TETRAHEDRON
Pergamon
Tetrahedron 58 (2002) 55±60
A mechanistic study of the ammonolysis of alkyl acetoacetates
in water. Formation of 1,5-dimethyl-2,6,9-triaza-
bicyclo[3.3.1]nonane-3,7-dione as the main product
Rodrigo Paredes,a Rodrigo Abonia,a,p John Cadavid,a Rodolfo Moreno-Fuquen,a
Alonso Jaramillo,a Angelina Hormaza,b Alfonso Ramirezc and Allan Kennedyd
aDepartment of Chemistry, Universidad del Valle, A.A. 25360 Cali, Colombia
b
Â
Department of Chemistry, Universidad Nacional, A.A. 3840 Medellõn, Colombia
Â
c
Department of Chemistry, Universidad del Cauca, Calle 2 No 1AÐ45, Popayan, Colombia
dDepartment of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, Scotland, UK
Received 25 September 2001; revised 8 November 2001; accepted 9 November 2001
AbstractÐAmmonolysis of alkyl acetoacetates with 15% NH3 in water at room temperature initially lead to formation of alkyl b-amino-
crotonates which slowly converted into 1,5-dimethyl-2,6,9-triaza-bicyclo[3.3.1]nonane-3,7-dione as the main product. q 2002 Published by
Elsevier Science Ltd.
1. Introduction
2. Results and discussion
We have presented evidence in favor of an enol mechanism
to explain the rapid alkaline hydrolysis of ethyl acetoacetate
in water and the ®rst-order kinetics observed when a dilute
equimolar (1.0£1024 M) solution of ester and HO2 is
allowed to react at room temperature.1 The mechanism
®rst involves the establishment of base catalyzed keto±
enol equilibrium, via the enolate anion, between the
ester and enols CH3C(OH)vCHCO2Et and CH3COCHv
C(OH)OEt. Of these enols, only the latter is reactive
toward nucleophylic addition of water, in the rate-
determining step, to form the dipolar ion CH3C(O2)v
CHC(OH)2O1(H)Et, whose breakdown losing EtOH leads
to the products.
2.1. Study of the products formed in the ammonolysis
reaction
In order to determine the nature of the organic product or
products formed in the ammonolysis reaction, we treated
CH3COCH2CO2Me with excess aqueous 15% NH3 at
room temperature. After about 20 min abundant white
crystals had formed whose analysis showed that they corre-
sponded to methyl b-aminocrotonate 6a (Scheme 1). After
initial formation of the white crystals, the mixture was left
standing at room temperature. After 4 weeks, the reaction
mixture had turned into a yellow aqueous solution. After
water and NH3 were taken off in vacuum, a brown syrupy
solid formed, which was washed with methanol. White
crystals were obtained after the washings. This white solid
was identi®ed as 1,5-dimethyl-2,6,9-triaza-bicyclo[3.3.1]-
In this work, we have investigated the ammonolysis in
water of ethyl and methyl acetoacetates and have
found that an enol mechanism, analogous to the one
proposed for the alkaline hydrolysis of ethyl acetoacetate,
explains the various experimental facts, characteristic of
the reaction.
1
nonane-3,7-dione 10 on the basis of its IR, H, 13C NMR
and mass spectra, X-ray crystallographic analysis and
con®rmed with the spectroscopic and analytical data
reported by Shim and co-workers.2 From the reaction
mixture, we isolated another solid. This solid corresponded
to a pure compound that appears to be another heterocycle
different from 10, 12 and 14 (Schemes 2and 3). We are at
present attempting to determine its structure.
Mechanistically, we believe that, 6a formed as shown in
Scheme 1 and that conversion of 6a into heterocycle 10
took place via intermediates 5a, 7a, 8a and 9 (Scheme 1).
For the conversion of methyl acetoacetate into aceto-
Keywords: acetoacetates; ammonolysis; enol mechanism; b-amino-
crotonates; heterocycles.
Corresponding author. Fax: 157-2-3392440;
e-mail: abonia@quimica.univalle.edu.co
p
0040±4020/02/$ - see front matter q 2002 Published by Elsevier Science Ltd.
PII: S0040-4020(01)01127-9