LITHIUM TETRAMETHYLPIPERIDIDE

LITHIUM TETRAMETHYLPIPERIDIDE Property

solubility 

sol most organic solvents including THF, Et2O, hexane.

form 

solid

InChI

InChI=1S/C9H18N.Li/c1-8(2)6-5-7-9(3,4)10-8;/h5-7H2,1-4H3;/q-1;+1

InChIKey

ANYSGBYRTLOUPO-UHFFFAOYSA-N

SMILES

C1CCC(C)(C)[N-]C1(C)C.[Li+]

Safety

Hazard Codes 

F,C

Risk Statements 

63-14/15-34-62

Safety Statements 

16-26-36/37/39-43-45

RIDADR 

UN 3131 8(4.3) / PGII

WGK Germany 

3

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H261In contact with water releases flammable gas

H314Causes severe skin burns and eye damage

Precautionary statements

P231+P232Handle under inert gas. Protect from moisture.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P310Immediately call a POISON CENTER or doctor/physician.

P422Store contents under …

LITHIUM TETRAMETHYLPIPERIDIDE Chemical Properties,Usage,Production

Physical properties

Lithium 2,2,6,6-Tetramethylpiperidide exists in THF solution as a dimer-monomer equilibrium mixture; additives such as HMPA increase monomer concentration. X-ray structure determination shows that LiTMP crystallizes as a tetramer from hexane/pentane mixtures.

Uses

Lithium 2,2,6,6-tetramethylpiperidide is a strong base and can be used:

• For the synthesis of enamines from terminal epoxides through trans-α-lithiated epoxide as an intermediate.
• For ortholithiation of arenes such as 1,3-bis(trifluoromethyl)benzene, 4,4-dimethyl-2-phenyl-2-oxazoline, 1,4-bis(trifluoromethyl)benzene and 1,3-dimethoxybenzene.
• In combination with Lewis donor ligand, N,N,N′,N′-tetramethylethylenediamine (TMEDA) for deprotonative metalation of methoxy-substituted arenes.{21]

Application

Lithium 2,2,6,6-Tetramethylpiperidide (LTMP) is a strong, highly hindered, nonnucleophilic base (pKa = 37.3) capable of selective deprotonation of aromatics, heteroaromatics, and aliphatic C-H acidic sites in the presence of a variety of functional groups; also compatible with several electrophiles for in situ quenching of kinetically derived lithiated species.

Preparation

Preparative Method of Lithium 2,2,6,6-Tetramethylpiperidide: prepared in Et2O or THF solutions immediately before use by treatment of commercially available dry 2,2,6,6-Tetramethylpiperidine with n-Butyllithium (1:1). Tetramethylpiperidine is dried by heating a mixture of the base with CaH2 at reflux for 4 h in a preflamed flask, followed by distillation at atmospheric pressure (bp 152 °C). It should be stored in a septum sealed bottle.

storage

LiTMP solutions are pyrophoric, can cause severe burns, and should always be handled and transferred under an inert atmosphere. Solutions of LiTMP show a loss of activity (50% in THF; 60% in Et2O) after 12 h at 24 °C. Use in a fume hood.