Viagra Synthesizing

The main component of Viagra which makes it a drug that we all know very well is sildenafil citrate. The utility of sildenafil consists in temporary restore of erectile function in male patients affected by impotence. The drug was first manufactured under its brand name in 1998, and the first appearance of molecule description dates back to January 1999, when the formula was published in Chemistry of Britain. However, the formula descried in the journal reflected the synthesis of the original discovery. For commercial production another process of synthesizing was used, and that had not been disclosed publically until relatively recent period. For those of you who are professionally curious to learn about Viagra synthesizing, are chemistry enthusiasts or would like to acquire this piece of knowledge for personal reference, we quote the formula as it appeared in Viagra patent issued on December 17, 1997.

The patent contained detailed description of the formula, supplemented with suggestions of the optimal solvents to use. Those, however, seem to be too explicit to fit into the format of the present piece. They can be found on the original patent document for a more detailed reference. More concise notes to the formula used in Viagra synthesizing are given below. However, the actual pathway of commercial Viagra manufacture is not made public due to economical and copyright reasons.

Figure 1: 2-ethoxybenzoic acid can be chlorosulphonated in order to achieve compound 2. In order to obtain compound 4 from compound 2, 1-methylpiperazine needs to be N-sulphonated using one or two-step reaction. By conducting any of the existing bond-forming reactions, compound 6 is bound with compound 4.

Figure 5 and 6: To achieve aminopyrazole, the corresponding nitropyrazole should be conventionally reduced. The solution that is obtained in the process can be bound with compound 4 immediately after having been filtered.

The yields percentage of successfully cyclisized into sildenafil equals 95%. If we take a closer look at correlation between sildenafil yields achieved as the result of one or two-step reaction, respectively, the figures will be 51.7% or 47.8%, which is much more fruitful as compared to the initially developed formula, where overall sildenafil yield was estimated at 27.6%.

The formula allows to synthesize sildenafil from compound 7 under either neutral or acidic conditions, in the presence of heat, a solvent, with or without addition of dehydrating agent, or, alternatively, a system that removes water mechanically. As for the acidic conditions, the reaction, too, can be optimized by employing a solvent. Acids engaged in acidic reaction would then be prolic or Lewis acid.

The patent was submitted alongside with the following recommendation as to the nature of reagents (subject to alternations based on availability and commercial suitability of produce):

The initial stage of Viagra synthesizing is conversion of 2-ethoxybenzoic into chlorosulphonylation. One pathway to do that is to react 1 equivalent mole of thionyl chloride with chlorosulphonic acid taken in the quantity of 4 equivalent mole. A one-step reaction employed to synthesize compound 4 is adding an aqueous suspension of compound 2 to 1-methylpiperazine.

N,N’-carbonyldiimidazole taken in 5% excess in ethyl acetate solution may be used to activate carboxylic characteristics of compound 4. By adding imidazolide to the compound 6 to the mediator described above, the process could be further facilitated. In order to obtain compound 6, the corresponding nitropyrazole 5 may be reduced with the help of hydrogenation catalysed in palladium carried out in ethyl acetate. The final stage of sildenafil synthesis would then be by cycling compound 7 that will yield sildenafil citrate molecule.

Viagra Synthesizing

Viagra Synthesizing