CH385886A - Process for the preparation of a heterocyclic compound - Google Patents
Process for the preparation of a heterocyclic compoundInfo
- Publication number
- CH385886A CH385886A CH877760A CH877760A CH385886A CH 385886 A CH385886 A CH 385886A CH 877760 A CH877760 A CH 877760A CH 877760 A CH877760 A CH 877760A CH 385886 A CH385886 A CH 385886A
- Authority
- CH
- Switzerland
- Prior art keywords
- solution
- phenylmercaptomethyl
- acid
- preparation
- homothioxanthone
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 12
- 238000002360 preparation method Methods 0.000 title claims description 4
- 150000002391 heterocyclic compounds Chemical class 0.000 title description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 229910015900 BF3 Inorganic materials 0.000 claims description 3
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Substances FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 238000007363 ring formation reaction Methods 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 239000000243 solution Substances 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- QXPRAGVOCILNHG-UHFFFAOYSA-N 2-(phenylsulfanylmethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1CSC1=CC=CC=C1 QXPRAGVOCILNHG-UHFFFAOYSA-N 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 238000009835 boiling Methods 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- 235000019341 magnesium sulphate Nutrition 0.000 description 7
- 235000011121 sodium hydroxide Nutrition 0.000 description 7
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 5
- 239000000155 melt Substances 0.000 description 4
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- ZEXQVHUDJCZFCC-UHFFFAOYSA-N 2-(phenylsulfanylmethyl)benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1CSC1=CC=CC=C1 ZEXQVHUDJCZFCC-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- QQOVRPBUAUNBAV-UHFFFAOYSA-N ethyl 2-(chloromethyl)benzoate Chemical compound CCOC(=O)C1=CC=CC=C1CCl QQOVRPBUAUNBAV-UHFFFAOYSA-N 0.000 description 3
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 230000001376 precipitating effect Effects 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000002026 chloroform extract Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 239000012259 ether extract Substances 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- HGYITBIPRDBEGZ-UHFFFAOYSA-N 2-benzylsulfanylbenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1SCC1=CC=CC=C1 HGYITBIPRDBEGZ-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- SOUAXOGPALPTTC-UHFFFAOYSA-N ethyl 2-methylbenzoate Chemical compound CCOC(=O)C1=CC=CC=C1C SOUAXOGPALPTTC-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- -1 phenylmercaptomethyl Chemical group 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- YRHRIQCWCFGUEQ-UHFFFAOYSA-N thioxanthen-9-one Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3SC2=C1 YRHRIQCWCFGUEQ-UHFFFAOYSA-N 0.000 description 1
- 238000004073 vulcanization Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
- C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
- C10M1/00—Liquid compositions essentially based on mineral lubricating oils or fatty oils; Their use as lubricants
- C10M1/08—Liquid compositions essentially based on mineral lubricating oils or fatty oils; Their use as lubricants with additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D337/00—Heterocyclic compounds containing rings of more than six members having one sulfur atom as the only ring hetero atom
- C07D337/02—Seven-membered rings
- C07D337/06—Seven-membered rings condensed with carbocyclic rings or ring systems
- C07D337/10—Seven-membered rings condensed with carbocyclic rings or ring systems condensed with two six-membered rings
- C07D337/12—[b,e]-condensed
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
- C08K5/00—Use of organic ingredients
- C08K5/0008—Organic ingredients according to more than one of the "one dot" groups of C08K5/01 - C08K5/59
- C08K5/0025—Crosslinking or vulcanising agents; including accelerators
-
- C—CHEMISTRY; METALLURGY
- C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
- C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
- C10M2219/00—Organic non-macromolecular compounds containing sulfur, selenium or tellurium as ingredients in lubricant compositions
- C10M2219/10—Heterocyclic compounds containing sulfur, selenium or tellurium compounds in the ring
-
- C—CHEMISTRY; METALLURGY
- C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
- C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
- C10M2219/00—Organic non-macromolecular compounds containing sulfur, selenium or tellurium as ingredients in lubricant compositions
- C10M2219/10—Heterocyclic compounds containing sulfur, selenium or tellurium compounds in the ring
- C10M2219/102—Heterocyclic compounds containing sulfur, selenium or tellurium compounds in the ring containing sulfur and carbon only in the ring
-
- C—CHEMISTRY; METALLURGY
- C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
- C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
- C10M2219/00—Organic non-macromolecular compounds containing sulfur, selenium or tellurium as ingredients in lubricant compositions
- C10M2219/10—Heterocyclic compounds containing sulfur, selenium or tellurium compounds in the ring
- C10M2219/104—Heterocyclic compounds containing sulfur, selenium or tellurium compounds in the ring containing sulfur and carbon with nitrogen or oxygen in the ring
-
- C—CHEMISTRY; METALLURGY
- C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
- C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
- C10M2219/00—Organic non-macromolecular compounds containing sulfur, selenium or tellurium as ingredients in lubricant compositions
- C10M2219/10—Heterocyclic compounds containing sulfur, selenium or tellurium compounds in the ring
- C10M2219/104—Heterocyclic compounds containing sulfur, selenium or tellurium compounds in the ring containing sulfur and carbon with nitrogen or oxygen in the ring
- C10M2219/106—Thiadiazoles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Description
Verfahren zur Herstellung einer heterocyclischen Verbindung
Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung des bisher unbekannten Homo thioxanthons der Formel I
EMI1.1
welches dadurch gekennzeichnet ist, dass man eine Verbindung der Formel II
EMI1.2
worin eines der Symbole X und Y Wasserstoff unc das andere eine freie oder eine funktionell abgewan delte Carboxylgruppe bedeuten, cyclisiert.
Das Verfahren kann beispielsweise wie folgt aus geführt werden: Zu einer siedenden Suspension vor Aluminiumchlorid in einem geeigneten Lösungsmit tel, wie z. B. Schwefelkohlenstoff oder Nitrobenzol lässt man die Lösung einer Verbindung der Forme II, z. B. S-Benzylthiosalicylsäurechlorid oder 2 (Phenylmercaptomethyl)-benzoylchlorid in Schwefel kohlenstoff oder Nitrobenzol zutropfen. Das Gemiscl wird gegebenenfalls zur Vervollständigung der Reak tion noch einige Stunden zum Sieden erhitzt. Nacl Entfernen des Lösungsmittels, z. B. durch Abdekan tieren oder durch Verdampfen im Vakuum, wird dei Rückstand mit Eis und konz. Salzsäure versetzt unc mit Äther extrahiert. Das Endprodukt wird nacl bekannten Methoden isoliert und durch Sublimatior und/oder Kristallisation gereinigt.
Bei Anwendung der freien Säure als Ausgangsmaterial kann die Cyclisierung vorteilhaft auch mit anorganischen oder organischen Säuren, z. B. mit konz. Schwefelsäure, ausgeführt werden. Die Ausführung des Verfahrens gestaltet sich beispielsweise wie folgt: Man lässt die Lösung von 2-(Phenylmercaptomethyl)-benzoesäure in konz. Schwefelsäure mehrere Stunden bei Raumtemperatur stehen. Die intensiv rot gefärbte Lösung wird nach Versetzen mit Eis mit Chloroform extrahiert, und das Endprodukt nach bekannten Methoden isoliert.
Als weiteres Cyclisierungsmittel eignet sich z. B. auch Bortrifiuorid-Äthylätherat. Der Ringschluss erfolgt in diesem Fall durch mehrstündiges Erwärmen der Lösung von 2-(Phenylmercaptomethyl)-benzoe- säure in Diäthyläther mit 48proz. Bortrifiuorid-Ärhyi ätherat. Das Homothioxanthon wird anschliessend aus der ätherischen Lösung in üblicher Weise isoliert.
Das bisher unbekannte Homothioxanthon soll als Antioxydans für Schmiermittel und als Vulkanisationsbeschleuniger Verwendung finden. Die verfahrensgemäss hergestellte Verbindung kann auch als Zwischenprodukt zur Herstellung von Hellmitteln, wie z. B. Antihistaminika und Neuropiegika, verwendet werden.
Die als Ausgangssubstanzen verwendeten Verbindungen der Formel II können, sofern sie noch nicht bekannt sind, beispielsweise hergestellt werden, indem man einen o-Toluylsäurealkylester halogeniert und den entstandenen 2-Halogenmethyl-benzoesäurealkylester mit Thiophenol kondensiert. Das Kondensationsprodukt der Formel III
EMI1.3
worin Alk eine niedere Alkylgruppe bedeutet, kann gegebenenfalls zur 2-(Phenylmercaptomethyl)-benzoesäure verseift und diese in das entsprechende Säurehalogenid übergeführt werden.
In den nachfolgenden Beispielen erfolgen alle Temperaturangaben in Celsiusgraden; die Schmelzrespektive Siedepunkte sind unkorrigiert.
Beispiel 1
Zu einer gut gerührten, siedenden Suspension von 13 g Aluminiumchlorid in 200 cm3 Schwefelkohlenstoff werden innert 1 Stunde 13,1 g SBenylthiosalicylsäurechlorid in 600 cm3 Schwefelkohlenstoff zugetropft und das Reaktionsgemisch anschlie- ssend 5 Stunden zum Sieden erhitzt. Nach Abkühlen wird der Schwefelkohlenstoff abdekantiert und der Rückstand mit 300 g Eis zerrieben. Nach Zusatz von 100 cm3 konz. Salzsäure wird mit 2000 cm3 Äther ausgeschüttelt Der Ätherextrakt wird darauf mit Wasser gewaschen und über Magnesiumsulfat getrocknet. Nach Verdampfen des Lösungsmiftels wird der ölige Rückstand am Hochvakuum bei 120 sublimiert und das Sublimat aus Äthanol umkristallisiert.
Das reine Homothioxanthon schmilzt bei 8po6".
Beispiel 2
Zu einer siedenden Suspension von 10 g Aluminiumchlorid in 30 cm3 Schwefelkohlenstoff wird innert 30 Minuten eine Lösung von 10 g 2-(Phenylmercaptomethyl)-benzoylchlorid in 70 cm3 Schwefelkohlenstoff zugetropft. Nach 15 Stunden wird der Schwefelkohlenstoff ab destilliert und der Rückstand unter Kühlung mit 50 g Eis und 15 cm3 konz. Salzsäure versetzt. Die saure Lösung wird anschliessend mit 100 cm3 Ather extrahiert, der Ätherauszug mit 30 cm3 2-n. Natronlauge ausgeschüttelt und mit Wasser neutral gewaschen. Nach Trocknen über Magnesiumsulfat wird der Äther abdestilliert.
Das Rohprodukt wird zur Reinigung in Äthanol mit Tierkohle aufgekocht, durch hochgereinigte Fullererde filtriert und das Filtrat etwas eingeengt, wobei das Homothioxanthon ausfällt. Nach Umkristallisieren aus Äthanol schmilzt das Homothioxanthon bei 84-860.
Beispiel 3
5 g 2-(Phenylmercaptomethyl)-benzoesäure werden in 20 cm3 konz. Schwefelsäure gelöst und 14 Stunden bei Zimmertemperatur stehengelassen. Die intensiv rot gefärbte Lösung wird dann auf 50 g Eis gegossen und mit 100 cm3 Chloroform extra hiert. Der Chloroformextrakt wird mit 40 cm3 2-n Natronlauge und anschliessend mit Wasser gewaschen und über Magnesiumsulfat getrocknet. Das Lösungsmittel wird am Vakuum entfernt und das ausgefallene Homothioxanthon aus Äthanol umkristallisiert.
Smp. 84-869.
Beispiel 4
Eine Lösung von 10 g 2-(Phenylmercaptomethyl)- benzoesäure in 80 cm3 Diäthyläther wird mit 4 cm3 48proz. Bortrifluorid-Äthylätherat 24 Stunden zum Sieden erhitzt. Anschliessend wird die Ätherlösung mit 40 cm3 2-n Natronlauge und Wasser gewaschen und über Magnesiumsulfat getrocknet. Nach Abdestillieren des Äthers wird das ausgefallene Homothioxanthon aus Äthanol umkristallisiert. Smp.
886C.
Die in den Beispielen Nrn. 2, 3 und 4 verwendeten Ausgangssubstanzen können wie folgt hergestellt werden: a) 2-Chlormethyl-benzoesäureäthylester
100 g o-Toluylsäureäthylester, 107,3 g Sulfurylchlorid und 760 mg Dibenzoylperoxyd werden unter Belichten im Ölbad auf 600 erhitzt. Zur Entfernung von Ausgangsmaterial. wird das Reaktionsgemisch nach beendeter Gasentwicklung bei einem Druck von 13 mm Hg mit einer kleinen Raschigkolonne vordestilliert.
Der Rückstand wird mit einer Kolonne bei 0,03 mm Hg destilliert, wobei der 2-Chlormethylbenzoesäureäthylester bei 100-102 übergeht. b) 2- (PhenylmercaptomethyD benzoesäureäthylester
Zu einer Lösung von 48,2 g Thiophenol, 17,5 g Ätznatron in 90 cm3 Wasser und 350 cm3 Äthanol lässt man 87,0 g 2-Chlormethyl-benzoesäureäthylester zutropfen und erhitzt das Gemisch 75 Minuten am Rückfluss zum Sieden. Nach Abkühlen wird das ausgefallene Natriumchlorid abfiltriert und das Filtrat am Wasserstrahlvakuum eingeengt. Der Rückstand wird in 300 cm3 Chloroform aufgenommen, mit 50 cm3 eiskalter l-n Natronlauge ausgeschüttelt, neutral gewaschen und über Magnesiumsulfat getrocknet.
Nach Entfemen des Chloroforms destil liert der 2(Phenylmercaptomethyl) -benzoesäureäthyl- ester bei 140-142 bei einem Druck von 0,02 mm Hg. c) 2-(Phenylmercaptomethyl)-benzoesäure
78 g 2-(Phenylmercaptomethyl)-benzoesäureäthylester werden in einer Lösung von 13,0 g Ätznatron in 78 cm3 Wasser und 53 cm3 äthanol 1 Stunde zum Sieden erhitzt. Anschliessend wird die Reaktionslösung am Vakuum eingeengt, mit 200 cm3 Wasser verdünnt und mit 50 cm3 Chloroform gewaschen. Die wässerige, alkalische Lösung wird mit 5-n Salzsäure sauer gestellt und mit 1200 cm3 Chloroform extrahiert.
Nach Waschen des Chloroformextraktes mit Wasser und Trocknen über Magnesiumsulfat wird die Lösung etwas eingeengt und mit Petroläther versetzt, wobei die 2-(Phenylmer captométhyl)-benzoesäure ausfällt. Nach Umkristallisieren aus Chloroform/Petroläther schmilzt die Verbindung bei 111-113 . d) 2-(Phenylmercaptomethyl)-benzoyichlorid
15 g 2-(Phenylmercaptomethyl)-benzoesäure werden mit 60 g reinem Thionylchlorid 15-20 Minuten auf 600 erhitzt. Das überschüssige Thionylchlorid wird im Vakuum abdestilliert und das 2-(Phenyl mercaptomethyl)-benzoylchlorid im Luftbad bei 1600 und 0,01 mm Hg destilliert.
Beispiel 5
Zu 32,0 g 85proz. Phosphorsäure werden unter gutem Rühren bei 80-100" 46,5 g Phosphorpentoxyd gegeben. Innert 5 Minuten versetzt man die entstandene Polyphosphorsäure portionenweise mit 15,0 g 2-(Phenylmercaptomethyl)-benzoesäure und rührt das Gemisch während 30 Minuten bei 100 .
Anschliessend wird das Reaktionsgemisch noch heiss unter Rühren auf 250 g Eis gegossen und mit 200 cm3 Benzol verdünnt. Nach Filtration durch hochgereinigte Diatomeenerde wird die Benzollösung abgetrennt und die wässerige Phase mit 100 cm3 Benzol extrahiert. Die vereinigten Benzolauszüge werden mit zweimal 50 cm3 2-n Natronlauge ausgeschüttelt, mit Wasser neutral gewaschen und über Magnesiumsulfat getrocknet. Nach Eintfernen des Lösungsmittels im Vakuum wird der kristalline Rückstand in siedendem Äthanol gelöst, mit Tierkohle gereinigt und die Lösung abgekühlt, wobei das Homothioxanthon kristallin ausfällt. Nach Kristallisieren aus Äthanol schmilzt die Verbindung bei 86869.
Process for the preparation of a heterocyclic compound
The present invention relates to a process for the preparation of the previously unknown homo thioxanthone of the formula I.
EMI1.1
which is characterized in that a compound of the formula II
EMI1.2
wherein one of the symbols X and Y is hydrogen and the other is a free or a functionally modified carboxyl group, cyclized.
The process can be carried out, for example, as follows: To a boiling suspension of aluminum chloride in a suitable solvent tel, such as. B. carbon disulfide or nitrobenzene, the solution of a compound of the formula II, z. B. S-benzylthiosalicylic acid chloride or 2 (phenylmercaptomethyl) benzoyl chloride in carbon disulfide or nitrobenzene is added dropwise. The Gemiscl is optionally heated to the boil for a few hours to complete the reaction. After removing the solvent, e.g. B. by decanting animals or by evaporation in vacuo, dei residue with ice and conc. Hydrochloric acid is added and extracted with ether. The end product is isolated according to known methods and purified by sublimation and / or crystallization.
When using the free acid as the starting material, the cyclization can advantageously also be carried out with inorganic or organic acids, e.g. B. with conc. Sulfuric acid. The process is carried out, for example, as follows: The solution of 2- (phenylmercaptomethyl) benzoic acid in conc. Sulfuric acid for several hours at room temperature. The intensely red colored solution is extracted with chloroform after adding ice, and the end product is isolated by known methods.
Another suitable cyclizing agent is, for. B. also boron trifluoride ethyl etherate. In this case, the ring is closed by heating the solution of 2- (phenylmercaptomethyl) benzoic acid in diethyl ether at 48% for several hours. Boron trifluoride etherate. The homothioxanthone is then isolated from the ethereal solution in the usual way.
The previously unknown homothioxanthone is said to be used as an antioxidant for lubricants and as a vulcanization accelerator. The compound produced according to the method can also be used as an intermediate product for the production of lightning agents, such as. B. antihistamines and neuropiegics can be used.
The compounds of the formula II used as starting substances can, if they are not yet known, be prepared, for example, by halogenating an o-toluic acid alkyl ester and condensing the 2-halomethyl-benzoic acid alkyl ester formed with thiophenol. The condensation product of formula III
EMI1.3
in which Alk denotes a lower alkyl group can, if appropriate, be hydrolyzed to give 2- (phenylmercaptomethyl) benzoic acid and this can be converted into the corresponding acid halide.
In the following examples, all temperatures are given in degrees Celsius; the melting and boiling points are uncorrected.
example 1
To a well-stirred, boiling suspension of 13 g of aluminum chloride in 200 cm3 of carbon disulfide, 13.1 g of SBenylthiosalicylic acid chloride in 600 cm3 of carbon disulfide are added dropwise within 1 hour and the reaction mixture is then heated to boiling for 5 hours. After cooling, the carbon disulfide is decanted off and the residue is triturated with 300 g of ice. After adding 100 cm3 of conc. Hydrochloric acid is extracted with 2000 cm3 of ether. The ether extract is then washed with water and dried over magnesium sulfate. After evaporation of the solvent, the oily residue is sublimed in a high vacuum at 120 and the sublimate is recrystallized from ethanol.
The pure homothioxanthone melts at 8po6 ".
Example 2
A solution of 10 g of 2- (phenylmercaptomethyl) benzoyl chloride in 70 cm3 of carbon disulfide is added dropwise within 30 minutes to a boiling suspension of 10 g of aluminum chloride in 30 cm3 of carbon disulfide. After 15 hours, the carbon disulfide is distilled off and the residue is cooled with 50 g of ice and 15 cm3 of conc. Hydrochloric acid added. The acidic solution is then extracted with 100 cm3 of ether, the ether extract with 30 cm3 of 2-n. Sodium hydroxide solution extracted and washed neutral with water. After drying over magnesium sulfate, the ether is distilled off.
For purification, the crude product is boiled in ethanol with animal charcoal, filtered through highly purified fuller's earth and the filtrate is concentrated somewhat, the homothioxanthone precipitating out. After recrystallization from ethanol, the homothioxanthone melts at 84-860.
Example 3
5 g of 2- (phenylmercaptomethyl) benzoic acid are concentrated in 20 cm3. Dissolved sulfuric acid and left to stand for 14 hours at room temperature. The intensely red colored solution is then poured onto 50 g of ice and extracted with 100 cm3 of chloroform. The chloroform extract is washed with 40 cm3 of 2N sodium hydroxide solution and then with water and dried over magnesium sulfate. The solvent is removed in vacuo and the precipitated homothioxanthone is recrystallized from ethanol.
M.p. 84-869.
Example 4
A solution of 10 g of 2- (phenylmercaptomethyl) benzoic acid in 80 cm3 of diethyl ether is 48% with 4 cm3. Boron trifluoride ethyl etherate heated to boiling for 24 hours. The ether solution is then washed with 40 cm3 of 2N sodium hydroxide solution and water and dried over magnesium sulfate. After the ether has been distilled off, the precipitated homothioxanthone is recrystallized from ethanol. M.p.
886C.
The starting substances used in Example Nos. 2, 3 and 4 can be prepared as follows: a) Ethyl 2-chloromethyl-benzoate
100 g of ethyl o-toluate, 107.3 g of sulfuryl chloride and 760 mg of dibenzoyl peroxide are heated to 600 in an oil bath with light. For removing starting material. the reaction mixture is pre-distilled after the evolution of gas has ceased at a pressure of 13 mm Hg with a small Raschig column.
The residue is distilled in a column at 0.03 mm Hg, the 2-chloromethylbenzoic acid ethyl ester passing over at 100-102. b) 2- (PhenylmercaptomethyD benzoic acid ethyl ester
87.0 g of ethyl 2-chloromethylbenzoate are added dropwise to a solution of 48.2 g of thiophenol, 17.5 g of caustic soda in 90 cm3 of water and 350 cm3 of ethanol, and the mixture is refluxed for 75 minutes. After cooling, the precipitated sodium chloride is filtered off and the filtrate is concentrated in a water jet vacuum. The residue is taken up in 300 cm3 of chloroform, extracted with 50 cm3 of ice-cold 1N sodium hydroxide solution, washed neutral and dried over magnesium sulfate.
After removing the chloroform, the 2 (phenylmercaptomethyl) benzoic acid ethyl ester is distilled off at 140-142 at a pressure of 0.02 mm Hg. C) 2- (phenylmercaptomethyl) benzoic acid
78 g of ethyl 2- (phenylmercaptomethyl) benzoate are heated to boiling for 1 hour in a solution of 13.0 g of caustic soda in 78 cm3 of water and 53 cm3 of ethanol. The reaction solution is then concentrated in vacuo, diluted with 200 cm3 of water and washed with 50 cm3 of chloroform. The aqueous, alkaline solution is acidified with 5N hydrochloric acid and extracted with 1200 cm3 of chloroform.
After the chloroform extract has been washed with water and dried over magnesium sulfate, the solution is concentrated somewhat and petroleum ether is added, with the 2- (phenylmercaptomethyl) benzoic acid precipitating out. After recrystallization from chloroform / petroleum ether, the compound melts at 111-113. d) 2- (phenylmercaptomethyl) benzoyichloride
15 g of 2- (phenylmercaptomethyl) benzoic acid are heated to 600 for 15-20 minutes with 60 g of pure thionyl chloride. The excess thionyl chloride is distilled off in vacuo and the 2- (phenyl mercaptomethyl) benzoyl chloride is distilled in an air bath at 1600 and 0.01 mm Hg.
Example 5
At 32.0 g 85% Phosphoric acid is added with good stirring at 80-100 "46.5 g of phosphorus pentoxide. Within 5 minutes, the polyphosphoric acid formed is mixed in portions with 15.0 g of 2- (phenylmercaptomethyl) benzoic acid and the mixture is stirred at 100 for 30 minutes.
The reaction mixture is then poured onto 250 g of ice while still hot while stirring and diluted with 200 cm3 of benzene. After filtration through highly purified diatomaceous earth, the benzene solution is separated off and the aqueous phase is extracted with 100 cm3 of benzene. The combined benzene extracts are extracted twice with 50 cm3 of 2N sodium hydroxide solution, washed neutral with water and dried over magnesium sulfate. After removing the solvent in vacuo, the crystalline residue is dissolved in boiling ethanol, cleaned with animal charcoal and the solution cooled, the homothioxanthone precipitating in crystalline form. After crystallization from ethanol, the compound melts at 86869.
Claims (1)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH877760A CH385886A (en) | 1960-08-02 | 1960-08-02 | Process for the preparation of a heterocyclic compound |
| OA51508A OA01261A (en) | 1960-08-02 | 1964-12-31 | New derivatives of homothiaxanthene and their preparation. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH877760A CH385886A (en) | 1960-08-02 | 1960-08-02 | Process for the preparation of a heterocyclic compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH385886A true CH385886A (en) | 1964-12-31 |
Family
ID=4344622
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH877760A CH385886A (en) | 1960-08-02 | 1960-08-02 | Process for the preparation of a heterocyclic compound |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH385886A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3954994A (en) * | 1968-10-03 | 1976-05-04 | Pfizer Inc. | Intermediates for preparing hipolipemic agents and method of lowering the blood lipid level in mammals with said agents |
-
1960
- 1960-08-02 CH CH877760A patent/CH385886A/en unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3954994A (en) * | 1968-10-03 | 1976-05-04 | Pfizer Inc. | Intermediates for preparing hipolipemic agents and method of lowering the blood lipid level in mammals with said agents |
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