DD143771A1 - PROCESS FOR THE PREPARATION OF 1,2-DIHYDRO-CHINOXALINE-2-THIONES - Google Patents

Abstract

The invention relates to a process for the preparation of 3-aryl or 3-heteroaryl-1,2-dihydro-quinoxaline-2-thionen, because of their spectrum of activity in particular to Pharmaceutical field, z.T. are also of interest to the film and paint industry. goal of Invention is, by a simple implementation previously described only sporadically 1,2-dihydro-quinoxaline thiones to make more widely available. The essence of the invention lies in the reaction of the reactive α-oxo-aryl-dithioacetic acid alkyl esters with o-diaminoaromatics, e.g. o-phenylenediamine, optionally by alkyl, alkoxy or NO 2 groups or halogen on or are substituted several times. Quinoxaline derivatives represent potential tuberculostatic agents, bacteriostats, Antibiotics, psychotropic drugs, antivirals, pesticides, fungicides, metal complexing agents, active substances in the Film industry and intermediates in color chemistry. R = aryl or heteroaryl, X, Y = H, Alkyl, alkoxy or NO 2, wherein X and Y are the same or different or X, Y = (-CH ~) 4 (Benzene ring). - Formula -

Description

"Process for the preparation of 1,2-dihydrocarboxylate ~ 2 ~ th

Field of application of the invention

Quinoxaline compounds show a wide spectrum of activity and therefore claim strong interest, especially in pharmacy * So far, Ghinoxalinverbindungen have become known as potential ^r Aiberkulostatika, bacteriostats, antibiotics and pesticides or fungicides «Furthermore, their suitability has been examined as psychotropic drugs. More recently, the virostatic activity of quinoxaline derivatives has been increasingly investigated. To. Agar diffusion inhibitors and virus yielding yeast tests are effective against DNA and RNA viruses. Moreover, especially 1,2-dihydroquinoxaline-2-thiones are metal complexing agents and starting compounds for dyes and organic pigments,

Characteristic of the known technical solutions

1,2-Dihydro-quinoxaline-2-thiones have hitherto only become known in isolated cases. Their synthesis was carried out from the 1,2-dihydroquinoxalin-2-ones by sulfurization with IV ^ q or after conversion in'2 ~ Chlorchinoxaline by. Reaction with thiourea. Recently, about the formation of 3-phenyl-1,2-dihydro-quinoxaline-2-thione from acetophenone and 10- to 15-fold excess SOGIp in the presence of small amounts of pyridine and subsequent reaction of. Removing the excess

SOGIp resulted in complex products mixed with

Likewise, the formation of 3- (p-Diniethylaminophenyl) -1,2-dihydroquinoxaline-2-thione in the reaction of quinoxaline hydrochloride with di-

methylaniline in the presence of sulfur. Object of the invention

The aim of the invention is the simplification and shortening of the previous multistage syntheses. Furthermore, a synthesis was found, which opens up the Chinoxalinthione in a wide range. '·

Explanation of the essence of the invention

The known technical solutions represent multi-stage reactions, which are generally based on ester condensation; for the synthesis of the <\ - Oxocarbonsäurederivate with subsequent condensation with o-pbenylenediamine or other 1,2-Dia- 'minoaromaten, sulfurization with PzjS ^ q or "conversion into 2-chloroquinoxalines and subsequent thiolysis, for example with thiourea, build Synthesis of acetophenone and S'OCL ·) are detrimental to the large excess of SOOIp, the formation of resinous intermediates and unclean end-products.These disadvantages have so far only led to the isolated synthesis of 1'-dihydroquinoxaline S-thiones ChinoxaIinverbindungen was to find a synthesis that uses readily accessible, borrowed starting compounds and the 1,2-dihydroquinoxaline-2-thiones synthetically opens up a broad range.For the invention, the object is achieved in that <* -Oxodithioester the general formula

R-CO- CSSR '

with ortho-Diaminoaromaten such as o-phenylenediamine, advantageously in a solvent or solvent mixture, to 3-aryl-1 _s 2-dihydro-2-thiones or * the tautomeric 2-mercapto-3-arylchinoxalinen of the general formula

or"

implemented four the, where in the formulas

R = aryl or heteroaryl,

R ¹ = alkyl or aralkyl,

X and Y are the same or different, = H, halogen, NO ₂ - * alkyl or alkoxy groups or a fused ring, for example a fused benzo ring (X, Y = (-CH =) ^)

mean"

Due to the reactivity of the σ ^ -Oxodithioesters only weak heating of the reaction mixture is required. The reaction sets in. general at about 30-60 ⁰ O, sometimes even at lower temperatures, a. Advantageously, a solvent bzv. used in which the starting components readily soluble and the 'reaction product well crystallized, for example, aromatic hydrocarbons, alcohols, ither, etc. The crystallizing after a short time at the reaction temperature Chinoxalinthione can be easily separated by suction of the solvent.

embodiments

example 1

3- (4-chlorophenyl ^f) -1 ^ -dihydro ^ -thione-quinoxaline

A mixture of 2.5 parts by weight of cx.-oxo-p-chlorophenyl-dithioacetic acid methyl ester and 1.2 parts by weight of o-phenylenediamine is heated to about 30 ⁰ C in ethanol. After a short time, a yellow precipitate falls (3 parts by weight, 84- 4 % of theory) _a us. Recrystallization from diethyl ketone or nitroethane gives pure quinoxalinthione (2.2 parts by weight, 62.2 % of theory) of melting point 242-255 ° C (subl.).

Example 2

3- (3 *, 4'-Dihydroxyphenyl) -1,2-dihydro-quinoxaline-2-thione

Upon heating of _$ 2 3 parts by weight <X. _0XO-3-y t ^z ~ ~ dihydroxy-phenyl dithioessigsäuremetl ^ yl ester with 1.2 parts by weight in ethanol 0-Phenylendiaa.in fall at about 70 ⁰ G 1.6 parts by weight (59j3 % d "Th") of a yellow-orange precipitate from the Chmp. 281-2-85 ⁰ G (crystal transformation at 267-269 ° G). Umlcristal-

lization from glycol monoethyl ether / ltfasser yields 1.2 parts by weight (44.4% of theory) ^ö chmp. 284-286 ⁰ C (267-269 ° C crystal conversion). By adding water to the mother liquor further Chinoxalinthion can be obtained.

Example 3.

3_ (1 ^f ~ naphthyl) -1,2 ~ dihydro-quinoxaline-2-thione

2 parts by weight of methyl oxo-1-naphthyldithioacetate and 0.85 part by weight of o-phenylenediamine are heated to 3O-35 ° C. in 20-25 parts by volume of benzene. After about 30 min. Slowly a yellow precipitate (1.6 GeeichtsteiIe) crystallized from which to Umio? Istallisation from benzene 1 part by weight (44.8% of theory) ^{above sea} chmp. 240-243 ° C,

Example 4

3- (4 ^f-diphenyl) -1,2-dihydro ~ quinoxalin-2-thione

1.35 parts by weight of ^ -Oxo- ^ diphenyl-dithioessigsäuremethylester, 0.6 parts by weight of o-phenylenediamine are heated to about 50 ⁰ C in 10-20 parts by volume of benzene. After a short time precipitates ocher-colored precipitate (0.8 parts by weight, 51 % of theory), which gives after recrystallization from a mixture of propanol, ethyl glycol and pyridine yellow crystals of mp »259-265 ° C.

Example 5 3- (3'-Nitropheny: 1-) 1,2-dihydro-choloxalin-2-thione

1.4 parts by weight of methyl-oxo-3-nitrophenyl-dithio-acetic acid are provided in 10 parts by volume of benzene with 0.6 part of o-phenylenediamine by weight. It immediately precipitates a yellow precipitate, which is filtered off with suction after 45 min, washed with benzene and then dried (crude yield: 1.3 parts by weight, 82.8 % of theory) "For [cleaning is cooked with HCCIo and recrystallizes the yellow residue from butanol / pyridine. This gives 0.72 parts by weight (46 % of theory) of S _C hiap. 264 ~ 267 ° C.

ZI 3. 1

Example 6

3- (4 ^f ~ methoxyphenyl) -1,2-dilaydro-ohino2: alin-2-thione

2.3 parts by weight of a-oxo-4-methoxyphenyl-dithioessigsäuremethylester are dissolved in 50 "volumes of ethanol, 1 part by weight of o-phenylenediamine and about 2 h heated to Rüclcfluß» The precipitated yellow precipitate is filtered off with suction and recrystallized from propanol . There are obtained 2 parts by weight (74.6% of theory) of melting point 235-240 * C ^0.

Claims (1)

1 3 1 invention claim A process for the preparation of 1-dihydroquinoxaline S-thionen, characterized in that C *. Oxo-aryldithioacetic acid ester of the general formula R-CO-OSSSR ', with ortho-Diaminoaro-Eiaten, which are optionally mono- or polysubstituted with alkyl, alkoxy or NOp groups or halogen atoms, with or without solvent or, mixture at temperatures of from - 20 to 200 ⁰ C, preferably at room or slightly elevated temperature {to 3 ^ 2 ^ 1 ^ ^ dihydro-quinoxaline - ^ - thiones or the tautomeric 2-mercapto-3 ~ aryl -quinoxalines of the general formula or. implemented, whereby R = aryl or heteroaryl, R * = alkyl or aralkyl, X and Y, which are identical or different, are H, halogen, ITO ₂ - "alkyl or alkoxy groups or an ankonäensierten ring, for example a fused benzene ring, mean.