Organic Syntheses Procedure

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Org. Synth. 1997, 74, 130

DOI: 10.15227/orgsyn.074.0130

NITROACETALDEHYDE DIETHYL ACETAL

[Ethane, 1,1-diethoxy-2-nitro-]

Submitted by V. Jäger and P. Poggendorf¹.

Checked by E. Jnoff and Leon Ghosez.

1. Procedure

CAUTION! Distillation of nitromethane and reactions using it as a solvent or a reactant at an elevated temperature, as well as reactions of nitroalkanes in general, should be conducted behind a safety shield. In one instance a minor deflagration was observed upon erroneously aerating the distillation residue while it was still hot. The apparatus, therefore, should only be ventilated after cooling to ambient temperature, and nitrogen, not air, is recommended for this purpose.

A 500-mL, round-bottomed flask, equipped with a magnetic stirring bar, 20-cm Vigreux column, column head, Claisen distilling head, and thermometer, is charged with 89.3 g (602 mmol) of triethyl orthoformate (Note 1), 180 g (2.95 mol) of nitromethane (Note 2), and 5.00 g (36.6 mmol) of anhydrous zinc chloride. The solution is heated to 90°C (oil bath temperature, (Note 3)). After 16 hr (overnight) ca. 30 mL of ethanol is collected (Note 4). The remaining mixture, a brown suspension, is cooled to room temperature, and filtered by suction through a sintered glass funnel. The brown liquid obtained is distilled from a 100-mL, round-bottomed flask through a 20-cm Vigreux column at reduced pressure. First, excess nitromethane is removed (bp ca. 30°C/35 mm), then the fraction boiling at 58–60°C/1 mm (Note 3) is collected to afford 39–41 g (40–42% yield) of nitroacetaldehyde diethyl acetal 1 as a colorless liquid (Note 4), (Note 5).

2. Notes

1. All reagents were purchased from Fluka Feinchemikalien GmbH, Neu-Ulm, Germany and used without further purification.

2. Nitromethane, 98% purity, was used.

3. The rate of heating depends on the type of Vigreux column used, in this case a 20-cm, silver-plated Vigreux column with 4-cm outer and 1 1/2-cm inner diameter. The bath temperature should not be raised above 110°C when using this type of column, to avoid co-distillation of nitromethane (bp at 760 mm, 101°C). Ethanol should be distilled off at a rate of about 10 drops/min.

4. The spectroscopic properties of nitroacetaldehyde diethyl acetal are as follows: IR (film) n_max cm⁻¹: 2970 (CH), 2920 (CH), 2880 (CH), 1550 (N=O), 1365 (N=O), 1340, 1120 (C-O), 1060; ¹H NMR (250 MHz, CDCl₃) δ: 1.15 (t, 6 H, CH₂CH₃), 3.56 and 3.67 (2 q, 4 H, J = 7.1, 2 CH₂CH₃), 4.44 ("d", 2 H, J = 5.8, CH₂NO₂), 5.09 ("t", 1 H, J = 5.8, CH); ¹³C NMR (63 MHz, CDCl₃) δ: 15.0 (q, CH₂CH₃), 63.3 (t, CH₂CH₃), 76.8 (t, CH₂NO₂), 98.7 [d, CH(OEt)₂].

5. This reaction was carried out in the submitter's group more than 30 times, with yields ranging from 32–41% (lit.²: 49%). The purity of this material was repeatedly determined by gas chromatographic analysis to be >98%. GLC analysis: Column PS 086/.30 mm × 20 m glass capillary, 95:5 methyl/phenylsilicone. Program T₁, 40°C (1 min), rate 10°C/min; T₂, 300°C, 0.4 mm hydrogen pressure; R_t = 9.37 min.

Handling and Disposal of Hazardous Chemicals

The procedures in this article are intended for use only by persons with prior training in experimental organic chemistry. All hazardous materials should be handled using the standard procedures for work with chemicals described in references such as "Prudent Practices in the Laboratory" (The National Academies Press, Washington, D.C., 2011 www.nap.edu). All chemical waste should be disposed of in accordance with local regulations. For general guidelines for the management of chemical waste, see Chapter 8 of Prudent Practices.

These procedures must be conducted at one's own risk. Organic Syntheses, Inc., its Editors, and its Board of Directors do not warrant or guarantee the safety of individuals using these procedures and hereby disclaim any liability for any injuries or damages claimed to have resulted from or related in any way to the procedures herein.

3. Discussion

This procedure describes the preparation of nitroacetaldehyde diethyl acetal 1 according to the method of René and Royer.²

Two other procedures for the preparation of 1 are known, i.e., by treatment of chloroacetaldehyde diethyl acetal with silver nitrite,³ and by the reaction of α,α-diethoxymethyltriethylammonium tetrafluoroborate and nitromethane.⁴ These alternate methods are less suited and less economic for preparation of 1 on a large scale. The dimethyl acetal has been obtained by treatment of 1-chloro-2-nitroethene with sodium methoxide.⁵

Diethyl acetal 1 has been used to obtain various other acetals by transacetalization,⁶^,⁷ such as the dimethyl, the ethyleneglycol, and the neopentylglycol acetal (2,2-dimethyl-1,3-propylidene acetal).

Aliphatic nitro compounds are highly versatile building blocks in organic synthesis⁸ ⁹ ¹⁰ ¹¹^,¹² ¹³ (see Scheme 1). For example, the nitroaldol addition (Henry reaction)¹⁴ leads to the formation of 1,2-nitro alcohols, 2, which are easily transformed into 1,2-amino alcohols, 3, by reduction, and into α-hydroxycarbonyl compounds, 4, by hydrolysis¹⁵ (Nef reaction). The former process, mostly using nitromethane, has been widely employed in carbohydrate chemistry.¹⁶ ¹⁷ ¹⁸ ¹⁹ ²⁰ ²¹ ²²

Dehydration of primary nitro compounds (Mukaiyama reaction)²³ affords nitrile oxides, which may dimerize to yield furoxans, or otherwise be trapped by suitable dipolarophiles such as double or triple bond systems, leading to the formation of various heterocyclic systems, 5.²⁴ ²⁵ The latter have been used for further derivatization in the heterocyclic series, or in "return" as precursors of acyclic products after ring cleavage,¹¹^,²⁶ ²⁷ ⁷ for example, 1,3-amino alcohols 6 or β-hydroxycarbonyl compounds, 9.

Both nitroaldol²⁸ ²⁹ and 1,3-dipolar cycloaddition products (e.g., isoxazolines, from alkenes)²⁴^,²⁵^,²⁶^,²⁷^,⁷ have shown that nitroacetaldehyde diethyl acetal 1 constitutes a versatile C₂ building block in organic synthesis, notably what concerns amino sugar target structures. Recent work both on nitroaldol and nitroalkane derived dipolar additions has concentrated on the study and elaboration of stereoselective C-C forming steps with nitroalkanes.

Further uses of nitroalkanes are in 1,4-additions (Michael reaction) to α,β-unsaturated carbonyl compounds and the like. Recent reports deal with transformations of 1,4-nitro ketones, 7, into 1,4-keto aldehydes, 8, and cyclization to cyclopentenones.³⁰ ³¹

This preparation is referenced from:

Org. Syn. Coll. Vol. 10, 577

References and Notes

Institut für Organische Chemie und Isotopenforschung der Universität Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart, Germany.
René, L.; Royer, R. Synthesis 1981, 878.
Losanitsch, M. S. Ber. Dtsch. Chem. Ges. 1909, 42, 4044.
Kabusz, S.; Tritschler, W. Synthesis 1971, 312.
Francotte, E.; Verbruggen, R.; Viehe, H. G.; van Meerssche, M.; Germain, G.; Declercq, J.-P. Bull. Soc. Chim. Belg. 1978, 87, 693.
Müller, R. Dissertation, Universität Würzburg, 1992.
Jäger, V.; Schohe, R. Tetrahedron 1984, 40, 2199.
Schickh, O. von.; Apel, G.; Padeken, H. G.; Schwarz, H. H.; Segnitz, A. In "Methoden der Organischen Chemie (Houben-Weyl)", 4th ed.; Müller, E., Ed.; Georg Thieme Verlag: Stuttgart, 1971; Vol. X. Part 1, pp. 1–462;
Behnisch, R.; Behnisch, P.; Mattmer, R. In "Methoden der Organischen Chemie (Houben-Weyl)", 4th ed.; Klamann, D., Ed.; Georg Thieme: Stuttgart, 1992; Vol. E 16d, Part 1, pp. 142–254;
Nielsen, A. T. In "The Chemistry of the Nitro and Nitroso Groups"; Feuer, H., Ed.; Wiley: New York, 1969, pp. 349–486;
Torssell, K. B. G. "Nitrile Oxides, Nitrones, and Nitronates in Organic Synthesis"; VCH: New York, 1987
Baer, H. H. Adv. Carbohydr. Chem. Biochem. 1969, 24, 67;
Wade, P. A.; Giuliano, R. M. In "Nitro Compounds; Recent Advances in Synthesis and Chemistry"; Feuer, H.; Nielsen, A. T., Eds.; VCH: Weinheim, 1990, pp. 137–265.
Henry, L. C. R. Hebd. Acad. Sci. 1895, 120, 1265.
Noland, W. E. Chem. Rev. 1955, 55, 137.
Sowden, J. C. Adv. Carbohydr. Chem. 1951, 6, 291;
Sowden, J. C. Methods Carbohydr. Chem. 1962, 1, 132;
Whistler, R. L.; BeMiller, J. N. Methods Carbohydr. Chem. 1962, 1, 137;
Sowden, J. C.; Oftedahl, M. L. Methods Carbohydr. Chem. 1962, 1, 235;
Paulsen, H.; Brieden, M.; Sinnwell, V. Liebigs Ann. Chem. 1985, 113;
Baer, H. H. J. Am. Chem. Soc. 1962, 84, 83;
Lichtenthaler, F. W.; Nakagawa, T. Chem. Ber. 1968, 101, 1846.
Mukaiyama, T.; Hoshino, T. J. Am. Chem. Soc. 1960, 82, 5339.
Jäger, V.; Grund, H.; Buß, V.; Schwab, W.; Müller, I.; Schohe, R.; Franz, R.; Ehrler, R. Bull. Soc. Chim. Belg. 1983, 92, 1039;
Jäger, V.; Müller, I.; Schohe, R.; Frey, M.; Ehrler, R.; Häfele, B.; Schröter, R. Lect. Heterocycl. Chem. 1985, 8, 79.
Jäger, V.; Grund, H. Angew. Chem. 1976, 88, 27; Angew. Chem. Int. Ed. Engl. 1976, 15, 50;
Jäger, V.; Müller, I. Tetrahedron 1985, 41, 3519 and references therein;
Wehner, V.; Jäger, V. Angew. Chem. 1990, 102, 1180; Angew. Chem. Int. Ed. Engl. 1990, 29, 1169;
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Rosini, G.; Ballini, R.; Sorrenti, P. Tetrahedron 1983, 39, 4127;
Rosini, G.; Ballini, R.; Petrini, M.; Sorrenti, P. Tetrahedron 1984, 40, 3809.

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

dimethyl, the ethyleneglycol

neopentylglycol acetal (2,2-dimethyl-1,3-propylidene acetal)

ethanol (64-17-5)

hydrogen (1333-74-0)

nitrogen (7727-37-9)

sodium methoxide (124-41-4)

zinc chloride (7646-85-7)

triethyl orthoformate (122-51-0)

Nitromethane (75-52-5)

silver nitrite (7783-99-5)

chloroacetaldehyde diethyl acetal (621-62-5)

Nitroacetaldehyde diethyl acetal,
Ethane, 1,1-diethoxy-2-nitro- (34560-16-2)

α,α-diethoxymethyltriethylammonium tetrafluoroborate

1-chloro-2-nitroethene

Notes

References/EndNotes

Article Compounds

Authors