2-(Dimethylamino)-3-butenenitrile1

(1; R1 = H, R2 = Me, Me)

[96840-18-5]  · C6H10N2  · 2-(Dimethylamino)-3-butenenitrile  · (MW 110.18) (2; R1 = H, R2 = (CH2)4)

[96840-19-6]  · C8H12N2  · 2-(1-Pyrrolidino)-3-butenenitrile  · (MW 136.20) (3; R1 = H, R2 = (CH2)5)

[96840-20-9]  · C9H14N2  · 2-(1-Piperidino)-3-butenenitrile  · (MW 150.25) (4; R1 = R2 = Me, Me)

[74603-42-2]  · C7H12N2  · 2-(Dimethylamino)-3-pentenenitrile  · (MW 124.21) (5; R1 = Me, R2 = Et, Et)

[81540-41-2]  · C9H16N2  · 2-(Diethylamino)-3-pentenenitrile  · (MW 152.27) (6; R1 = Me, R2 = (CH2)4)

[74603-43-3]  · C9H14N2  · 2-(1-Pyrrolidino)-3-butenenitrile  · (MW 150.25) (E)-(7; R1 = Me, R2 = (CH2)4)

[101132-09-6]  · C9H14N2  · 2-(Dimethylamino)-3-butenenitrile  · (MW 150.25) (E)-(8; R1 = Me, R2 = (CH2)5)

[101132-11-0]  · C10H16N2  · 2-(Piperidino)-3-pentenenitrile  · (MW 164.28)

(lithiation gives ambident anions for nucleophilic acylation (acrolein C-1 anion) and for use as ester homoenolate equivalents; synthesis of a-cyano enamines, a-hydroxy-a,b-enones, g-lactones, and, by Grignard alkylation, allylic amines)

Physical Data: (3) bp 94 °C/10 mmHg; d 0.981 g cm-3. (4) bp 64-65 °C/10.5 mmHg; d 0.876 g cm-3. (7) bp 51 °C/0.015 mmHg. (8) bp 55 °C/0.015 mmHg.

Metalation.

Deprotonation of either b,g- or a,b-unsaturated a-(dialkylamino)nitriles with Lithium Diisopropylamide or n-Butyllithium at low temperatures generates ambident nitrile-stabilized carbanions.2-6

Alkylation.

Alkylation of the nitrile-stabilized carbanions from b,g- and a,b-unsaturated a-(dialkylamino)nitriles with various electrophiles occurs regioselectively at the g-position to give a-cyano enamines (a-amino acrylonitriles) (eq 1).2-6 Substitution at the b-position of these substrates does not change the regioselectivity for g-alkylation; however, a combination of increased steric hindrance at the b-position and diminished size of the a-dialkylamino group leads to mixtures of a- and g-alkylation products (eq 1; NR1R2 = NMe2).6 In contrast, the b,g-unsaturated a-(morpholino)nitriles show high a-regioselectivity in alkylations.7

Addition of the nitrile-stabilized anions derived from these unsaturated a-(dialkylamino)nitriles to aromatic3,4,6 and aliphatic4 aldehydes occurs at the g-carbon. However, the corresponding reaction with ketones provides either the kinetic a-alkylation product or the thermodynamic g-alkylation product depending on conditions. In the former case, hydrolysis of the a-adducts affords a-hydroxy-a,b-unsaturated ketones (eq 2),5 whereas in the latter case, hydrolysis of the d-hydroxy-a-cyano enamines gives rise to g-lactones (eq 3).3-5 The addition of an equivalent of anhydrous Zinc Chloride to these reactions reduces competing aldol condensations.5 The reaction of the anions of unsaturated a-(dialkylamino)nitriles with a,b-unsaturated ketones generally results in alkylation at the g-carbon of the nitrile and 1,4-addition to the a,b-unsaturated ketone. With b-substituents on the a,b-unsaturated ketone the kinetic 1,2-g-product is favored at low temperatures and the thermodynamic 1,4-g-product is formed at 25 °C.2

Cyano Group Substitution by Grignard Reagents (Bruylant's Reaction).

The reaction of primary and secondary aliphatic, aromatic, or vinylic Grignard reagents with a-dialkylamino-b,g-unsaturated nitriles leads to a-substituted allylic amines (eq 4).8

Related Reagents.

2-(t-Butylamino)-3-methyl-2-butenenitrile; 1,3-Dibutoxy-1-lithio-1-propene; 1-Ethoxy-1-(trimethylsilyloxy)cyclopropane; 1-Methoxyallenyllithium; (E)-3-Methylthio-2-propenyl p-Tolyl Sulfone.


1. Albright, J. D. T 1983, 39, 3207.
2. Lesur, B.; Toye, J.; Chantrenne, M.; Ghosez, L. TL 1979, 2835.
3. Costisella, B.; Gross, H. T 1982, 38, 139 (CA 1982, 97, 55 908k).
4. Costisella, B.; Gross, H.; Schick, H. T 1984, 40, 733 (CA 1984, 101, 54 818v).
5. Jacobson, R. M.; Clader, J. W. TL 1980, 21, 1205.
6. Ahlbrecht, H.; Vonderheid, C. S 1975, 512 (CA 1975, 83, 206 350m)
7. Takahashi, K.; Honma, A.; Ogura, K.; Iida, H. CL 1982, 1263.
8. Ahlbrecht, H.; Dollinger, H. S 1985, 743.

David Watt & Miroslaw Golinski

University of Kentucky, Lexington, KY, USA



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