N,N-Diethylaminoacetonitrile1

Et2NCH2CN

[3010-02-4]  · C6H12N2  · N,N-Diethylaminoacetonitrile  · (MW 112.17)

(application as formyl anion and formaldehyde dianion equivalents; synthesis of a-amino nitriles, a-amino-b-hydroxy nitriles, aldehydes, ketones, and a,b-enals)

Physical Data: bp 53 °C/10 mmHg,2 61-63 °C/14 mmHg,3 170 °C;4 d 0.866 g cm-3.

Solubility: sol water and most common organic solvents.

Form Supplied in: liquid; commercially available.

Preparative Method: prepared from diethylamine, formaldehyde, sodium cyanide, and sodium disulfite.3

Handling, Storage, and Precautions: is an organic cyanide and should be handled with due care in a fume hood.

Lithiation.

Lithio-N,N-diethylaminoacetonitrile [67685-64-7] is generated from N,N-diethylaminoacetonitrile using Lithium Diisopropylamide in ether or THF at -78 °C.

Alkylation.

Lithio-N,N-diethylaminoacetonitrile functions as a formyl anion equivalent. Other analogs of N,N-diethylaminoacetonitrile having different alkyl groups on nitrogen have been reviewed elsewhere.1 Alkylation of N,N-diethylaminoacetonitrile with alkyl chlorides, bromides, iodides, and tosylates,5,6 as well as Michael acceptors, and hydrolysis of the monoalkylation and dialkylation products with Oxalic Acid,5 Copper(II) Sulfate,5,7 or Hydrochloric Acid6 in aqueous THF, furnishes aldehydes and ketones, respectively. Oxalic acid5 will not hydrolyze dialkylation products unless b,g-unsaturation is present. The deprotection method using copper(II) sulfate leaves acetal groups intact and allows the preparation of keto aldehyde acetals (eq 1).5 Alkylation with allylic bromides followed by hydrolysis proceeds with concomitant isomerization of the alkene to afford a,b-unsaturated aldehydes.8 Similar alkylations with epoxides followed by acid-catalyzed hydrolysis proceed with concomitant dehydration to provide a,b-unsaturated aldehydes.5 An unusual addition to azulene and a subsequent oxidation and hydrolysis of the amino nitrile with aqueous Silver(I) Nitrate furnishes a mixture of 4- and 6-azulenecarbaldehydes.9

In contrast to N,N-diethylaminoacetonitrile, alkylations10 of N,N-dimethylaminoacetonitrile with allylic halides proceed through N-alkylation and subsequent [2,3]-sigmatropic rearrangement. However, alkylation with 2-octyl iodide occurs at carbon.11 Addition of lithio-N,N-diethylaminoacetonitrile to saturated12-14 or a,b-unsaturated carbonyl compounds15 leads to diastereomeric b-hydroxy-a-diethylamino nitriles, and a subsequent dehydration affords a-(diethylamino)acrylonitriles in modest yield.13

Reactions with Heteroelectrophiles.

The anion of N,N-diethylaminoacetonitrile reacts with Dimethyl Disulfide16 and Chlorotrimethylgermane17 to give the a-methylthio and a-trimethylgermyl derivatives, respectively. Direct silylation of the anion of N,N-diethylaminoacetonitrile with Chlorotrimethylsilane failed,12 but the LDA-induced rearrangement of a silylammonium salt12 formed from N,N-diethylaminoacetonitrile and chlorotrimethylsilane gives the a-trimethylsilyl derivative (eq 2).18

Other Reactions.

N,N-Diethylaminoacetonitrile undergoes a Ritter reaction with 1-adamantol19 to give an a-(diethylamino)acetamide, and participates in a Bis(cyclopentadienyl)cobalt-catalyzed reaction with acetylene to form 2-(diethylaminomethyl)pyridine.20

Related Reagents.

N,N-Dimethyldithiocarbamoylacetonitrile; 2-(2,6-Dimethylpiperidino)acetonitrile; (4aR)-(4aa,7a,8ab)-Hexahydro-4,4,7-trimethyl-4H-1,3-benzoxathiin; 2-Lithio-1,3-dithiane; Methoxyacetonitrile; Nitromethane; 1,1,3,3-Tetramethylbutyl Isocyanide; p-Tolylthiomethyl Isocyanide; 2-(Trimethylsilyl)thiazole.


1. Albright, J. D. T 1983, 39, 3207.
2. Luten, D. B. Jr., JOC 1938, 3, 588.
3. Allen, C. F. H.; VanAllan, I. A. OSC 1955, 3, 275.
4. Sen, A. B.; Gupta, S. K. JIC 1962, 39, 129.
5. Stork, G.; Ozorio, A. A.; Leong, A. Y. W. TL 1978, 19, 5175.
6. Schill, G.; Rissler, K.; Fritz, H. CB 1983, 116, 1866 (CA 1983, 99, 5616j).
7. Büchi, G.; Liang, P. H.; Wüest H. TL 1978, 19, 2763.
8. Dauben, W. G.; Saugier, R. K.; Fleischhauer, I. JOC 1985, 50, 3767.
9. Hünig, S.; Hafner, K.; Ort, B.; Müller, M. LA 1986, 1222 (CA 1986, 105, 60 333g).
10. (a) Stella, L. TL 1984, 25, 3457. (b) Stella, L.; Amrollah-Madjdabadi, A. SC 1984, 14, 1141. (c) Stella, L.; Amrollah-Madjdabadi, A. BSF 1987, 350 (CA 1988, 108, 112 768m). (d) Suzuki, T.; Sato, E.; Unno, K.; Kametani, T. CPB 1986, 34, 3135. (e) Weinreb, S. M.; Basha, F. Z.; Hibino, S.; Khatri, N. A.; Kim, D.; Pye, W. E.; Wu, T.-T. JACS 1982, 104, 536.
11. Hebert, E.; Maigrot, N.; Welvart, Z. TL 1983, 24, 4683 (CA 1984, 100, 138 265e).
12. Padwa, A.; Eisenbarth, P.; Venkatramanan, M. K.; Wong, G. S. K. JOC 1987, 52, 2427.
13. Ferrier, R. J.; Tyler, P. C. Carbohydr. Res. 1985, 136, 249.
14. For related reactions involving N-methyl-N-phenylaminoacetonitrile, see: (a) Takahashi, K.; Shibasaki, K.; Ogura, K.; Iida, H. JOC 1983, 48, 3566. (b) Jonczyk A.; Owczarczyk, Z. S 1986, 297. (c) Fang J.-M.; Yang C.-C.; Wang Y.-W. JOC 1989, 54, 477.
15. Gill, M.; Bainton, H. P.; Rickards, R. W. TL 1981, 22, 1437.
16. Jonczyk, A.; Owczarczyk, Z.; Makosza, M.; Winiarski, J. BSB 1987, 96, 303.
17. Marumo, K.; Inoue, S.; Sato, Y. S 1991, 169.
18. Okazaki, S.; Sato, Y. S 1990, 36.
19. Plakhotnik, V. M.; Kovtun, V. Yu.; Yashunskii, V. G. JOU 1982, 18, 867.
20. Ivanov, A. P.; Levin, D. Z.; Mortikov, E. S.; Promonenkov, V. K. JOU 1989, 25, 566.

David Watt & Miroslaw Golinski

University of Kentucky, Lexington, KY, USA



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