GB1581359A - Substituted acetylenic compounds - Google Patents

Substituted acetylenic compounds Download PDF

Info

Publication number
GB1581359A
GB1581359A GB22108/77A GB2210877A GB1581359A GB 1581359 A GB1581359 A GB 1581359A GB 22108/77 A GB22108/77 A GB 22108/77A GB 2210877 A GB2210877 A GB 2210877A GB 1581359 A GB1581359 A GB 1581359A
Authority
GB
United Kingdom
Prior art keywords
general formula
hydrogen
compounds
process according
carbon atoms
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.)
Expired
Application number
GB22108/77A
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Chinoin Private Co Ltd
Original Assignee
Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Zrt
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Zrt filed Critical Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Zrt
Publication of GB1581359A publication Critical patent/GB1581359A/en
Expired legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
    • C07C1/26—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from organic compounds containing only halogen atoms as hetero-atoms
    • C07C1/30—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from organic compounds containing only halogen atoms as hetero-atoms by splitting-off the elements of hydrogen halide from a single molecule
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C17/00—Preparation of halogenated hydrocarbons
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C17/00—Preparation of halogenated hydrocarbons
    • C07C17/25—Preparation of halogenated hydrocarbons by splitting-off hydrogen halides from halogenated hydrocarbons
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C25/00—Compounds containing at least one halogen atom bound to a six-membered aromatic ring
    • C07C25/24—Halogenated aromatic hydrocarbons with unsaturated side chains
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/63—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/65—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The compounds of formula I, in which R<1> is H, alkyl, aralkyl or diaralkyl, R<2> is H or a halogen and R<3> is H, alkyl, aralkyl, aryl, aryloxy, benzoyl or 2-thienocarbonyl, R<2> and R<3> not being simultaneously H, are obtained by halogenation of a ketone of formula II, followed by dehydrohalogenation of the intermediate halogenated derivative of formula III by means of a strong base. The compounds of formula I are useful as intermediates for the preparation of pharmaceutically active compounds. <IMAGE>

Description

(54) SUBSTITUTED ACETYLENIC COMPOUNDS (71) We, CHINOIN GYOGYSZER ES VEGYESZETI TERMEKEK GYARA RT., a body corporate organised under the laws of Hungary, of 1-5 To u., Budapest IV, Hungary, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- The present invention relates to new substituted phenyl-acetylenes and a process for the preparation thereof. The new phenylacetylenes have the general formula I
wherein (a) R' is alkyl of 5 or 6 carbon atoms or diaralkyl wherein the alkyl moiety has 2-6 carbon atoms; R2 is hydrogen or halogen; and R3 is hydrogen, alkyl having I to 6 carbon atoms, aralkyl having 1 to 6 atoms in the alkyl moiety, aryl or aryloxy or an aroyl group of the general formula ArCO, wherein Ar is phenyl or a 2-thienyl group; with the proviso that R2 and R3 are not both hydrogen; or (b) RX is hydrogen, alkyl having 1 to 6 carbon atoms, aralkyl wherein the alkyl moiety has 1 to 6 carbon atoms, or diaralkyl wherein the alkyl moiety has 2 to 6 carbon atoms, R2 is halogen; and R3 is hydrogen; with the proviso that when R1 is methyl and R3 is hydrogen, R2 is not m-chloro, p-chloro, p-bromo or pfluoro.
The new compounds of the formula I can be prepared by reacting a compound of the general formula II
wherein the substituents are as defined above, with a halogenating agent, preferably with a phosphorus halide, and reacting the compounds thus obtained of the general formula III
wherein the substituents are as defined above, if desired without isolation, with a strong base.
According to an advantageous embodiment of the present invention, compounds of the general formula II are reacted with phosphorus pentachloride without any solvent or in an organic inert solvent, such as diethylether at a temperature of 20 to 1000C, preferably at the boiling point of the solvent. The reaction may be carried out in the solvent, preferably, at a temperature of 50 to 900 C.
The hydrogen halide can be split off with strong bases, preferably with alkali metal hydroxides, such as potassium hydroxide or alkali metal alcoholates, such as sodium methoxide or sodium or potassium tert.
butoxide, preferably in an organic solvent.
As an organic solvent alcohols, or aromatic hydrocarbons, preferably toluene, may be used.
Hydrogen halides are preferably split off with sodium methoxide and as a solvent preferably dimethylsulfoxide or dimethylformamide are used.
The hydrogen halide is split off preferably at 20 to 1300C, advantageously at the boiling point of the solvent employed; the preferred solvent dimethylsulfoxide boils at 70"C.
On a large-scale the hydrogen halide may be split off by subjecting the halo-olefin of general formula III to dehydrohalogenation without purification or isolation.
The phenyl-acetylene compounds of the general formula (I) can be used in the pharmaceutical industry, primarily as intermediates for the preparation of valuable pharmaceutically active phenylalkyl carboxylic acids (cf. our copending Application Serial No.
1,552,202). Hitherto the compounds of the present invention had not been prepared because of technical problems with the known synthetic routes, such as the unavailability of the starting materials. The synthesis of compounds related to those of general formula (I) by the above-described route is further illustrated in our Hungarian Patent Application No. CI-l668 laid open under number T/15127 (equivalent to our Spanish Patent No. 459,087).
One embodiment of our invention is illustrated in the following Example.
Example 41.6g. of m-bromo-propiophenone and 52g. of phosphorus pentachloride are heated on a water bath at 750C until evolution of hydrogen chloride ceases, i.e.
for about 20 to 25 minutes. After cooling, the reaction mixture is fractionated in vacuo.
The cut of boiling point 108---112"C at 1.5 mmHg (31g.) is dissolved in 150 ml. of anhydrous toluene, 70g. sodium tert.
butoxide are added and the mixture is heated for 7 hours under vigorous stirring.
The reaction mixture is decomposed with water, the two layers are separated and the aqueous layer is extracted with 3x 100 ml. of toluene. The toluene is distilled off after drying and the residue is fractionated in vacuo. The hot cut boiling at 11-1120C/1.5 mmHg is 1 - (3 - bromophenyl) - 2 methyl - acetylene.
nD4=1.5885.
Analysis: Calculated: Bromine 40.98 Found: Bromine41.40"/, WHAT WE CLAIM IS: 1. Compounds of the general formula I
wherein (a) R1 is alkyl of 5 or 6 carbon atoms or diaralkyl wherein the alkyl moiety has 2-6 carbon atoms; R2 is hydrogen or halogen; and R3 is hydrogen, alkyl having 1 to 6 carbon atoms, aralkyl having 1 to 6 carbon atoms in the alkyl moiety, aryl or aryloxy or an aroyl group of the general formula ArCO, wherein Ar is phenyl or a 2-thienyl group; with the proviso that R2 and R3 are not both hydrogen; or (b) R1 is hydrogen, alkyl having 1 to 6 carbon atoms, aralkyl wherein the alkyl moiety has 1 to 6 carbon atoms, or diaralkyl wherein the alkyl moiety has 2 to 6 carbon atoms, R2 is halogen; and R3 is hydrogen; with the provisos that when R1 is methyl and R3 is hydrogen, R2 is not m-chloro, pchloro, p-bromo or p-fluoro.
2. 1 - (3 - Bromophenyl) - 2 - methyl acetylene.
3. A process for the preparation of the compounds of the general formula I as defined in claim 1, which comprises reacting a compound of the general formula II.
wherein the substituents are as defined in claim 1, with a halogenating agent and reacting the corresponding compounds of the general formula III thus obtained
with a strong base.
4. A process according to claim 3 wherein said halogenating agent is a phosphorus halide.
5. A process according to claim 4 wherein said halogenating agent is phosphorus pentachloride.
6. A process according to claim 5 wherein said compound of general formula (III) is reacted with phosphorus pentachloride at 50 to 900C in the absence of a solvent.
7. A process according to claim 5 wherein said compound of general formula (III) is reacted with phosphorus pentachloride at 200 to 1000C in the presence of an organic solvent.
8. A process according to claim 7 wherein the reaction temperature is 50 to 900 C.
9. A process according to any of claims 3 to 8 wherein said strong base is an alkali metal hydroxide or alkali metal alcoholate.
10. A process according to claim 9, which
**WARNING** end of DESC field may overlap start of CLMS **.

Claims (14)

**WARNING** start of CLMS field may overlap end of DESC **. with sodium methoxide and as a solvent preferably dimethylsulfoxide or dimethylformamide are used. The hydrogen halide is split off preferably at 20 to 1300C, advantageously at the boiling point of the solvent employed; the preferred solvent dimethylsulfoxide boils at 70"C. On a large-scale the hydrogen halide may be split off by subjecting the halo-olefin of general formula III to dehydrohalogenation without purification or isolation. The phenyl-acetylene compounds of the general formula (I) can be used in the pharmaceutical industry, primarily as intermediates for the preparation of valuable pharmaceutically active phenylalkyl carboxylic acids (cf. our copending Application Serial No. 1,552,202). Hitherto the compounds of the present invention had not been prepared because of technical problems with the known synthetic routes, such as the unavailability of the starting materials. The synthesis of compounds related to those of general formula (I) by the above-described route is further illustrated in our Hungarian Patent Application No. CI-l668 laid open under number T/15127 (equivalent to our Spanish Patent No. 459,087). One embodiment of our invention is illustrated in the following Example. Example 41.6g. of m-bromo-propiophenone and 52g. of phosphorus pentachloride are heated on a water bath at 750C until evolution of hydrogen chloride ceases, i.e. for about 20 to 25 minutes. After cooling, the reaction mixture is fractionated in vacuo. The cut of boiling point 108---112"C at 1.5 mmHg (31g.) is dissolved in 150 ml. of anhydrous toluene, 70g. sodium tert. butoxide are added and the mixture is heated for 7 hours under vigorous stirring. The reaction mixture is decomposed with water, the two layers are separated and the aqueous layer is extracted with 3x 100 ml. of toluene. The toluene is distilled off after drying and the residue is fractionated in vacuo. The hot cut boiling at 11-1120C/1.5 mmHg is 1 - (3 - bromophenyl) - 2 methyl - acetylene. nD4=1.5885. Analysis: Calculated: Bromine 40.98 Found: Bromine41.40"/, WHAT WE CLAIM IS:
1. Compounds of the general formula I
wherein (a) R1 is alkyl of 5 or 6 carbon atoms or diaralkyl wherein the alkyl moiety has 2-6 carbon atoms; R2 is hydrogen or halogen; and R3 is hydrogen, alkyl having 1 to 6 carbon atoms, aralkyl having 1 to 6 carbon atoms in the alkyl moiety, aryl or aryloxy or an aroyl group of the general formula ArCO, wherein Ar is phenyl or a 2-thienyl group; with the proviso that R2 and R3 are not both hydrogen; or (b) R1 is hydrogen, alkyl having 1 to 6 carbon atoms, aralkyl wherein the alkyl moiety has 1 to 6 carbon atoms, or diaralkyl wherein the alkyl moiety has 2 to 6 carbon atoms, R2 is halogen; and R3 is hydrogen; with the provisos that when R1 is methyl and R3 is hydrogen, R2 is not m-chloro, pchloro, p-bromo or p-fluoro.
2. 1 - (3 - Bromophenyl) - 2 - methyl acetylene.
3. A process for the preparation of the compounds of the general formula I as defined in claim 1, which comprises reacting a compound of the general formula II.
wherein the substituents are as defined in claim 1, with a halogenating agent and reacting the corresponding compounds of the general formula III thus obtained
with a strong base.
4. A process according to claim 3 wherein said halogenating agent is a phosphorus halide.
5. A process according to claim 4 wherein said halogenating agent is phosphorus pentachloride.
6. A process according to claim 5 wherein said compound of general formula (III) is reacted with phosphorus pentachloride at 50 to 900C in the absence of a solvent.
7. A process according to claim 5 wherein said compound of general formula (III) is reacted with phosphorus pentachloride at 200 to 1000C in the presence of an organic solvent.
8. A process according to claim 7 wherein the reaction temperature is 50 to 900 C.
9. A process according to any of claims 3 to 8 wherein said strong base is an alkali metal hydroxide or alkali metal alcoholate.
10. A process according to claim 9, which
comprises reacting said compound of the general formula (III) with sodium methoxide in the presence of dimethylsulfoxide or dimethylforamide.
I I. A process according to any of claims 3 to 10 wherein said compound of the general formula (III) is reacted with a strong base without isolation.
12. A process according to claim 3 substantially as illustrated in the Example herein.
13. Compounds according to claim 1 whenever made by the process of any of claims 3 to 12.
14. Compounds according to claim 1 wherein R1 is other than hydrogen.
GB22108/77A 1976-05-25 1977-05-25 Substituted acetylenic compounds Expired GB1581359A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
HU76CI00001668A HU172938B (en) 1976-05-25 1976-05-25 Process for producing substituted phenyl-acethylenes

Publications (1)

Publication Number Publication Date
GB1581359A true GB1581359A (en) 1980-12-10

Family

ID=10994618

Family Applications (1)

Application Number Title Priority Date Filing Date
GB22108/77A Expired GB1581359A (en) 1976-05-25 1977-05-25 Substituted acetylenic compounds

Country Status (9)

Country Link
JP (1) JPS52144633A (en)
CH (1) CH622485A5 (en)
DK (1) DK226977A (en)
ES (1) ES459087A1 (en)
GB (1) GB1581359A (en)
HU (1) HU172938B (en)
NL (1) NL7705680A (en)
SE (1) SE431867B (en)
SU (1) SU656499A3 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4665246A (en) * 1984-03-09 1987-05-12 Chem Biochem Research, Inc. Method of producing ethynyl aromatic compounds
WO2005037758A1 (en) * 2003-10-13 2005-04-28 Applied Research Systems Ars Holding N.V. Method for preparing para-phenyl alkynyl benzaldehydes

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS54109952A (en) * 1978-02-18 1979-08-29 Takayuki Shioiri 3**fluoroo4**phenylpropiophenone and its manufacture
JPS54128553A (en) * 1978-03-27 1979-10-05 Takayuki Shioiri Novel 3**benzoylpropiophenone and its manufacture
JP2003037511A (en) * 2001-07-26 2003-02-07 Niigata Seimitsu Kk Circuit for extracting weak signal

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4665246A (en) * 1984-03-09 1987-05-12 Chem Biochem Research, Inc. Method of producing ethynyl aromatic compounds
WO2005037758A1 (en) * 2003-10-13 2005-04-28 Applied Research Systems Ars Holding N.V. Method for preparing para-phenyl alkynyl benzaldehydes
US7479575B2 (en) 2003-10-13 2009-01-20 Laboratoires Serono Sa Method for preparing para-phenyl alkynyl benzaldehydes

Also Published As

Publication number Publication date
JPS52144633A (en) 1977-12-02
NL7705680A (en) 1977-11-29
CH622485A5 (en) 1981-04-15
SU656499A3 (en) 1979-04-05
SE431867B (en) 1984-03-05
ES459087A1 (en) 1978-04-16
HU172938B (en) 1979-01-28
DK226977A (en) 1977-11-26
SE7705840L (en) 1977-11-26

Similar Documents

Publication Publication Date Title
DE3881817T2 (en) 3,5-Dihydroxy-6,8-nonadienoic acids and derivatives as hypocholesterolemic agents.
GB1581359A (en) Substituted acetylenic compounds
KR950003120B1 (en) Improved process for preparing 5-(2,5-dimethyl phenoxy)-2,2-dimetheyl pentanoic acid
US4027040A (en) Novel benzophenone derivatives
US3948896A (en) N-mono(alkoxymethyl) phenobarbitals, process therefor and therapeutic composition and method containing same
US3468900A (en) Process for preparing isoxazole compounds
DE2558356A1 (en) DEHYDROBIOTIN COMPOUNDS
US3317541A (en) Decahydroisoquinoline esters of substituted benzoic acid and methods for their preparation
EP0022606B1 (en) Process for the manufacture of halogenated hydrocarbons
US3383420A (en) 5-(gamma-hydroxypropyl)-5h-dibenzo [a, d] cycloheptenes
DE2711656C2 (en)
US3839568A (en) Selected 5-substituted-5-phenylalkyl barbituric acids in analgetic compositions and methods of use
US3256335A (en) Method of making 5h-dibenzo [a, d] cyclohepten-5-ones
US3478133A (en) Cyclic phosphate esters and process for producing same
SU968025A1 (en) Process for producing 1-chloro-1-phenyl-2-arylethanes
SUGAI et al. Studies on Isoxazoles. XII. Novel Syntheses of 4-Isothiazolin-3-thiones and Bis (3-isoxazolyl) Disulfides from 4-Isoxazolin-3-thiones
GB1561153A (en) Process for the preparation of thiochroman derivatives
US3784547A (en) Selected 5-substituted-5-phenylalkyl barbituric acids
US3733364A (en) 5-chloro-2-ethynylbenzyl methyl sulfoxide and its preparation
US4451682A (en) Process for the preparation of true acetylene hydrocarbons having a perfluorinated chain
US4054565A (en) Process for preparing N-mono(alkoxymethyl) phenobarbitals
US3246010A (en) 1, 5-diaryl-2-pyrrole propanols and ethers
EP0080053B1 (en) 3,5-diphenyl-1h-1,2,4-triazoles with contragestational activity, pharmaceutical compositions thereof and process for their preparation
US3189519A (en) Method of killing nematodes with disulfides
SU434647A3 (en)

Legal Events

Date Code Title Description
PS Patent sealed [section 19, patents act 1949]
PCNP Patent ceased through non-payment of renewal fee