3,4-Dihydro-2H-pyrido[1,2-a]pyrimidin-2-one

[5439-14-5]  · C8H8N2O  · 3,4-Dihydro-2H-pyrido[1,2-a]pyrimidin-2-one  · (MW 148.16)

(synthesis of esters and amides from carboxylic acids; glycosylation)

Physical Data: mp 155-156 °C; mp (HCl salt) 284-285.5 °C (dec); mp (HBr salt) 299-300 °C (dec); mp (HI salt) 263-264 °C (dec).

Solubility: sol MeOH, EtOH, H2O.

Form Supplied in: both the free base and salts are obtained as colorless solids.

Analysis of Reagent Purity: the reagent has a betaine-like structure and behaves as a salt in terms of the reagent's solubility. The literature reports various melting points values for both the anhydrous and hydrated forms of the reagent but the conditions used to determine melting point have been shown to be critical and care must be exercised if this property is to be used as a measure of reagent purity.1

Preparative Methods: is prepared by reaction of 2-aminopyridine with either Acrylic Acid itself or an equivalent (2-bromo- or 2-iodopropionic acid, Methyl Acrylate, ethyl 2-bromopropionate, b-Propiolactone).1,2

Purification: the free base and salts are readily recrystallized from MeOH-Et2O.1

Handling, Storage, and Precautions: the reagent may be dried over P2O5 in vacuo (135 °C/17 mmHg).

Introduction.

The principal synthetic application of 3,4-dihydro-2H-pyrido[1,2-a]pyrimidin-2-one (1) is an acid scavenger; it is an example of a proton sponge (see 1,8-Bis(dimethylamino)naphthalene). The reagent has been used in the esterification and amination of alkyl and aryl carboxylic acids and also in glycosylation of 2-amino-2-deoxy sugars.

Synthesis of Esters from Carboxylic Acids.3

Esterification (eq 1) proceeds by activation of the carboxyl component using a 2-halopyridinium salt (2; X = Cl, Y = I or X = F, Y = OTs) and (1) (2.4 equiv) in the presence of an alcohol. The best solvents for this process are CH2Cl2 or MeCN, but a range of other solvents may also be used.

Synthesis of Amides from Carboxylic Acids.4

In the corresponding amidation process (eq 2) there is a requirement for the addition of 1 equiv of a tertiary amine (Tri-n-butylamine) to ensure efficient utilization of the amine component (R2R3NH). Once again, carboxyl activation is achieved using a 2-halopyridinium salt (2) but, unlike the esterification reaction, amidation is best carried out as a two-step one-pot process.

Yields for both the esterification (eq 1) and amidation (eq 2) reactions are generally high, but the advantages associated with use of (1) over other reagents for these types of transformation have yet to be clearly defined.

Glycosylation.5

3,4-Dihydro-2H-pyrido[1,2-a]pyrimidin-2-one has been used in conjunction with Silver(I) Trifluoromethanesulfonate as a reagent combination to mediate the glycosylation of N-protected 2-amino-2-deoxy sugars using a glycosyl bromide as the glycosyl donor (eq 3).


1. Hurd, C. D.; Hayao, S. JACS 1955, 77, 117.
2. (a) Magidson, O. Y.; Elina, A. S. JGU 1946, 16, 1933 (CA 1947, 41, 6219). (b) Adams, R.; Pachter, I. J. JACS 1952, 74, 4906, 5491. (c) Krishnan, M.; PIA(A) 1955, 42, 289. (d) Baltrusis, R.; Maciulis, A.; Purenas, A. Lietuvos TSR Moksln Akad. Darbai. Ser. B 1962, 125 (CA 1963, 58, 6827a). (e) Biniecki, S.; Modrzejewska, W. Acta Pol. Pharm. 1984, 41, 607 (CA 1986, 104, 50 843p).
3. Mukaiyama, T.; Toda, H.; Kobayashi, S. CL 1976, 13.
4. Mukaiyama, T.; Aikawa, Y.; Kobayashi, S. CL 1976, 57.
5. Ogawa, T.; Nakabayashi, S.; Sasajima, K. CR, 1981, 96, 29.

Timothy Gallagher

University of Bristol, UK



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