The reaction of dialkylmalonyl dichlorides with 1,3-diaminopropanes a new route to macrocyclic polyamides and polyamines

✍ Scribed by F. Vellaccio Jr.; R.V. Punzar; D.S. Kemp

• Publisher: Elsevier Science
• Year: 1977
• Tongue: French
• Weight: 200 KB
• Volume: 18
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(01)92690-5

✦ Synopsis

We wish to report convenient syntheses of the macrocyclic amides, l_andH, and their amine NO. 6 9 derivatives. An attempt to establish ;;e presence in L of a strong transannularhydrogen bond,by nmr exchange studies in D20-DMSO have thus far failed, due to the difficulty of obtaining data of precision sufficient to assign an exchange rate to the fourth of four amide protons. An average exchange half-time of 50 hr is observed (10% 020, 25"). Verification of the hydrogen-bonded structures proposed for L,;, and_& as well as the template hypothesis of their formation must await further structural studies and model investigations with n-alkyl derivatives. Reduction of l_ or Zwith excess diborane in THF (20 hr, reflux), followed by evaporation, acidic hydrolysis, basification, and extraction results in7the formation of the tetramine, 2, 75 %, m.p. 154-157", (M' 340 m/e; nmr [CDCl,] 0.93,$.35 6) fromJ, or the hexamine& 75 %, m.p. 118120°, (M+ 510 m/e; nmr [CDC13j0.93,2.40 6). The formation of i from2 in reasonable yield suggests that proper combinations of fragments may generateL,z, or higher homologs by short, simple routes, and this possibility is currently under investigation. The sixteen-memkred amide derived from dimethylmalonyl dichloride and 2,2-bis(hydroxymethyl)-1,3_propanediamine is of special interest to us as a precursor for a variety of chelating agents with cage structures. The diborane reduction of this tetramide yields the corresponding tetramine as a crystalline hydrochloride salt in 23 % overall yield, based on the propane diamine, m.p.268'd. ACKNOWLEDGEMENT Financial support from the National Science Foundation, Grant CHE 75-07771 and from the Dreyfus foundation is gratefully acknowledged.