Density
functional theory calculations, including Poisson–Boltzmann
implicit solvent and free energy corrections, are applied to construct
a free energy map of formaldehyde and ammonia co-oligomerization in
aqueous solution at pH 7. The stepwise route to forming hexamethylenetetramine
(HMTA), the one clearly identified major product in a complex mixture,
involves a series of addition reactions of formaldehyde and ammonia
coupled with dehydration and cyclization reactions at key steps in
the pathway. The free energy map also allows us to propose the possible
identity of some major peaks observed by mass spectroscopy in the
reaction mixture being the result of stable species not along the
pathway to HMTA, in particular those formed by intramolecular condensation
of hydroxyl groups to form six-membered rings with ether linkages.
Our study complements a baseline free energy map previously worked
out for the self-oligomerization of formaldehyde in solution at pH
7 using the same computational protocol and published in this journal
(<i>J. Phys. Chem. A</i> <b>2013</b>, <i>117</i>, 12658)