JP2007320938A - Lithium t-butyldiethyl zincate, method for producing the same and method for using the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new zinc ate complex, lithium organic zincate, and to provide a method for using the same. <P>SOLUTION: Lithium t-butyldiethyl zincate represented by chemical formula: t-BuEt<SB>2</SB>ZnLi. The method for using the lithium t-butyldiethyl zincate comprises using the lithium t-butyldiethyl zincate for a halogen-zinc exchange reaction with an organic halogen compound. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to lithium t-butyldiethyl zincate, which is a novel organozinc ate complex.

  Since an organozinc compound is a low nucleophilic reactant, it is known to be useful for reactions in the presence of electrophilic functional groups that are difficult with organolithium and organomagnesium. Lithium organozincate, an art complex synthesized from zinc compound and organolithium, has intermediate properties between organolithium and organozinc, and even halogenated aromatic compounds with functional groups can be selectively halogen-metal exchanged. It is known that reaction can be carried out and o-metalation of functional group-containing aromatic compounds can be carried out.

Lithium trimethylzincate represented by the chemical formula Me ₃ ZnLi and lithium tri-t-butylzincnate represented by the chemical formula t-Bu ₃ ZnLi undergo iodine-zinc exchange reaction with an iodobenzene derivative, and the corresponding aryl dialkylzinc Give lithium acid. In this reaction, even if iodobenzene has a functional group such as a methoxycarbonyl group or a nitro group, lithium aryldialkylzincate is obtained without reacting with these functional groups. The produced lithium aryldialkylzincate can react with an electrophilic agent such as an aldehyde to be derivatized into an aryl adduct (Non-patent Documents 1 and 2).

Lithium (2,2,6,6-tetramethylpiperidino) di-t-butylzincate represented by the chemical formula t-Bu ₂ (TMP) ZnLi is an aromatic compound having two functional groups at the m-position. A proton at the o-position can be selectively extracted without reacting with a functional group, and then reacted with an electrophile to give a 1,2,3-trisubstituted aromatic compound (Patent Document 1). 2, Non-Patent Document 3). At this time, even if the functional group is halogen such as bromine or chlorine, the o-position proton is selectively extracted without reacting with these.

On the other hand, lithium (2,2,6,6-tetramethylpiperidino) dimethylzincate represented by the chemical formula Me ₂ (TMP) ZnLi is reacted with a compound having a leaving group such as a halogen atom in the aromatic ring. In this case, benzyne is selectively generated (Patent Document 3 and Non-Patent Document 3).

  As described above, it is known that the reactivity and selectivity to an aromatic compound can be changed by changing the type of the substituent of the lithium organic zincate. Various organic lithium zincates have been proposed and used in organic reactions and polymerization initiators.

However, so far, lithium t-butyldiethylzincate represented by the chemical formula t-BuEt ₂ ZnLi has not been known.
JP 2004-10583 A JP 2004-10588 A JP 2004-10585 A J. et al. Org. Chem. 1994, 59, 4717 The Pharmaceutical Society of Japan 2002, 122, 11, p. 919 J. et al. Am. Chem. Soc. 2002, 124, 8514

  An object of the present invention is to provide a lithium zinc zincate which is a novel zinc ate complex and a method for using the same.

That is, the present invention has the chemical formula t-BuEt ₂ ZnLi.
And a method for using lithium t-butyldiethylzincate, characterized in that it is used in a halogen-zinc exchange reaction with lithium t-butyldiethylzincate and an organic halogen compound.

  The lithium t-butyldiethylzincate of the present invention is a novel compound. The lithium t-butyldiethylzincate of the present invention can be used as a polymerization initiator for various organic reactions, halogen-zinc exchange reactions, and anionic polymerizable monomers.

  The lithium t-butyldiethylzincate of the present invention can be produced by reacting diethylzinc with an equivalent amount of t-butyllithium in an inert gas atmosphere.

  Diethyl zinc used in the reaction may be a neat product or a solution diluted with a solvent such as heptane, hexane, toluene, THF, diethyl ether, dibutyl ether or the like. A zinc chloride produced in-situ by reacting with an ethylating agent such as ethyllithium or triethylaluminum can also be used. In this case, by-product lithium chloride is lithium t-butyldiethylzincate. May be mixed in solution, and when used in organic reactions, may affect reactivity, selectivity or purity.

  As the t-butyllithium used in the reaction, a commercially available t-butyllithium / pentane solution or t-butyllithium / heptane solution can be used.

  In the reaction, diethylzinc and t-butyllithium solution may be reacted as they are, or ether solvents such as tetrahydrofuran, diethyl ether, dibutyl ether, cyclopentyl methyl ether or hydrocarbons such as pentane, hexane, heptane, toluene. You may carry out with a solvent. Among these, it is preferable to carry out the reaction using an ether solvent from the viewpoint of controlling the temperature during the reaction or maintaining uniformity.

  The reaction between diethylzinc and t-butyllithium can be carried out at a temperature from -80 ° C to the boiling point of the solvent. In particular, when an ether solvent is used as a solvent, t-butyllithium is decomposed by a reaction with an ether solvent as a side reaction.

  It is preferable to use t-butyl diethyl zinc zincate as a solution without isolation from the viewpoints of safety and handleability. From the viewpoint of solubility of the produced lithium t-butyldiethylzincate, ether solvents such as tetrahydrofuran, diethyl ether, dibutyl ether, cyclopentyl methyl ether, or ether solvents and hydrocarbons such as pentane, hexane, heptane, toluene, etc. A mixed solution with a solvent can be used as the solvent.

  The lithium t-butyldiethylzincate in the present invention can also be used for organic reactions, and in particular, can be used for derivation of various organic zinc complexes by halogen-zinc exchange reaction. It can also be used as a polymerization initiator for anionic polymerizable monomers.

The halogen-zinc exchange reaction is to exchange a halogen atom for zinc by reacting a halogen atom of an organic halogen compound with lithium t-butyldiethylzincate in the present invention. By reacting with an electrophilic agent, an organic compound in which a zinc atom is substituted with an electrophilic group can be obtained.
The lithium t-butyldiethylzincate used in the halogen-zinc exchange reaction is used in an amount of 1 to 3 equivalents relative to the organic halogen compound. More preferably, it is 1-1.5 equivalent.

  The solvent used in the reaction is not particularly limited as long as the organic halogen compound and lithium t-butyldiethylzincate are soluble. Examples of such a solvent include diethyl ether, tetrahydrofuran, di-n-butyl ether, Examples thereof include ether solvents such as dioxane, dimethoxyethane, t-butyl methyl ether and cyclopentyl methyl ether, hydrocarbon solvents such as toluene, xylene, hexane and heptane or mixtures thereof.

  The reaction between the organic halogen compound and lithium t-butyldiethylzincate can be carried out at a temperature from -80 ° C to the boiling point of the solvent.

  By using the lithium t-butyldiethylzincate of the present invention, it is possible to select an organic halogen compound having a functional group such as a hydroxyl group, a carbonyl group, a nitrile group, or an amino group without protecting the functional group. Only the halogen-zinc exchange reaction proceeds.

  The organic halogen compound used in the halogen-zinc exchange reaction is not particularly limited, but is preferably an aromatic halogen compound or a halogen-containing heterocyclic compound. Moreover, as a halogen compound, an iodine and a bromine atom are especially preferable. Specific examples of such organic halogen compounds include o-bromoacetophenone, m-bromoacetophenone, p-bromoacetophenone, o-bromobenzonitrile, m-bromobenzonitrile, p-bromobenzonitrile, o-bromobenzonitrile. M-bromobenzonitrile, p-bromobenzonitrile, o-bromobenzamide, m-bromobenzamide, p-bromobenzamide, ethyl o-bromobenzoate, ethyl m-bromobenzoate, ethyl p-bromobenzoate, o -Bromobenzaldehyde, m-bromobenzaldehyde, p-bromobenzaldehyde, o-bromobenzyl alcohol, m-bromobenzyl alcohol, p-bromobenzyl alcohol, p-iodobenzyl alcohol, 5-bromoindanone, 4-bromoindo And 5-bromoindole.

  Further, the electrophilic reagent used in the present invention is not particularly limited as long as it is a compound having an electron accepting ability. Specifically, halogen atoms such as chlorine, bromine and iodine; carbon dioxide; oxygen; acetaldehyde, benzaldehyde and the like. Aldehydes; ketones such as acetone, acetophenone and benzophenone; esters such as ethyl acetate and ethyl benzoate; alkyl halides such as methyl iodide, ethyl iodide and ethyl bromide; Examples thereof include halogenated silanes.

  Examples of the present invention will be described below.

Synthesis of t-BuEt ₂ ZnLi Under a nitrogen atmosphere, 95 mL of THF and 13.73 (103.1 mmol) of diethyl zinc were added to a 300 mL three-necked flask and cooled to −60 ° C. Under stirring conditions, 48.56 g (108.4 mmol) of a 14.3 wt% t-butyllithium pentane solution was added dropwise. After dropping, the temperature was raised to room temperature. The solvent was concentrated under reduced pressure to obtain 28.9 wt% of a solution of t-BuEt ₂ ZnLi in THF.

1H-NMR (THF-d6) d 1.36 (t, 6H), 1.03 (s, 9H), -0.06 (q, 4H)
Moreover, when this solution was decomposed with dilute sulfuric acid and the amount of generated gas was measured, it was confirmed that a gas having a 3-fold molar amount with respect to Zn was generated.

Reaction of o-bromobenzonitrile and t-BuEt ₂ ZnLi Under a nitrogen atmosphere, 2.04 g (11.2 mmol) of o-bromobenzonitrile and 30 mL of THF were added to a 300 mL three-necked flask and cooled to -70 ° C. After adding 7.58 g (11.6 mmol) of 28.9 wt% t-BuEt ₂ ZnLi in THF, the mixture was warmed to room temperature and stirred for 1 hour. The reaction solution was quenched with 30 mL of 1N hydrochloric acid, and the organic layer was extracted and concentrated to recover 1.03 g (yield 89%) of benzonitrile.
A compound in which an alkyl group reacted with a nitrile group was not detected, and it was confirmed that a halogen-zinc exchange reaction proceeded selectively.

Reaction of p-iodobenzyl alcohol and t-BuEt2ZnLi Under a nitrogen atmosphere, 1.07 g (4.6 mmol) of p-iodobenzyl alcohol and 20 mL of THF were added to a 300 mL three-necked flask, and 28.9 wt% of t-BuEt at room temperature. ₂ 3.45 g (5.3 mmol) of ZnLi in THF was added and reacted for 1 hour. The reaction solution was quenched with 1N-hydrochloric acid, and the organic layer was extracted and concentrated for analysis. The product was analyzed by NMR and benzyl alcohol was obtained in 92.9% yield.
It was confirmed that even when an organic halogen compound containing a hydroxyl group was used, the halogen-zinc exchange reaction proceeded without deactivation of t-BuEt ₂ ZnLi.

  The novel lithium t-butyldiethylzincate of the present invention is useful as a reagent for halogen-zinc exchange reaction.

Claims (4)

Chemical formula t-BuEt ₂ ZnLi
Lithium t-butyldiethyl zincate represented by A solution comprising lithium t-butyldiethylzincate. A method for producing lithium t-butyldiethylzincate, comprising reacting diethylzinc with an equivalent t-butyllithium solution. A method for using lithium t-butyldiethyl zincate, characterized in that lithium t-butyldiethylzincate is used in a halogen-zinc exchange reaction with an organic halogen compound.