LSD and Chlorine; Mechanisms of nucleophilic addition
Psychadelic_Paisly, I realise you probably understand much of this already, but to hopefully broaden the general reader understanding, I’ve started with some pretty basic stuff. Although it might not initially seem like a difficult task, it has proved to be quite daunting, as to grasp it properly, it is necessary to have an understanding of nucleophilic addition chemistry, and more importantly, the effect of substitutions on rates of addition. All pretty deep stuff. So I’ll take it as far as I dare. Maybe Biscuit can fill in the gaps, and better still, pull me up on anything incorrectly or badly explained. Smileyfish may like to correct or expand on Chlorine in tap water.
Here goes….
Chlorine in Tap Water
Chlorine is a particularly reactive element, often more reactive than the other halogens including fluorine (try sticking a fluoride ion on a benzene ring). The reactivity of the many
Chlorine reactive species’ is why most harmful bacteria present in our drinking water catchments, reservoirs and dams, are killed before the water reaches us. Chlorine in tap water is also the reason some 5,000 or more Americans die from cancer every year, although many more would die without it. As it very soluble, chlorine gas is usually bubbled through water. Free chlorine can also be achieved by adding hypochlorite/ate salts.
Whether chlorination is the principle means of water purification, or is employed as a support for ozone treatment (as with our local tap water), the idea is to add (slightly) more chlorine than is considered necessary. Another means of chlorination uses monochloroamines, and while these may be less reactive towards LSD
[questionable], some chlorine will be produced via enzymatic breakdown resulting in similar reactions as shown below.
One would then perhaps expect chlorine in tap water to be predominately made up of dissolved chlorine gas as Cl2, and Cl- ( chloride ions). There will however, also be some free radical chlorine (Cl*). In reacting with organic materials in the presence of other dissolved species, free radicals will produce other reactive species, too numerous to list. In the presence of LSD or a similar molecule of relative fragility, any of the resulting reactions with free radicals would effectively destroy the molecule.
Nucleophilic Addition & Free Radicals
When learning double bond addition chemistry, it is usual to describe the actions of halogens on the ethylene molecule ( CH2=CH2 ). Different mechanisms exist for nucleophilic attack when chlorine ( & Bromine & sometimes Iodine) exists either as a gas (Cl2), as the chloride ion (Cl-) (present as hydrochloric acid H+Cl-), and as a free radical (Cl*). If addition across a double bond results in a mono-halo-compound, Markivnokov orientation usually occurs which says the halogen will bond to the
most substituted carbon. Radical addition however, is non-Markivnokov, resulting in the halogen attaching to the least substituted carbon. Relating this to the susceptible double bond of LSD,
position 9 is the least substituted of the two.
Free radicals are often produced by the action of UV (sunlight) on water containing dissolved chlorine, but small amounts are produced with seemingly no such energy source. To prevent Cl* forming in the lab, special reaction conditions are usually employed. During the formation of Cl- free ions in tap water purification, some free radicals would also be produced. These may destroy several molecules before forming more stable Chloro-LSD compounds. Other parts of the LSD molecule are also susceptible to attack by free radicals.
Susceptibility of LSD's weak double bond to nucleophilic attack
The double bond on the LSD molecule (across positions 9 & 10) differs somewhat from the ethylene molecule. This has to do with electron densities, conjugation, and other effects from bonded and neighboring groups (an in-depth look perhaps being a bit beyond the scope of this explanation /hypothesis).
This double bond (across positions 9 & 10) is
very fragile because of differences in electron density across the pi bonds, due among other things to the effects of substituted groups on each carbon (9 & 10).
When exposed to tap water, the relative concentrations of each substance present (Chlorine and LSD) ultimately equates to using a molar excess of Chlorine in the lab.
Molecular weights and the destructive relationship of chlorine and LSD
The amounts of Chlorine present in tap water should be no more than 5mg/L. 10 mL therefore contains a possible 0.05mg or 50ug of Cl2 (or Cl-) At first glance it doesn't seem that much, with reason saying a large drop (~ 100uL) of water contains a miniscule 0.5ug
To get an initial idea of how much this actually represents, we look at what reacts with what. We are not concerned with direct weight for weight relationships, but rather in the
molar relationship of the substances. If an ideal chemical reaction states:
Compound A + Compound B = Compound C
To a chemist, this implies 1 mole of A reacts with one mole of B to produce 1 mole of C. It
does not say 1 gram of A + 1 gram of B = 1 gram of C.
Atomic weights (found on most periodic tables) are added together for each element present, to give the
molecular weight = to 1 mole of a compound.
Example 1: 1 mole of pure water equals approximately 18 grams
H = 1.0079g
O = 15.999g
therefore H2O = ~18, which means 1 mole of water is ~18g.
Of course it’s possible to have far less than 1 mole of a substance, but if conditions exist so that substance A reacts mole for mole with substance B, it only takes a corresponding amount of the substance B (
in moles) to potentially alter all of the substance A.
Example 2: How 50ug of Chlorine "equals" 235ug of LSD
1 mole of Chlorine (Cl2) = ~70.9g (also = to 2 x 35.45g of Cl-)
1 mole of LSD = 323.44g,
50ug of Chlorine = 0.00005g / 70.90g = 7.05 E-07 moles
50ug of LSD = 0.00005g/ 323.44g = 1.50E-07 moles
Therefore, on a molar basis, if 1 mole of chlorine reacts with 1 mole of LSD, expressing that as a weight for weight value means 1 gram of chlorine would destroy 4.7 grams of LSD (from above; 7.05 / 1.5 = 4.7)
Referring to Reactions in 1,2,3 and 4 listed below
In this way, 1 mole of LSD can react with 1 mole of chlorine as Cl2. But as reaction 3 demonstrates, in the presence of water the reaction goes further, releasing 1 chlorine ion, which may in turn react with another LSD molecule via reaction 2
In the above reasoning, it is assumed 1 mole of chlorine will react with 1 mole of LSD. This means 50ug of Cl2 can destroy 235ug of LSD. But if a chloride ion was to be generated each time, this could effectively mean 470ug of LSD may be destroyed by 50ug of Chlorine. Unfortunately, it does not stop there. This is merely one reaction sequence which may occur, and it is less severe by far than the free radical mechanism of Reaction 4 (below).
Example 3; Typical reactions involving LSD and Chlorine
Representative of many similar reactions, any of the following 4 examples will result in the de-activation of LSD’s psychotropic properties.
Reaction:
- LSD + Cl2 = dichloro-LSD
- LSD + Cl- = chloro-LSD
- LSD + Cl2 + H2O = halohydrin-LSD + H+Cl- (see diagram 1 below)
- LSD + Cl* = Chloro-LSD* + HCl => Cl2 + Chloro-LSD* =Cl* + Chloro-LSD. Repeat over and over.
These steps in Reaction 4 should be looked upon as likely first steps rather than a beginning to end fate of LSD in the presence of a Chlorine radical. Other rearrangements, intra and intermolecular reactions would also occur over time, possibly producing structures only remotely similar to that of the original LSD molecule.
Diagram 1: Proposed mechanisms involved in Reaction 3:
Adapted from "Mechanism in Organic Chemistry" by Peter Sykes & "Organic Chemistry" by John McMurry