US3812132A - Reduction of thebaine - Google Patents

Reduction of thebaine Download PDF

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Publication number
US3812132A
US3812132A US00204298A US20429871A US3812132A US 3812132 A US3812132 A US 3812132A US 00204298 A US00204298 A US 00204298A US 20429871 A US20429871 A US 20429871A US 3812132 A US3812132 A US 3812132A
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US
United States
Prior art keywords
thebaine
dihydrothebaine
sulphonic acid
hydrazide
dihydrocodeinone
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 - Lifetime
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US00204298A
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English (en)
Inventor
E Grew
A Robertson
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Macfarlan Smith Ltd
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Macfarlan Smith Ltd
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Publication of US3812132A publication Critical patent/US3812132A/en
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    • 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)
US00204298A 1970-12-11 1971-12-02 Reduction of thebaine Expired - Lifetime US3812132A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB5892670 1970-12-11

Publications (1)

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US3812132A true US3812132A (en) 1974-05-21

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US00204298A Expired - Lifetime US3812132A (en) 1970-12-11 1971-12-02 Reduction of thebaine

Country Status (17)

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US (1) US3812132A (en:Method)
JP (1) JPS5511678B1 (en:Method)
AU (1) AU459401B2 (en:Method)
BE (1) BE776304A (en:Method)
CA (1) CA958412A (en:Method)
CH (1) CH556340A (en:Method)
CS (1) CS176251B2 (en:Method)
DE (1) DE2159348A1 (en:Method)
DK (1) DK139974B (en:Method)
FR (1) FR2117924B1 (en:Method)
GB (1) GB1317210A (en:Method)
HU (1) HU164465B (en:Method)
IL (1) IL38268A (en:Method)
NL (1) NL175622C (en:Method)
PL (1) PL81441B1 (en:Method)
SE (1) SE388422B (en:Method)
YU (1) YU39064B (en:Method)

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060009479A1 (en) * 2004-07-09 2006-01-12 Bailey Timothy S Process for the synthesis of hydromorphone
US20080125592A1 (en) * 2006-10-17 2008-05-29 Penick Corporation Process for preparing oxymorphone, naltrexone, and buprenorphine
US20080146601A1 (en) * 2006-12-14 2008-06-19 Johnson Matthey Public Limited Company Method for making analgesics
US20090227796A1 (en) * 2008-03-07 2009-09-10 Fist Anthony J Papaver Somniferum Strain With High Concentration Of Thebaine
US20100234600A1 (en) * 2008-05-29 2010-09-16 Fist Anthony J Papaver somniferum with high concentration of codeine
US20110071297A1 (en) * 2009-09-22 2011-03-24 Mallinckrodt Inc. Methods for Producing Hydrocodone, Hydromorphone or a Derivative Thereof
US8134002B2 (en) 2006-10-17 2012-03-13 Penick Corporation Process for preparing oxymorphone
US8921556B2 (en) 2010-06-11 2014-12-30 Rhodes Technologies Process for N-dealkylation of tertiary amines
US9108974B2 (en) 2006-10-17 2015-08-18 Penick Corporation Process for preparing oxymorphone, naltrexone, and buprenorphine
US9120800B2 (en) 2013-08-02 2015-09-01 Johnson Matthey Public Limited Company Process for the preparation of oxymorphone alkaloid and oxymorphone salts
US9127014B2 (en) 2010-06-11 2015-09-08 Rhodes Technologies Transition metal-catalyzed processes for the preparation of N-allyl compounds and use thereof
WO2015134003A1 (en) 2014-03-05 2015-09-11 Johnson Matthey Public Limited Company Processes for making hydrocodone, hydromorphone and their derivatives
US9273060B2 (en) 2014-03-05 2016-03-01 Johnson Matthey Public Limited Company Processes for making hydrocodone, hydromorphone and their derivatives
US10155771B2 (en) 2015-11-04 2018-12-18 Noramco, Inc. Selective reduction of morphinan alkaloids

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS59142770A (ja) * 1983-02-02 1984-08-16 Trio Kenwood Corp カセツトテ−プレコ−ダの駆動機構

Cited By (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060009479A1 (en) * 2004-07-09 2006-01-12 Bailey Timothy S Process for the synthesis of hydromorphone
WO2006005112A1 (en) * 2004-07-09 2006-01-19 Tasmanian Alkaloids Pty Ltd Process for the synthesis of hydromorphone
GB2429206A (en) * 2004-07-09 2007-02-21 Tasmanian Alkaloids Pty Ltd Process for the synthesis of hydromorphone
US20110118466A1 (en) * 2006-10-17 2011-05-19 Penick Corporation Process for preparing oxymorphone, naltrexone, and buprenorphine
US9108974B2 (en) 2006-10-17 2015-08-18 Penick Corporation Process for preparing oxymorphone, naltrexone, and buprenorphine
US20080125592A1 (en) * 2006-10-17 2008-05-29 Penick Corporation Process for preparing oxymorphone, naltrexone, and buprenorphine
US8357802B2 (en) 2006-10-17 2013-01-22 Penick Corporation Process for preparing oxymorphone
US8134002B2 (en) 2006-10-17 2012-03-13 Penick Corporation Process for preparing oxymorphone
US9487532B2 (en) 2006-10-17 2016-11-08 Penick Corporation Process for preparing oxymorphone, naltrexone, and buprenorphine
US7851482B2 (en) 2006-12-14 2010-12-14 Johnson Matthey Public Limited Compnay Method for making analgesics
US20080146601A1 (en) * 2006-12-14 2008-06-19 Johnson Matthey Public Limited Company Method for making analgesics
US20090227796A1 (en) * 2008-03-07 2009-09-10 Fist Anthony J Papaver Somniferum Strain With High Concentration Of Thebaine
US9131649B2 (en) 2008-03-07 2015-09-15 Tasmanian Alkaloids Pty. Ltd Papaver somniferum strain with high concentration of thebaine
US9909137B2 (en) 2008-03-07 2018-03-06 Tasmanian Alkaloids Pty. Ltd. Papaver somniferum strain with high concentration of thebaine
US10760090B2 (en) 2008-03-07 2020-09-01 Tasmanian Alkaloids Pty. Ltd. Papaver somniferum strain with high concentration of thebaine
WO2009109012A1 (en) 2008-03-07 2009-09-11 Tasmanian Alkaloids Pty. Ltd. Papaver somniferum with high concentration of thebaine
US20100234600A1 (en) * 2008-05-29 2010-09-16 Fist Anthony J Papaver somniferum with high concentration of codeine
US8541647B2 (en) 2008-05-29 2013-09-24 Tasmania Alkaloids Pty, Ltd. Papaver somniferum with high concentration of codeine
US10791691B2 (en) 2008-05-29 2020-10-06 Tasmanian Alkaloids Pty. Ltd. Papaver somniferum with high concentration of codeine
US9648815B2 (en) 2008-05-29 2017-05-16 Tasmanian Alkaloids Pty. Ltd. Papaver somniferum with high concentration of codeine
AU2010298514B2 (en) * 2009-09-22 2014-11-20 SpecGx LLC Methods for producing hydrocodone, hydromorphone or a derivative thereof
US8399671B2 (en) 2009-09-22 2013-03-19 Mallinckrodt Llc Methods for producing hydrocodone, hydromorphone or a derivative thereof
US20110071297A1 (en) * 2009-09-22 2011-03-24 Mallinckrodt Inc. Methods for Producing Hydrocodone, Hydromorphone or a Derivative Thereof
WO2011037854A3 (en) * 2009-09-22 2011-05-12 Mallinckrodt Inc. Methods for producing hydrocodone, hydromorphone or a derivative thereof
WO2011037854A2 (en) 2009-09-22 2011-03-31 Mallinckrodt Inc. Methods for producing hydrocodone, hydromorphone or a derivative thereof
US8921556B2 (en) 2010-06-11 2014-12-30 Rhodes Technologies Process for N-dealkylation of tertiary amines
US9309258B2 (en) 2010-06-11 2016-04-12 Rhodes Technologies Process for N-dealkylation of tertiary amines
US9499557B2 (en) 2010-06-11 2016-11-22 Rhodes Technologies Transition metal-catalyzed processes for the preparation of N-allyl compounds and use thereof
US9593124B2 (en) 2010-06-11 2017-03-14 Rhodes Technologies Transition metal-catalyzed processes for the preparation of N-allyl compounds and use thereof
US9624232B2 (en) 2010-06-11 2017-04-18 Rhodes Technologies Transition metal-catalyzed processes for the preparation of N-allyl compounds and use thereof
US9657030B2 (en) 2010-06-11 2017-05-23 Rhodes Technologies Transition metal-catalyzed processes for the preparation of N-allyl compounds and use thereof
US9127014B2 (en) 2010-06-11 2015-09-08 Rhodes Technologies Transition metal-catalyzed processes for the preparation of N-allyl compounds and use thereof
US9120800B2 (en) 2013-08-02 2015-09-01 Johnson Matthey Public Limited Company Process for the preparation of oxymorphone alkaloid and oxymorphone salts
US9273060B2 (en) 2014-03-05 2016-03-01 Johnson Matthey Public Limited Company Processes for making hydrocodone, hydromorphone and their derivatives
US9657028B2 (en) 2014-03-05 2017-05-23 Johnson Matthey Public Limited Company Processes for making hydrocodone, hydromorphone and their derivatives
US9657027B2 (en) 2014-03-05 2017-05-23 Johnson Matthey Public Limited Company Processes for making hydrocodone, hydromorphone and their derivatives
WO2015134003A1 (en) 2014-03-05 2015-09-11 Johnson Matthey Public Limited Company Processes for making hydrocodone, hydromorphone and their derivatives
US10155771B2 (en) 2015-11-04 2018-12-18 Noramco, Inc. Selective reduction of morphinan alkaloids

Also Published As

Publication number Publication date
BE776304A (fr) 1972-06-06
CS176251B2 (en:Method) 1977-06-30
IL38268A0 (en) 1972-01-27
GB1317210A (en) 1973-05-16
HU164465B (en:Method) 1974-02-28
YU308671A (en) 1982-06-30
PL81441B1 (en:Method) 1975-08-30
IL38268A (en) 1974-11-29
DK139974B (da) 1979-05-28
FR2117924B1 (en:Method) 1975-02-07
DE2159348A1 (de) 1972-06-15
NL175622C (nl) 1984-12-03
FR2117924A1 (en:Method) 1972-07-28
CA958412A (en) 1974-11-26
YU39064B (en) 1984-04-30
NL175622B (nl) 1984-07-02
AU3646971A (en) 1973-06-07
CH556340A (de) 1974-11-29
AU459401B2 (en) 1975-03-27
SE388422B (sv) 1976-10-04
NL7117082A (en:Method) 1972-06-13
DK139974C (en:Method) 1979-12-10
JPS5511678B1 (en:Method) 1980-03-26

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