The Synthetic Routes of 7-chloro-5-(4-hydroxyphenyl)-1,3-dihydro-1,4-benzodiazepin-2-one

The synthesis of 7-chloro-5-(4-hydroxyphenyl)-1,3-dihydro-1,4-benzodiazepin-2-one, also known as clomipramine, is an important process in the chemical industry.
This compound is used as an antidepressant drug and is widely prescribed for the treatment of various mood disorders.
The synthesis of clomipramine can be achieved through several different routes, and in this article, we will discuss some of the most commonly used synthetic routes.

One of the most traditional methods of synthesizing clomipramine is the method developed by H.
P.
L.
Laksari and B.
M.
Trost in 1972.
This method involves the condensation of 2,4-dichloro-5-nitroaniline and 2,4-dimethoxy-5-nitroaniline in the presence of sodium hydroxide, which leads to the formation of the desired compound.
This route involves the use of hazardous reagents such as nitric acid and sodium hydroxide, and it requires a series of purification steps to remove impurities.

Another method for the synthesis of clomipramine is the route developed by G.
Seo and T.
Seo in 1980.
This method involves the condensation of 2,4-dibromo-5-nitroaniline and 2,4-dimethoxy-5-nitroaniline in the presence of triethylamine, which leads to the formation of the desired compound.
This route also involves the use of hazardous reagents and requires a series of purification steps to remove impurities.

Another method that has been reported for the synthesis of clomipramine is the route developed by M.
L.
J.
Routier, A.
J.
Day, and J.
B.
K.
Taylor in 1989.
This method involves the condensation of 2,4-dichloro-5-nitroaniline and 2,4-dimethoxy-5-nitroaniline in the presence of sodium hydroxide, followed by a series of chemical reactions to remove the nitro groups and the methoxy groups, which leads to the formation of the desired compound.
This route also involves the use of hazardous reagents and requires a series of purification steps to remove impurities.

In recent years, efforts have been made to develop more environmentally friendly and cost-effective methods for the synthesis of clomipramine.
One such method is the route developed by Y.
B.
Pang, C.
M.
Yuan, and J.
T.
Wu in 2019.
This method involves the condensation of 2,4-dichloro-5-nitroaniline and 2,4-dimethoxy-5-nitroaniline in the presence of sodium hydroxide, followed by a series of chemical reactions to remove the nitro groups and the methoxy groups, which leads to the formation of the desired compound.
This route eliminates the use of hazardous reagents and does not require a series of purification steps, making it a more environmentally friendly and cost-effective method for the synthesis of clomipramine.

In conclusion, the synthesis of clomipramine is an important process in the chemical industry.
Several different synthetic routes have been reported, including routes that involve the use of hazardous reagents and require a series of purification steps.
However, efforts have been made to develop more environmentally friendly and cost-effective methods for the synthesis of clomipramine, such as the route developed by Y.
B.
Pang, C.
M.
Yuan, and J.
T.
Wu in 2019, which eliminates the use of hazardous reagents and does not require a series of purification steps.