Epinephrine
| Chemical formula | C9H13NO3 |
|---|---|
| OTP appearance | solid |
| Molar Mass(g/mol) | 183.20 |
| Density(g/cc) | 1.283 |
| Melting Point(°C) | 212 |
| Boiling Point(°C) | decomp |
| NFPA 704 |  0
0
0
|
Uses
Primary
- WHO LEM component Epinephrine
Natural occurrence
- Epinepherine occurs naturally in most animals. It is extracted from the adrenal gland, which is atop (toward the head) of the kidney.
Hazards
- Potentially toxic in overdose.
Character
The actions of epinephrine are complex, owing to its stimulation of α- and β-adrenergic receptors (or adrenoceptors, so named for their reaction to the adrenal hormones), which produce various responses, depending on the specific receptor and the tissue in which it occurs. Hence, epinephrine causes constriction in many networks of minute blood vessels but dilates the blood vessels in the skeletal muscles and the liver. In the heart, it increases the rate and force of contraction, thus increasing the output of blood and raising blood pressure. In the liver, epinephrine stimulates the breakdown of glycogen to glucose, resulting in an increase in glucose levels in the blood. It also acts to increase the level of circulating free fatty acids. The extra amounts of glucose and fatty acids can be used by the body as fuel in times of stress or danger, when increased alertness and exertion are required. Epinephrine also causes contraction of the dilator muscles of the iris in the eye, resulting in mydriasis (dilation of the pupil) and improved visual acuity. [1]
Production
Extraction
A sketch of the extraction process introduced by Takemine and used throughout the early thirties appears in The Chemistry of the Hormones[2]
Takamine's method of preparing epinephrine is, in its essential details, still the method used to this day. The minced glands are extracted with acidulated water for 5 hours at So. to so°, and the temperature is next raised to 95° for l hour to coagulate proteins. To prevent the oxidation of the active principle, Takamine used a layer of fat floating on the surface of the liquid. He also recommends the are of an inert gas like carbon dioxide. The mass is pressed and separated from the liquid portion (which contains the active principle). The residue is again treated with acidulated water, and the process is repeated. The combined extracts are concentrated in vacuo and three volumes of ethyl (or methyl) alcohol are added. The inert precipitate consists of organic and inorganic substances; this is filtered off and washed with alcohol. The filtrate is evaporated in vacuo to get rid of the alcohol, and ammonia is added until the solution is distinctly alkali.. The product is allowed to stand for several hours, yielding a yellowish-brown precipitate, which represents the crude epinephrine. This precipitate is filtered, washed with water and dried. (Takamine states in this paper that sodium hydroxide can be used in the place of ammonia, but the former has the disadvantage in that an excess of it would tend to dissolve the hormone.) To purify the material, it is dissolved in acid, and alcohol and ether are added in sufficient quantity. The precipitate is inert. The filtrate is treated with ammonia, as already described.
The same text offers a more specific acidification step by Bertrand:
A modified method of preparing epinephrine, developed by Bertrand, may now be given: 600 grams of gland, with fat removed, are finely minced and mixed with 5 grams of oxalic acid and enough 95 percent alcohol to fill brim-full a 2-litre bottle. The bottle is stoppered and shaken at intervals for two days. The proteins remain behind and the epinephrine goes into solution in the form of an oxalate. The product is filtered through cloth and pressed. The filtrate is concentrated in vacuo to remove the alcohol. Colored substances, lecithin, fat, etc., separate out. The mixture is shaken with petroleum ether, transferred to or separatory funnel, allowed to settle, and the lower layer (free from lipins) is drawn off and lead acetate added to it until precipitation is complete. (If an excess is added, add sulfuric acid-) The product is filtered, and the filtrate evaporated et meta to 200 cc. A slight excess of ammonia is added. The product is kept in a cool place not exposed to sir. The yield is 0.8 to 1.0 gram epinephrine. To purify it, the precipitate is dissolved in 2 times its weight of 10% sulfuric acid and an equal volume of alcohol is added. The mixture is filtered and the filtrate precipitated with ammonia.
And a purification step more concisely by Pauli:
For example, 12 grams of crude epinephrine are solved with 50 cc of 85 to 100 per cent alcohol containing 7 grains of oxalic acid. The product in filtered, the filtrate diluted to 100 cc, and the active substance is precipitated with ammonia. The precipitate is washed with water to get rid of the adhering ammonium oxalate. The process is repeated. The precipitate may be still further purified by precipitating its acid solution with ammonia.
In all cases, it is important to avoid oxidation, so where possible neutral gasses (such as CO2, N2, etc.) may be used to purge the system.
Synthesis
F Stoltz
First synthesized in 1906
- Combine benzene-1,2-diol with chloroacetic acid, catalyzed by POCl3, producing chloroacetyl catechol
- Combine chloroacetyl catechol with 40% methylamine in water, producing methylaminocarbonyl catechol
- Reduce methylaminocarbonyl catechol with sodium amalgam
Honors cup
In this article[3] epinephrine is synthesized in three steps from catechol, adding chloroacetic acid, phosphorus trichloride, and methylamine.
See Also
References
- ↑ Encyclopedia Britannica
- ↑ Harrow, Benjamin; Sherwin, Carl P. (1935) "The Chemistry of the Hormones" (local copy)
Sans Tache
link courtesy Indian National Agricultural Research System. - ↑ Do, Angelique
Sao‐Mai; Mitchell, Brittany; Browalsk, Jonathan "Adrenaline from mild to wild"
Honors Cup Synthetic Proposal
link courtesy UMich.