Transformation en dihydrocodeine à porté de cuisine...

Bonjour à tous
Je me tourne vers vous aujourd'hui car je tombe sur cette étude.
Je suis traité a haut dosage de Dicodin. Mais je possède également des sirops codéine. Et a lire ce que veut dire ce compte rendu, la codéine 5 minutes à 450Wat au micro onde et hop une transformation parfaite en DHCodeine se produit.

Pouvez vous m'aider à dechiffrer cette étude parce que ça me paraît trop simple, trop facile ou bien en réalité trop beau.

Voici le texte pdf original en ang. Mais.je peux vous le poster en fr si besoin

International Scholarly Research Network
ISRN Organic Chemistry
Volume 2012, Article ID 104975, 4 pages
doi:10.5402/2012/104975

Research Article
Microwave-Assisted Hydrogenation of Codeine in Aqueous Media
F. Taktak1 and I. Bulduk2

Correspondence should be addressed to F. Taktak, fulya.taktak@usak.edu.tr

Received 8 August 2012; Accepted 15 September 2012

Academic Editors: F. V. Gonzalez and F. L. Van Delft

Copyright © 2012 F. Taktak and I. Bulduk. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

An e?cient one-pot microwave-assisted hydrogenation of codeine was achieved in aqueous solution. This technique is simple, fast, environmentally friendly, and highly e?cient. Structure of produced dihydrocodeine was approved by using FT-IR, 1H NMR, 13C NMR, EIMS, and elemental analysis technique. Its purity analysis was performed by using HPLC and assay analysis was performed by using potentiometric titration methods.

1. Introduction

Dihydrocodeine is a semisynthetic alkaloid that has preven­tive e?ects of shortness of breath and cough, as well as used extensively in killing postoperative pain [1]. Importance of dihydrocodeine is increasing day by day as second step of the “analgesic ladder” proposed for the treatment of cancer pain [2–4]. By extending the duration of action of the drug, since dihydrocodeine became available as a slow-release preparation, in this regard, it has begun to replace codeine [5]. Dihydrocodeine is also an important intermediate used in synthesis of other alkaloids such as hydrocodone [6].

A number of methods have been reported to pre­pare dihydrocodeine. Grew and coworkers have prepared dihydrocodeine by hydrogenation of hydrocodone [7, 8]. However, when compared with the hydrogenation process from codeine, additional steps are incorporated into the process and this ultimately increases the cost for obtaining dihydrocodeine. For hydrogenation of codeine palladium supported on carbon, catalysts are generally studied [6, 9]. In these methods, generally there is a need for excessive amounts of organic solvent for hydrogenation these pro­cesses bear risks in terms of health as well as causing envi­ronmental pollution. Therefore, Rapoport and Lithotworik used water as a solvent in the hydrogenation process of codeine [10, 11]. Disadvantages of some of these methods are a number of side reactions di?cult to control, undesirable side products, long reaction times, and necessity of using a deactivating agent which is connected to the surface of catalytic metal that can minimize isomerisation side reactions of codeine. Microwave-assisted organic synthesis is an invaluable technology for drug synthesis because it often reduces reaction times, typically from days or hours to minutes or even seconds [12–14]. On the other hand, the use of microwave irradiation to accelerate catalytic reactions can be used to obtain good results from low-yielding reactions [15, 16]. With the employment of microwaves in metal catalysed reaction are reduced other unwanted side reactions [17–19].

Here, we describe the microwave-assisted synthesis of dihydrocodeine, which achieved reductions in reaction times, higher yields, and cleaner reactions than for the previously reported synthetic processes. Dihydrocodeine was obtained in purity suitable for use in pharmacopy (99.80%) in high e?ciency (98%) without using any deactivating agent and using metal catalyst in lower rate.

2. Results and Discussion
Synthesis of Dihydrocodeine. Synthesis of the dihy-drocodeine which is a semi-synthetic opioid was achieved under microwave irradiation out of codeine as outlined in Scheme 1. In this study, an extremely simple, inexpensive,

Scheme 1: Hydrogenation of codeine to dihydrocodeine.

and highly e?cient and noncomplex method has been reported. In addition, white crystalline dihydrocodeine in pharmacopical purity is easily obtained alkalinizing the solution environment. Catalyst ratio used is very low when compared with values reported so far; any deactivating agent required to minimize side reactions in reaction environment was not used in these study. Catalyst amount used in selected reaction conditions was determined optimally, the highest e?ciency (98%) reported so far in this reaction conditions was obtained, as well as formation of side reactions was sig­ni?cantly eliminated and product in pharmacopy standards was obtained.

Optimization of Reaction Conditions. In ordertodeter-mine optimized conditions for the hydrogenation under microwave irradiation, codeine was exposed to di?erent reaction variables. The e?ect of temperature, reaction time, and microwave power on hydrogenation yield was studied and the initial hydrogen pressure and catalyst ratio ?xed as 5 psi and 1% (Pt/C), respectively, in the following experi­ments. Fixing reaction temperature and time to 20?Cand 5 min, respectively, the e?ect of microwave power on yield of dihydrocodeine was studied. Dihydrocodeine conversion increased from 60 to 98% as microwave power increased from 250 to 450 W, as exhibited in Table 1. Keeping reaction temperature and microwave power to 20?C and 450 W, respectively, the e?ect of reaction time on the yield of dihydrocodeine was determined. Table 1 indicated that the yield of dihydrocodeine slightly decreased as the irridation time was increased from 5 to 10 min. On the other hand, when the microwave power was set as 350 W, the yield of dihydrocodeine increased as the reaction time was increased from 5 to 10 min. The e?ect of reaction temperature on dihydrocodeine conversion was investigated. The microwave power and reaction time were set as 450 W and 5 min, respectively. When the temperature was increased from 20 to 40?C, hydrogenation yield decreased signi?cantly. This result was attributed to the fact that side reactions were such as isomerisation of codeine to hydrocodone and cleavage of 4, 5-epoxymorphinane ring of codeine to form dihydrothebainone overly induced at high temperature [11].

Consequently, 20?C, 450 W, and 5 min reaction time are determined as the best conditions in this process. When the temperature and reaction time increased, product yield decreased due to more induced side-reactions. Nevertheless, the reaction e?ciency was highly microwave oven power dependent.

Purity Analysis of Dihydrocodeine. The mV titration curve of this agent is shown in Figure 1. Potentiometric assay showed that dihydrocodeine product conforms to the stated limit as required by the BP [20]. Measurements were repeated ?ve times and the percent purity of dihydrocodeine was calculated as 100.3 on average.

The well-exhibited HPLC chromatogram of dihy-drocodeine was shown in Figure 2. HPLC of the product revealed the presence of a single peak with a Rt of 13.666 min. The chromatographic purity of puri?ed dihydrocodeine was 99.80%.

Finally, it was potentiometrically and chromatographi-cally determined that dihydrocodeine product obtained in the study is in pharmacopy standards. This value complies with the values given in o?cial documents [20].

3. Conclusions

Microwave-assisted preparation procedure stated in this study for dihydrocodeine synthesis o?ers reduction in the reaction time, operation simplicity, cleaner reaction, easy work-up, and improved yields. All spectroscopic analysis con?rmed the proposed structure of this compound.


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H2O

Dernière modification par pierre (27 avril 2021 à  21:19)