The nucleophilic substitution reactions of aromatic halides having electron-attracting groups on ortho or para position with various primary and secondary amines were accelerated by high pressure to give the corresponding N-substituted anilines in high yields. The bulkiness of amines affects its reactivity to lower the yields of the products. Although the secondary amines are usually less reactive than primary amines, cyclic secondary amines such as morpholine, piperidine, and pyrrolidine were found very reactive. 1,4-Diazabicyclo[2.2.2]octane and quinuclidine gave N-quaternary ammonium halides in high yields in contrast to the low reactivity of acyclic tertiary amines. Dichloro- and trichloro-nitrobenzenes also react with diethylamine, pyrrolidine, and morpholine to give mono-, di-, and trisubstitution products depending upon the amount of amine and the position of nitro group in these chlorides.

The reaction of aromatic chlorides, bromides and iodides with various primary or secondary amines in a tetrahydrofuran solution under high pressure of 6–12 kbar gave the corresponding secondary and tertiary aromatic amines. The yields of the products depend on the bulkiness of amines used. 1,4-Diazabicyclo[2.2.2]octane and quinuclidine gave N-aryl quarternary ammonium halides in high yields in contrast to the low reactivity of acyclic tertiary amines.

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A shorter and more practical method for the preparation of N-[1-(3-phenylpropane-1-yl)piperidin-4-yl]-5-thia-1,8b-diazaacenaphthylene-4-carboxamide (4) as an upregulator of the LDL receptor has been developed. 1-(3-Phenylpropyl)piperidin-4-amine (7) was synthesized with 71% yield by the alkylation of 4-aminopyridine (5) with 3-phenylpropylbromide followed by reduction with NaBH 4 in the presence of base in a mixture of 2-propanol and methanol. The addition of base (1 equiv), for example, KOH and NaOMe, in the above reduction afforded a decrease of 1-(3-phenylpropyl)-N-[1-(3-phenylpropyl)piperidin-4-yl]piperidin-4-amine (8) to increase the yield of 7. The amidation of 5-thia-1,8b-diazaacenaphthylene-4-carboxylic acid (1) with the primary amine (7) using EDCI in the presence of HOBt (0.2 equiv) provided 4 in 94% yield.

The high pressure Diels–Alder reactions of 5-methoxy-2-methyl-4-(p-nitrophenyl)oxazole with ethylenic dienophiles such as N-methylmaleimide, N-phenylmaleimide, dimethyl maleate and dimethyl fumarate gave the corresponding adducts in good to excellent yields. The effects of pressure, temperature, solvents on the yields were investigated. The high pressure also increased the formation of 3-hydroxypyridine derivatives via the elimination of methanol from the adducts. The stereospecificity of the reaction was confirmed for the reactions with maleate and fumarate.