Production and use of zinc amides

Patent metadata

Field	Value
Publication number	US-9688701-B2
Application number	US-201615088285-A
Country	US
Kind code	B2
Filing date	Apr 1, 2016
Priority date	Feb 13, 2009
Publication date	Jun 27, 2017
Grant date	Jun 27, 2017

Abstract

Compounds, methods of making the compounds and methods of using the compounds are generally described herein. The compounds are generally of formula R 1 R 2 N—ZnY LiY, wherein R 1 and R 2 are independently selected from H, aryl, heteroaryl containing one or more heteroatoms, alkyl, alkenyl, alkynyl, and silicon derivatives thereof; and each Y is independently selected from F, Cl, Br, I, CN, SCN, NCO, HalO 3 , HalO 4 , NO 3 , BF 4 , PF 6 , H, an alcoholate of formula OR 5 , a carboxylate of formula R 5 CO 2 ; a thiolate of formula SR 5 , R 5 P(O)O 2 , SCOR 5 , SCSR 5 , O n SR 5 and NO n , wherein n=2 or 3; wherein R 5 is selected from substituted or unsubstituted aryls or heteroaryls containing 3 to 24 carbon atoms and one or more heteroatoms selected from B, O, N, S, Se, P, linear, branched or cyclic, substituted or unsubstituted alkyls, alkenyls, alkynyls or H; and wherein Hal is a halogen selected from Cl, Br and I.

First claim

The invention claimed is:

1. A compound of formula R 1 R 2 N—ZnY LiY wherein
R 1 and R 2 form together in connection with N to form a cyclic amide structure which is derived from a divalent saturated or unsaturated, linear or branched alkyl, alkenyl or alkynyl moiety; and
each Y is independently selected from F, Cl, Br, I, CN, SCN, NCO, HalO 3 , HalO 4 , NO 3 , BF 4 , PF 6 , H, and NO R , wherein n=2 or 3; and wherein Hal is a halogen selected from Cl, Br and I.

2. The compound of claim 1 , wherein the cyclic amide structure has one or more substituents derived from aliphatic, alicyclic, aromatic or heteroaromatic hydrocarbons, and wherein each substituent is bound to the cyclic structure via a carbon atom.

3. The compound of claim 2 , wherein the cyclic amide structure comprises piperidide and wherein each Y is independently selected from F, Cl, Br and I.

4. The compound of claim 1 , wherein each Y is independently selected from F, Cl, Br, and I.

5. The compound of claim 1 , wherein Y is Cl.

6. A process for the preparation of a compound comprising:
reacting R 1 R 2 N—H with a lithium alkyl in the presence of ZnY 2 and a solvent to form the compound having the formula R 1 R 2 N—ZnY LiY, wherein
R 1 , R 2 form together in connection with N to form a cyclic amine structure which is derived from a divalent saturated or unsaturated, linear or branched alkyl, alkenyl or alkynyl moiety; and
Y is independently selected from F, Cl, Br, I, CN, SCN, NCO, HalO 3 , HalO 4 , NO 3 , BF 4 , PF 6 , H, and NO R , wherein n=2 or 3; and wherein Hal is a halogen selected from Cl, Br and I.

7. The process of claim 6 , wherein the cyclic amine structure has one or more substituents derived from aliphatic, alicyclic, aromatic or heteroaromatic hydrocarbons, and wherein each substituent is bound to the cyclic structure via a carbon atom.

8. The process of claim 7 , wherein the cyclic amine structure comprises piperidine and wherein Y is selected from F, Cl, Br and I.

9. The process of claim 7 , wherein Y is selected from F, Cl, Br, and I.

10. The process of claim 7 , wherein the solvent is selected from cyclic, linear or branched mono or polyethers, thioethers, amines, phosphines, and derivatives thereof containing one or more additional heteroatoms selected from O, N, S and P; cyclic, linear or branched alkanes and/or alkenes wherein one or more hydrogens are replaced by a halogen; urea derivatives; aromatic, hetero aromatic or aliphatic hydrocarbons; CS 2 ; or combinations thereof.

11. The process of claim 10 , wherein the solvent is selected from cyclic, linear or branched mono or polyethers, thioethers, amines, phosphines, and derivatives thereof containing one or more additional heteroatoms selected from O, N, S and P.

12. The process of claim 7 , wherein the lithium alkyl is sec-butyl lithium or n-butyl lithium.

13. A process comprising zincating a substrate having a deprotonatable aromatic ring with a compound of formula R 1 R 2 N—ZnY LiY wherein
R 1 and R 2 form together in connection with N to form a cyclic amide structure which is derived from a divalent saturated or unsaturated, linear or branched alkyl, alkenyl or alkynyl moiety; and
each Y is independently selected from F, Cl, Br, I, CN, SCN, NCO, HalO 3 , HalO 4 , NO 3 , BF 4 , PF 6 , H, and NO R , wherein n=2 or 3; and wherein Hal is a halogen selected from Cl, Br and I,
to form a zincated product.

14. The process of claim 13 , wherein the cyclic amide structure comprises piperidide and wherein Y is selected from F, Cl, Br, and I.

15. The process of claim 13 , wherein the substrate is 3,6-dichloropyridazine, 4,6-dichloropyrimidine, 2,6-dichloropyrazine, caffeine, 2,4-difluoronitrobenzene, 2-chloro-3-nitropyridine, 4-fluoro-1-methoxy-2-nitrobenzene, methyl 5-nitrofuran-2-carboxylate, or benzo[b]thiophene-3-carbaldehyde.

16. The process of claim 13 , further comprising contacting the zincated product and an electrophile.

17. The process of claim 16 , wherein the electrophile is iodine, 1-iodo-3-(trifluoromethyl)-benzene, allyl bromide, furoyl chloride, ethyl 4-iodobenzoate, ethyl 2-(bromomethyl)acrylate, 1-chloro-4-iodo-benzene, or 3-bromocyclohexene.

Assignees

• Univ Muenchen Ludwig Maximilians
• Ludwig-Maximilians-Universitat Munchen

Inventors

• Knochel Paul
• Mosrin Marc

Classifications

• C07D211/10

  with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms · CPC title

• C07D405/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07F3/003 Primary

  without C-Metal linkages · CPC title

• C07D241/16

  Halogen atoms; Nitro radicals · CPC title

• C07D239/30

  Halogen atoms or nitro radicals · CPC title