[75-17-2]  · CH3NO  · Formaldoxime  · (MW 45.05)

(formylation of arenes via diazonium salts;1,2 1,3-dipolar cycloaddition with electron-deficient alkenes and alkynes to form isoxazolidines3)

Alternate Name: formaldehyde oxime.

Physical Data: mp 2.5 °C; bp 84 °C.

Solubility: frequently used in aqueous solution or in admixture with aqueous methanolic solution.

Form Supplied in: commercially available as hydrochloride.

Preparative Methods: reaction of 37% aqueous formaldehyde with hydroxylamine hydrochloride to which sodium hydroxide in 30% aqueous methanol is added (eq 1).3-5 This procedure affords useful solutions of formaldoxime in aqueous methanol.3 Alternatively, paraformaldehyde with hydroxylamine hydrochloride in the presence of sodium acetate in aqueous medium produces a 10% solution of formaldoxime.2

Handling, Storage, and Precautions: stable as hydrochloride; the oxime readily polymerizes at room temperature and is more stable in aqueous solution. Handle in a fume hood.

In the older literature, the trimer of formaldoxime is often reported, although this form was an open-chain polymer.6 In contrast, O-acetyl and O-benzoyl derivatives of formaldoxime are cyclic trimeric compounds, i.e. derivatives of 1,3,5-trihydroxyhexahydro-1,3,5-triazine.6 The hydrochloride (CH2NOH)3.HCl and other salts also exist as the cyclic trimer. They depolymerize into monomeric formaldoxime by neutralization. The cyclic trimer, which can be isolated, is water soluble and rearranges fast into the water-insoluble polymer. 1H NMR spectra (D2O) demonstrate equilibration between the monomer and the trimer. At high pH, this equilibrium is completely shifted to the monomeric form.6 The 13C NMR chemical shift and 13C-15N coupling constant have been reported.7

Formylation of Arenes via Diazonium Salts.

Formaldoxime reacts with aromatic diazonium salts to give the corresponding substituted benzaldehyde oxime derivative, which is hydrolyzed in acid medium to afford aromatic aldehydes (eqs 2 and 3).1,2 The net reaction constitutes the conversion of anilines into aryl aldehydes (eq 4).3,8-12

1,3-Dipolar Cycloaddition with a,b-Unsaturated Nitriles and Acrylates.

Formaldoxime acts as a 1,3-dipole in cycloaddition reactions with acrylonitrile (eq 5) and methyl acrylate (eq 6), affording functionalized isoxazolidines.3 In both cases, the 1,3-cycloadduct is partially converted into the Michael adduct of the isoxazolidine with the a,b-unsaturated nitrile or acrylate. In contrast, acetaldoxime reacts with the same electron-deficient alkenes to give mixtures of regioisomeric isoxazolidines.13

Cycloaddition with Propiolates.

The reaction of formaldoxime with ethyl propiolate (see Methyl Propiolate) in 50% aqueous methanol leads to diethyl pyridine-3,5-dicarboxylate, during which a 1,4-dipolar cycloaddition mechanism is operative (eq 7).3

Additions of Carbanions Across the Carbon-Nitrogen Double Bond.

Formaldoxime undergoes addition of fluorodinitromethane in a biphase system of water-diethyl ether in the presence of sodium carbonate to afford 2-fluoro-2,2-dinitroethylhydroxylamine in moderate yield (eq 8).14

Related Reagents.

Acetaldoxime; Benzenediazonium Chloride; Benzenediazonium Tetrafluoroborate; Formaldehyde; Hydroxylamine; Methyl Propiolate.

1. Beech, W. F. JCS 1954, 1297.
2. Jolad, S. D.; Rajagopal, S. OS 1966, 46, 13.
3. Ochiai, M.; Obayashi, M.; Morita, K. T 1967, 23, 2641.
4. Dunstan, W. R.; Bossi, A. L. JCS 1898, 353.
5. Dunstan, W. R.; Goulding, E. JCS 1901, 628.
6. Jensen, K. A. AG 1974, 86, 314; AG(E) 1974, 13, 348.
7. Lichter, L.; Dorman, D. E.; Wasylishen, R. JACS 1974, 96, 930.
8. Jolad, S. D.; Rajagopal, S. J. Sci. Ind. Res. (India) 1961, 20B, 359 (CA 1962, 56, 1381).
9. Gudi, N.; Hiremeth, S.; Badiger, V.; Rajagopal, S. AP 1962, 295, 16.
10. Vernekar, S. S.; Jolad, S. D., Rajagopal, S. M 1962, 93, 271.
11. Jolad, S. D.; Rajagopal, S. N 1961, 48, 645.
12. Jolad, S. D.; Rajagopal, S. C 1962, 16, 196.
13. Grigg, R.; Jordan, M.; Tangthongkum, A.; Einstein, F. W. B.; Jones, T. JCS (P1), 1984, 47.
14. Adolph, H. G. JOC 1975, 40, 2626.

Norbert De Kimpe

University of Gent, Belgium

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