Hello again. Can anyone help me with information on what esters of testosterone are suitable for use as a pharmaceutical (i.m. injection)?
I know there is a difference between long-chain, medium-chain and short-chain esters but I don't always know which ones are suitable for human consumption and which ones are not.
I have found an esterfication procedure in a patent that can be generally adapted, as long as the boiling point of the respective carboxylic acid is well above that of water. This elimnates the need for carboxylic acid anhydrides or chlorides, such as acetic or propionic anhydride, which are often hard to get due to their use in opiate manufacture. (should the anhydride or chloride be accessible, no pyridine is necessary as is sometimes assumed, or it can be exchanged for another acid scavenger like K2CO3 or triacetoneamine. Pyridine has a lingering, sickening stench and is watched due to its role in the manufacture of some illegal drugs.)
Basically the procedure is to heat a mixture of testosterone with a molar excess of the acid around 200°C in an atmosphere free of oxygen (argon) for 3 hours. From US patent 2109400, example 5:
Equal parts of testosterone and capric acid are heated together in an atmosphere of nitrogen for 3 hours at 200 C. The mass is then taken up with ether, the ethereal solution being washed with sodium carbonate solution and water and then evaporated. The residue which crystallizes after standing for some time is re-crystallized from absolute alcohol or aqueous methyl alcohol so as to obtain the testosterone capric acid ester of melting point 55—57°C.
In quite analogous manner for example the esters of capronic acids, oenanthic acids, caprilic
acids, pelargonic acids and the like may also be obtained.
I know about the preference for long-chain esters like those made from enanthic acid and caproic acid. But what about:
benzoic acid (testosterone benzoate)
3-methylbenzoic acid
phenylpropionic acid (= hydrocinnamic acid)
(iso)valeric acid
I know that for example benzoic acid can cause allergic reactions in some people. Where can I find which esters are suitable for human consumption and which not?
Also, there is an interesting patent (US2933514) which describes the preparation of testosterone-17-chloral hemiacetal. It is basically a condensation of testosterone with chloral, whicdh has local anaesthetic properties. There is still a free -OH left so all the usual esters can be formed from it. The advantage is that irritation or initial pain on the injection site is numbed this way. The downside is that chloral is a controlled substance in many countries (was used to sedate potential victims by slipping some in their alcoholic drink, a so-called 'Mickey Finn', in the pre-WW II era), and that such a local anaesthetic effect could mask infection pain from a contaminated black market batch, I think?
Anyway it is still interesting and I attached both patents for your reading pleasure.
I know there is a difference between long-chain, medium-chain and short-chain esters but I don't always know which ones are suitable for human consumption and which ones are not.
I have found an esterfication procedure in a patent that can be generally adapted, as long as the boiling point of the respective carboxylic acid is well above that of water. This elimnates the need for carboxylic acid anhydrides or chlorides, such as acetic or propionic anhydride, which are often hard to get due to their use in opiate manufacture. (should the anhydride or chloride be accessible, no pyridine is necessary as is sometimes assumed, or it can be exchanged for another acid scavenger like K2CO3 or triacetoneamine. Pyridine has a lingering, sickening stench and is watched due to its role in the manufacture of some illegal drugs.)
Basically the procedure is to heat a mixture of testosterone with a molar excess of the acid around 200°C in an atmosphere free of oxygen (argon) for 3 hours. From US patent 2109400, example 5:
Equal parts of testosterone and capric acid are heated together in an atmosphere of nitrogen for 3 hours at 200 C. The mass is then taken up with ether, the ethereal solution being washed with sodium carbonate solution and water and then evaporated. The residue which crystallizes after standing for some time is re-crystallized from absolute alcohol or aqueous methyl alcohol so as to obtain the testosterone capric acid ester of melting point 55—57°C.
In quite analogous manner for example the esters of capronic acids, oenanthic acids, caprilic
acids, pelargonic acids and the like may also be obtained.
I know about the preference for long-chain esters like those made from enanthic acid and caproic acid. But what about:
benzoic acid (testosterone benzoate)
3-methylbenzoic acid
phenylpropionic acid (= hydrocinnamic acid)
(iso)valeric acid
I know that for example benzoic acid can cause allergic reactions in some people. Where can I find which esters are suitable for human consumption and which not?
Also, there is an interesting patent (US2933514) which describes the preparation of testosterone-17-chloral hemiacetal. It is basically a condensation of testosterone with chloral, whicdh has local anaesthetic properties. There is still a free -OH left so all the usual esters can be formed from it. The advantage is that irritation or initial pain on the injection site is numbed this way. The downside is that chloral is a controlled substance in many countries (was used to sedate potential victims by slipping some in their alcoholic drink, a so-called 'Mickey Finn', in the pre-WW II era), and that such a local anaesthetic effect could mask infection pain from a contaminated black market batch, I think?
Anyway it is still interesting and I attached both patents for your reading pleasure.
