Guanadrel, (1,4-dioxaspiro[4,5]dec-2-ylmethyl)guanidine (12.3.8), is synthesized when cyclohexanone undergoes ketalization by 3-chloro-1,2-proandiol, forming 2-
chloromethyl-1,4-dioxyspiro[4,5]decane (12.3.5), which is further akylated by sodium
phthalimide. After alkyline hydrazinolysis, the resulting phthalimide derivative (12.3.6) is
transformed into 2-aminomethyl-1,4-dioxyspiro[4,5]decane (12.3.7), which is reacted
with S-methylthiourea, giving the desired guanadrel (12.3.8) [80¨C82].