Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
  • C07D489/02—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone

Definitions

• hydrazine and certain of its derivatives are highly selective reducing agents for carbon-carbon or nitrogen-nitrogen double bonds, and a number of such reductions have been described.
• the primary products of this decomposition are the aryl sulphinic acid and diimine, although in the absence of a base the benzene sulphinic acid may undergo further reaction to form sulphur compounds such as S-phenyl benzenethiosulphonate and diphenyl sulphide which can lead to a reduced yield of diimine. If, however, a base such as ethanolamine is present reaction of the benzene sulphinic acid can be prevented and the formation of these sulphur compounds largely avoided. It should be noted that this method of forming diimine does not require the use of either free hydrazine or oxygen and thus eliminates the hazard associated with the Rapoport procedure. More eflicient utilization of the hydrazine in the reduction of carbon-carbon double bonds can also be achieved by using benzene sulphonyl hydrazide as the source of diimine rather than hydrazine/oxygen.
• the process according to the invention leads to improved overall yields of dihydrocodeinone prepared from the 8:14-dihydrothebaine produced compared with those yields obtained when the first stage is the catalytic hydrogenation process or the Eppenberger procedure using bydrazine and oxygen mentioned above. It also obviates the explosion hazard associated with the use of free hydrazine and free oxygen. It is also applicable to a technical grade of thebaine which is not of sufiicient purity for use in the catalytic hydrogenation process because of the fact that it causes the hydrogenation catalyst to become rapidly poisoned.
• the aryl sulphonic acid may be one in which the aryl group is a benzene or naphthalene radical or a substituted benzene or substituted naphthalene radical, e.g. a monoor polyalkyl substituted benzene radical.
• Preferred aryl sulphonic acids are benzene and p-toluene sulphonic acid.
• acid hydrazide which may be used is benzene sulphonic acid hydrazide, but others in which the aromatic group or the alkyl group or both are substituted may also be employed.
• the hydrazide may be in the form of a solid, a slurry or solution which is added to the reaction mixture or may be formed in situ.
• Diimine can also be produced by the thermal decomposition of disodium azodicarboxylate in the presence of a proton supplying substance. Any substance which is capable of supplying protons may be used, for example, acids, alcohols, water.
• Disodium azocarboxylate may be prepared from azodicarbonamide (commercially available as Genitron AC, which is a trademark) by treatment with cold aqueous concentrated sodium hydroxide solution as described in Annalen der Chemie, 271, 130 (1892).
• the reac tion according to the invention is preferably carried out in the presence of a base, either organic or inorganic although this is not essential. If an organic base is used it should have a boiling point above that at which the diimine-producing compounds decompose. A practical lower limit in this respect is a boiling point of at least 80 C.
• Suitable bases which may be used include alkali metal hydroxides, ammonia, alkylamines, substituted alkylamines, aralkylamines, substituted aralkylamines and heterocyclic bases. Specific examples of such bases include sodium hydroxide solution, ethanolamine, morpholine, benzylarnine and ethylene diamine.
• the molar ratio of the reactants required is determined by the necessity to employ sufiicient diimine-producing compound to achieve as near total reduction of the 8:14 double bond of thebaine as practical. This can generally be achieved in accordance with the invention by using a molar ratio of diimine-producing compound to thebaine of not greater than 4: 1, and usually a ratio of 2:1 sufiices.
• Example 1 was repeated using diiferent solvents. The results are shown in Table I.
• EXAMPLE 2 40 g. of p-toluene sulphonyl chloride was suspended in 75 ml. of methyl oxitol and cooled in an ice bath. 12 ml. of ethanolamine and 12 ml. of hydrazine hydrate (98%) were added slowly keeping the temperature below 20 C.
• EXAMPLE 3 31 g. of technical thebaine, 30 m1. of ethanolamine, 75 ml. of hydrazine hydrate (98%) and 75 ml. of methyl oxitol were brought to reflux temperature in a nitrogen atmosphere. 40 g. of p-toluene sulphonylchloride dissolved in 75 ml. of methyl oxitol was then added to the refluxing solution over 15 minutes. Work-up of the reaction mixture as described in Example 1 yielded 27 g. of crude 8:14-dihydrothebaine, M.P. 162166 C.
• EXAMPLE 4 31 g. of technical thebaine, ml. of ethanolamine and 75 ml. of methyl oxitol were brought to reflux temperature and 35 g. of benzene sulphonyl hydrazide (trade name Genitron BSH) in 75 ml. of methyl oxitol added over the course of minutes. Work-up of the reaction mixture as described in Example 1 yielded 28 g. of crude 8:14-dihydrothebaine, M.P. 162-164" C.
• EXAMPLE 6 '31 g. of technical thebaine, 10 ml. of ethanolamine and 75 ml. of diglyme (diethylene glycol dimethyl ether) were brought to reflux temperature and 37 g. of p-toluene sulphonyl hydrazide dissolved in diglyme was added as described in Example 1. Work-up as in Example 1 yielded 28 g. of crude 8:14-dihydrothebaine, M.P. 162164 C.
• a process for the preparation of 8:14-dihydrothebaine from thebaine which comprises the step of reducing thebaine by heating it with a thermally decomposable sulphonic acid hydrazide selected from the group consisting of a monoor dicarbocyclic sulphonic acid bydrazide, an alkylated monoor dicarbocyclic sulphonic acid hydrazide, a lower alkyl sulphonic acid hydrazide, and an monocarbocyclic aryl lower alkyl sulphonic acid hydrazide.
• a thermally decomposable sulphonic acid hydrazide selected from the group consisting of a monoor dicarbocyclic sulphonic acid bydrazide, an alkylated monoor dicarbocyclic sulphonic acid hydrazide, a lower alkyl sulphonic acid hydrazide, and an monocarbocyclic aryl lower alkyl sulphonic

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

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Cited By (14)

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• 1970
  • 1970-12-11 GB GB5892670A patent/GB1317210A/en not_active Expired
• 1971
  • 1971-11-24 PL PL1971151754A patent/PL81441B1/pl unknown
  • 1971-11-30 DE DE19712159348 patent/DE2159348A1/de not_active Withdrawn
  • 1971-11-30 CA CA128,915A patent/CA958412A/en not_active Expired
  • 1971-11-30 IL IL38268A patent/IL38268A/en unknown
  • 1971-12-02 US US00204298A patent/US3812132A/en not_active Expired - Lifetime
  • 1971-12-03 AU AU36469/71A patent/AU459401B2/en not_active Expired
  • 1971-12-06 BE BE776304A patent/BE776304A/xx not_active IP Right Cessation
  • 1971-12-07 JP JP9899371A patent/JPS5511678B1/ja active Pending
  • 1971-12-07 FR FR7143867A patent/FR2117924B1/fr not_active Expired
  • 1971-12-09 YU YU03086/71A patent/YU39064B/xx unknown
  • 1971-12-09 DK DK603371AA patent/DK139974B/da unknown
  • 1971-12-09 CS CS8571A patent/CS176251B2/cs unknown
  • 1971-12-10 SE SE7115886A patent/SE388422B/sv unknown
  • 1971-12-10 HU HUMA2294A patent/HU164465B/hu unknown
  • 1971-12-10 CH CH1811571A patent/CH556340A/xx not_active IP Right Cessation
  • 1971-12-13 NL NLAANVRAGE7117082,A patent/NL175622C/xx not_active IP Right Cessation

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