ethanol = 9:1) Analysis:
Calculated for C18H19N3O4 (molecular weight: 341)
C % = 63.39; H % = 5.61; N % = 12.32; found: C % = 63 ; H % = 5.7 ; N % = 12.2 .
Example 24
Preparation of 2 ,2-dimethyl-6-ethoxy-7-methoxy- -4-chromanon semicarbazone 10 g (40 mmoles) of 2,2-dimethyl-6-ethoxy- -7-methoxy-4-chromanone are refluxed with 4.8 g of semicarbazide hydrochloride and 5 g of ammonium acetate in 100 ml of ethanol for 12 hours, then evaporated. The solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 185-188 °C. Rf = 0.12 (benzene/ethyl acetate = 1:1)
0.51 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.35 (chloroform/ethanol = 9:1) Ana lysi s : Calculated for C15H21N3O4 (molecular weight: 307) C % = 58.68; H % = 6.9 ; N % = 13.69; found: C % = 57 ; H % = 6.0 ; N % = 13.75.
Example 25
Preparation of 4-phenyl-4H-selenadiazolo- [5,4-c][1]benzopyran
14.06 g (0.05 mole) of 2-phenyl-4-chromanone semicarbazone (prepared as described in Example 22) is heated in the solution of 5.55 g (0.05 mole) of selenium dioxide in 50 ml of glacial acetic acid at 80 °C for 3 hours under stirring. Then, the mixture Is diluted with water, extracted with chloroform and the combined organic phase is dried and evaporated under vacuum. When necessary, the thus-obtained title product is recrystallized (e.g. from methanol, ethanol, petroleum ether or ethyl acetate), m.p.: 168-171 ºC. Rf = 0.22 (benzene/ethyl acetate = 1:1) 0.60 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.52 (chloroform/ethanol = 9:1) Analysis:
Calculated for C15H10N2OSe (molecular weight: 313) C % = 57.51; H % = 3.22; N % = 8.95 ; found: C % = 57.43; H % = 3.30; N % = 9.12 .
Example 26
Preparation of 4 ,4-dimethyl-7-methoxy-4H-selena- diazolo[5,4-c][1]benzopyran
5.1 g (20 mmoles) of 2,2-dimethyl-7-methoxy- -4-chromanone semicarbazone and 2.22 g (20 mmoles) of selenium dioxide are heated in 50 ml of glacial acetic acid under stirring until the gas evolution ceases, then evaporated. The residue is washed with water. On rubbing, the product solidifies, m.p.: 57- -60 °C. Rf = 0.68 (benzene/ethyl acetate = 1:1)
0.71 (benzene/ethyl acetate/glacial acetic acid = 7:3:1)
0.78 (chloroform/ethanol = 9:1) Analysis: Calculated for C12H12N2O2Se (molecular weight: 295)
C % = 48.85 H % = 4.10; N % 9.49 ; found : C % = 49.0 ; H % = 4.1 ; N % 9.6 .
Example 27 Preparation of 7 ,8-dimethoxy-
-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]benzo- pyran
5.87 g (20 mmoles) of 6,7-dimethoxy-2,2-di- methyl-4-chromanone semicarbazone and 2.5 g (22 mmoles) of selenium dioxide are heated in 50 ml of glacial acetic acid under stirring until the gas evolution ceases. The mixture is evaporated, the oily residue is dissolved in chloroform, washed with sodium hydrogen carbonate solution and then with water, dried, filtered through celite and then evaporated to give the title compound, m.p.: 98-100 °C. Rf = 0.62 (benzene/ethyl acetate = 1:1)
0.69 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)
0.86 (chloroform/ethanol = 9:1) Analysis: Calculated for C13H12N2O3Se (molecular weight: 325)
C % = 48.04; H % = 4.34; N % = 8.62 ; found: C % = 48.3 ; H % = 4.4 ; N % = 8.6 .
Example 28
Preparation of 4,4-dimethyl-7-ethoxy-8-methoxy- -4H-selenadiazolo[5,4-c][1]benzopyran 1.6 g (5 mmoles) of 2,2-dimethyl-6-methoxy-
-7-ethoxy-4-chromanone are heated in 12 ml of formic acid under stirring, whilst 0.6 g (about 5.4 mmoles) of selenium dioxide are added in several portions. After cessation of the gas evolution, the mixture is evaporated, the residue is dissolved in an 1:1 mixture of benzene and ethyl acetate and filtered through a silicagel layer. After evaporation, the residue solidifies (eventually rubbing is necessary), m.p.: 84-87 °C. Rf = 0.68 (benzene/ethyl acetate = 1:1)
0.68 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)
0.77 (chloroform/ethanol = 9:1) Analysis:
Calculated for C14H16N2O3Se (molecular weight: 339) C % = 49.6 ; H % = 4.76; N % = 8.26 ; found: C % = 49.4 ; H % = 4.9 ; N % = 8.3 .
Example 29
Preparation of 6 ,7-dimethoxy-4,4-dimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran 2.93 g (10 mmoles) of 7,8-dimethoxy-2,2-di- methyl-4-chromanone semicarbazone are heated in 25 ml of propionic acid under stirring, whilst 1.33 g (12 mmoles) of selenium dioxide are portionwise added. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated and the product is recrystallized to give the title compound, m.p.: 225-227 °C. Rf = 0.66 (benzene/ethyl acetate = 1:1)
0.71 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)
0.77 (chloroform/ethanol = 9:1) Analysis:
Calculated for C13H14N2O3Se (molecular weight: 325) C % =48.04; H % = 4.34; N % = 8.62 ; found: C % = 48.2 ; H % = 4.3 ; N % = 8.8 . E x amp le 30
Preparation of 7-methoxy-4.4,9-trimethy1- -4H-selenadiazolo[5,4-c][1]benzopyran To a heated solution of 27.7 g (100 mmoles) of 7-methoχy-2,2,5-trimethyl-4-chromanone semicarbazone in 250 ml of glacial acetic acid, 13.3 g (12 mmoles) of selenium dioxide are portionwise added under stirring and reacted until cessation of the gas evolution. The complet ion o f the cyclizat ion i s control led by TLC . The mixture is evaporated and the oily residue is crystallized by rubbing to give the title compound, m.p.: 90-93 °C. Rf = 0.72 (benzene/ethyl acetate = 1:1)
0.75 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)
0.75 (chloroform/ethanol = 9:1) Analysis:
Calculated for C13H14N2O2Se (molecular weight: 309) C % = 50.53; H % = 4.57; N % = 9.07 ; found: C % = 50.7 ; H % = 4.5 ; N % = 9.2 .
Example 31
Preparation of 7-methoxy-4,4,6-trimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran 2.77 g (10 mmoles) of 7-methoxy-2,2,8-trimethyl-
-4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and control by TLC, the mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for the cyclization.) The oily residue is crystallized to give the title compound in a yield of 85.8 % , m.p.: 50-53 °C. Rf = 0.73 (benzene/ethyl acetate = 1:1) 0.77 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.77 (chloroform/ethanol = 9:1) Analysis:
Calculated for C13H14N2O2Se (molecular weight: 309).
C % = 50.53; H % 4.57; N % = 9.07 ; found: C % = 50.3 ; H % 4.5 ; N % = 9.2 .
Example 32
Preparation of 7-propargyloxy- -4,4,9-trimathyI-4H-selenadiazolo[5,4-c][1]- benzopyran 3.01 g (10 mmoles) of 7-propargyloxy-2,2,5-
-trimethyl-4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used in the cyclization reaction). The oily residue is crystallized to give the title compound, m.p.: 63-65 ºC. Rf = 0.69 (benzene/ethyl acetate = 1:1) 0.72 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.76 (chloroform/ethanol = 9:1) Analysis:
Calculated for C15H14N2O2Se (molecular weight: 333) C % = 54.1 ; H % = 4.24; N % = 8.41 ; found: C % = 54 ; H % = 4.4 ; N % = 8.3 .
Example 33
Preparation of 7 ,9-dimethoxy-4,4-dimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran
29.3 g (0.1 mole) of 5,7-dimethoxy-2,2-dimethyl- -4-chromanone semicarbazone dissolved in 250 ml of glacial acetic acid are reacted with 14.43 g of selenium dioxide added in several portions while heating and stirring. After cessation of the gas evolution, the mixture is filtered, evaporated and the residue is washed with water to give the title compound, m.p.: m.p. : 113-114 °C.
Rf = 0.67 (benzene/ethyl acetate = 1:1)
0.66 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1) 0.86 (chloroform/ethanol = 9:1) Analysis: Calculated for C13H14N2O3Se (molecular weight: 325)
C % = 48.04; H % = 4.34; N % = 8.62 ; found: C % = 48.0 ; H % = 4.3 ; N % = 8.7 .
Example 34
Preparation of 4,4-dimethyl-7,8-dipropargyl- oxy-4H-selenadiazolo[5,4-c][]benzopyran 3.41 g (10 mmoles) of 2,2-dimethyl-6,7-di- propargyloxy-4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound, m.p.: 78-81 °C. Rf = 0.71 (benzene/ethyl acetate = 1:1)
0.71 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1)
0.74 (chloroform/ethanol = 9:1) Analysis:
Calculated for C17H14N2O3Se (molecular weight: 373) C % = 54.74; H % = 3.78; N % = 7.51 ; found: C % = 54.4 ; H % = 4.0 ; N % = 7.4 .
Example 35
Preparation of 7-propargyloxy-4,4,6-trimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran 3.01 g (10 mmoles) of 7-propargyloxy-2,2,8-
-trimethyl-4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound, m.p.: 113-115 ºC. Rf = 0.74 (benzene/ethyl acetate = 1:1)
0.74 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)
0.74 (chloroform/ethanol = 9:1) Analysis: Calculated for C15H14N2O2Se (molecular weight: 333)
C % = 54.1 ; H % = 4.24; N % = 8.41 ; found: C % = 54.21; H % = 4.04; N % = 8.5 .
Example 36
Preparation of 4,4-dimethyl-8-ethoxy-7-methoxy- -4H-selenadiazolo[5,4-c][1]benzopyran 3.07 g (10 mmoles) of 2,2-dimethyl-6-ethoxy- -7-methoxy-4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound, m.p.: 70-72 °C. Rf = 0.69 (benzene/ethyl acetate = 1:1)
0.67 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1)
0.74 (chloroform/ethanol = 9:1) Analysis:
Calculated for C14H16H2O3Se (molecular weight: 339) C % = 49.6 ; H % = 4.76; N % = 8.26; found: C % = 48.8 ; H % = 4.6 ; N % = 8.1 . E x amp le 37
Preparation of 4,4-dimethyl-selenadiazolo- [5,4-c]-dioxano[2,3-f]-4H-[1]benzopyran 2.91 g (10 mmoles) of 2,2-dimethyl-7,8-dioxano- -4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound, m.p.: 127-131 °C. Rf = 0,6 (benzene/ethyl acetate = 1:1)
0,73 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)
0,55 (chloroform/ethanol = 9:1) Analysis:
Calculated for C13H12N2O3Se (molecular weight: 323) C % = 48.34; H % = 3.75; N % = 8.67; found: C% = 48.0 H % = 4.1 ; N % = 8.7 .
Example 38
Preparation of 4 ,4-dimethylselenadiazolo- [5,4-c]-dioxolo[4,5-f]-4H-[1]benzopyran 2.77 g (10 mmoles) of 2,2-dimethyl-7,8-methy- lenedioxy-4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound, m.p.: 151-154 °C . Rf = 0 . 64 ( benzene/ethy l aceta te = 1 : 1 )
0.7 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.73 (chloroform/ethanol = 9:1) Ana lysis :
Calculated for C12H10N2O3Se (molecular weight: 309)
C % = 46.64; H % = 3.26; N % = 9.07 ; found: C % = 46.4 ; H % = 3.0 ; N % = 9.1 .
Example 39
Preparation of 4 ,4-dimethylselenadiazolo- [5,4-c]-dioxano[2,3-e]-4H-[1]benzopyran 2.91 g (10 mmoles) of 2,2-dimethyl-6,7-dioxano- -4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound, m.p.: 102-106 °C. Rf = 0.64 (benzene/ethyl acetate = 1:1)
0.76 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)
0.64 (chloroform/ethanol = 9:1) Analysis:
Calculated for C13H12N2O3Se (molecular weight: 323) C % = 48.34; H % = 3.75; N % = 8.67 ; found: C % = 48.4 ; H % = 4.1 ; N % = 8.3 .
Example 40
Preparation of 4 ,4-dimethylselenadiazolo- [5,4-c]-dioxolo[4,5-e]-4H-[1]benzopyran 2.77 g (10 mmoles) of 2,2-dimethyl-6,7-methy- lenedioxy-4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound, m.p.: 87-104 °C. Rf = 0.83 (benzene/ethyl acetate = 1:1)
0.75 (benzene/ethyl acetate/glacial acetic acid
= 7:3:1) 0.75 (chloroform/ethanol = 9:1) Analysis: Calculated for C12H10N2O3Se (molecular weight: 309)
C % = 46.64; H % = 3.26; N % = 9.07 ; found: C % = 46.4 ; H % = 3.0 ; N % = 9.17 .
Example 41
Preparation of 6,7-dimethoxy-2,2-dimethyl- -4-chromanone acetylhydrazone 2.36 g (10 mmoles) of 6,7-dimethoxy-2,2-di- methyl-4-chromanone and 0.8 g (11 mmoles) of acetyl- hydrazine are refluxed in 25 ml of ethanol till the complete transformation. Then, the solvent is evaporated and the residue is recrystallized to give the title compound, m.p.: 98-102 °C.
Rf = 0.54 (benzene/ethyl acetate = 1:1)
0.52 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.48 (chloroform/ethanol = 9:1) Analysis:
Calculated for C15H20N2O4 (molecular weight: 292)
C % = 61.64; H % = 6.85; N % = 9.59 ; found: C % = 61.4 : H % = 6.8 ; N % = 9.4 .
Example 42
Preparation of 7,9-dimethoxy-4,4-dimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran 33.6 g (0.1 mole) of 5,7-dimethoxy-2,2-dimethyl- -4-chromanone isopropyloxycarbonylhydrazone in 300 ml of glacial acetic acid are cyclized by portionwise adding 12.2 g (0.11 mole) of seleniumdioxide while mildly heating and stirring. The completion of the reaction is controlled by TLC. Then, the solvent is e.vaporated under vacuum and, if necessary, the residue is purified by recrystallization to give the title compound, m.p.: 113-114 ºC.
Rf = 0.67 (benzene/ethyl acetate = 1:1)
0.66 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.86 (chloroform/ethanol = 9:1) Analysis:
Calculated for C13H14N2O3Se (molecular weight: 325)
C % = 48.04; H % = 4.34; N % = 8.62 ; found: C % = 48.0 ; H % = 4.4 ; N % = 8.7 .
Example 43
Preparation of 7 ,8-dimehoxy-4,4-dimethyI- -4H-selenadiazolo[5,4-c][1]benzopyran To 3.09 g (10 mmoles) of 6,7-dimethoxy-2,2- -dimethyl-4-chromanone thiosemicarbazone dissolved in 25 ml of tetrahydrofuran, 10 ml (13 mmoles) of selenous acid solution are dropwise added while stirring. The stirring is continued till the complete transformation (as detected by TLC). Then, the mixture is partially evaporated and water and chloroform are added to the residue. The organic phase is separated, washed with water, dried and evaporated to give the title compound, m.p.: 98-100 ºC.
Rf = 0.62 (benzene/ethyl acetate = 1:1)
0.69 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.86 (chloroform/ethanol = 9:1) Analysis: Calculated for C13H14N2O3Se (molecular weight: 325)
C % = 48.04; H % = 4.34; N % = 8.62 ; found: C % = 48.2 ; H % = 4.3 ; N % = 8.7 . Example 44
Preparation of 7-methoxy-4,4,9-trimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran 2.93 g (10 mmoles) of 7-methoxy-2,2,5-trimethyl- -2H-4-chromanone thiosemicarbazone are suspended in
15 ml of dioxane and cyclized by adding 1 ml (13 mmoles) of selenous acid under stirring. The end of the reaction is observed on the cessation of the gas evolution and by TLC control. The product is obtained by extraction or evaporation. In the most cases, the oily residue contains only the target compound and crystallizes readily to give the title compound, m.p.: 90 - 92.5 °C. Rf = 0.72 (benzene/ethyl acetate = 1:1)
0.75 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)
0.75 (chloroform/ethanol = 9:1) Analysis:
Calculated for C13H14N2O2Se (molecular weight: 309) C % = 50.53; H % = 4.57; N % = 9.07 ; found C% 50.7 ; H % = 4.6 ; N % = 9.0 .
Example 45
Preparation of 4 , 4-dimethyl-7-ethoxy-4H- -selenadiazolo[5,4-c][1]benzopyran 1.44 g (13 mmoles) of selenium dioxide are portionwise added to the solution of 3.06 g (10 mmoles) of 2,2-dimethyl-7-ethoxy-4-chromanone N-ethoxycarbonyl- hydrazone in 25 ml of glacial acetic acid while heating and stirring. After completion of the reaction, the mixture is filtered and the solution is evaporated under vacuum for recovering the solvent. The oily residue becomes crystalline; it is uniform according to TLC and can directly be used in this form or as intermediate for further transformations without any purification, m.p 104-106 ºC. Rf = 0.75 (benzene/ethyl acetate = 1:1)
0.72 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.72 (chloroform/ethanol = 9:1) Analysis:
Calculated for C13H14N2O2Se (molecular weight: 309)
C % = 50.53; H % = 4.57; N % = 9.07 ; found: C % = 50.4 ; H % = 4.5 ; N % = 9.2 .
Example 46
Preparation of 4-phenyl-4H-selenadiazolo- [5,4-c][1]benzopyran
1.33 g (12 mmoles) of selenium dioxide are portionwise added to the solution of 2.97 g (10 mmoles) of 2-phenyl-4-chromanone thiosemicarbazone in 25 ml of glacial acetic acid at 60 °C under stirring. The stirring is continued until the cessation of gas evolution and complete transformation of the starting material (as detected by TLC). Then, the mixture is evaporated and the recoved glacial acetic acid is used for the next cyclization. The residue is dissolved in chloroform, washed with alkali, dried and evaporated. If necessary, the residue is recrystallized to give the title compound, m.p.: 168-171 ºC. Rf = 0.22 (benzene/ethyl acetate = 1:1)
0.60 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.52 (chloroform/ethanol = 9:1) Analysis: Calculated for C15H10N2OSe (molecular weight: 313) C % = 57.51; H % = 3.22; N % = 8.95 ; found: C % = 57.30; H % = 3.3 ; N % = 9.10 . Example 47
Preparation of 7-methoxy-4,4,6-trimethyl-4H- -selenadiazolo[5,4-c][1]benzopyran 2.92 g (10 mmoles) of 7-methoxy-2,2,8-trimethyl- -4-chromanone N-methoxycarbonylhydrazone in the mixture of 30 ml of dioxane and 10 ml of water are cyclized by adding 5 ml (11 mmoles) of selenous acid under stirring. The completion of the reaction is followed by TLC. Then, the reaction mixture is filtered, evaporated and recrystallized from benzene, if necessary, to give the title compound, m.p.: 58-60 ºC. The thus-obtained product can directly be used in this form or as intermediate.
Rf = 0.68 (benzene/ethyl acetate = 1:1) 0.71 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.78 (chloroform/ethanol = 9:1) Analysis:
Calculated for C13H14N2O2Se (molecular weight: 309) C % = 48.85; H % = 4.10; N % = 9.49 ; found: C % = 49.0 ; H % = 4.2 ; N % = 9.6 .
Example 48
Preparation of 4,4-dimethyl-7-methoxy-4H- -selenadiazolo[5,4-c][1]benzopyran
2.78 g (10 mmoles) of 2,2-dimethyl-7-methoxy- -4-chromanone N-methoxycarbonylhydrazone are stirred with 1.33 g (12 mmoles) of selenium dioxide in 25 ml of glacial acetic acid under mildly stirring till the cessation of the gas evolution. The stirring is continued up to completion of the reaction (as detected by TLC), then filtered and evaporated to give the title compound, m.p.: 58-60 ºC, which can directly be used in this form or as intermediate Rf = 0.68 (benzene/ethyl acetate = 1:1)
0.71 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.78 (chloroform/ethanol = 9:1) Analysis:
Calculated for C12H12N2O2Se (molecular weight: 295)
C % = 48.85; H % = 4.10; N % = 9.49 ; found: C % = 48.9 ; H % = 4.2 ; N % = 9.6 .
Example 49
Preparation of 7-allyloxy-4,4-dimethyl-4H- -selenadiazolo[5,4-c][1]benzopyran 11.52 g (40 mmoles) of 7-allyloxy-2,2-dimethyl- -4-chromanone acetylhydrazone in 100 ml of propionic acid are cyclized by portionwise adding 5.0 g (45 mmoles) of selenium dioxide. After cessation of the gas evolution and completion of the reaction (as detected by TLC), the mixture is evaporated, whereby 90 to 95 % of the propionic acid are recovered. The working-up may be carried out in such a way that the thus-obtained product is dissolved in ethyl acetate, the organic phase is washed with alkali, dried and evaporated to give the title compound in a yield of 88 % , m.p.: 63- -65 ºC after recrystallization from a mixture of benzene and ethyl acetate).
Rf = 0.69 (benzene/ethyl acetate = 1:1)
0.78 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.70 (chloroform/ethanol = 9:1) Analysis: Calculated for C14H14N2O2Se (molecular weight: 321)
C % = 52.33; H % = 4.36; N % = 8.72 ; found: C % = 52.2 ; H % = 4.2 ; N % = 8.8 . E xa mp le 50
Preparation of 4,4-dimethyl-7-proparqyloχy- -4H-selenadiazolo[5,4-c][1]benzopyran 39.8 g (0.1 mole) of 2,2-dimethyl-7-propargyl- oxy-2H-4-chromanone tosylhydrazone are suspended in 150 ml of dioxane and 10 ml of water and cyclized by adding 13.32 g (0.12 mole) of selenium dioxide while stirring. The completion of the reaction is controlled by TLC. Then, the reaction mixture is evaporated and the oily residue is crystallized to give the title compound, m.p.: 83-85 ºC. Rf = 0.7 (benzene/ethyl acetate = 1:1)
0.73 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1) 0.66 (chloroform/ethanol = 9:1) Analysis: Calculated for C14H12N2O2Se (molecular weight: 319)
C % = 52.71; H % = 3.79; N % = 8.78 ; found: C % = 52.4 ; H % = 3.7 ; N % = 8.9 .
Example 51
Preparation of 6,7-dimethoxy-4,4-dimethyl-4H- -selenadiazolo[5,4-c][1]benzopyran 2.5 g of 7,8-dimethoxy-2,2-dimethyl-4-chroma- none hydrazone are cyclized in 25 ml of tetrahydrofuran by portionwise adding 2.0 g (12 mmoles) of selenium oxychloride while stirring. After the complete transformation of the starting material (as detected by TLC), the reaction mixture is heated under stirring for one additional hour, then evaporated, if necessary, and the residue is recrystallized from a suitable solvent to give the title compound. Rf = 0.66 (benzene/ethyl acetate = 1:1)
0.71 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)
0.77 (chloroform/ethanol = 9:1) Analysis:
Calculated for C13H14N2O3Se (molecular weight: 325)
C % = 48.04; H % = 4.34; N % = 8.62 ; found: C % = 48.2 ; H % = 4.3 ; N % = 8.7 .
Example 52
Preparation of 4,4-dimethyl-7-ethoxy-8- -methoxy-4H-selenadiazolo[5,4-c][1]benzopyran 34.2 g (0.1 mole) of 2,2-dimethyl-6-methoxy- -7-ethoxy-4-chromanone N-methanesulfonylhydrazone are cyclized in 350 ml of formic acid by portionwise adding 14.43 g (0.13 mole) of selenium dioxide while stirring. After TLC control, the reaction mixture Is diluted with water, neutralized and the product is separated by extraction into chloroform. After evaporation, the title product becomes crystalline, m.p.: 85-87 ºC, and can be used either directly in this form or as intermediate.
Rf = 0.68 (benzene/ethyl acetate = 1:1) 0.68 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.77 (chloroform/ethanol = 9:1) Analysis:
Calculated for C14H16N2O3Se (molecular weight: 339) C % = 49.6 ; H % = 4.76; N % = 8.26 ; found C % = 49.4 ; H % = 4.8 N% = 8.4
Example 53
Preparation of 4,4-dimethyl-7,8-dipropargyl- oxy-4H-selenadiazolo[5,4-c][1]benzopyran 3.41 g (10 mmoles) of 2, 2-dimethyl-6,7-di- propargyloxy-4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound, m.p.: 78-81 ºC. Rf = 0.71 (benzene/ethyl acetate = 1:1)
0.71 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.74 (chloroform/ethanol = 9:1) Analysis: Calculated for C17H14N2O3Se (molecular weight: 373) C % = 54.74; H % = 3.78; N % = 7.51 ; found: C % = 54.4 ; H % = 4.0 ; N % = 7.4 .
Example 54 Preparation of 4,4-dimethyl-8-ethoxy-7-methoxy-
-4H-selenadiazolo[5,4-c][1]benzopyran 3.07 g (10 mmoles) of 2,2-dimethyl-6-ethoxy- -7-methoxy-4--chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound, m.p.: 70-72 °C. Rf = 0.69 (benzene/ethyl acetate = 1:1)
0.67 (benzene/ethyl acetate/glacial acetic acid = 0.74 = 7:3:1)
(chloroform/ethanol = 9:1) Analysis:
Calculated for C14H16N2O3Se3 (molecular weight: 339)
C % = 49.6 ; H % = 4.76; N % = 8.26 ; found: C % = 48.8 ; H % = 4.6 ; N % = 8.1 . Example 55
Preparatin of 4,4-dimethylselenadiazolo- [5,4-c]-dioxolo[4,5-e]-4H-[1]benzopyran 2.77 g (10 mmoles) of 2,2-dimethyl-6,7-methyle- nedioxy-4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture Is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound, m.p.: 87-104 ºC. Rf = 0.83 (benzene/ethyl acetate = 1:1)
0.75 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.75 (chloroform/ethanol = 9:1) Analysis:
Calculated for C12H10N2O3Se (molecular weight: 309) C % = 46.64; H % = 3.26; N % = 9.07 ; found: C % = 46.4 H % = 3.0 N % = 9.17
Example 56
Preparation of 4 ,4-dimethylselenadiazolo- [5,4-c]-dioxolo[4,5-f]-4H-[1]benzopyran 2.77 g (10 mmoles) of 2,2-dimethyl-7,8-methyle- nedioxy-4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound, m.p.: 151-154 °C. Rf = 0.64 (benzene/ethyl acetate = 1:1)
0.7 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.73 (chloroform/ethanol = 9:1) Analysis: Calculated for C 12H10N2O3Se (molecular weight: 309)
C % = 46.64; H % = 3.26; N % = 9.07 ; found: C % = 46.4 ; H % = 3.0 ; N % = 9.1 .
Example 57
Preparation of 4,4-dimethylselenadiazolo- [5,4-c]-dioxano[2,3-f]-4H-[1]benzopyran 2.91 g (10 mmoles) of 2,2-dimethyl-7,8-dioxano- -4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound, m.p.: 127-131 ºC. Rf = 0.6 (benzene/ethyl acetate = 1:1)
0.73 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)
0.55 (chloroform/ethanol = 9:1) Analysis:
Calculated for C13H12N2O3Se (molecular weight: 323) C% = 48.34; H % = 3.75; N % = 8.67; found: C % = 48.0 ; H % = 4.1 ; N % = 8.7 .
Example 58
Preparation of 4 ,4-dimethylselenadiazolo- [5,4-c]-dioxano[2,3-e]-4H-[1]benzopyran 2.91 g (10 mmoles) of 2,2-dimethyl-6,7-dioxano- -4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cycliza- tion.) The oily residue is crystallized to give the title compound, m.p.: 102-106 ºC.
RF = 0.64 (benzene/ethyl acetate = 1:1)
0.76 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)
0.64 (chloroform/ethanol = 9:1) Analysis: Calculated for C13H12N2O3Se (molecular weight: 323)
C % = 48.34; H % = 3.75; N % = 8.67 ; found: C % = 48.4 ; H % = 4.1 ; N % = 8.3 .
Example 59
Preparation of 7-propargyloxy-4,4,9-trimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran 3.01 g (10 mmoles) of 7-propargyloxy-2,2,5-
-trimethyl-4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound, m.p.: 63-65 ºC. Rf - 0.69 (benzene/ethyl acetate = 1:1)
0.72 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.76 (chloroform/ethanol = 9:1) Analysis: Calculated for C15H14N2O2Se (molecular weight: 333)
C % = 54.1 ; H % = 4.24; N % = 8.41 ; found: C % = 54.0 ; H % = 4.4 ; N % = 8.3 .
Example 60
Preparation of 7-propargyloxy-4,4,6-trimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran 3.01 g (10 mmoles) of 7-propargyloxy-2,2,8- -trimethyl-4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound m. p 113-115
Rf = 0.74 (benzene/ethyl acetate = 1:1)
0.74 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.74 (chloroform/ethanol = 9:1) Analysis:
Calculated for C1 5H14N2O2Se (molecular weight: 333)
C % = 54.1 H % = 4.24; N % = 8.41 ; found C% = 54.21; H % = 4.04; N % = 8.5 .
Example 61
Preparation of 4-phenyl-4H-selenadiazolo- [5,4-c][1]benzopyran
A mixture containing 2.87 g (10 mmoles) of 2-phenyldihydrobenzopyran-3-selenone, 1.11 g (11 mmoles) of triethylamine, and 2.18 g (11 mmoles) of tosyl azide in 15 ml of acetonitrile is kept at 22 °C for one day, then evaporated and the residue is recrystallized to give the title compound in a yield of 94 % m.p.: 168- -171 °C. Rf = 0.22 (benzene/ethyl acetate = 1:1)
0.60 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.52 (chloroform/ethanol = 9:1) Analysis: Calculated for C15H10N2OSe (molecular weight: 313)
C % = 57.51; H % = 3.22; N % = 8.95 ; found: C % = 57.43; H % = 3.30; N % = 9.12 . Example 62
Preparation of 4,4-dimethyl-7-methoxy-4H-selena diazolo[5,4-c][1]benzopyran A mixture containing 2.69 g (10 mmoles) of 2,2-dimethyl-7-methoxy-dihydrobenzopyran-3-selenone,
2.18 g (11 mmoles) of tosyl azide and 1.11 g of triethylamine in 15 ml of dioxane is stirred at 20 to 25 °C for 20 hours, then evaporated and the residue is recrystallized to give the title compound in a yield of 92 %, m.p.: 57-60 °C.
Rf = 0.68 (benzene/ethyl acetate = 1:1)
0.71 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.78 (chloroform/ethanol = 9:1) Analysis:
Calculated for C12H12N2O2Se (molecular weight: 295)
C % = 48.85; H % = 4.10; N % = 9.49 ; found: C % = 49.0 ; H % = 4.1 ; N % = 9.6 .
Example 63
Preparation of 7,8-dimethoxy-4,4-dimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran A mixture containing 29.9 g (0.1 mole) of 6,7-dimethoxy-2,2-dimethyldihydrobenzopyran-3-selenone, 11.1 g (110 mmoles) of triethylamine and 21.8 g (110 mmoles) of tosyl azide in 150 ml of acetonitrile is kept at 22 ºC for 22 hours, then evaporated and the residue is recrystallized to give the title compound in a yield of 92 %, m.p.: 98-100 °C. Rf = 0.62 (benzene/ethyl acetate = 1:1)
0.69 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.86 (chloroform/ethanol = 9:1) Analysis: Calculated for C13H14N2O3Se (molecular weight: 325) C % = 48.04; H % = 4.34; N % = 8.62 ; found: C % = 48.3 ; H % = 4.4 ; N % = 8.6 . E xamp le 64
Preparation of 4,4-dimethyl-7-ethoxy-8-methoxy-
-4H-selenadiazolo[5,4-c][1]benzopyran A mixture containing 3.13 g (10 mmoles) of 2,2-dimethyl-7-ethoxy-6-methoxydihydrobenzopyran-3- -selenone, 1.11 g (11 mmoles) of triethylamine and 2.18 g (11 mmoles) of tosyl azide in 20 ml of acetonitrile is kept at 20 °C for 20 hours. The solvent is recovered by evaporation under vacuum and the residue is crystallized to give the title compound, m.p.: 84-87 °C. Rf = 0.68 (benzene/ethyl acetate = 1:1)
0.68 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1) 0.77 (chloroform/ethanol = 9:1) Analysis: Calculated for C14H1 6N2O3Se (molecular weight: 339)
C % = 49.6 ; H % = 4.76; N % = 8.26 ; found: C % = 49.4 ; H % = 4.9 ; N % = 8.3 .
Example 65
Preparation of 6,7-dimethoxy-4,4-dimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran 2.18 g (11 mmoles) of tosyl azide are added to the solution of 2.99 g (10 mmoles) of 7,8-dimethoxy- -2,2-dimethyldihydrobenzopyran-3-selenone and 1.11 g (11 mmoles) of N-methylmorpholine in 15 ml of tetrahydrofuran, the mixture is kept at 15 to 25 °C for one day, then the solvent is recovered by evaporation and the product is recrystallized to give the title compound, m.p.: 225-227 °C. Rf = 0.66 (benzene/ethyl acetate = 1:1)
0.71 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1) 0.77 (chloroform/ethanol = 9:1) Analysis:
Calculated for C13H1 4N2O3Se (molecular weight: 325)
C % = 48.04; H % = 4.34; N % = 8.62 ; found: C % = 48.2 ; H % = 4.3 ; N % = 8.8 .
Example 66
Preparation of 7,9-dlmethoxy-4,4-dimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran A mixture of 2.99 mg (1 mmole) of 5,7-dimethoxy- -2,2-dimethyl-dihydrobenzopyran-3-selenone, 0.111 g of triethylamine and 218 mg of tosyl azide in 3.0 ml of acetonitrile is kept at 20 to 25 °C for one day, then diluted with water, the precipitate is filtered and recrystallized to give the title compound in a yield of 88 %, m.p.: 113-114 °C.
Rf = 0.67 (benzene/ethyl acetate = 1:1)
0.66 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.86 (chloroform/ethanol = 9:1) Analysis:
Calculated for C13H1 4N2O3Se (molecular weight: 325)
C % = 48.04; H % = 4.34; N % = 8.62 ; found: C % = 48.0 ; H % = 4.3 ; N % = 8.7 .
Example 67
Preparation of 7-methoxy-4,4,6-trimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran A mixture of 2.83 g (10 mmoles) of 7-methoxy- -2,2,8-trimethyldihydrobenzopyran-3-selenone, 1.1 g of N-methylpiperidine and 2.18 g of tosyl azide in 15 ml of acetonitrile is kept at 20 to 25 °C for 20 hours, then the solvent is recovered by evaporation under vacuum and the residue is recrystallized to give the title compound in a yield of 89% m .p 50-53 Rf = 0.73 (benzene/ethyl acetate = 1:1)
0.77 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.77 (chloroform/ethanol = 9:1) Analysis:
Calculated for C13H14N2O2Se (molecular weight: 309)
C % = 50.53; H % = 4.57; N % = 9.07 ; found: C % = 50.3 ; H % = 4.5 ; N % = 9.2 .
Example 68
Preparation of 7-methoxy-4,4,9-trimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran A solution of 2.83 g (10 mmoles) of 7-methoxy- -2,2,5-trimethyl-dihydrobenzopyran-3-selenone, 1.0 g of piperidine and 2.18 g of tosyl azide in 25 ml of ethanol is reacted at 25 °C for 24 hours, then the solvent is recovered by distillation under vacuum and the residue is recrystallized to give the title compound in a 96 % yield, m.p.: 90-93 °C. R = 0.72 (benzene/ethyl acetate = 1:1)
0.75 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.75 (chloroform/ethanol = 9:1) Analysis: Calculated for C13H14N2O2Se (molecular weight: 309) C % = 50.53; H % = 4.57; N % = 9.07 ; found: C % = 50.7 ; H % = 4.5 ; N % = 9.2 .
Example 69
Preparation of 7-proparqyloxy-4,4,9-trimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran 3.07 g (10 mmoles) of 7-propargyloxy-2,2,5- -trimethyldihydrobenzopyran-3-selenone are reacted with 2.18 g of tosyl azide and an equimolar amount of phenyllithium in 30 ml of ether at 20 °C. The reac tion is followed by TLC. After the completion of the reaction, the solvent is evaporated under vacuum, the residue is dissolved in chloroform, washed with acid and then with saturated sodium chloride solution, then dried and evaporated to give the title compound in a yield of 76 % , m.p.: 63-65º C.
Rf = 0.69 (benzene/ethyl acetate = 1:1)
0.72 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.76 (chloroform/ethanol = 9:1)
Analysis:
Calculated for C15H14N2O2Se (molecular weight: 333)
C % =.54.1 ; H % = 4.24; N % = 8.41 ; found: C % = 54.0 ; H % = 4.4 ; N % = 8.3 .
Example 70
Preparation of 4,4-dimethyl-7,8-dipropargyl- oxy-4H-selenadiazolo[5,4-c][1]benzopyran
3.47 g (10 mmoles) of 2,2-dimethyl-6,7-di- propargyloxydihydrobenzopyran-3-selenone are reacted with 0.95 g (11 mmoles) of piperidine and 2.18 g (11 mmoles) of tosyl azide in 25 ml of dichloromethane at 20 to 25 °C. The completion of the reaction is detected by TLC. Then, the solvent is evaporated and the residue. is recrystallized to give the title compound in a yield of 85 %, m.p.: 78-81 °C.
Rf = 0.71 (benzene/ethyl acetate = 1:1)
0.71 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.74 (chloroform/ethanol = 9:1)
Analysis:
Calculated for C17H14N2O3Se (molecular weight: 373)
C % = 54.74; H % = 3.78; N % = 7.51 ; found: C % = 54.4 ; H % = 4.0 ; N % = 7.4 . E x amp le 71
Preparation of 4,4-dimethyl-8-ethoxy-7-methoxy- -4H-selenadiazolo[5,4-c][1]benzopyran A mixture containing 3.13 g (10 mmoles) of 2,2-dimethyl-6-ethoxy-7-methoxydihydrobenzopyran-3-
-selenone, 0.65 g (11 mmoles) of trimethylamine, 2.18 g (11 mmoles) of tosyl azide and 30 ml of acetonitrile is reacted at 20 to 25 °C for 20 hours. Then, the solvent is recovered by evaporation under vacuum and the residue is recrystallized to give the title compound in a yield of 88 %, m.p.: 70-72 °C. Rf = 0.69 (benzene/ethyl acetate = 1:1)
0.67 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1) 0.74 (chloroform/ethanol = 9:1) Analysis:
Calculated for C14H16N2O3Se (molecular weight: 339) C % = 49.6 ; H % = 4.76; N % = 8.26 ; found: C % = 48.8 ; H % = 4.6 ; N % = 8.1 .
Example 72
Preparation of 4,4-dimethylselenadiazolo- [5,4-c]-dioxolo[4,5-f]-4H-[1]benzopyran A mixture of 2.83 g (10 mmoles) of 2,2-di- methyl-7,8-methylenedioxydihydrobenzopyran-3-selenone, 0.81 g (11 mmoles) of diethylamine, 2.18 g (11 mmoles) of tosyl azide and 20 ml of ethanol is reacted. The reaction is followed by TLC. After completion of the reaction, the solvent is recovered by evaporation and the residue is recrystallized to give the title compound in a yield of 94 %, m.p.: 151-154 °C. Rf = 0.64 (benzene/ethyl acetate = 1:1)
0.7 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1) 0.73 (chloroform/ethanol = 9:1) Analysis:
Calculated for C12H10N2O3Se (molecular weight: 309)
C % = 46.64; H % = 3.26; N % = 9.07 ; found: C % = 46.4 ; H % = 3.0 ; N % = 9.1 .
Example 73
Preparation of 4,4-dimethylselenadiazolo- [5,4-c]-dioxano[2,3-e]-4H-[1]benzopyran A mixture of 2.97 g (10 mmoles) of 2,2-dlmethyl- -6,7-dioxanodihydrobenzopyran-3-selenone, 25 ml of diethylamine and 2.18 g (11 mmoles) of tosyl azide is reacted. The reaction is followed by TLC. After completion of the reaction, the solvent is evaporated (and again used). The residue is recrystallized to give the title compound in a yield of 92 %, m.p.: 102- -106 °C. Rf = 0.64 (benzene/ethyl acetate = 1:1)
0 .76(benzene/ethyl acetate/glacial acetic acid.= = 7:3:1) 0.64 (chloroform/ethanol = 9:1) Analysis: Calculated for C13 H12N2O3Se (molecular weight: 323)
C % = 48.34; H % = 3.75; N % = 8.67 ; found: C % = 48.4 : H % = 4.1 ; N % = 8.5 .
Example 74
Preparation of 4,4-dimethylselenadiazolo- [5,4-c]-dioxolo[4,5-e]-4H-[1]benzopyran A mixture of 2.83 g (10 mmoles) of 2,2-dimethyl- -6,7-methylenedioxydihydrobenzopyran-3-selenone, 0.94 g (11 mmoles) of piperidine, 2.18 g of tosyl azide and 20 ml of acetonitrile is reacted at 20 to 25 °C for 20 hours. After completion of the reaction, the solvent is evaporated and again employed. The residue is recrystallized to give the title compound in a yield of 96 %, m.o.: 97-104 °C. Rf = 0.83 (benzene/ethyl acetate = 1:1)
0.75 (benzene/ethyl acetate/glacial acetic acid
= 7:3:1) 0.75 (chloroform/ethanol = 9:1) Analysis: Calculated for C12H10N2O3Se (molecular weight: 309)
C % = 46.64; H % = 3.26; N % = 9.07 ; found: C % = 46.4 ; H % = 3.0 ; N % = 9.17 .
Example 75
Preparation of 4,4-dimethylselenadiazolo- [5,4-c]-dioxano[2,3-f]-4H-[1]benzopyran A mixture containing 2.97 g (10 mmoles) of 2,2-dimethyl-6,7-dioxanodihydrobenzopyran-3-selenone, 1.11 g (11 mmoles) of triethylamine, 2.18 g (11 mmoles) of tosyl azide and 20 ml of acetonitrile is reacted at 20 °C for 20 hours. Then, the solvent is recovered by evaporation under vacuum and the product is recrystallized to give the title compound in a yield of 82 %, m.p.: 127-131 °C.
Rf = 0.6 (benzene/ethyl acetate = 1:1)
0.73 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.55 (chloroform/ethanol = 9:1) Analysis:
Calculated for C13H12N2O3Se (molecular weight: 323) C % = 48.34; H % = 3.75; N % = 8.67 ; found: C% = 48.0 H % = 4.1 N % = 8.7
Example 76
Preparation of 7-propargyloxy-4,4,6-trimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran A mixture containing 3.07 g (10 mmoles) of 7-propargyloxy-2,2,8-trimethyldihydrobenzopyran-3-sele- none, 1.11 g (11 mmoles) of triethylamine, 2.18 g (11 mmoles) of tosyl azide and 25 ml of metanol is reacted at 20 to 25 °C for 24 hours. Then, the solvent is recovered by evaporation under vacuum and the product is recrystallized to give the title compound in a yield of 91 %, m.p.: 113-115 °C. Rf = 0.74 (benzene/ethyl acetate = 1:1)
0.74 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.74 (chloroform/ethanol = 9:1) Analysis: Calculated for C15H14N2O2Se (molecular weight: 333) C % = 54.1 ; H % = 4.24; N % = 8.41 ; found: C % = 54.21; H % = 4.04; N % = 8.5 .
Example 77 Preparation of 4-phenyl-4H-selenadiazolo- [5,4-c][1]benzothiopyran
2.18 g (11 mmoles) of tosyl azide are added to a mixture of 3.03 g (10 mmoles) of 2-phenyldihydro- benzothiopyran-3-selenone, 1.11 g (11 mmoles) of triethyl- amine and 30 ml of dichloromethane, then the mixture is let stand for 20 hours. The solvent is recovered by evaporation and the residue is recrystallized to give the title compound in a yield of 82 %, m.p.: 55- -58 °C. R = 0.73 (benzene/ethyl acetate = 1:1)
0.78 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.79 (chloroform/ethanol = 9:1) Analysis: Calculated for C15H10N9SeS (molecular weight: 329)
C % = 54.765 H % = 3.06; N % = 8.52 ; found: C % = 55.1 ; H % = 3.13; N % = 8.38 . E x amp l e 78
Preparation of 7,8-dimethoxy-4,4-dimethyl- thiadiazolo[5,4-c][1]benzopyran A mixture containing 2.52 g (10 mmoles) of 6,7-dimethoxy-2,2-dimethyl-3,4-dihydro-2H-benzopyran- -3-thione, 0.96 g (11 mmoles) of morpholine, 2.18 g (11 mmoles) of tosyl azide and 25 ml of ethanol is reacted at 20 to 25 °C for 24 hours. The solvent is recovered by evaporation and the residue is recrystallized to give the title compound in a yield of 79 % , m.p.: 118-120 °C. Rf = 0.62 (benzene/ethyl acetate = 1:1)
0.59 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1) 0.86 (chloroform/ethanol = 9:1) Analysis: Calculated for C13H14N2O3Se (molecular weight: 278)
C % = 56.16; H % = 5.07; N % = 10.08; found: C % = 56.4 ; H % = 5.0 ; N % = 10.20.
Example 79
Preparation of 6,7-dimethoxy-2,2-dimethyl- -3,4-dihydro-2H-benzopyran-3-thione 2.36 g (10 mmoles) of 6,7-dimethoxy-2,2- -dimethyl-3,4-dihydro-2H-benzopyran-3-on and 4.44 g (20 mmoles) of phosphorus pentasulfide are refluxed in 50 ml of pyridine for 3 hours, and after completion of the reaction, the mixture is poured into 250 ml of ice-water. The precipitate is thoroughly triturated, filtered and dried to give the title compound in a yield of 88 %.
IR: 2960, 1620, 1520, 1260, 865 cm-1 1H-NMR ( ppm, DMSO-d6): 1.8 (6H), 3.6 (6H), 4.2 (2H),
7.2 (1H), 7.4 (1H) Analysis
Calculated for C13H16O3S (molecular weight: 252)
C % = 61.96; H % = 6.4 ; S % = 12.7 ; found: C % = 62.0 ; H % = 6.51; S % = 11.68.
Example 80
Preparation of 6,7-dimethoxy-2,2-dimethyl- -3,4-dihydro-2H-benzopyran-3-selenone 2.36 g (10 mmoles) of 6,7-dimethoxy-2,2-di- methyl-3,4-dihydro-2H-benzopyran-3-one are refluxed with 9.2 g (20 mmoles) of phosphorous pentaselenide in 50 ml of pyridine for 3 hours, then poured in 200 ml of ice-cold 1:1 hydrochloric acid, and the product separated is extracted into chloroform, or benzene. The combined organic phase Is dried over anhydrous calcium chloride and evaporated to give the title compound in a yield of 92 %, which is pure enough for the next step.
IR: 2960, 1615, 1530, 1100, 870 cm-1 1H-NMR ( ppm, DMSO-d6): 2.0 (6H), 3.6 (6H), 4.2 (2H), 7.3 (1H), 7.5 (1H) Analysis:
Calculated for C13H16O3Se (molecular weight: 299) C % = 52.22; H % = 5.39; found: C % = 53.0 ; H % = 5.46;
Example 81 Preparation of 4,4-dimethyl-7-methoxy-4H- selenadiazolo[5,4-c][1]benzopyran A solution of 2.81 g (10 mmoles) of 3-hydroxy- -1-(2'-hydroxy-4-methoxyphenyl)-3-methylbutanon-1-one semicarbazone in 25 ml of glacial acetic acid is boiled for one hour, then 1.11 g (10 mmoles) of selenium dioxide are portionwise added under continuous heating and stirring. The stirring and heating are continued until the gas evolution ceases and the starting substance disappears (as detected by TLC). Then, the acetic acid is evaporated under vacuum and the residue is recrystallized from ethanol or from a hydrocarbon to give the title compound, m.p.: 57-60 °C. Rf = 0.68 (benzene/ethyl acetate = 1:1)
0.71 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)
0.78 (chloroform/ethanol = 9:1) Analysis: Calculated for C12H12N2O2Se (molecular weight: 295)
N % = 9.49; found: N % = 9.6 .
The following compunds were prepared by using method described in Example 81:
4-Phenyl-4H-selenadiazolo[5,4-c][1]benzopyran, m.p.: 168-171 °C;
4,4-dimethyl-7-ethoxy-8-methoxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, m.p.:84-87 ºC;
6,7-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: 125 - 127 °C;
7,9-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]ben- zopyran, m.p.: 113-114 °C;
7-methoxy-4,4,6-trimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: 50-53 °C;
7-methoxy-4,4,9-trimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: 90-93 °C;
7-propargyloxy-4,4,9-trimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran, m.p.: 63-65 °C;
4,4-dimethyl-7,8-dipropargyloxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, m.p.: 78-81 °C; and 4,4-dimethyl-8-ethoxy-7-methoxy-4H-selenadiazolo[5,4-c][1] be nzop yr an , m . p . : 70 -72 °C. 4,4-dimethyl-7,8-dimethoxy-4H-selenadiazolo[5,4-c[1]benzopyran, m.p. 98-100ºC Example 82
Preparation of 4,4-dimethylselenadiazolo- [5,4-c]-dioxolo[4,5-f]-4H-[1]benzopyran A solution containing 3.27 g (10 mmoles) of 5-(1'-hydroxy-1'-methyl)ethyl-4-(2-hydroxy-3,4- -methylenedioxy)phenyl-1,2,3-selenadiazole in 30 ml of glacial acetic acid is boiled for one hour, then set aside overnight. Then, the acetic acid is recovered by distillation (under atmospheric or reduced pressure) and the residue is recrystallized or dissolved in a water-immiscible solvent (e.g. chloroform) and washed with water to give the title compound, m.p.: 151-154 °C. Rf = 0.64 (benzene/ethyl acetate = 1:1)
0.70 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.73 (chloroform/ethanol = 9:1) Analysis: Calculated for C12H10N2O3Se (molecular weight: 309)
C % = 46.64; H % = 3.26; N % = 9.07; found: C % = 46.4; H % = 3.0; N % = 9.1.
The following compounds were prepared by using the process described in Example 82: 7,8-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: 98-100 °C;
4,4-dimethylselenadiazolo[5,4-c]-dioxano[2,3-e]-4H-[1]- benzopyran, m.p.: 102-106 °C;
4,4-dimethylselenadiazolo[5,4-c]-dioxolo[4,5-e]-4H-[1]- benzopyran, m.p.: 87-104 °C;
4,4-dimethylselenadiazolo[5,4-c]-dioxano[2,3-f]-4H-[1]- benzopyran, m.p.: 127-131 °C;
7-propargyloxy-4,4,6-trimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: 113-115 °C; 4,4-dimethyl-8-ethoxy-7-methoxy-4H-selenadiazolo[5,4-c]-[1]-benzopyran, m.p.: 70-72 °C; 4,4 -dimethyl-7-ethoxy-8-methoxy-4H-selenadiazolo[5,4-c]-[1]benzopyran, m.p. : 84-87 °C;
4,4-dimethyl-7-methoxy-4H-selenadiazolo[5,4-c][1]benzo- pyran, m.p. : 57-60 °C;
6,7-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p. : 125-127 °C; and
7-propargyloxy-4,4,9-trimethyl-4H-selenadiazolo[5,4-c][1] benzopyran, m.p. : 63-65 °C.
Example 83
Preparation of 4-phenyl-4H-selenadiazoIo- [5,4-c][1]benzothiopyran A mixture containing 3.90 g (10 mmoles) of
N-nitroso-N-(thiaflavanon-3-selenon-4-yl)urea, 50 ml of tetrahydrofuran and 10 ml of 10 % potassium hydroxide solution is stirred at 25 °C for 2 hours, then the solvent is evaporated under vacuum and the residue is purified by chromatography on a Kieselgel column to give the title compound, m.p.: 55-58 °C. Rf = 0.73 (benzene/ethyl acetate = 1:1)
0,78 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1) 0.79 (chloroform/ethanol = 9:1) Analysis: Calculated for C15H10N2SSe (molecular weight: 329)
N % = 8.52 ; found: N % = 8.38 .
The following compounds were prepared by using the process described in Example 83: 4-Phenyl-4H-selenadiazolo[5,4-c][1]benzopyran, m.p.: 168-171; 4,4-dimetnyl-7-methoxy-4H-selenadiazolo[5,4-c][1]benzo- pyran, m.p.: 57-60 ºC.
7,8-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: 98-100 °C;
4,4-dimethyl-7-ethoxy-8-methoxy-4H-seIenadiazolo[5,4-c]- [1]benzopyran, m.p.: 84-87 °C.
6, 7-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: 125-127 °C;
7,9-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: 113-114 °C; 7-methoxy-4,4,6-trimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: 50-53 °C; 7-methoxy-4,4,9-trimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: 90-93 °C;
7-propargyloxy-4,4,9-trimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran, m.p. : 63-65 °C; 4,4-dimethyl-7,8-dipropargyloxi-4H-selenadiazolo[5,4-c]- [1]benzopyran, m.p.: 78-81 °C;
4,4-dimethyl-8-ethoxy-7-methoxy-4H-selenadiazolo[5,4-c]- [1[benzopyran, m.p.: 70-72 °C;
4,4-dimethylselenadiazolo[5,4-c]-dioxolo[4,5-f]-4H- -[1]benzopyran, m.p.: 151-154 °C;
4,4-dimethylselenadiazolo[5,4-c]-diσxano[2,3-e]-4H-
-[1]benzopyran, m.p.: 102-106 °C;
7-ρropargyloxy-4,4,6-trimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran, m.p.: 113-115 °C; and 7,8-dimethoxy-4,4-dimethyl-4H-thiadiazolo[5,4-c][1]benzo- pyran, m.p.: 118-120 °C.
Example 84
Preparation of 7,8-dimethoxy-4,4-dimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran A mixture containing 3.11 g (10 mmoles) of 7,8-dimethoxy-4H-selenadiazolo[5,4-c][1]benzopyran- -4-one in 50 ml of anhydrous ether is added to the solution of 20 mmoles of methyl magnesium iodide in 20 ml of ether, then the mixture is refluxed for 2 hours under stirring and then evaporated. To the residue 25 ml of glacial acetic acid are added, the mixture is refluxed for one hour and then mixed with water and extracted with chloroform. The organic phase is washed with sodium carbonate solution, dried and evaporated to give the title compound in a yield of 85 %, m.p.: 98-100 °C. Rf = 0.62 (benzene/ethyl acetate = 1:1)
0.69 (benzene/ethyl acetate/glacial acetic acid =
= 7:3:1) 0.86 (chloroform/ethanol = 9:1) Analysis:
Calculated for C13H14N2O3Se (molecular weight: 325)
C % = 48.04; H % = 4.34; N% = 8.62 found: C % = 48.3 ; H% = 4.4 : N % = 8.6
The following compounds were prepared by using the process described in Example 84: 4,4-dimethyl-7,8-dipropargyloxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, m.p.: 78-81 °C; 4,4-dimethyl-8-ethoxy-7-methoxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, m.p.: 70-72 °C; 7,8-diethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: < 50 °C;
7-allyloxy-4,4-dImethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: 63-65 °C;
7,8-dimethoxy-4,4-dimethyl-4H-thiadiazolo[5,4-c7[1]benzo- pyran, m.p.: 118-120 °C;
7-propargyloxy-4,4,6-trimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran, m.p.: 113-115 °C; 7-propargyloxy-4,4,9-trimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran, m.p.: 63-65 °C;
4,4-dimethyl-7-propargyloxy-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: 83-85 °C;
4,4-dimethyl-7-ethoxy-8-methoxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, m.p.: 84-87 °C;
4,4-dimethyl-7-ethoxy-4H-selenadiazolo[5,4-c7[1]benzo- pyran, m.p.: 104-106 °C;
7,9-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c7[1]- benzopyran, m.p.: 113-114 °C; 7-methoxy-4,4,9-trimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: 90-93 °C;
6,7-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]-benzopyran, m.p.: 30-32 °C; and
7-methoxy-4,4,6-trimethyl-4H-selenadiazolo[5,4-c][1]-benzopyran, m.p.: 50-53 °C. Biological action
The effects of the compounds of the invention were studied by using the following biological tes t systems: 1) the in vivo insecticide and allatocide action on freshly shedded L4-stage locust (Locusta migratoria) nymphs;
2) the in vitro allatocide action on the corpora allata taken from freshly shedded L5-stage locust nymphs by using the method of Shoeneveld (1982);
3) the nematocide action on synchronized Ll-stage larvae of Caenorhabditis elegans Cb 678 strain;
4) the insecticide action on the large white butterfly (Pieris brassicae), fall webworm (Hyphantria cunea), potato beetle (Leptinotarsa decemlineata) and pea green-fly aphis (Acyrthosiphon pisum);
5) in other bactericidal, fungicidal and insecticidal including acaricidal tests.
1) In vivo tests on locusts
The locusts were bred and kept according to the international standards, in rooms thermostated at 29 °C under a stable moisture content, with a day- -part change of the temperature. The L4 nymphs of the locust (Locusta migratoria) freshly shedded within
24 hours were topically treated with the test compounds dissolved in acetone. The animals were anaesthetized by carbon dioxide. The control animals were treated only with acetone. The locusts were daily observed for 21 days and the time and number of the perishments and sheddings were registered. After 21 days, the presence of the eventual adultoids were also investigated.
The effects of the compounds tested were as follows: 4,4-dimethyl-7-methoxy-4H-selenadiazolo[5,4-c][1]benzopyran:
On using a dose of 50 μg/ anima l , one ou t o f 40 animals on ly surv ived , whereas the perishment was total by using a higher dose.
4,4-dimethyl-7-ethoxy-8-methoxy-4H-selenadiazolo[5,4-c]- [1]benzopyran:
The LC50 value of this compound is at a dose of 25 to 50 μg/animal. Survival was observed even at a dose of 100 μg/animal.
6,7-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran: Nearly no survival was observed at a dose of 50 μg/animal.
7-Methoxy-4,4,6-trimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran: The lethality is 95 to 100 % by using a dose of 400 or 100 μg/animal.
2) In vitro CA test
These investigations were carried out by using Schoeneveld's in vitro test (1982). Most of the test compounds were used at four dose levels (5, 10, 50 or 100 μg/ml of medium). The surviving glands were not stained by using a vital dye (acridine orange) after 24 hours, whereas the perished organs showed a staining.
The results of the in vitro CA test determined by using the above method are summarized in Table 1.
Notes to Table 1:
* These values are expressed as μg of selenium. + It is important that no allatocide effect is observed in vitro up to 100 μg.
0: No effect Not determined
The chemical names of the numbered compounds in Table 1 are as follows:
1: 4,4-dimethyl-7-methoxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, 2: 7,8-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran, 3: 4-phenyl-4H-selenadiazolo[5,4-c][1]benzopyran,
4: 7-methoxy-4,4,6-trirnethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran, 5: 6,7-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran,
6: 7-methoxy-4,4,9-trimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran, 7: 7,9-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran, 8: 4,4-dlmethyl-7-ethoxy-8-methoxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, 9: 4,4-dimethyl-7-propargyloxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, 10: 7-propargyloxy-4,4,6-trimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran,
11: 4,4-dimethyl-4H-[1,4]-dioxano[2,3-g]selenadiazolo- [5,4-c][1]benzopyran, 12. 4,4-dimethyl-4H-[1,4[-dioxano[2,3-h[selenadiazolo- [5,4-c][1]benzopyran, 13: 4,4-dimethyl-4H-[1,3[-dioxolo[4,5-g]selenadiazolo- [5,4-c][1]benzopyran and 14: selenium dioxide.
3) Study of the nematocide effect Synchronized L1-stage larvae obtained by the hypochlorite method from Caenorhabditis elegans (C. elegans, laboratory threadworm) CB 678 strain were put onto NGM agar chilled in the holes of a microtitrator sheet (Brenner, 1974) also containing the test substance in the appropriate concentrations. Usually, a dilution in the dose interval between 0 and 1000, or between 0 and 500 μg/ml, respectively was used. A part of the compounds was subjected to a preceeding experiment with concentrations of 5, 50, 500 and 5000 μg/ml. Four repetitions were carried out for each concentration with 15 to 20 animals for each repetition. The sheets also contained E. coli OP 50 bacterial nutriment. After 48 hours, the number of the living, normally developed animals was determined. The percentage ratio of this number related to the control represents the percentage of the survival. In the majority of the cases, this ratio was useful for the approximately accurate calculation of the LD50 and LD95 values.
The results of the nematocide test are summarized in Table 2. The numbering of the compounds in Table 2 is the same as shown in Table 1. Further substances are as follows: 15: 4,4-dimethyl-7-ethoxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, 16: KSeCN, 17: 7-allyloxy-4,4-dimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran, and 18: 4,4-dimethyl-4H-[1,3]-dioxolo[4,5-h]selenadiazolo- [5,4-c][1]benzopyran.
/ /

Claims

What we claim is
1. Compounds of the general formula (I)
(I)
wherein R1 and R2 are independently from each other hydrogen, an unsubstituted or optionally suitably substituted alkyl or aryl group; or
R1 and R2 together may be a cycloalkyl group; R3 is hydrogen; an optionally protected hydroxyl group; an alkyl, alkoxy, O-trialkyltin group; a phosphoric acid, thiophosphoric acid or phosphorous acid alkyl or aryl ester group connected through the oxygen atom; an acyloxy, acyloxyalkoxy, O-trialkylsilyl, aryloxy, alkenyloxy, alkynyloxy, cycloalkyloxy, cyclo- alkenyloxy, cycloalkylalkoxy group; an acyloxy or alkoxy group substituted by phosphoric acid, phosphonic acid or their esters; or two adjacent R3 groups together may represent: an -O-(CH2)m-O-group, wherein m is 1, 2, 3 or 4; or a condensed aromatic ring; or an -O-(CH2)m-(O)z- group, wherein m is as defined above and z is 0 or 1; or an -O-P(Cl)-O-, -O-P(OC2H5)-O-, -O-P=O(OC2H5)-O-, -O-P=S(OC2H5)-O-, -O-(C=O)-O-, -O-(C=S)-O-, -O-P=O(SC2H5)-O-, -O-P=S(SC2H5)-O- or an -O-(S=O)-O- group; or a halogen or a haloalkyl, nitro, amino or suitably substituted amino group; an alkoxy group substituted by an alkylamino or a dialkylamino group; or a nitrile, mercapto, optionally substituted alkylthio group; an optionally ring-substituted aralkyloxy group; an acyl group; or two adjacent R3 groups together may also represent a -C=C-C(=O)-O- and -C=C-C=(CH3)2-O- group; is 0, 1, 2, 3 or 4, and these R3 groups may have, independently from each other, any meaning defined for the R3 groups, Q1 is oxygen, sulfur, SO or SO2; Q2 is sulfur or selenium as well as their salts having valuable biological effects
2. A compound as claimed in claim 1, wherein R1 and R2 are each a methyl group.
3. A compound as claimed in claim 1 wherein
R3 is a methoxy group.
4. A compound as claimed in claim 1 wherein R3 is a methoxy group and n is 2.
5. A compound as claimed in claim 1, wherein
R1 and R2 are each a methyl group and R3 means a methoxy group.
6. A compound selected from the group consisting of 4-phenyl-4H-selenadiazolo[5,4-c][1]benzopyran, 4,4-dimethyl-7-methoxy-4H-selenadiazolo[5,4-c][1]benzo¬pyran, 7,8-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c]-[1]benzopyran, 4,4-dimethyl-8-ethoxy-7-methoxy-4H-selenadiazolo[5,4-c]- [1]beneopyran, 4,4-dimethyl-7-ethoxy-8-methoxy-4H-selenadiazolo[5,4-c]-[1]benzopyran, 6,7-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c]-[1]benzopyran, 7,9-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran,
7-methoxy-4,4,6-trimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, 7-methoxy-4,4,9-trimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, 7-propargyloxy-4,4,9-trimethyl-4H-selenadiazolo[5,4-c] [1]benzopyran, 4,4-dimethyl-7,8-dipropargyloxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, 4,4-dimethylselenadiazolo[5,4-c]-dioxolo[4,5-f]-4H- -[1]benzopyran,
4,4-dimethylselenadiazolo[5,4-c]-dioxano[2,3-e]-4H- -[1]benzopyran, 4,4-dimethylselenadiazolo[5,4-c]-dioxolo[4,5-e]-4H- -[1]benzopyran,
4,4-dimethylsεlenadiazolo[5,4-c]-dioxano[2,3-f]-4H- -[1]benzopyran,
7-propargyloxy-4,4,6-trimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran,
4-phenyl-4H-selenadiazolo[5,4-c][1]benzothiopyran, 7,8-dimethoxy-4,4-dimethyl-4H-thiadiazolo[5,4-c][1]- benzopyran and the salts of these compounds. 7. A fungicide, nematocide, acaricide, bactericide and insecticide composition which comprises as active ingredient a 4H-selenadiazolo[5,4-c][1]benzopyran derivative of the general formula (I), or a salt thereof in an amount of 0.0C1 to 99.5 % and optionally other active ingredients in admixture with solid and/or liquid carriers and/or vehicles and/or surface active additives, preferably a dispersing, emulsifying or wetting agent and/or other auxiliary materials.
8. A fungicide, nematocide, acaricide, bactericide and insecticide composition which comprises as active ingredient a 4H-selenadia.zolo[5,4-c][1]benzothio- pyran derivative of the general formula (I), or a salt thereof in an amount of 0.001 to 99.5 % and optionally other active ingredients in admixture with solid and/or liquid carriers and/or vehicles and/or surface active additives, preferably a dispersing, emulsifying or wetting agent and/or other auxiliary materials.
9. A fungicide, nematocide, acaricide, bactericide and insecticide composition which comprises as active ingredient a 4H-thiadiazolo[5,4-c][1]benzo- pyran derivative of the general formula (I), or a salt thereof in an amount of 0.001 to 99.5 % and optionally other active ingredients in admixture with solid and/or liquid carriers and/or vehicles and/or surface active additives, preferably a dispersing, emulsifying or wetting agent and/or other auxiliary materials.
10. A fungicide, nematocide, acaricide, bactericide and insecticide composition which comprises as active ingredient a 4H-thiadiazolo[5,4-c][1]benzothio- pyran derivative of the general formula (I), or a salt thereof in an amount of 0.001 to 99.5 % and optionally other active ingredients in admixture with solid and/or liquid carriers and/or vehicles and/or surface active additives, preferably a dispersing, emulsifying or wetting agent and/or other auxiliary materials.
11. An acaricide composition, which comprises as active ingredient a compound of the general formula (I) or a salt thereof in an amount of 0.001 to 99.5 % and optionally other active ingredients in admixture with solid and/or liquid carriers and/or vehicles and/or surface active additives, preferably a dispersing, emulsifying or wetting agent and/or other auxiliary materials.
12. A fungicide, nematocide, acaricide, bactericide and insecticide composition, which comprises as active ingredient a compound of the general formula (I), wherein Q1 is oxygen, Q2 is selenium and R1 as well as R2 are each a methyl group, whereas R3 and n are as defined in claim 1 or a salt thereof in an amount of 0.001 to 99.5 % and optionally other active ingredients in admixture with solid and/or liquid carriers and/or vehicles and/or surface active additives, preferably a dispersing, emulsifying or wetting agent and/or other auxiliary materials.
13. A process for the preparation of the novel compounds of the general formula (I),
(I)
wherein R1 and R2 are independently from each other hydrogen, an unsubstituted or optionally suitably substituted alkyl or aryl group; or R1 and R2 together may be a cycloalkyl group; R3 is hydrogen; an optionally protected hydroxyl group; an alkyl, alkoxy, O-trialkyltio group; a phosphoric acid, thiophosphoric acid or phosphorous acid alkyl or aryl ester group connected through the oxygen atom; an acyloxy, acyloxyalkoxy, O-trialkylsilyl, aryloxy, alkenyloxy, alkynyloxy, cycloalkyloxy, cycloalkenyloxy, cycloalkylalkoxy group; an acyloxy or alkoxy group substituted by phosphoric acid, phosphonic acid or their esters; or two adjacent R3 groups together may represent: an -O-(CH2)m-O-group, wherein m is 1, 2, 3 or 4; or a condensed aromatic ring; or an -O-(CH2)m-(O)z- group, wherein m is as defined above and z is 0 or 1; or an -O-P(Cl)- -O-, -O-P(OC2H5)-O-, -O-P=O(OC2H5)-O-, -O-P=S(OC2H5)-O-, -O-(C=O)-O-, -O-(C=S)-O-, -O-P=O(SC2H5)-O-, -O-P=S(SC2H5)-O- or an -O-(S=O)-O- group; or a halogen or a haloalkyl, nitro, amino or suitably substituted amino group; an alkoxy group substituted by an alkylamino or a dial- kylamino group; or a nitrile, mercapto, optionally substituted alkylthio group; an optionally ring-substituted aralkyloxy group; an acyl group; or two adjacent R3 groups together may also represent a -C=C-C(=O)-O- and -C=C-C=(CH3)2-O- group; is 0, 1, 2, 3 or 4, and these R3 groups may have, independently from each other, any meaning defined for the R groups, Q1 is oxygen, sulfur, SO or SO2; Q2 is sulfur or selenium as well as their salts having valuable biological effects which comprises transforming a compound of the general formula (IV),
(IV) wherein R1, R2, R3, Q1 and n are as defined above; and R4 is hydrogen, an aliphatic carboxylic acid ester group, an alkyl or aryl group, or a
-(C=O)-NH2, -(C=S)-NH2, -(C=O)-NH-NH2, -(C=S)-NHNH2, -(C=O)-NHR6. -(C=S)-NHR6, -(C=O)-NH-NHR6 , -(C=S)-NH-NHR6 , -(C=NH)-NH2,
-(C=NH)-(NH-NH2) or an -SO2-R6 group; is an optionally substituted alkyl or aryl group or -(C=O)-NH2 group;
to a benzopyran or benzothiopyran derivative of the general formula (I) and, if desired, converting the thus-obtained compound of the general formula (I) to a salt thereof.
14. A process for the preparation of the novel compounds of the general formula (I), wherein R1, R2, R3, Q1, Q2 and n are as defined in claim 13, which comprises transforming an appropriately substituted ketone of the general formula (II),
(II)
wherein R1, R2, R3, Q1 and n are as defined in claim
12, with a suitable reactant of the general formula
(III)
H2N-NH-R4
(III)
wherein R4 is as defined in claim 13, to a ketone derivative of the general formula (IV), wherein R1, R2, R3, R4, Q1 and n are as defined in claim 13 and cyclizing the thus-obtained compound of the general formula (IV) by using a suitably selected selenium-containing reagent, preferably selenium dioxide.
15. A process for the preparation of the compounds of the general formula (IV), wherein R1, R1, R2, R3, and n are as defined in claim 13 and Q1 is oxygen, which comprises cyclizing a compound of the general formula (V),
(v)
wherein R1, R2, R3, R4 and n are as defined in claim 13, by using an acid.
16. A process for the preparation of the novel compounds of the general formula (I), wherein R1, R2, R3, Q1, Q2 and n are as defined in claim 13, which comprises reacting a compound of the general formula (VI),
(VI)
wherein R1, R2, R3, Q1, Q2 and n are as defined in claim 13, with a diazo-transfer reagent in the presence of a base and spontaneously cyclizing the thus-obtained non-isolated intermediate product.
17. A process for the preparation of the novel compounds of the general formula (I), wherein
R1, R2, R3, Q1, Q2 and n are as defined in claim 13, which comprises cyclizing a compound of the general formula (VII),
(VII)
wherein R1, R2, R3, Q2 and n are as defined in claim
13, by using an acid, preferably acetic acid.
18. A process for the preparation of the novel compounds of the general formula (I), wherein R1, R2, R3, Q1, Q2 and n are as defined in claim 13, which comprises cyclizing a compound of the general formula (VIII),
(VIII)
wherein R1, R2, R3 , R5, Q1, Q2 and n are as defined in claim 13, through a non-isolated intermediate by using an alkaline reagent, preferably potassium hydroxide, sodium hydroxide or calcium hydroxide.
19. A process for the preparation of the novel compounds of the general formula (I), wherein
R1, R2, R3, Q1, Q2 and n are as defined in claim 13, which comprises reacting a coumarin derivative of the general formula (IX),
(IX)
wherein R3, Q1, Q2 and n are as defined in claim 13, with a Grignard reagent of the general formula R1 MgX and/or R2MgX or a metal alkyl, wherein R1 and R2 are as defined In claim 13.
20. A process for the preparation of the compounds of the general formula (X),
(X)
which comprises cyclizing a ketone derivative of the general formula (IV), wherein one R3 means a chain connecting two ketones and R1, R2, R4, Q1 and n are as defined in claim 13, by using an appropriately selected selenium-containing reagent, preferably selenium dioxide, selenous acid, selenites or selenium oxychloride.
21. A process for the preparation of the novel compounds of the general formula (I), wherein R1, R2, R3, Q1 and n are as defined in claim 13, which comprises cyclizing a ketone derivative of the general formula (XI),
(XI)
wherein R1, R2, R3, Q1 and n are as defined in claim 13 and R4 is for a C=O, C=S, or C=NH group.
22. A process for the preparation of the novel compounds of the general formula (I), wherein R1, R2, R3, Q2, and n are as defined in claim 13, whereas
Q1 is an SO or SO2 group, which comprises oxidizing a compound of the general formula (I), wherein Q1 means a sulfur atom and R1, R2, R3, Q2 and n are as defined in claim 13.
23. A process as claimed in claim 13, which comprises cyclizing the compounds of the general formula (IV) by using selenium dioxide.
24. A process as claimed in claim 13, which comprises cyclizing the compounds of the general formula (IV) by using selenous acid.
25. A process as claimed in claim 13, which comprises cyclizing the compounds of the general formula (IV) by using selenites.
26. A process as claimed in claim 13, which comprises cyclizing the compounds of the general formula (IV) by using selenium oxychloride.
27. A process as claimed in any one of the claims 13, 15, 17, 20, 21, or 23 to 26, which comprises carrying out the cyclization in a C1-6 aliphatic carboxylic acid, or in a mixture thereof, or in a mixture of such a carboxylic acid and an other solvent.
28. A process as claimed in any one of the claims 13, 20, 21 or 23 to 27, which comprises using the selenium-containing reagent in an amount of 1.0 to 1.5 equivalents.
29. A process as claimed in any one of the claims 13, 20, 21 or 23 to 28, which comprises carrying out the reaction resulting in a cyclization at a temperature of 0 to 120 °C, preferably at 20 to 80 °C.
30. A process as claimed in any one of the claims 13, 15, 17, 20, 21 or 23 to 29, which comprises obtaining the compound of the general formula (I), wherein R1, R2, R3, Q1, Q2 and n are as defined in claim 13 by evaporation and using repeatedly the thus-
-recovered solvent for the cyclization reaction.
31. A process as claimed in any one of the claims 13 to 29, which comprises obtaining the reaction product by filtration or extraction after pouring into water.
32. A process as claimed in claim 16, which comprises preparing the compounds of the general formula (I), wherein R1, R2, R3, Q1, Q2 and n are as defined in claim 13, by using tosyl azide in the presence of triethylamine.
33. A process as claimed in claim 16, which comprises carrying out the cyclization by using tosyl azide in the presence of trimethylamine.
34. A process as claimed in claim 16, which comprises carrying out the cyclization by using tosyl azide in the presence of morpholine.
35. A process as claimed in claim 16, which comprises carrying out the cyclization by using tosyl azide in the presence of N-methyl-piperidine.
36. A process as claimed in claim 16, which comprises carrying out the cyclization by using tosyl azide in the presence of piperidine.
37. A process as claimed in claim 16, which comprises carrying out the cyclization by using tosyl azide in the presence of phenyllithium.
38. A process as claimed in claim 16, which comprises carrying out the cyclization by using tosyl azide in diethylamine or in the presence of diethyl- amine.
39. A process as claimed in claim 16, which comprises carrying out the cyclization by using a diazo- -transfer reagent in the presence of an alkaline metal alkoxide.
40. A process as claimed in claim 16, which comprises using an appropriately selected organic nitrogen compounds as a base and/or as solvent.
41. A process as claimed in claim 16, which comprises using a diazo-transfer reagent differing from tosyl azide, preferably 4-azidosulfonylbenzoic acid.
42. A process as claimed in any one of the claims 16 or 32 to 39, or 41 which comprises using a C1-6 alcohol, acetonitrile, a halogenated hydrocarbon, aliphatic ether, a cyclic ether, an organic base or an aprotic dipolar liquid as solvent.
43. A process as claimed in any one of the claims 16, or 32 to 42, which comprises carrying out the reaction at a temperature between 0 °C and 120 °C, suitably but not exclusively at 20 to 25 °C.
44. A process for the preparation of a fungicide, nematocide, acaricide, bactericide and insecticide composition, which comprises mixing as active ingredient a novel compound of the general formula (I), wherein R1 , R2, R3, Q1, Q2 and n are as defined in claim 13, or a biologically active salt thereof in an amount of 0.001 to 99.5 %, prepared as claimed in any one of the claims 13, 14, 16, to 19, 21 or 22 optionally with other active ingredients and solid and/or liquid carriers, and/or vehicles and/or surface active additives, preferably a dispersing, emulsifying or wetting agent and/or other auxiliary materials.
EP19870904090 1986-06-26 1987-06-24 Benzopyran and benzothiopyran derivatives and compositions containing them Withdrawn EP0271550A1 (en)

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US10743535B2 (en) 2017-08-18 2020-08-18 H&K Solutions Llc Insecticide for flight-capable pests
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CN113149952B (en) * 2021-04-23 2023-04-25 河南理工大学 Chromene sulfonyl hydrazone derivative fluorescent probe and preparation method and application thereof

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