Sei sulla pagina 1di 10

LYSERGIC ACID DIETHYLAMIDE (LSD) SYNTHESES

from "Recreational Drugs" by Professor Buzz

INTRODUCTION
LSD is, without a doubt, the king of hallucinogens. t is rather difficult to make by total synthesis, but with the right starting materials !lysergic acid, ergotamine" it is as easy to #roduce as your a$erage %&' or am#hetamine. call it the king because of the awesome #otency, the usual hallucinogenic dose being about ()) to *)) micrograms orally. %he am#hetamine D+, !S%P", which is ()) times more #owerful than mescaline, re-uires a dose of . milligrams. %his gi$es one gram of LSD the #otential to contain *,))) to (),))) doses. /ith an a$erage of about 0,))) doses #er gram, the street $alue !based on 1. a hit" of one gram of LSD is 12),))).

LSD SYNTHESIS
3s with the rest of this book, will deal only with the synthetic manufacture of drugs !LSD included". f you want to grow the ergot alkaloids that begin the total synthesis of LSD, then you will ha$e to go to the ,erck nde4 and look u# the references to the o#eration. ,ichael 5. Smith6s book, Psychedelic 'hemistry, has a section on growing 'la$ice#s #ur#urea, which yield ergot com#ounds. %his section is $ery com#lete and informati$e, but think that you should also look u# the dangers of growing this fungus before doing it, as it causes a ty#e of gangrene that can kill you !not to mention making your arms and legs fall off" u#on contamination of your body. 3s ,r. Smith6s book states, this fungus is $ery tem#eramental, hard to obtain, e$en harder to grow and diffficult to work with. Smith6s book gi$es many references and many formulas that you will not see here, but which are of great interest in the making of all hallucinogens !not 7ust LSD". %his does not make my book incom#lete. +n the contrary, ha$e gi$en more than enough information to make e$ery ma7or ty#e of drug. ,y book is not intended to cut in on Smith6s book sales. t is intended to gi$e you information and formulas that Smith6s book lacks. /here he gi$es many different ty#es of formulas, gi$e only the fast, sim#le and high yielding formulas. 3lso, you will not see the same formula in both his and my book, unless it is a general method and not s#ecific. /hat his book lacks, my book gi$es !e-ui#ment, methods, basic chemistry, a wider $ariety of ty#es of different classes of drugs, glossary terms, easier to understand wordage, how to buy and make #recursors, etc.". /hat my book lacks, his book gi$es !more $ariety of hallucinogenic formulas, culti$ation of #ot and ergot, tests for acti$ity, etc.". feel it would be a good idea to buy his book and try some of these harder formulas after learning the basics and #racticing some of the formulas from my book, for com#lete understanding first. 8orgi$e me for wandering from the sub7ect of LSD synthesis. 3s this first cha#ter of formulas is for #sychedelics, felt it necessary to e4#lain the difference of the only other book of this ty#e. f you are shar#, and ha$e carefully read my cha#ter on buying #recursors, you should be able to get lysergic acid from a su##lier. Be warned, that the D93 must be informed of the #urchase by the su##lier, according to laws re-uiring them to do so. Lysergic acid can be made. 8ollowing is the general method to gi$e you a $ery good idea of the #rocedure and chemicals in$ol$ed. Synthesis of Lysergic Acid By reacting :;benzoyl;2;!B;carbo4yethyl";dihydroindole !see JCS, 3158 (1931) for the #re#aration of this com#ound" with thionyl chloride, followed by aluminum chloride gi$es (;benzoyl;.;keto; (,<,<a,2,*,.;he4ahydrobenzindole. %his is then brominated to gi$e the *;bromo;deri$ati$e, which is con$erted to the ketol;ketone by reacting with methylamine acetone ethylene ketol. %his is then hydrolized by acid to yield the diketone and treated with sodium metho4ide to con$ert it to the tetracyclic ketone. 3cetylate and reduce this ketone with sodium borohydride to get the alcohol, which is con$erted to the hydrochloride form, as usual. %he abo$e hydrochloride is treated with thionyl chloride in li-uid sulfur dio4ide, to #roduce an amor#hous chloride hydro chloride, which is con$erted to the nitrile with sodium cyanide in li-uid

hydrogen cyanide. ,ethanolysis then gi$es the ester of the nitrile. 3lkaline hydrolysis of this last com#ound, followed by catalytic dehydrogenation in water using a deacti$ated Raney :ickle catalyst !see =+'. (2, *.. (>*?" gi$es dl;lysergic acid.

TOTAL SYNTHESIS OF LYSERGIC ACID


%his is the easiest way to totally synthesize lysergic acid. %here are other ways, but after re$iewing other methods, found this to be su#erior. t is -uite com#licated and it takes good modern e-ui#ment. JACS, 78, 3087 (1956). 2; ndole#ro#ionic acid, >*.. g !).. mole" is dissol$ed in 0)) ml of water containing <) g of :a+&. %he solution is mi4ed with ()) g of Raney :ickle catalyst and hydrogenated at room tem# in a steel bomb at about 2,.)) #si until the u#take of hydrogen sto#s !about <);2) hours". 8ilter off the catalyst and wash it with a little water to remo$e the #roduct that is clinging to it. 3dd ?. ml of concd &'l acid to the filtrate, and cool. f your reduction is incom#lete, you will now ha$e unreacted starting material se#arate, and this must be remo$ed by filtration. Benzoylate the filtrate !the Schotten and Baumann method is #referable", using <() ml of (< : :a+& (?) ml of benzoyl chloride. @ee# the solution alkaline throughout the benzoylation, and kee# the tem# below *)A' by cooling. /hen the benzoyl chloride is fully reacted, the reaction mi4ture is cooled and acidified with 2)) ml of &'l acid. 8ilter the crude #roduct by filtration, wash with water, and e4tract with four ( liter #ortions of hot water. Se#arate, and crystallize the resulting syru#y #roduct from a few $olumes of methanol. 8ilter and wash with a little cold methanol to get a little o$er ()) g that melts at (.(;(.2A. %his is l;Benzoyl;2;beta;carbo4yethyl; <,2;dihydroindole. %his can be #urchased to eliminate this ste#. (;Benzoyl;.;keto;(,<,<a,2,*,.,;he4ahydrobenzindole. ((? g of the abo$e #roduct !(;benzoyl;2;B; carbo4yethyl;<,2;dihydroindole" is mi4ed with <)) ml of #ure thionyl chloride. %his solution is allowed to stand for 2) min, then it is warmed gently for (.;<( min on a steam bath. 94cess thionyl chloride is com#letely e$a#orated with the tem# maintained between <<;<0A' in $acuo. %he crude acid chloride is dissol$ed in dry carbon disulfate. %his solution is added, in a thin stream, to a well stirred sus#ension of <*) g of aluminum chloride in (B.) ml of carbon disulfate in a .,))) cc flask. :oteC this must be done under a fume hood. 3 com#le4 will se#arate and bog down the stirring de$ice. &eat this mi4ture under reflu4 with stirring for ( hour. Decom#ose this mi4ture by adding .)) g of ice, <.) ml of concd &'l acid, and .)) ml of water, all while good stirring is continued. 'ooling of this o#eration is affected by #eriodic distillation of the carbon disulfate in $acuo. 3fter the decom#osition is com#lete, any remaining carbon disulfate is remo$ed com#letely in $acuo, and the #roduct is e4tracted with < liters of benzene. %he e4tract is washed well with .)) ml of < : :a+& in three #ortions, and then with water. Dry !with the usual magnesium sulfate", and e$a#orate to a small $olume in $acuo. 3dd this small $olume to se$eral #ortions of ether to get the ketone to crystallize !add slowly", and filter, then wash with ether to get ?. g of #ure title #roduct, m#C (*0;(*BA'. (;Benzoyl;*;bromo;.;keto;(,<,<a,2,*,.;he4ahydrobenzindole. 3 solution of the abo$e indole !2). g" in <,<)) ml of glacial acetic acid is warmed to *)A'. /hile the reaction is illuminated with a <.) watt bulb, 2.< g of #yridine hydrobromide #erbromide is added in #ortions, o$er . min with shaking. %he solution is then heated to 0)A and is held between there and ..A' for 2) min. %reat the mi4ture with carbon, and e$a#orate to a small $olume in $acuo. %he residue is taken u# with <,<)) ml of chloroform, and wash this solution with se$eral #ortions of water, dry as abo$e, and concentrate in $acuo. 'rystallize the residue from <,<)) ml of .)D acetic acid and .)D ether to get <B) g of title #roduct that melts at (?)..;(?(..A'. 3nother cro# can be obtained from concentrating the fltrates. EieldC 2) g of less #ure #roduct. (;Benzoyl;<,<a,2,*;tetrahydro;*;methyl;<;methyl;(,2;dio4olan;<;yl;methyl;aminobenzindol;.; !(&"one. 3 solution of the last indole #roduct abo$e !<B) g" and 2)B g of methylaminoacetone ethylene ketol in *,.)) ml of dry benzene is reflu4ed for <( hours under a slow stream of nitrogen. %he mi4ture is cooled and (.( g of methylaminoacetone ethylene ketol hydrobromide is filtered off. %he filtrate is washed with ice water, then e4tracted with <.. liters of cold dilute &'l acid containing (.) ml of the concd acid. %he acid e4tracts are immediately added to an e4cess of ice cold dilute :a+&. 94tract with ( (iter of chloroform, dry o$er magnesium sulfate, treat with carbon and concentrate by e$a#oration in $acuo. %he residual ketol;ketone is crystallized from acetone to yield <<) g, m#C (2.;(20A'.

.;@eto;*;:;methyl;:;acetonylamino;(,<,<a,2,*,.;he4ahydrobenzindole. <) g of the abo$e #roduct is dissol$ed in a mi4ture of <.) ml of concd &'l acid and <.) ml of water, and the solution is ke#t under nitrogen for . days at 2BA. 'ool the mi4ture, treat with carbon, filter, and concentrate the filtrate in $acuo to a small $olume. %reat the residue with an e4cess of sodium bicarbonate, e4tract with cold chloroform, and remo$e the chloroform by e$a#oration in $acuo at room tem#. %he crude diketone is #owdered, slurried with B. ml of benzene;ether, and filtered. EieldC >.? g, m#C ().; ()BA'. >;keto;B;methyl;*,.,.a,0,0a,B,?,>;octahydroindolo;!*,2"iso-uinoline. <. g of the abo$e #roduct is mi4ed with ..) ml of absolute ethanol. Stir this mi4ture under nitrogen and cool to ;(.A with an e4ternal freezing mi4ture. Sodium metho4ide is added !(B g" and the mi4ture is stirred for () min at ;() to ;(<A. 'ool to ;<.A, and the #roduct is filtered and washed !while still in the funnel" with cold ethanol and ether. /ithout e4#osure to air the crude ketone is immediately slurried with a little ice water and filtered. /ash with ice water, ethanol, then ether !all cold" to yield (0 g of #roduct melting at (*.;(*BA. *;3cetyl;>;keto;B;methyl;*,.,.a,0,0a,B,?,>;octahydroindolo;*,2;-uinoline. <* g of the last #roduct is added to ?) ml of cold acetic anhydride. %he mi4ture is held at <.A for about . min, then thoroughly cooled, filtered, and the #roduct !a solid" washed with ether to yield <).. g, m#C (0>; (B)A. 3 second cro# is obtained by concentrating the mother li-uor by e$a#oration. 3 mi4ture of the last #roduct !(.) g" and () g of #alladium carbon !.D", in 2. ml of 4ylene, is heated under reflu4 for * hours. %he catalyst is filtered and e4tracted with hot methanol and chloroform. %he combined e4tract filtrates and the initial filtrate are combined and e$a#orated in $acuo. %he residue is recrystallized from water to gi$e ).0 g of a monohydrate #roduct that melts at <..;<.0A. %his #roduct is called *;acetyl;*,.,.a,0;tetrahydro;>;hydro4y;B;methylindolo;!*,2fg"; -uinolinium hydro4ide betaine. *;3cetyl;>;hydro4y;B;methyl;*,.,.a,0,B,?,>,();octahydroindolo;!*,2fg";-uinoline. ( g of the abo$e betaine in a mi4ture of <) ml of ethanol and . ml of water, is treated with ).)? g of sodium borohydride, and this solution is reflu4ed for () min and ke#t at <.A for ( hour after the reflu4 is finished. %he sol$ent is distilled off, and the residue is taken u# in a mi4ture of chloroform and water. %he chloroform solution is se#arated, dried as abo$e, and then the sol$ent is distilled off. %he residue is recrystallized from a nitromethane;ethyl acetate mi4ture to yield ).< g !<(D", m# (>2;(>0A. :ot only is this a small scale, but it is a #oor yield, re-uiring you to #erform it se$eral times to get enough #roduct to #erform the ne4t ste#. /hen you ha$e more than enough, con$ert the #roduct into its hydrochloride form by dissol$ing in dry methanol and #reci#itating with dry hydrogen chloride. *;acetyl;>;chloro;B;methyl;*,.,.a,0,0a,B,?,>;octahydroindolo;!*,2fg";-uinoline hydrochloride. 2.( g of the abo$e #roduct in its hydrochloride form is dissol$ed in B. ml of li-uid sulfur dio4ide contained in a glass lined, high #ressure bomb, or autocla$e. %hionyl chloride !(.< ml" is added and the $essel is sealed and ke#t at <.A for 0 hours. 5ent the $essel carefully and remo$e the mi4ture. 9$a#orate the sulfur dio4ide while kee#ing the $olume of the solution constant by the slow addition of dry ether. %he amor#hous chloro hydrochloride is filtered, washed with ether !dry" and dried by e$a#orating in $acuo to gi$e 2.. g of #roduct, m#C(2);(2.A. *;3cetyl;>;cyano;B;methyl;*,.,.a,0,0a,B,?,>;octahydroindolo;!*,2fg";-uinoline. *) g of dry, #owdered sodium cyanide, is added to ice cold li-uid hydrogen cyanide and stirred gently with ice bath cooling. S#eed u# the stirring, continue the cooling, and add B.. g of the amor#hous #roduct directly abo$e. 'ontinue stirring for 2) min, then the hydrogen cyanide is distilled under enough reduced #ressure to kee# it coming o$er the condenser at a tem# below ();(<A. %he residue is mi4ed with chloroform and ice water, and the resulting mi4ture is filtered. %he organic layer of the filtrate is se#arated and the a-ueous layer is e4tracted with two se#arate #ortions of chloroform. %he combined e4tracts !this would include the se#arated chloroform, as usual" are dried o$er magnesium sulfate, decolorized, and the sol$ent remo$ed by distillation in $acuo. 'rystallize the #roduct in ethyl acetate. EieldC 2.2 g, m#C (B2;(B*A. Recrystallize again for e4tra #urity. >;'arbometho4y;B;methyl;*,.,.a,0,0a,B,?,>;octahydroindolo;!*,2fg";-uinoline. ( g of the last #roduct is mi4ed with (. ml of methanol and ).<. ml of water. /ith e4ternal !ice bath" cooling add < ml of concd sulfuric acid slowly. Seal this solution in a high #ressure bomb with a glass liner !or

in a glass tube taking safety #recautions in case of e4#losion" with a nitrogen atmos#here, and heat at ())A for <2;<* hours. :oteC ha$e seen a big #ressure cooker !like gramma cans #eas with" work for some of these bomb #rocedures. do not recommend it, but here is how to do it right, if you feel you must. Fse only the great big hea$y duty models, in e4cellent condition, set the #o# off !relief $al$e" for near ma4imum #ositionG ne$er, e$er tam#er or modify this $al$e to get more #ressure. Put the #roduct in a glass beaker, #ut it in the cooker, flush with nitrogen, heat and stay in a different house during the reaction. 'arefully turn off heat, notice or record #ressure gauge after time has ela#sed. /ait until #ressure dro#s noticeably, bleed off remaining #ressure and get #roduct. %reat the mi4ture with decolorizing carbon and then e$a#orate in $acuo to () ml. Pour onto a mi4ture of 2) ml of chloroform, ice, and () g of sodium bicarbonate. Se#arate the chloroform layer, and e4tract the a-ueous #hase with three () ml #ortions of chloroform. %he combined chloroforms are dried, e$a#orated to dryness in $acuo, and the #roduct is crystallized from benzene to gi$e (H< g of #roduct that melts at (.>;(0)A. Eou may #urify more by recrystallizing from ethyl acetate. %his is not $ery much #roduct. 3s with the #rocedure * ste#s back, you will ha$e to #erform this ste# o$er and o$er. f you try to double or tri#le the amounts gi$en, you may get more #roduct, but you will hurt the yield. dl;Lysergic acid. 2.> g of the last #roduct is mi4ed with B? ml of (..D #otassium hydro4ide solution. Reflu4 for 2) min under nitrogen. ?.. g of hydrogen sodium arsonate, and Raney :ickle !(0 g wet", that has #re$iously been deacti$ated by boiling in 4ylene sus#ension !see =+', *.. !(>*?" to deacti$ate", is added and the mi4ture is reflu4ed and stirred under a nitrogen atmos#here for <) hours. %he solution is treated with carbon, and the crude lysergic acid is #reci#itated by neutralization to #& ..0, and then filter it off and wash with water. EieldC (.)* g. 3 second cro# is obtained in the usual manner !).(. g". Purify by dissol$ing in dilute ammonium hydro4ide, treat with decolorizing carbon, and re#reci#itate with carbon dio4ide to get a m# of <*<; <*2A. Eou may be able to get an analytical or laboratory consultant to make one of these #roducts near the final ste#, thereby eliminating the need to go through all of the ste#s as described. %his will sa$e you much time, but as these #eo#le are highly trained, their time will be costly. Lysergic acid can be made from many ergot deri$ati$es by hydrolysis of these com#ounds. %hese com#ounds include ergono$ine, ergotamine, ergokry#tine, ergosine, methysergide, ergine, and a few others. %otal synthesis of these com#ounds is im#ractical, as lysergic acid is made before the alkaloid. Eou could sto# the o#eration as soon as you reach lysergic acid, otherwise you will ha$e to hydrolyze as described below. %here are many analogs of these alkaloids that end with the ine suffi4. %hese are not as sus#icious as the former because they lead to an inacti$e iso;LSD. %hey will look like thisC the ergotamine isomer I ergotaminine, the ergono$ine isomer I ergono$inine, etc. %hese analogs are easily con$erted to the acti$e forms or they may be used e4actly as the non;iso $ersions to gi$e the iso;LSD, which is con$erted $ery easily to LSD as also described below.

LYSERGIC ACID FROM ERGOT ALKALOIDS.


Dissol$e <) g of the alkaloid !use any of the abo$e or one of its isomers or a combination" in <)) ml of ( , methanolic @+& solution !this is made by dissol$ing (* g of @+& in <.) ml of dry methanol" in a ( (iter e$a#oration flask !hea$y walled construction". 9$a#orate the methanol off. 3dd *)) ml of ?D a-ueous !water" @+& solution to the residue and boil for one hour under a slow stream of nitrogen that is allowed to flow through a small orifice for e4hausting #ur#oses. 'ool, acidify with dilute sulfuric acid, and shake in a se#aratory funnel with ( (iter of dry ether. Se#arate the lower a-ueous layer and filter it with $acuum assist. /ash the #reci#itate with <) ml of dilute sulfuric acid. %his is lysergic acidG store as described later in this cha#ter. %here remains a small amount of lysergic acid in the filtrate solution. Remo$e it by basifying the solution with sodium carbonate, and then bubbling '+< through it. 8ilter it off and add it to the other lysergic acid. :ow you will need to #reci#itate the iso;lysergic acid out and con$ert it. f you did not use any iso;alkaloid then you will ha$e $ery little iso;lysergic acid, but it is still worth con$erting. f you used iso;alkaloid, this is a must. Preci#itate the iso;lysergic acid by adding some ()D &:+2, filter, add more #ortions until no more #reci#itate forms. 'on$ert it to lysergic acid by adding 2 ml of ()D @+& #er e$ery ).( g of iso;

lysergic acid, heat on steam bath for ( hour under a nitrogen atmos#here. Preci#itate the changed lysergic acid by acidifying with glacial acetic acid. %he total yield of this entire o#eration !including the iso change" is a little under () grams. 3s stated earlier, you may use only iso;alkaloid in the hydrolysis ste# abo$e to get iso;lysergic acid which can be used in the synthesis of LSD to get iso; LSD, which can be changed to the acti$e LSD as described later. :oteC iso;LSD is not acti$e. Some sources say that lysergic acid does not need to be #urifed. feel that e$erything should be #urified. n the e$ent that something should go wrong with the formula, you can immediately rule out im#urities as the cause. 3lso, im#urities create unwanted by#roducts which can be #oisonous, creating dangers for the drug user. Purification of lysergic acid is $ery easy. Dissol$e the acid in dilute ammonium hydro4ide, treat with decolorizing carbon, re#reci#itate !after filtering off and washing #roduct from the carbon" with carbon dio4ide. 'on$ert iso;LSD to LSD. 3dd .) ml of ethanol and . ml of * : @+& #er e$ery gram of iso;LSD. Let this mi4ture stand for < hours at room tem#. 9$a#orate in $acuo to get the LSD. Se#arate iso;LSD from LSD. Dissol$e the residue of the mi4ture of LSDs from the end of the formula in (<) ml of benzene and *) ml of chloroform. 3dd tartaric or maleic acid to #reci#itate the LSD, filter off, add a little ether and #ut in refrigerator for se$eral days to get a little more LSD, which is filtered off and added to the rest. 9$a#orate the filtrate in $acuo to get the iso;LSD and con$ert as abo$e. LSD from Lysergic 3cid. %his is based on the formula taken from '3, .), ()?)2d !(>.0" Dissol$e ... g of dry lysergic acid in (<. ml of acetonitrile that has been cooled to ;()A and cool further to ;<)A with an e4ternal freezing mi4ture. 3dd ?.? g of trifluoroacetic anhydride in B. ml of acetonitrile !this solution must be cooled to ;<)A before the addition". Be careful making this addition, so as not to raise the tem#, etc. Let stand at ;<)A until all the lysergic acid dissol$es !about (H< hours". 3dd B.0 g of diethylamine !or analog" in (.) ml of acetonitrile and allow to set at room tem# in darkness for < hours. 9$a#orate in $acuo to get the LSD, which can be se#arated from the iso;LSD as abo$e.

LSD FROM LYSERGIC ACID


%his is taken from '3, .B, .>B> !(>0<". t is designed by &ofmann to gi$e (;methyl;D;lysergic acid, and is modified to gi$e LSD and iso;LSD. Dissol$e )..* g of lysergic acid in () ml of freshly distilled #hos#horous o4ychloride, stir ).*< g of #owdered, fresh #hos#horous #entachloride. 3llow to stand at room tem# for < min, then at >)A for < min, then e$a#orate in $acuo. 94tract the residue with he4ane to gi$e lysergic acid chloride hydrochloride. %o sa$e time you may e4tract the reaction mi4ture without e$a#orating. 3dd <.. g of the hydrochloride to a cooled solution of B ml of diethylamine !or analog" in <. ml of methylene chloride that is cooled to )A :ote %his solution is cooled to )A before the addition. /ith stirring add (2.B. ml of dry #yridine and stir for 2) min with cooling to kee# the tem# at )A or a little below. /arm to room tem# and continue the stirring for >) min. 9$a#orate in $acuo to get the LSDs. Se#arate as already described.

LSD FROM LYSERGIC ACID MONOHYDRATE


%his is, in my o#inion, the best of all the methods. t was designed to be used to e4#eriment with different ty#es of amines, so if you would like to substitute diethylamine with another amine this would be the best bet. t also gi$es good yields !.)D or better" and is $ery easy. %he reference that gi$es it !=,', (0, .2< !(>B2"", also gi$es #otency data for many lysergamides and many of their formulas. %he reading is good, interesting, informati$e, and the method gi$en below gi$es no useful amount of iso;LSD, so se#aration of that #roduct is not necessary. Both method 3 and B were from =,', (0, .2<. ,ethod 3. 3 slurry of 2.(. g d;lysergic acid monohydrate !monohydrate means dry" and B.2 g of diethylamine !or ).( mole of similar amine" in (.) ml of #ure chloroform is heated to reflu4. 3fter the lysergic acid is dissol$ed !a few min" cool the mi4ture down to where reflu4 has sto##ed by remo$ing the heat. Before the mi4ture cools any further < ml of #hos#horous o4ychloride is added at such a rate as to gi$e reflu4 !about < min". 3fter addition, reflu4 for *;. min further until an amber;colored solution results. 'ool to room tem# and wash the mi4ture with <)) ml of ( ,

ammonium hydro4ide. %he chloroform solution was dried with ,gS+* !this would ha$e to be after se#aration", filtered, and concentrated by e$a#oration in $acuo under a tem# of 2?A !at no time let the tem# go o$er *)A". %he last traces of sol$ent are remo$ed at <;. mm. Dissol$e the residue in a minimum amount of methanol and acidify with freshly #re#ared solution of <)D maleic acid in methanol !not a-ueous" to #reci#itate the LSD in its maleate form. 8ilter the fluffy white needles, wash with cold methanol and air dry to get <.< g of LSD that re-uires no further #urification. ,ethod B. %his is #ro$en to be more effecti$e for using substituted amines. ,i4 the following slurryG 2.(. g of dry d;lysergic acid in (.) ml of chloroform and reflu4 in a 2 necked flask. 3s soon as you ha$e the reflu4 ad7usted add B.2 g of diethylamine !or ).( mole of analog" in <. ml of chloroform and at the same time, from another addition funnel mounted in the o##osite neck of the flask, add < ml of #hos#horous o4ychloride so that both the additions begin at the same time. %he additions should be timed so that they both finish after <;2 min. @ee# at reflu4 with gentle heating for another 2;. min until a clear amber;colored solution results. 'ool thesolution to room tem# and finish the work u#, as in method 3 directly abo$e, to get < g of LSD maleate. 3s in method 3, this method gi$es $ery little or no iso;LSD, so don6t worry about remo$ing that.

LYSERGIC ACID MONOHYDRATE


#ut this formula in this book s#ecifically for the two methods !3 and B" directly abo$e, howe$er, lysergic acid monohydrate can be used on any of the LSD formulas with #ossible success. feel this may be easier than the first method gi$en at the beginning of this cha#ter. Dissol$e (B. g of @+& in (,B.) ml of water in a flask of . liters $olume e-ui##ed with a reflu4 condenser and a gas inlet tube. f a stirring de$ice is not re-uired, it should be remo$ed and the o#en neck sto##ered. &eat the mi4ture to ?)A under a stream of nitrogen and add .)) g of ergotamine tartrate. &old the tem# at ?)A for < (H< hours with bubbling from the nitrogen filled gas inlet tube. Pour the mi4ture into a . gallon #olyethylene bucket !made from the same material as a #lastic gas can" filled with about 0 liters of ice. Put the bucket in a cooling mi4ture to cool below ()A. :eutralize the mi4ture by adding cold dilute sulfuric acid to a congo red end #oint !#& *.<". Lysergic acid and #otassium sul#hate will be seen to #reci#itate. Let stand for <;2 hours in the .;()A cooling mi4ture. 8ilter with $acuum assist, and let $acuo suck as dry as #ossible. Break u# the filter cake and #ut in a < liter beaker. ,ake a solution from (.) ml of li-uid ammonia and <.. liters of $ery cold dry denatured ethanol and add to the reaction mi4ture. Stir for ( hour and filter. @ee# the fltrate and treat the filter cake to (H< the ammonia ethanol mi4ture as abo$e. %his second e4tract is filtered and the cake is washed with <.) ml of the ammoniacal ethanol mi4ture. 'ombine the fitrates, and e$a#orate to total dryness with a strong $acuum and gently heating. Do not heat at too high of a tem#. Scra#e the #roduct from the $acuum $essel and #ut into a mortar. ,i4 ((2 ml of methanol with 2? ml of water, and rinse the rest of the residue from the e$a#oration $essel and dum# into the mortar with the rest of the #roduct. %he slurry in the mortar is ground u# well and filtered. /ash the flter cake with (.) ml of cold water and use $acuum to suck dry for ( hour. Break u# the filter cake and dry at ?);?.A under a high $acuum to get about 0.;B. g of cream;white to gray;white #owder. %his is lysergic acid monohydrate. think that if you dry the lysergic acid !obtained from the ergot alkaloids by hydrolysis as described earlier" it will also work in methods 3 and B. %his is how you dry lysergic acidC dry under high $acuum at (*);(*.A for <;2 hours.

LSD FROM ERGOT ALKALOIDS


%his was in$ented by &ofmann and is a su#erior method because you may #roceed from the ergot alkaloids to LSD without isolating the lysergic acid. '3, .B, (<.0? !(>0<". 3dd (.< g of ergotamine hydrochloride to * ml of anhydrous hydrazine and heat ( hour at >)A. 3dd <) ml of water and e$a#orate in $acuo, to get d;iso;lysergic acid hydrazine. ( g of the lysergic hydrazine is #owdered well and added to *) ml of ).( : !ice cold" &'( acid. %o this, cooled to )A, is added * ml of ( : :a nitrite, with good stirring. +$er <;2 min, add *) ml of ).( : &'( acid to get #& to .. Let stand for . min, basify with ( : :a&'+2, e4tract with ()) ml of ether, and then with .) ml of ether. /ash the ether layer with water and dry, then e$a#orate in $acuo at ()A. Dissol$e the resulting yellow azide in about . ml of diethylamine at )A and then heat in a metal bomb at 0)A for ( hour. f a bomb is una$ailable you may get by with heating for 2;* hours at *.A

in a $ented flask under a nitrogen atmos#here. 3lso, would flush the bomb with nitrogen before sealing and heating. Remo$e heat after time ela#ses and let stand !after bleeding off #ressure for bomb method" for < hours and e$a#orate in $acuo to get ).B g of LSD and ).(. g of iso;LSD. %he iso;LSD will not do anything !good or bad" if consumed, so you may lea$e it in with the LSD. Eou may also se#arate it and con$ert it to LSD as in the formulas aho$e.

LSD FROM LYSERGIC ACID JOC, 24, 368 (19 9)


%his is a sim#le method that gi$es good yields of LSD with $ery little !if any" iso;LSD. Eou will be re-uired to #urchase sulfur trio4ide from 3llied 'hemical and Dye 'or# !ask for Sulfan B, or S+2", but this is not a sus#icious chemical so ordering is not a #roblem. Sulfur trio4ide;Dimethylformamide com#le4 !S+2;D,8". %his is a reagent re-uired for this method of LSD #roduction. 3 com#letely dry << liter flask !round bottom" in an ice cooling bath is fitted with a condenser, stirring de$ice, addition funnel, then is filled with ();(( liters of D,8 !dimethylformamide" that has been freshly distilled under reduced $acuum. Fse drying tubes to #rotect the reaction from all moisture !including atmos#heric moisture". < #ounds of sulfur trio4ide !S+2" are then added, with a great deal of caution, o$er *;. hours with stirring, dro#wise. %he tem# must be held between )A;.A during this addition. Stir for (;< hours after the addition until some se#arated, crystalline S+2;D,8 com#le4 has dissol$ed. Store in the dark in a suitable $essel, in a refrigerator for not more than 2 months. F#on storage, the com#le4 will turn yellow and then orange. %his is normal. 3s long as it is less than 2;* months, it is still good. %his mi4ture gi$es a molarity of ( !( ," and can be made using (H< or (H* of the amounts abo$e to scale down the $ersion, still gi$ing a ( , solution. Lysergic 3cid Diethylamide. 3 solution of B.( g of lysergic acid monohydrate. 3s with any of the formulas calling for the monohydrate, you may substitute dry or anhydrous lysergic acid in #lace of the lysergic acid monohydrate by using a smaller amount of the dry lysergic acid. ha$e found that di$iding the amount of the monohydrate by the constant of (.( gi$es a close amount of dry lysergic to use, e.g., B.( di$ided by (.( I 0.. g, to substitute in the formula. Likewise, the monohydrate can be figured into a formula calling for dry lysergic, 0.. times (.( I B.( g. 3lso, if a formula does not s#ecify if the lysergic acid is to be dry, e.g., add )..* g of d;lysergic acid, then always use dry or monohydrate as any water will kill the yield. Dry as stated abo$e. 3s a general rule dry your lysergic acid as soon as you #lan to use it !because it collects &<+ from air". ( g of lithium hydro4ide hydrate in <)) ml of methanol is #re#ared. Distill off the sol$ent !methanol" on a low tem# steam bath under reduced #ressure, or e$a#orate under $acuum. %he resulting glass;like lithium lysergate residue, is dissol$ed in *)) ml dry dimethylformamide !D,8". <)) ml of this D,8 is distilled off with (. mm #ressure through a (< inch helices;#acked fractional column. 'ool the resulting solution to )A, and with stirring, -uickly add the S+2;D,8 solution !.) ml of ( ,". %he mi4ture is stirred with cooling for () min and (<..) mmol. of the desired amine is added !that would be >.). g of diethylamine". %he stirring and cooling are continued for () min after the amine addition, and then the reaction is decom#osed by adding *)) ml of water. 3fter stirring thoroughly the reaction mi4ture is treated with a saturated solution of :a'l. %able salt and water are fine for this if the salt is not iodized. Fse <)) ml of the saturated solution on the reaction mi4ture. 94tract the amide !LSD" with re#eated #ortions of ethylene dichloride. %est for com#leteness of e4traction with 5an Frk test or hold e4tract under black light briefly and look for fluorescence as com#ared with non;e4tracted ethylene dichloride, or use any indole test. %he combined e4tracts are dried !with ,gS+* as usual", and then e$a#orated under $acuo to a syru#. @ee# the tem# below at least room tem#. Dissol$e the residue in about 0) ml of dry methanol, acidify with solid maleic acid, treat to turbidity with dry ether, and refrigerate for 2;0 hours to get colorless soft needles of LSD maleate which are filtered from the mother li-uor. ,ore crystals may be obtained by e$a#orating the mother li-uor in a cool, dark #lace under $acuum.

THINGS TO REMEM!ER "HEN "ORKING "ITH ERGOT ALKALOIDS, LYSERGIC ACID, AND LSD
%hese com#ounds are $ery sensiti$e and e$en unstable. %his means that the following ste#s must be taken to kee# from ruining your com#ound or yield.

1. Always use red or yellow photographic dark room light bulbs during any step of LSD manufacture. Direct sunlight, electric filament, or fluorescent light bulbs (etc.) will hurt the abo e compounds. Dark room bulbs are cheap and are a must. !. "eep all forms of #!$ out of the reaction. %horoughly dry all the glass ware to be used. &se a drying tube filled with anhydrous 'gS$( (calcium chloride reacts with amines in an unfa orable way and should not be used). ) can*t be there to hold your hand and guide you through e ery step, so unless the formula says to add water, the drying tube should be in use, and after the water addition is o er, the drying tube goes back on. %his way the reaction is always protected e en if it does not need to be. +etter safe than sorry. Also, if you*re not sure if you should use dry reagents, use dry reagents anyway. Also dry the lysergic acid (as described abo e) and any other precursors in whate er drying process re,uired for that compound before use. Dry the finished LSD or e en any intermediate along the way after you ha e completed the product. Likewise, dry an intermediate that you may ha e purchased from a chemical supplier. -. "eep o.idi/ing agents from these items. 0 en the o.ygen in the air can o.idi/e some of these compounds. %he formula states that during some of the reactions abo e, an inert gas (nitrogen) must be used for an atmosphere inside the reaction essel. 1itrogen can be obtained in small bottles (tanks) at a ery reasonable fee, without any ,uestions asked. 'ake sure you use a regulator and introduce a slow stream into the essel by way of a gas inlet tube or an e,ui alent. Always flush the essel before putting any reagents into it (flush the air out with nitrogen). ) would use a nitrogen atmosphere from the ery beginning of the formula to the ery end, e en if the formula did not specify its use. 2ery few of the abo e formulas call for a nitrogen atmosphere during e aporation, but ) feel this may be bad for yield and or potency. LSD has many doses per gram, and if you lose 13! g because you were too cheap to use three dollars worth of nitrogen, you ha e lost about !,444 doses at 56 a dose 7 514,444 of LSD wasted. +etter safe than sorry8 Also, any precursors you make or buy should be stored in a nitrogen atmosphere, as should LSD. %his can be done by poking a gas inlet tube into the essel trust abo e or a little below the substance) flushing the air out with a moderate stream of nitrogen then ,uickly reinstall the cap or stopper. %he best way to store LSD is by producing it in the maleate form. %his not only makes it resistant to o.idation, but it purifies it, too. &se the procedure abo e (9$:, !(, -;<, or :A, 6=, 6>=>) when you get to the last dry?and?e aporate?in? acuo step, then treat the residue as specified. (. 1e er sub@ect these compounds to e.cessi e heat, or any type of temperature warmer than the inside of your refrigerator. 0 en LSD maleate will decompose in e.cess heat, so store in a refrigerator. "eep e aporation procedures cooled. %his will slow the e aporation process down, but that is better than losing the product. Some of the abo e formulas re,uire heat for a reaction. %his is $k, but do not e.ceed the temp stated at any time and ne er heat longer than

needed. Also, nitrogen atmospheres are used during heating operation.

SU!STITUENTS
LSD analogs !lysergic acid amides" can be #re#ared by substituting amines in #lace of diethylamine. %he #otency usually dro#s anywhere from 22D to B.D de#ending on the substituent. Diethylamine is highly sus#icious, and the substituent will #roduce a lysergamide that is most likely legal, as legislation has only singled out lysergic acid diethylamide. Little work has been done on the #otency of substituted ysergamides, so a little e4#erimentation by you may be in order. Personally, would like to try substituting a #otent #henethylamine or #henyliso#ro#ylamine such as D+, !S%P" or *;bromo;<,.;dimetho4yam#hetamine. f could get a go$ernment grant, or maybe a grant from a ma7or #harmaceutical cor#oration, like F#7ohn or Lilly, then could #lay around with such e4#eriments. %he following substituents gi$e lysergamides with #otencies as indicated in doses #er gram !remember that LSD gi$es about 0,))) to >,))) doses"C 9thyl#ro#ylamine ,or#holide Di#ro#ylamine ,ethylethylamine Dimethylamine Pyrrolidide <,))) to .,))) 0)) to <,))) 0)) to (,))) *)) to 0)) 2)) to *)) 2)) to *))

,ethyl#ro#ylamine 0)) to (,)))

3s a #oint of reference, D+, !S%P" is one of the most #owerful am#hetamines, at <)) doses #er gram. 3t 1. a line, its $alue is about . times <)) I 1(,))) a gram. 8or more info see =,', (0, .2< !(>B2". 'la$ice#s #ur#urea is not the only #lace to get d;lysergic amides. %he #lant grou# of 'on$ol$ulacea has been found to #osses lysergic acid amides such as ergine and se$eral others. %hese 'on$ol$ulacea ty#e of #lants do not cause the dreaded St. 3nthony6s fire, as does cla$ice#s #ur#urea, and as a matter of fact, they are hallucinogenic if eaten in large doses. 'are must be taken that the seeds ha$e not been treated with #oison to discourage usage as a mind alterant, or treated with methyl mercury to #re$ent s#oilage. /hen these seeds are to be used for LSD syntheses, make sure to clean off the white layer that surrounds them by singeing or mild burning. 3lso, ask for &awaiian Rose /ood, as these are the only ones that contain an a##reciable amount of lysergic related com#ounds. %hese com#ounds must be e4tracted as below, hydrolyzed !like ergotamine" as abo$e, and then used in any of the formulas that re-uire d;lysergic acid or #ossibly used directly in the &ofmann hydrazine methodG '3, .B, (<.0? !(>0<". %hese seeds ha$e $ery little amide, so you can #lan on -uite a lot of work in the e4traction ste#. 3ccording to 3. &offer and &. +smond, the most amide #lentiful s#ecies !/oodrose" has a minute 2 to 0 mg of amide #er e$ery gram of seed. %his means that if you e4tract $ery thoroughly, you will re-uire a little o$er <)) g of seeds to get ( g of amide, which will be reduced further after hydrolysis to gi$e you about ).. g of usable d;lysergic acid. 94tract as follows. Pul$erize the seeds in a clean blender until they are a fine #owder. Put this #owder into a beaker, add ( (iter of #etroleum ether to e$ery >)) to ()))g of #owdered seeds, sto##er the beaker to #re$ent e$a#oration and let set for 2 days. 8ilter off the #etroleum ether and let e$a#orate to make sure no amides were e4tracted !there should not be much, if any" from the ether. 3dd ( (iter of methanol !dry is best" and let soak for * days with $igorous shaking, now and then. 8ilter off the methanol and e$a#orate it under $acuo !$acuum s#eeds the #rocess". n the meantime, add .)) ml of fresh methanol to the #owder and e4tract it again for 2 or * days.

8ilter as before and e4tract again with about 2)) ml of methanol. 'ombine the residues of all e4tractions and hydrolyze.