melphalan

sign up! Jenny Saravia  **In the first step AlCl3 acts as a catalyst to aid in the alkylation of the benzene ring with an alkyl cholirde (R-CL)**  **The Clemmensen Reduction allows the deoxygenation of aldehydes or ketones, to produce the corresponding hydrocarbon. This is seen in the second step with adding Zn(Hg) ** **An electrophilic aromatic substitution reaction, the benzene ring reacts with a mixture of concentrated nitric acids to create nitrobenzene in the third step of the mechanism. ** **The Raney nickel allows the reduction of the functional group (NO2) on the benzene ring.**

In general, this is a good synthetic scheme, especially in that it puts the most labile groups, the alkyl chlorides on last. The starting alpha amino malonoyl monochloride would probably not exist, because it would polymerize upon formation. I think you should protect the amine from the start. I think that reacting diethyl-2-amino-malonate with ethyl glycinate would cover both the the amine and the acid. The amine displaces the alcohol of the glycine ester to form an amide. The next step is a repeat of the same reaction, this time on the malonate ester. This reaction is called a trans amination, and is discussed in Chapter 21, if you want to review it. The six member ring that would be formed by this would protect the amine to the end of the reaction sequence. It could also be removed in aqueoud acid at the end. As long as the pH doesn't go above about 3, the chlorides should be ok. The other ethyl group would be there to keep it from decarboxylating. You can carefully remove it in base and replace it with the acyl chloride with thionyl chloride or oxaloyl chloride. Bruce Bondurant