[www.rhodium.ws] [] [Chemistry Archive]

Potential for gamma-Butyrolactone Synthesis from Tetrahydrofuran and 1,4-Butanediol

by J. A. Morris

Microgram XXXIII(11), 321-324 (2000)


Since FDA imposed restrictions on GHB and subsequently scheduled it this past spring, users have gradually shifted their use from GHB to gamma-butyrolactone (GBL) and 1,4-butanediol (BDO). It is well-documented that ingestion of either solvent brings about the gradual metabolic conversion into GHB1. For this reason, as well as being the direct precursor in GHB synthesis, GBL was designated a List I controlled chemical2 while 1,4-butanediol remains uncontrolled.

As the supply of GBL quickly diminishes, a recent survey of Internet sites relating to GHB indicates a potential shift in the clandestine manufacture of GHB. Recently, increasing inquiries regarding the synthesis of GBL from tetrahydrofuran (THF) and 1,4-butanediol (BDO) have appeared.

On the Chemistry section of Rhodium's web site, there is a section listing GHB Related Articles. One of the links, entitled "References for the Synthesis of gamma-butyrolactone from tetrahydrofuran," documents 77 separate citations specifically concerning the oxidation of THF into GBL. In actuality, the list contains a significant number of repeated citations. There are approximately 25 to 30 different citations on the site. A related link on the same site, entitled "References for the synthesis of gamma-butyrolactone from 1,4-butanediol," lists numerous citations involving the oxidation of BDO into GBL. As with the THF page, several of the citations are listed more than once.

Several posts from individuals on "The Hive" web site show a high level of interest in the potential of the conversion of these precursors into GBL. A few individuals have elaborated on one or two of the oxidation methods, but few people have taken the theory to the lab for actual experimentation. However, the increased interest in the synthesis routes and the relative ease of conversion warrant an examination of the published methods of oxidation.

Literature Review for THF

Of the numerous THF oxidation citations listed on Rhodium's page, the majority of the papers deal with oxidation procedures surpassing the typical level of chemistry expertise of clandestine laboratory chemists. The reaction conditions are either too sophisticated or the oxidizing agent is too obscure for the average underground chemist to pursue the proposed reaction route despite superior yields. However, there appear to be four referenced routes of oxidation which show strong clandestine potential.

Calcium hypochlorite3: This particular reaction has received the most attention from user groups interested in the THF to GBL conversion. More stable that its sodium counterpart in solution, calcium hypochlorite converts 68% of the THF into GBL in the presence of acetonitrile and acetic acid when the reaction proceeds at room temperature for up to 16 hours. Under these conditions, heating had no effect on the overall yield of the reaction.

Although the paper mentions continued studies to improve the ether oxidation, personal communication with one of the authors revealed that this was not pursued. However, simple modification in the reaction solvent could be expected to increase the yield4.

At present, proposed conversion routes related to this reaction have significant variations. Methanol or absolute ethanol or used in place of acetonitrile and hydrochloric acid has been used rather than acetic acid. Positive results have been mentioned yet the only means of identification by the cook has been personal taste testing or ingesting.

Zinc dichromate trihydrate5: Boasting the highest yield, this reagent must be prepared by the chemist due to the lack of a commercial source. The reaction is performed at room temperature in dichloromethane and only requires 1 hour to obtain a 70% yield. The reported reaction was done at room temperature leaving any effect of temperature variation unknown.

According to the paper, collection of the final product involves chromatographing the reaction solution on a silica gel column followed by solvent elution and distillation. Other common means of collection and purification are probably required in a clandestine setting.

Zinc permanganate6: Although this reagent is only cited as giving a 51% yield, the authors admit very little effort in attempting to optimize the reaction. Also performed in chloroform or dichloromethane, zinc permanganate was found to be a superior oxidant compared to both potassium and magnesium manganates.

This particular reaction requires a silica gel support system as well as preparation of the reagent. Once prepared, the authors mention that zinc permanganate and magnesium permanganate "reacted instantly, with fires in some cases, when added to common laboratory solvents..."

Peroxyphosphoric acid7: Having the lowest yield of the four oxidants, peroxyphosphoric acid does not necessarily require the presence of a solvent. A yield of 45% was obtained by refluxing THF in the presence of peroxyphosphoric acid for two hours. The low yield occurred when the THF and the oxidant were in equimolar amounts. The authors postulate that 2 equivalents worth of the acid could raise the yield to 80-90%.

Literature Review of BDO

In converting 1,4-butanediol into GBL, the specific reaction mechanism involves oxidation/dehydrogenation of the precursor molecule followed by cyclization into the lactone. As with the THF to GBL citations, most of the reaction conditions and catalysts are impractical for an underground chemist. There are a few reagents, however, which have strong indications for future abuse.

This specific route of obtaining GBL appears to have less potential compared to the THF route since simple ingestion of BDO will also metabolically produce GBL. The reactions therefore require obtaining a chemical already noted for its abuse by GHB users. Those interested in the conversion cite the added danger to BDO ingestion and the unknown long term effects.

Copper chromite8: This reagent initiated the dicussion of the BDO to GLB reaction on "The Hive". Numerous posts involve the reaction conditions and reagent preparation and acquisition. The reported yield using the copper chromite catalyst is 99%.

The reagent and subsequent reaction yields are part of a patent regarding the dehydration of diols. The authors explain the various reaction conditions as well as several catalyst mixtures of copper chromite and cupric oxide. Although Rhodium outlines the synthesis of copper chromite9, several commercial sources of pure copper chromite and chromite/oxide mixtures are listed.

Despite several reaction conditions, the prefered condition involves heating BDO in a liquid phase solution of the reagent at 195-200°C for 2-3 hours. The yield is 99% conversion with a purity of 99% as well. The catalyst may be used multiple times.

Cupric oxide10: This reagent is mentioned in the patent above as background research. Simpler than the cupric chromite reaction, this reagent requires only a liquid phase environment and high temperatures.

When in the presence of BDO, cupric oxide produces GBL at an 80% yield when reacted for 15 hours at 200°C. The high purity of this and the previous reagent is offset by the high temperature requirements. The chemist must have the proper chemical equipment to reach the necessary temperature in an aqueous solution.

N-Iodosuccinimide/silver acetate11: This reagent combination requires less complicated reaction conditions to achieve similar results a sthe previous reagents. When dissolved in benzene and protected from light, only five to seven hours of refluxing is required to obtain 80-85% of the expected GBL. The reaction involves a two-step oxidation which necessitates a 2:1 ratio of reagent to precursor.


Despite federal efforts to curb GHB and GBL abuse, the clandestine chemists are finding new ways to obtain the desired substance. Since THF is a common solvent in most chemical laboratories and 1,4-butanediol is still readily available, the above oxidation and dehydration reactions offer a high potential for synthesizing GBL for either direct ingestion or subsequent conversion into GHB.

The Author



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  2. Federal Register 65(49), Monday March 13, 2000, p 13235
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  4. Dr P Keehn, personal communication 2000
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  8. US Patent 5110954
  9. http://www.rhodium.ws/chemistry/copperchromite.html
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