freakyDMT (Stranger)
05-23-03 15:46
No 435048
      DMT synthese via bromoethylindole  Bookmark   

does any one have some more information about the synthesis route bromoethylindole + dimethylamine __> DMT
05-23-03 16:09
No 435049
      I found some interesting patent about this...  Bookmark   

I found some interesting patent about this route its number is Patent US5382592,the yield from 3-(2-bromoethyl)indole __>DMT is 92 %


To a solution of triphenylphosphine (2.83 g,0,011 mol) in 100 ml acetonitrile was added a solution of 3-(2-hydroxyethyl)indole (1.56 g 0,0097 mol) in 25 ml acetonitrile,followed by a solution of CBr4 (3.60 g,0,011 mol) in 25 ml acetonitrile,at 0C under argon.
The mixture was stirred at roomtemperature for 18 hrs. and then another 0,283 g(1,1 mmol) triphenylphosphine and 0,360 g (1,1 mmol) CBr4 were added,after 2,5 hrs. the mixture was deluted with ethylacetate,washed (water,brine) dried(Na2SO4 and evaporated and the residu was chromatographed(SiO2/ethylacetate-hexane 1:4)
yield 87%
(Chief Bee)
05-23-03 16:59
No 435057
      Tryptophol halogenation  Bookmark   

UTFSE for "tryptophol", bromination of that alcohol gives 3-(2-bromoethyl)indole, so any post discussing that is likely to contain some info on both.
05-25-03 05:35
No 435391
      second part DMT synthesis  Bookmark   

3(2-bromoethyl)indole __>DMT

Into 50 ml of absolute ethanol cooled at 0C was bubbled dimethylamine for 30 minutes.
to this solution was added a solution of 3(2-bromoethyl)indole (0,42 g,1.86 mmol) in 50 ml absolute ethanol and the mixture was transferred to a pressure vessel and heated at 80C for 2 hrs.
The cooled mixture was then evaporated and the residu was partitioned between 1N NaOH and ethylacetate,the organic phase was seporated,washed(brine),dried(Na2SO4 and evaporated to give tittle compound
yield 92%

Reference: Patent US5382592
05-25-03 11:05
No 435453
      Instead of CBr4 in the bromo-ethylindole ...  Bookmark   

Instead of CBr4 in the bromo-ethylindole synthesis above plain Br2 can be used, at least if you add equimolar amounts of imidazole.
05-25-03 11:35
No 435459
      lilienthal,what kind of imidazole do you mean  Bookmark   

lilienthal,what kind of imidazole do you mean,reference please?
05-25-03 17:04
No 435503
      tryptophol patents
(Rated as: excellent)

I also founds some really interesting patent about the synthesis of tryptophol,the numbers are:
Patent US4062869 and Patent US4904799 i hope that some one can use the info.
MAKE DMT,NOT WAR!!!winklaughsmiletongue
(Hive Bee)
05-26-03 01:03
No 435571
      Nice  Bookmark   

The first patent [patent]4062869[/patent] is damn excellent! Thank you FreakyDMT!smile

The dihydrofuran condensation of the second patent[patent]4904799[/patent] is low yieldingfrown. Search patents office for etodolac, there is some nice papers on this subject.

BTW: use the patent tag [patent]
(Chief Bee)
05-26-03 04:18
No 435595
      How to write proper Patent/Medline/DOI link tags
(Rated as: good read)

Look here everybody: Note that patent links are made by writing: [patent]US4062869[/patent]

1) You write the two-letter country-code, directly followed by the patent number, without any commas or spaces: US4062869

2) You enclose all this in [patent]patent tags[/patent] (we even have a button for this tag on the post editing panel, click once to generate the opening tag, and a second time to generate the closing tag).

The immensely useful MedLine and DOI tags works just the same, see the posts below, or the FAQ (

Post 425177 (Lilienthal: "Please use the DOI for citations", General Discourse)
Post 340100 (Lilienthal: "New [medline] markup tag", The Server Room)
(Chief Bee)
05-26-03 05:35
No 435601
      Tryptophol from 3-Indoleglyoxyl chloride + NaBH4
(Rated as: excellent)

That find was really great! Now we finally have an extremely easy and high-yielding route from Indoles to Tryptophols, which of course are only two steps away from N,N-dialkyltryptamines such as DMT.

First step: Indoleglyoxyl chloride from Indole

This is performed by adding oxalyl chloride to an etheral solution of indole, and filtering off the precipitated product, using the well-known Speether-Anthony procedure, see Patent US2825734 for some examples.

Second step (Reduction of the acid chloride directly):

As sodium borohydride according to the patent can reduce 3-indoleglyoxylic acid ester and indoleglyoxyl chloride, but not 3-indoleglyoxylic acid  itself, care must be taken to exclude all moisture from this reaction, as the acid chloride is hydrolyzed to 3-indoleglyoxylic acid  by water. Therefore,  this acid chloride is swiftly added to either diglyme (so that it can be directly reduced to tryptophol, as in example 7)

Second step (Reduction of the acid chloride directly):

The alternative is to go via an 3-indoleglyoxylic acid ester, in which case the acid chloride is dissolved carefully in dried methanol or isopropanol (heat evolution!) to form the methyl (For Example 8) or isopropyl 3-indolylglyoxylate (For Example 1), respectively.

As the isopropyl ester is reduced in isopropanol, that method is advantageous, as it becomes a one-pot reaction - when the isopropyl ester has been formed, sodium borohydride is directly added to the same solution. The same cannot be done in the case of the methanol ester, as sodium borohydride decomposes too fast in methanol. It is probably not advantageous to attempt to make the ethyl ester for reduction of this in ethanol, as ethanol almost always contain a few percent water, which as said will hydrolyze the 3-Indoleglyoxyl chloride to the by sodium borohydride irreducible 3-Indoleglyoxylic acid.

After this, go on to brominate (or tosylate) the tryptophol as described earlier in this forum, and aminate the formed bromide or tosylate. Both these steps should work very well.

Patent US4062869 Process for preparation of tryptophols


A process for preparing tryptophol derivatives comprises reducing a 3-indolylglyoxylic acid ester or acid halide using an alkali metal borohydride in the presence of an alcohol or ether solvent. The tryptophol derivatives prepared are useful as intermediates to pharmacologically active compounds.

This invention relates to a process for the preparation of 1-unsubstituted-3-(2-hydroxyethyl)indole derivatives, such as tryptophol.

Patent US3076814 describes the preparation of 3-(2-hydroxyethyl)indoles by reducing 3-indoleglyoxylic acids using lithium aluminium hydride. The patent also discloses the partial reduction of the 3-indoleglyoxylic acids using sodium borohydride to give 3-indoleglycolicacids; which compounds, it states, can be reduced further to the 3-(2-hydroxyethyl)indoles by lithium aluminium hydride.

It has now surprisingly been found that, in certain solvents, 1-unsubstituted-3-indoleglyoxylic acid esters and acid halides may be reduced with alkali metal borohydride reducing agents to give 1-unsubstituted 3-(2-hydroxyethyl)indole derivatives.

The ability to carry out the reduction to give tryptophols using borohydrides gives the process of this invention advantages over the known process using lithium aluminium hydride. For example alkali metal borohydrides are relatively safe reagents and reduction may be effected smoothly. Reductions using lithium aluminium hydride on the other hand are more hazardous. The present invention, therefore, provides a process which is suitable for large - scale preparations. The use of sodium borohydride is particularly advantageous as this reagent is less expensive than lithium aluminium hydride. Further advantages over the use of LiAlH4 include the ability to have substituents present on the indole ring which are unaffected by the borohydride reducing conditions and which would be reduced by the more powerful LiAlH4.

In one aspect therefore this invention provides a process for preparing a 1-unsubstituted-3-(2-hydroxyethyl) indole which comprises reducing a 1-unsubstituted-3-indoleglyoxylic acid ester or acid halide with an alkali metal borohydride in the presence of an alcohol or ether solvent suitable for effecting the reduction.

Many of the compounds of formula I prepared by the process of this invention are useful as starting materials for the preparation of therapeutically active compounds for example, as described in Patent GB1375836. The compounds of formula I may also be converted to the 2-(indol-3-yl) ethyl halides using hydroxyl/halogen exchange reagents, e.g. to the bromide using PBr3 ; which compounds may then be used to prepare therapeutically active compounds as described in Patent GB1218570, corresponding to Patent US3527761. By "a hydroxyl/halogen exchange reagent" is meant a reagent capable of displacing the hydroxyl group of an alcohol by a halogen atom. Typical examples are PBr3, PCl3, sulphonyl chloride, etc.

The 3-indoleglyoxylic acid ester or acid halide derivatives used as starting materials are known compounds or may be prepared by knwon procedures. For example an indole may be reacted with an oxalyl halide to give a 3-indoleglyoxylyl halide which may then be reacted with an alcohol, e.g. an alcohol of formula ROH wherein R is as defined above, preferably in the presence of a base to give the corresponding 3-indoleglyoxylic acid ester. Examples of alcohols of formula ROH are methanol, ethanol, butyl alcohol, benzyl alcohol, m-cresol and the like.

EXAMPLE 1 - 3-(2-Hydroxyethyl)indole

A vigorously-stirred mixture of isopropanol (3 1), methyl 3- indolylglyoxylate (305 g) and sodium borohydride (125 g) was warmed to 40C - 50C and held at that temperature until the initial exothermic reaction was complete. The mixture was then heated to reflux for 4 hours, cooled and diluted with water (5 l). After acidification with hydrochloric acid the product was extracted into dichloromethane. The separated extract was washed with sodium carbonate solution to remove 3-indolylacetic acid and then with water. Evaporation of the solvent gave the crude product as a brown oil. This was distilled at 0.5 - 1 mm pressure (vapour temperature 160-190C ) and crystallised from toluene (1 l) to give the title compound as white to pale brown crystals m.p. 57-59C. Yield 170 g. (70% of theory).

EXAMPLE 7 - 3-(2-Hydroxyethyl)indole

A suspension of sodium borohydride (22.6 g.) in diglyme (800 ml.) was stirred in a jacketted flask with water cooling. 3-Indolylglyoxylyl chloride (41.5 g.) was cautiously added in small portions then the mixture was heated to 95C-100C for 5 hours. The cooled reaction mixture was diluted with water (2 l.), acidified with hydrochloric acid and extracted with dichloroethane. The extract was washed with sodium carbonate solution then with water and evaporated to give crude tryptophol as a brown oil. This was distilled at 0.1 mm and the distillate collected at 155C-160C was crystallised from toluene (50 ml.), giving pure tryptophol as white crystals m.p. 57C-59C. Yield: 17.7 g.

EXAMPLE 8 - 3-(2-Hydroxyethyl)indole

Methyl 3-indolyglyoxylate (30.4g.) was added to a stirred suspension of sodium borohydride (17.0g.) in ethanol (industrial methylated spirit, 300 ml). the exothermic reaction raising the temperature of the mixture from 20C to 45C. After heating to reflux for 5 hours the mixture was cooled, diluted with water (21/2 l.) and extracted with dichloromethane. The extract was concentrated under reduced pressure to an oil, which crystallised from toluene (40 ml.) to give the title compound as a buff-coloured powder, purity 98% by GLC. Yield 15.2g.
05-26-03 14:31
      new tryptophol patent
(Rated as: incomprehensible)
(Hive Bee)
05-27-03 04:27
No 435843
      Tryptophol from 3-indoleglyoxylyl chloride + LAH
(Rated as: excellent)

This synth is from another interesting patent Patent GB778823.

It is pretty much the same synthesis as in Patent US2825734

Tryptophol - [3-(2-hydroxyethyl)indole]

To a solution of 25g of indole in 500mL of anhydrous ether at room temp. was added 25mL of oxalyl chloride. After the vigorous reaction has subsided, the precipitate, 3-indoleglyoxylyl chloride, was collected, washed with ether and added to 200mL of absolute EtOH. After standing for about 60 h, the precipitate was collected, washed with a smal amount of EtOH and dried to amount 38g of ethyl 3-indole-glyoxylate (mp 183.5-184.5C).

A suspension of 30g of ethyl 3-indole-glyoxylate and 700mL of THF was added over a period of 1 h to a refluxing mixture of 1000mL of THF ang 13.1g LAH. After refluxing for 4 h, the mixture was cooled and a solution of 5mL water and 50mL THF was added dropwise, followed by the addition of 50mL 10% NaOH. The precipitate was collected, washed with ether, and the combined filtrates were concentrated. The residue was distilled, yielding 18.8g of tryptophol (bp 150-154C/0.06 mmHg). Upon cooling the distillate crystallized (mp 56.8C).


To a solution of 17.6g (0.079 mole) of 5-benzyloxyindole in 800mL of anhydrous ether was added a solution of 9.6g (0.076 mole) of oxalyl chloride in 100mL of dry ether. A light yellow precipitate began to separate from the ether solution after 15 min; after 4 h the mixture was cooled in an ice bath and the yellow precipitate was recovered by filtration. After washing with several portions of dry ether, the compound was dried in a vacuum desiccator at 146-150C. The yield of crystalline 5-benzyloxy-3-indoleglyoxylyl chloride was 14g (88%).

1g of 5-benzyloxy-3-indoleglyoxylyl chloride was added to 20mL of anhydrous EtOH, and the solution was refluxed for 1 h and thereupon cooled. Product, ethyl 5-benzyloxy-3-indoleglyoxylate, was precipitated, filtered, and recrystallized from EtOH (mp 213-215C).

5-Benzyloxytryptophol is produced by reducing ethyl 5-benzyloxy-3-indoleglyoxylate with LAH by the procedure disclosed in first example.

I'm dreaming of the white crystals.