Becomingjulie-yes. Only, use of butyric (aka butanoic) acid, in highly concentrated form, the glacial acid, would almost certainly lead to 6-monobutyrylmorphine, never tried it, but apparently glacial acetic acid selectively esterifies the '6 position phenolic -OH to give 6-monoacetylmorphine. Which I can only presume would follow a similar pattern using butyric acid, rather than either its anhydride, or butyryl halides other than fluoride (chloride, bromide and iodide), the iodide would likely give the highest yields out of the butyryl halides since iodine is the best leaving group out of the three (fluorine forms much stronger bonds, and whereas the other acid halides give off HCl gas, HBr or HI when they form an ester from an alcohol or phenol with acid fluorides, they are nasty in general, and HF is hideously toxic. Its actually the weakest of the simple hydrohalic acids of the formula HX where X is one of the halogens, and H is of course, hydrogen. This is because fluorine is the most electronegative of the elements, and forms the strongest covalent bonds. This combined with its steric similarity to hydrogen, makes quite often for good candidates for enzyme inhibitors, since a fluorinated substrate will generally not rearrange the C-F covalent bond in any way.
So the fluorinated compound where F replaces a hydrogen can often fit in place in the active site of an enzyme, such as for instance, the military nerve agents are generally organofluorophosphate esters, and once bound to acetylcholinesterase, which usually serves to hydrolyse acetylcholine, the neurotransmitter that controls amongst many other things, muscular contraction, when ACh binds to the neuromuscular junction, normally its hydrolysed straight away after doing its thing and initiating a muscle movement, but in the case of the fluorophosphate nerve agents for example, acetylcholinesterase cannot hydrolyse the much stronger bond that a fluorine atom makes and essentially causes these acetylcholine mimics to end up stuck in place, resulting in continuous muscular contraction, which results in at first muscular contraction then exhaustion, and first a spastic paralysis progressing to a flaccid paralysis, along with massive increases in glandular secretions. Fluoroacetate, another such nasty metabolic poison instead ends up metabolized to fluorocitrate, and enters the kreb's cycle, within mitochondria and roughly worded, throws a spanner in the works of an enzyme called aconitase responsible for a critical part of the biochemical pathway for generating ATP, adenosine triphosphate, the basic, most fundamental cellular energy 'currency', and much akin (although by a different mechanism) cyanides and azides starve the body of energy also). Because essentially, in the case of fluoroacetate/fluoroacetic acid (di- and trifluoroacetic acids are much, much much less toxic, monofluoroacetate on the other hand is lethal stuff, and extremely difficult to treat. And unfortunately, happened to be a metabolite of some of those fluoroalkylindole or fluoroalkylindazole synthetic cannabinoids, where the indole/indazole fluorinated alkyl group had an even number of carbons, it ends up as fluoroacetate, whereas before the govt started forcing careless, stupid or both, manufacturers of that kind of RC to switch from the typical 5-fluoropentyl group, which doesn't release fluoroacetate, to a 4-fluorobutyl group. Which would, resulting in a nasty as hell cumulative toxin easily on a par with some of the mid-level military nerve agents and which selectively (whilst attacking all cells that are metabolically active, and living, but doing most damage to those tissue types with the greatest metabolic energy demand. Such as brain, heart lungs etc.
Ionic inorganic fluorides such as for example, sodium or potassium fluoride are still somewhat toxic, but not in the same manner, they generally act as kidney damaging poisons if toxic. HF is a weak acid due to its strong H-F bond resulting in poor dissociation in solution, which allows it to penetrate intact skin, whereafter, the very strong affinity of fluorine for calcium ends up chelating the bodily calcium reserves, precipitating insoluble calcium fluoride, and unless treated aggressively and quickly can easily end up killing the victim.
So the choice with acyl halides, if one has any sense, is chloride, bromide or iodide. The ability to serve as a leaving group being lowest of all with fluorine and best, out of the halides, with iodine, the most easily displaced of all, which would give somewhat better yields. A base is needed with the acyl halides though, but only heating with the anhydrides. Although the latter generate an equimolar proportion of the carboxylic acid when forming a carboxylic acid ester or amide. In the case of butyric acid, it stinks, and it follows one around quite persistently too if it gets on any article of clothing, traces making for a pretty persistent vomit-like stench.
Although n-butyric anhydride itself, doesn't smell so bad as n-butyric acid, it still isn't what you'd call pleasant. But out of the lower carboxylic acid morphine diesters, the butyrate esters and pentanoic/valeric and isovaleric acid esters are the only ones I've yet to try. Aside from diformylmorphine, although given the potential for toxicity I don't trust that one enough to want to try it in the first place. Dibutyrylmorphine though is reportedly less potent than diamorphine, whereas dipropionylmorphine is significantly more potent and an awful lot longer lasting (think 15 hours or more, dose dependent, compared with 6-7 hours for morphine and heroin themselves) dipropionyl seems to be the sweet spot as far as potency, and duration of action go, and dibenzoylmorphine isn't half bad either but dibutyrylmorphine I've never yet tried. Was just curious to see if anyone here had done, because it would be easy as piss to make from morphine sulfate or hydrochloride (best in salt form when using the halides, to avoid inadvertent formation of amides as byproducts)
Quantitatively, if wikipedia is to be believed, its less potent than H, but qualitatively there is nothing to go on really. Not that I place a huge amount of trust in wikipedia articles as sole sources of information. Certainly not after reading that alpha-chloromorphide is some 10x the potency of morphine. Then trying it, only to find out that whilst it obviously possesses some Mu-opioid receptor agonist properties, given it could effectively relieve morphine withdrawal, it was absolutely nothing like anything one would think of as opioid-like in any other way, instead, being a weird-arsed psychostimulant, but in a very non-monoamine releaser/reuptake inhibitor-esque feeling manner.
It just struck me as logical to try the diester with a 1-carbon longer chain, since dipropionylmorphine beats the absolute shit out of heroin any day. Fill in the gaps so to speak, perhaps going as far as divaleroylmorphine, the dipentanoyl/diamyl ester, since n-butyryl seems from what I've read, to be about where the potency starts to drop off. Its more the qualitative than the quantitative that I find intriguing really.
![:\](https://bluelight.org/xf/BL_Images/Orig_Emoji/wrygrin.gif "wry grin :\")
