4111-54-0

Basic information

• Product Name: Lithium diisopropylamide
• Synonyms: 2-Propanamine,N-(1-methylethyl)-,lithiumsalt;n-(1-methylethyl)-2-propanaminlithiumsalt;LITHIUM DIISOPROPYLAMIDE THF COMPLEX;LITHIUM DIISOPROPYLAMINE;LITHIUM DIISOPROPYLAMIDE;LDA THF COMPLEX;LDA;DIISOPROPYLAMINOLITHIUM
• CAS NO: 4111-54-0
• Molecular Formula: C₆H₁₄LiN
• Molecular Weight: 107.12306
• EINECS: 223-893-0
• Product Categories: Organic-metal salt;Classes of Metal Compounds;Li (Lithium) Compounds;Typical Metal Compounds
• Mol File: 4111-54-0.mol

Chemical Properties

• Melting Point: decomposes [MER06]
• Boiling Point: 65 °C
• Flash Point: 91 °F
• Appearance: brown/liquid
• Density: 0.864 g/mL at 25 °C(lit.)
• Vapor Density: >1 (vs air)
• Storage Temp.: 2-8°C
• Water Solubility: decomposes
• Sensitive: Air & Moisture Sensitive
• Merck: 14,3196
• BRN: 3655042
• CAS DataBase Reference: Lithium diisopropylamide(CAS DataBase Reference)
• NIST Chemistry Reference: Lithium diisopropylamide(4111-54-0)
• EPA Substance Registry System: Lithium diisopropylamide(4111-54-0)

Safety Data

• Hazard Codes: C,N,F
• Statements: 14-17-34-67-65-51/53-35-19-15-11-50/53-14/15-10-40-23/24/25-62-63-37-48/20
• Safety Statements: 26-36/37/39-43-45-60-61-62-8-16-23-33-27
• RIDADR: UN 3399 4.3/PG 2
• WGK Germany: 3
• F: 1-10
• TSCA: Yes
• HazardClass: 4.2
• PackingGroup: I
• Hazardous Substances Data: 4111-54-0(Hazardous Substances Data)

Usage

Synthesis

Lithium diisopropylamide has been synthesized by two classical routes. Th 1ost widely adopted route involves in situ formation by deprotonation of diisopropylamineby an alkyllithium reagent, such as butyllithium.Addition of a solutionof butyllithium (in hexane) to a stirred solution of diisopropylamine (freshly distilledfrom CaCl) in tetrahydrofuran directly gives the required solution of lithium diisopropylamide in tetrahydrofuran. This deprotonation process has been reported to be efficient over a wide temperature range (from -78°C to 25°C). The resulting solution of lithium diisopropylamide in tetrahydrofuran appears to be stable, and consequently canbe stored at room temperature for a short period without loss of basicity.Lithium diisopropylamide can also be synthesized directly by addition of lithium todiisopropylamine.This approach gives better quality crystalline lithium diisopropylamide, especially if required for single-crystal X-raystructure determination, than the butyllithium route.The synthesis of lithium diiso-propylamide by in situ deprotonation of diisopropylamine in tetrahydrofuran by analkyllithium reagent is, however, the most commonly used method.Butyllithium isusually the alkyllithium of choice, but otheralkyllithiums have been used (e.g., MeLi)

Purification Methods

It is purified by refluxing over Na wire or NaH for 30minutes and then distilled into a receiver under N2. Because of the low boiling point of the amine, a dispersion of NaH in mineral oil can be used directly in this purification without prior removal of the oil. It is HIGHLY FLAMMABLE, and is decomposed by air and moisture. [Wittig & Hesse Org Synth 50 69 1970, Beilstein 4 H 154, 4 I 369, 4 II 630, 4 III 274, 4 IV 510.]

InChI:InChI=1/C6H15N.Li/c1-5(2)7-6(3)4;/h5-7H,1-4H3;/q;+1

Synthetic route

diisopropylamine (108-18-9) → lithium diisopropyl amide (4111-54-0)

Conditions	Yield
With styrene; lithium In tetrahydrofuran at -5 - 35℃; Solvent; Inert atmosphere;	97.6%
With styrene; lithium In diethyl ether for 2h; Heating;	95%
With n-butyllithium In pentane at 0 - 20℃; for 1.33333h;	71%

picoline (108-89-4) + diethyl ether (60-29-7) + 4-fluoro-N-methoxy-N-methylbenzamide (116332-54-8) → 2-(4-Cyanophenyl)-4-(4-fluorophenyl)-1-N-hydroxy-5-(4-pyridyl)imidazole (152121-20-5) + lithium diisopropyl amide (4111-54-0)

Conditions	Yield
In diisopropylamine	A 72% B n/a
With n-butyllithium In diisopropylamine	A 72% B n/a

2-pyridylmethyllithium (1749-29-7) + diisopropylamine (108-18-9) → α-picoline (109-06-8) + lithium diisopropyl amide (4111-54-0)

Conditions	Yield
In tetrahydrofuran; diethyl ether at 27℃; Equilibrium constant;

n-butyllithium (109-72-8, 29786-93-4) + diisopropylamine (108-18-9) → lithium diisopropyl amide (4111-54-0)

Conditions	Yield
With tetramethylsilane In tetrahydrofuran; hexane at -73℃; for 0.0333333h;	100 % Spectr.
In tetrahydrofuran; hexane at -78℃; for 0.25h;
In tetrahydrofuran; hexane

N,N,N,N,-tetramethylethylenediamine (110-18-9) + diisopropylamine (108-18-9) → lithium diisopropyl amide (4111-54-0)

Conditions	Yield
With n-butyllithium In hexane at 0℃;

2,2,6,6-tetramethylpiperidinyl-lithium (38227-87-1) + diisopropylamine (108-18-9) → 2,2,6,6-tetramethyl-piperidine (768-66-1) + lithium diisopropyl amide (4111-54-0)

Conditions	Yield
In tetrahydrofuran at -47℃; Thermodynamic data; Rate constant; ΔG(excit.);
In tetrahydrofuran at -47℃; Thermodynamic data; Equilibrium constant; Rate constant; ΔG(excit.);

diphenylmethyllithium (881-42-5) + diisopropylamine (108-18-9) → Diphenylmethane (101-81-5) + lithium diisopropyl amide (4111-54-0)

Conditions	Yield
In tetrahydrofuran at 30℃; Equilibrium constant;

C5H7Li (99631-63-7) + diisopropylamine (108-18-9) → lithium diisopropyl amide (4111-54-0) + isoprene (78-79-5)

Conditions	Yield
In tetrahydrofuran at -70℃; Equilibrium constant;

Li(cis-2,6-dimethylpiperidine(-1H)) (38227-84-8, 84602-07-3, 84602-08-4) + diisopropylamine (108-18-9) → (2R,6S)-2,6-dimethylpiperidine (766-17-6, 1218906-26-3) + lithium diisopropyl amide (4111-54-0)

Conditions	Yield
In tetrahydrofuran at -65℃; Thermodynamic data; Rate constant; ΔG(excit.);
In tetrahydrofuran at -65℃; Thermodynamic data; Equilibrium constant; Rate constant; ΔG(excit.);

(4,4'-Dimethyldiphenylmethyl)lithium (68695-92-1) + diisopropylamine (108-18-9) → 4,4'-dimethyldiphenylmethane (4957-14-6) + lithium diisopropyl amide (4111-54-0)

Conditions	Yield
In tetrahydrofuran at 30℃; Equilibrium constant;

C21H27Li (110426-35-2) + diisopropylamine (108-18-9) → 1,1-bis(4-t-butylphenyl)methane (19099-48-0) + lithium diisopropyl amide (4111-54-0)

Conditions	Yield
In tetrahydrofuran at 30℃; Equilibrium constant;

LACTIC ACID (849585-22-4) → lithium diisopropyl amide (4111-54-0)

Conditions	Yield
With n-butyllithium; diisopropylamine In tetrahydrofuran

n-butyllithium (109-72-8, 29786-93-4) + N-ethyl-N,N-diisopropylamine (7087-68-5) → lithium diisopropyl amide (4111-54-0)

Conditions	Yield
In hexane
In tetrahydrofuran; hexane at -78 - 0℃; for 0.333333 - 0.566667h; Product distribution / selectivity;
In tetrahydrofuran at -70 - -5℃;

n-butyllithium (109-72-8, 29786-93-4) + isopropylamine (75-31-0) → lithium diisopropyl amide (4111-54-0)

Conditions	Yield
In hexane at 0℃;
In tetrahydrofuran; hexane at 0℃; for 0.166667h; Product distribution / selectivity;
In tetrahydrofuran; hexanes at 0℃; Product distribution / selectivity;

1-Bromo-2,4-dimethoxybenzene (17715-69-4) + diethyl malonate (105-53-3) → lithium diisopropyl amide (4111-54-0)

Conditions	Yield
With n-butyllithium; NaH; nitrogen In tetrahydrofuran

pyridin-3-yl-acetic acid ethyl ester (39931-77-6) + 4-(dimethylamino)pyridinium tribromide + ammonium chloride → bromo-pyridin-3-yl-acetic acid ethyl ester (347186-70-3) + lithium diisopropyl amide (4111-54-0)

Conditions	Yield
With n-butyllithium; diisopropylamine In tetrahydrofuran

pyridin-3-yl-acetic acid ethyl ester (39931-77-6) + 4-(dimethylamino)pyridinium tribromide → bromo-pyridin-3-yl-acetic acid ethyl ester (347186-70-3) + lithium diisopropyl amide (4111-54-0)

Conditions	Yield
With n-butyllithium; chloro-trimethyl-silane; diisopropylamine In tetrahydrofuran

cis dioxolanone (62094-47-7) + diisopropylamine (108-18-9) → lithium diisopropyl amide (4111-54-0)

Conditions	Yield
With n-butyllithium In tetrahydrofuran; hexane

5-(1-methyl-3-trifluoromethyl-1H-pyrazol-5-yl)thiophene-2-carboxy aldehyde + 4-chloro-1-(diethoxyphosphorylmethyl)-2-fluorobenzene → 5-[5-[(E)-2-(4-chlorophenyl)-2-fluorovinyl]-2-thienyl]-1-methyl-3-trifluoromethyl-1H-pyrazole + lithium diisopropyl amide (4111-54-0)

Conditions	Yield
In tetrahydrofuran

methyl 3-(5-benzyloxyindolyl)propanoate + 1-iodo-propane (107-08-4) → lithium diisopropyl amide (4111-54-0)

Conditions	Yield
In tetrahydrofuran

2-(2,4,6-tri-tert-butylphenyl)phosphaacetylene (100938-86-1) + lithium diisopropyl amide (4111-54-0) + methyl iodide (74-88-4) → 1-diisopropylamino-3-methyl-1,3-diphosphacyclobutane-2,4-diyl (736135-44-7, 943220-13-1)

Conditions	Yield
Stage #1: 2-(2,4,6-tri-tert-butylphenyl)phosphaacetylene; lithium diisopropyl amide In tetrahydrofuran at -78 - 20℃; for 1.25h; Stage #2: methyl iodide In tetrahydrofuran	100%

CH3OBC13H18 + lithium diisopropyl amide (4111-54-0) → Li(1+)*CH3OBC13H17(1-)=Li[CH3OBC13H17]

Conditions	Yield
In tetrahydrofuran; hexane N2-atmosphere; stirring (room temp., 80 h), evapn.; extg. (hexane), filtering, evapn. (vac.);	100%

1--1-cyclopentanol (162147-89-9) + lithium diisopropyl amide (4111-54-0) → benzenesulfinic acid diisopropylamide (66633-64-5) + 2-Chlorocyclohexanone (822-87-7)

Conditions	Yield
With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 2h;	A 99% B 30%

malononitrile (109-77-3) + (Z)-N-(3-(dimethylamino)-2-(trifluoromethyl)allylidene)-N-methylmethanaminium chloride salt + lithium diisopropyl amide (4111-54-0) → diisopropylammonium 1,1,5,5-tetracyano-3-trifluoromethyl-1,3-pentadienide

Conditions	Yield
Stage #1: malononitrile; lithium diisopropyl amide In tetrahydrofuran; hexane at 0℃; for 0.5h; Stage #2: (Z)-N-(3-(dimethylamino)-2-(trifluoromethyl)allylidene)-N-methylmethanaminium chloride salt In tetrahydrofuran; hexane at 20℃; for 3h;	99%

1-Iodoheptane (4282-40-0) + trimethylstannane (1631-73-8) + lithium diisopropyl amide (4111-54-0) → n-heptane (142-82-5) + hexamethyldistannane (661-69-8) + diisopropyl(trimethylstannyl)amine (1068-71-9)

Conditions	Yield
In hexane; cyclohexane to soln. of 1-iodoheptane (1.0 mmol) and TMTH (1.0 mmol) in hexane at 0°C added LDA (1.0 mmol, 1.6 M soln. in cyclohexane) under Ar, react. time 10 min; analyzed by GLPC;	A 99% B 0% C n/a
In hexane; cyclohexane to soln. of 1-iodoheptane (1.0 mmol) and TMTH (1.0 mmol) in hexane at 0°C added LDA (0.8 mmol, 1.6 M soln. in cyclohexane) under Ar, react. time 10 min; analyzed by GLPC;	A 98% B 0% C n/a
In hexane; cyclohexane to soln. of 1-iodoheptane (1.0 mmol) and TMTH (1.0 mmol) in hexane at 0°C added LDA (0.6 mmol, 1.6 M soln. in cyclohexane) under Ar, react. time 10 min; analyzed by GLPC;	A 94% B 0% C n/a
In hexane; cyclohexane to soln. of 1-iodoheptane (1.0 mmol) and TMTH (1.0 mmol) in hexane at 0°C added LDA (0.4 mmol, 1.6 M soln. in cyclohexane) under Ar, react. time 10 min; analyzed by GLPC;	A 84% B 0% C n/a
In hexane; cyclohexane to soln. of 1-iodoheptane (1.0 mmol) and TMTH (1.0 mmol) in hexane at 0°C added LDA (0.2 mmol, 1.6 M soln. in cyclohexane) under Ar, react. time 10 min; analyzed by GLPC;	A 74% B 0% C n/a

1,1,5,5-tetra(tert-butyl)-hexamethyl-1,5-distanna-2,3,4-trisilapentane (223565-68-2) + lithium diisopropyl amide (4111-54-0) → 1,5-dilithio-1,1,5,5-tetra(tert-butyl)-hexamethyl-1,5-distanna-2,3,4-trisilapentane (339048-86-1)

Conditions	Yield
In tetrahydrofuran; hexane byproducts: HN(Pr-i)2; 2 equiv. of Li-amide compd. in 1:1 THF was added dropwise to a cooled (0°C) soln. (THF-hexane(1:1)) of Sn-compd., stirring for 1 h at th is temp.; temp. may be varied between -30 and 0 °C, under Ar or N2; detected by NMR;	99%

1,1'-bis-benzyloxy-4,4'-diisopropyl-1,6,1',6'-tetrahydro-[2,2']biborininyl + lithium diisopropyl amide (4111-54-0) → 2Li(1+)*((CH3)2CHC5H3BOCH2C6H5)2(2-)=Li2((CH3)2CHC5H3BOCH2C6H5)2

Conditions	Yield
In tetrahydrofuran addn. of LDA in THF to a soln. diborabiphenyl derivative in THF at room temp. under stiring, stirring for 1 h at room temp.; removal of volatiles under vac.,;	99%

trimethylstannane (1631-73-8) + lithium diisopropyl amide (4111-54-0) → hydrogen (1333-74-0) + hexamethyldistannane (661-69-8)

Conditions	Yield
With O In cyclohexane byproducts: i-Pr2NH; LDA (1.88 mmol) in C6H12 placed in Schlenk tube at 0°C under Ar, TMTH (3.76 mmol) added, stirred for 30 min, hydrolysis; Sn2Me6 detected by GC;	A 98% B 93%
In diethyl ether; cyclohexane byproducts: i-Pr2NH; TMTH in Et2O cooled to 0°C under Ar, LDA in cyclohexane (1.6 M) added via syringe, stirred for 60 min at room temp., hydrolysis;	A 95% B 90%
In diethyl ether byproducts: i-Pr2NH; LDA (1.88 mmol) in C6H12 placed in Schlenk tube at 0°C under Ar, TMTH (3.76 mmol) added, stirred for 30 min, hydrolysis; Sn2Me6 detected by GC;	A 93% B 83%

10-dicyclohexylsulfamoyl-D-isobornyl (E)-7-bromohept-2-enoate (162732-80-1) + lithium diisopropyl amide (4111-54-0) → 10-dicyclohexylsulfamoyl-D-isobornyl 7-bromo-3<(1-methylethyl)amino>heptanoate

Conditions	Yield
In tetrahydrofuran at -72 - -68℃; for 1.83333h;	97%

trimethylstannane (1631-73-8) + 6-Bromo-1-hexene (2695-47-8) + lithium diisopropyl amide (4111-54-0) → 1-hexene (592-41-6) + methyl-cyclopentane (96-37-7) + hexamethyldistannane (661-69-8)

Conditions	Yield
In diethyl ether; cyclohexane to 6-bromo-1-hexene (1.04 mmol) and 2 equiv. of Me3SnH in Et2O at 0°C added LDA (1.04 mmol, in cyclohexane) under Ar, react. time 20 min, quenched with water; analyzed by GLPC;	A 77% B 16% C 97%
In diethyl ether; cyclohexane to 6-bromo-1-hexene (1.04 mmol) and 1 equiv. of Me3SnH in Et2O at 0°C added LDA (1.04 mmol, in cyclohexane) under Ar, react. time 20 min, quenched with water; analyzed by GLPC;	A 41% B 18% C 86%
In hexane; cyclohexane to 6-bromo-1-hexene (1.04 mmol) and 2 equiv. of Me3SnH in hexane at 0°C added LDA (1.04 mmol, in cyclohexane) under Ar, react. time 20 min, quenched with water; analyzed by GLPC;	A 76% B 18% C 27%
In hexane; cyclohexane to 6-bromo-1-hexene (1.04 mmol) and 1 equiv. of Me3SnH in hexane at 0°C added LDA (1.04 mmol, in cyclohexane) under Ar, react. time 20 min, quenched with water; analyzed by GLPC;	A 45% B 32% C 48%

1-bromo-octane (111-83-1) + tri-n-butyl-tin hydride (688-73-3) + lithium diisopropyl amide (4111-54-0) → octane (111-65-9) + bis(tri-n-butyltin) (813-19-4)

Conditions	Yield
In hexane; cyclohexane to 1-bromooctane (1 mmol) and Bu3SnH (1 mmol) in hexane at 0°C added LDA (1 mmol, in cyclohexane) under Ar, stirred for 20 min, quenched; analyzed by GLPC;	A 97% B 0%

C5H25B22N2(1-)*C3H9N*H(1+) + lithium diisopropyl amide (4111-54-0) → C5H24B22LiN2(2-)*2Li(1+)

Conditions	Yield
In tetrahydrofuran at -78℃; for 2h; Inert atmosphere; Schlenk technique;	97%

bis(1-methyl-1H-imidazol-3-yl)dihydroboronium iodide (337529-91-6) + lithium diisopropyl amide (4111-54-0) → Li(1+)*CH3C3H2N2BH2C3H2N2CH3(1-)=LiCH3C3H2N2BH2C3H2N2CH3

Conditions	Yield
In tetrahydrofuran at -78 - 20℃;	96%

ferrocenyl triflate + lithium diisopropyl amide (4111-54-0) → lithium 2-(trifluoromethylsulfonyl)ferrocenolate

Conditions	Yield
With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at 2 - 78℃; for 0.333333h; Inert atmosphere; Schlenk technique;	96%

pentafluoropropionitrile (422-04-8) + O,O-diethyl benzylphosphonate (1080-32-6) + lithium diisopropyl amide (4111-54-0) → diisopropylamine 2-ethoxy-2-oxo-3-phenyl-4,6-bis(pentafluoroethyl)-2,5-dihydro-1,5,2-diazaphosphinine adduct

Conditions	Yield
Stage #1: O,O-diethyl benzylphosphonate; lithium diisopropyl amide In tetrahydrofuran at 0℃; for 1h; Stage #2: pentafluoropropionitrile In tetrahydrofuran at 20℃; for 15h;	95%

1-bromo-octane (111-83-1) + trimethylstannane (1631-73-8) + lithium diisopropyl amide (4111-54-0) → octane (111-65-9) + hexamethyldistannane (661-69-8)

Conditions	Yield
In diethyl ether; cyclohexane to 1-bromooctane (1 mmol) and TMTH (1 mmol) in Et2O at 0°C added LDA (1 mmol, in cyclohexane) under Ar, stirred for 20 min, quenched; analyzed by GLPC;	A 54% B 95%
With p-benzoquinone In hexane; cyclohexane to 1-bromooctane (1 mmol), TMTH (1 mmol), and benzoquinone (10 mol%) in hexane at 0°C added LDA (1 mmol, in cyclohexane) under Ar, stirred for 20 min, quenched; analyzed by GLPC;	A 91% B 5%
With meta-dinitrobenzene; p-benzoquinone In hexane; cyclohexane to 1-bromooctane (1 mmol), TMTH (1 mmol), benzoquinone (10 mol%), and m-dinitrobenzene (5 mol%) in hexane at 0°C added LDA (1 mmol, in cyclohexane) under Ar, stirred for 20 min, quenched; analyzed by GLPC;	A 83% B 2%
In hexane; cyclohexane to 1-bromooctane (1 mmol) and TMTH (1 mmol) in hexane at 0°C added LDA (1 mmol, in cyclohexane) under Ar, stirred for 20 min, quenched; analyzed by GLPC;	A 70% B 50%

N,N-dimethyl acetamide (127-19-5) + chlorotrimethylgermane (1529-47-1) + lithium diisopropyl amide (4111-54-0) → N,N-dimethyl(trimethylgermyl)acetamide (123347-42-2)

Conditions	Yield
In tetrahydrofuran; hexane (Ar or N2); dropwise addn. of N,N-dimethylacetamide to a soln. of LDA at -78 °C; after 1 h stirring dropwise addn. of GeCl(CH3)3 and addnl. stirring for 2 h at the same temp.; quenching (satd. aq. NH4Cl); extn. (benzene); drying (MgSO4) of the organic layer; concn.; distn.;	95%

ethylzinc chloride (2633-75-2) + lithium diisopropyl amide (4111-54-0) → N-(ethylzinc) diisopropylamine (109930-69-0)

Conditions	Yield
In diethyl ether byproducts: LiCl; ether soln. of EtZnCl was added to a suspn. of i-Pr2NLi in ether over 2 min under N2, stirred for 15 min; filtered, evapd., residue was dissolved in pentane, filtered, evapd; elem. anal.;	95%

N,N-diethyl-1-amino-1,2-dihydro-1-boratanaphthalene (220696-16-2) + N,N-diethyl-1-amino-1,4-dihydro-1-boratanaphthalene (220696-18-4) + lithium diisopropyl amide (4111-54-0) → lithium N,N-diethyl-1-amino-1-boratanaphthalene

Conditions	Yield
In diethyl ether N2-atmosphere; addn. of LDA (1.1 equiv.) to mixt. of boratanaphthalenes at -78°C, stirring (2 h at -78°C, 10 h at 25°C); evapn., washing (pentane), drying;	95%

chloro-trimethyl-silane (75-77-4) + 3',5'-difluoro-[1,1'-biphenyl]-4-carbonitrile (1365272-12-3) + lithium diisopropyl amide (4111-54-0) → C22H29F2NOSi (1381940-52-8)

Conditions	Yield
at -68℃; Inert atmosphere;	95%

lithium diisopropyl amide (4111-54-0) → C6H14N3O(1-)*Li(1+)

Conditions	Yield
With dinitrogen monoxide In tetrahydrofuran for 4h;	95%
With dinitrogen monoxide In tetrahydrofuran at 20℃; under 760.051 Torr; for 3h;

4,4,5,5-tetramethyl-2-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl]-1,3,2-dioxaborolane (78782-17-9) + lithium diisopropyl amide (4111-54-0) → bis((4,4,5,5,-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)lithium

Conditions	Yield
In tetrahydrofuran; hexane at -25 - 20℃; for 1.33333h; Inert atmosphere; Glovebox;	95%

1-Iodoheptane (4282-40-0) + trimethylstannane (1631-73-8) + lithium diisopropyl amide (4111-54-0) → n-heptane (142-82-5) + hexamethyldistannane (661-69-8)

Conditions	Yield
In hexane; cyclohexane to 1-iodoheptane (1 mmol) and TMTH (1 mmol) in hexane at 0°C added LDA (1 mmol, in cyclohexane) under Ar, stirred for 20 min, quenched; analyzed by GLPC;	A 94% B 0%
In diethyl ether; cyclohexane to 1-iodoheptane (1 mmol) and TMTH (1 mmol) in Et2O at 0°C added LDA (1 mmol, in cyclohexane) under Ar, stirred for 20 min, quenched; analyzed by GLPC;	A 78% B 26%

tri-n-butyl-tin hydride (688-73-3) + lithium diisopropyl amide (4111-54-0) → hydrogen (1333-74-0) + bis(tri-n-butyltin) (813-19-4)

Conditions	Yield
In diethyl ether; cyclohexane byproducts: i-Pr2NH; Bu3SnH in Et2O cooled to 0°C under Ar, LDA in cyclohexane (1.6 M) added via syringe, stirred for 60 min at room temp., hydrolysis;	A 90% B 94%

acetylferrocene (1271-55-2) + diethyl chlorophosphate (814-49-3) + lithium diisopropyl amide (4111-54-0) → ferroceneacetylene (1271-47-2)

Conditions

Yield

With water In tetrahydrofuran inert atmosphere; addn. of LDA in THF at -78°C to soln. of Fe-complex; reaction for 1 h; addn. of phosphate; reaction for 1 h; mixt. raised to room temp.; addn. of LDA in THF at -78°C; warmed to room temp.; hydrolysis at 0°C;; extn. of organic layer with CH2Cl2; dried over MgSO4; evapn.; purifn. of oil by flash chromy. (pentane-ether 2:1); crystn. of first yellow fraction (0°C, pentane); elem. anal.;

94%

(CO)4WCC6H4CH3(NHCH2CHCH2) (77310-69-1) + lithium diisopropyl amide (4111-54-0) → cis-tetracarbonyl[((Z)-η2-N-allyl-N-methylamino)(p-tolyl)carbene]tungsten(0) (90245-85-5)

Conditions	Yield
With CH3I In tetrahydrofuran a soln. of lithium diisopropylamide in THF was added to soln. of W-complex in THF at -72°C, soln. was warmed to room temp., cooled back to -72°C and CH3I was added, soln. was warmed to room temp. underN2; preparative TLC (silica gel, CH2Cl2-hexane) gave solid ppt.;	94%

(CO)4Re(η2-C(Me)C(CO2Me)C(OEt)) + bis(triphenylphosphine)iminium chloride (21050-13-5) + lithium diisopropyl amide (4111-54-0) → (Ph3P)2N[(CO)4Re(η2-C(=CH2)C(CO2Me)C(OEt))] (724461-50-1)

Conditions	Yield
In tetrahydrofuran; hexane (Ar); addn. of a soln. of lithium compd. in hexane to a soln. of rheniumcomplex in THF at -78°C, stirring for 1 h at -78°C, addn. of PPNCl, stirring and warming to room temp.; filtration, concn., addn. of hexane, cooling to 0°C, sepn., washing ppt. with hexane, drying for 24 h in vac.;	94%

Upstream product

• 1749-29-7 2-pyridylmethyllithium 
• 108-18-9 diisopropylamine 
• 109-72-8 n-butyllithium 
• 110-18-9 N,N,N,N,-tetramethylethylenediamine 
• 849585-22-4 LACTIC ACID 
• 7087-68-5 N-ethyl-N,N-diisopropylamine 
• 75-31-0 isopropylamine 
• 17715-69-4 1-Bromo-2,4-dimethoxybenzene 
• 105-53-3 diethyl malonate 
• 39931-77-6 pyridin-3-yl-acetic acid ethyl ester 
• 62094-47-7 cis dioxolanone 
• 107-08-4 1-iodo-propane 
• 105-58-8 Diethyl carbonate 
• 40899-71-6 1-benzenesulfonylindole 

Downstream Products

• 59906-55-7 3-Methyl-2-nitro-1-phenylbutanon 
• 20383-28-2 N,N-diisopropyl benzamide 
• 63478-12-6 2-(4,4-dimethyl-4,5-dihydro-oxazol-2-yl)-N,N-diisopropyl-aniline 
• 63478-16-0 2-(4,4-dimethyl-4,5-dihydro-oxazol-2-yl)-N,N-diisopropyl-6-methoxy-aniline 
• 70950-20-8 C₂₁H₃₄N₂O 
• 38227-87-1 2,2,6,6-tetramethylpiperidinyl-lithium 
• 108-18-9 diisopropylamine 
• 1749-29-7 2-pyridylmethyllithium 
• 1120-87-2 4-bromopyridin 
• 85452-81-9 4-(diisopropylamino)pyridine 
• 85452-80-8 N,N-bis(propan-2-yl)pyridin-3-amine 
• 85452-83-1 3-bromo-4-n-butylpyridine 
• 40247-51-6 bromo-4 (ethyl-1 hydroxy-1 propyl)-3 pyridine 
• 85452-82-0 bromo-3 (ethyl-1 hydroxy-1 propyl)-4 pyridine 

Relevant articles and documents

229. Bestimmung des Aggregationsgrads lithiumorganischer Verbindungen durch Kryoskopie in Tetrahydrofuran

The association behaviour of alkyl-, aryl- and alkinyl-lithium compounds as well as of lithium enolates and chiral lithium azaenolates is determined from-freezing point depression values in dilute tetrahydrofuran solutions at -108 grad C.Compared to X-ray-crystallographic data (lithiated methyldithiane, phenyllithium, lithio derivatives of a ketone, carboxylic amide and -ester, and a diketopiperazine-bislactim-ether), desaggregation is found under these conditions.The structutres determined by 13C-NMR spectroscopy for BuLi, lithiophenylacetylene and (t-butyl)lithioacetylene are confirmed.The dilithio salt of a carboxylic acid is polymeric, a chiral lithio-hydrazone and a chiral lithio-oxazolidine are monomeric and dimeric, respectively.Lithium diisopropylamide is a monomer-dimer equilibrium mixture.The apparatus described permits both synthesis and measurement of the reactive species under inert atmosphere conditions in the same vessel.

Synthesis of novel carborane-containing terminal alkynes

Lithiation of 1-bromomethyl-o-carborane with lithium diisopropylamide (LDA) in THF results in the in situ formation of 1-lithio-2-bromomethyl-o-carborane, the reaction of which with 3-trimethylsilylprop-2-ynal gives 2-(2-trimethylsilylethynyl)-3,4-(о-carborano)-2,5-dihydrofuran. Subsequent base-catalyzed desilylation furnishes new terminal alkynes of closoand nido-carborane series.

Insight into the solvation and isomerization of 3-halo-1-azaallylic anions from ab initio metadynamics calculations and NMR experiments

A study performed ab initio metadynamics calculations and nuclear magnetic resonance investigations, to demonstrate the solvation and isomerization of 3-halo-1-azaallylic anions. The 3-halo-1-azaallylic anions were solvated and isomerized from the N-isopr

Synthesis of C-5a-substituted derivatives of 4-epi-isofagomine: Notable β-galactosidase inhibitors and activity promotors of GM1-gangliosidosis related human lysosomal β-galactosidase mutant R201C

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A novel bornane synthesis by an old idea

Aiming at a synthesis of spiro [2.4]hepta-4,6-dienes with a carbon substituent at C-4, we investigated solvolysis reactions of the thiatricycle 2, obtained from spiro[2.4]hepta-4,6-diene (1) and thiophosgene by [4 + 2] cycloaddition. With methanol or ethanol a mixture of the esters 7 and 8 was formed. Desulfurization of the thionoesters 8 gave methyl and ethyl spiro[2.4]hepta-4,6-diene-4-carboxylate (10a,b). The corresponding alcohol (11) was prepared from 10b by LiAlH4 reduction. Ethene-tetracarbonitrile combined with the 4-substituted spiro[2.4]hepta-4,6-dienes to give the [4 + 2] cycloadducts 12a-c. Diels-Alder reaction between 11 and 2-chloroacrylonitrile afforded the spiro(bicyclo[2.2.1]hept-5-ene-7,1′-cyclopropane) derivative 14a that was transformed in three steps to rac-10-hydroxycamphor (17). This synthesis of a bornane derivative opens opportunity for variations and thus may find further applications.

Synthesis of a potent antimalarial amphilectene

7-Isocyano-11(20),14-epiamphilectadiene, the most potent of antimalarial amphilectenes, is synthesized in seven steps from readily available materials. The synthesis is enabled by a new dendrimeric triene (Danishefsky [3]-dendralene) and a new method for stereo- and chemoselective isocyanation. This chemistry provides a useful entry into an underexplored yet promising family of antimalarial terpenoids.

The donor-base-free aggregation of lithium diisopropyl amide in hydrocarbons revealed by a DOSY method

Abstract Lithium diisopropyl amide (LDA) is a very prominent reagent that plays a key role in organic synthesis, serving as a base par excellence for a broad range of deprotonation reactions. However, the state of aggregation in solution in the absence of donor bases was unclear. In this paper we solved this problem by employing DOSY NMR experiments based on a newly elaborated external calibration curve (ECC) approach with normalized diffusion coefficients. An important reagent: Lithium diisopropyl amide plays a key role in organic synthesis, serving as a base par excellence for a broad range of deprotonation reactions. However, its state of aggregation in solution in the absence of donor bases was unclear. This problem has been solved by application of a new DOSY NMR experiment.

Total synthesis of marine eicosanoid (-)-hybridalactone

(-)-Hybridalactone (1) is a marine eicosanoid isolated from the red alga Laurencia hybrida. This natural product contains cyclopropane, cyclopentane, 13-membered macrolactone and epoxide ring systems incorporating seven stereogenic centers. Moreover, this compound has an acid-labile skipped Z,Z-diene motif. In this paper, we report on the total synthesis of (-)-hybridalactone (1). The unique eicosanoid (-)-hybridalactone (1) was synthesized starting from optically active γ-butyrolactone 2 in a linear sequence comprising 21 steps with an overall yield of 21.9 %. A key step in the synthesis of (-)-hybridalactone (1) is the methyl phenylsulfonylacetate-mediated one-pot synthesis of the cis-cyclopropane-γ-lactone derivative. This reaction provided an efficient and stereoselective access to cis-cyclopropane-γ-lactone 12. Further elaboration of the latter compounds through desulfonylation, epoxidation, oxidation, Wittig olefination and Shiina macrolactonization afforded (-)-hybridalactone.

In situ ortho -lithiation/functionalization of pentafluorosulfanyl arenes

A general method for ortho-functionalization of pentafluorosulfanyl arenes has been developed. ortho-Lithiation with lithium tetramethylpiperidide at -60 °C in the presence of silicon, germanium, and tin electrophiles affords trapped products in moderate

Synthesis method of 3-oxo-5-hydroxy-6-cyanohexanoic acid tert-butyl ester

The invention relates to a synthesis method of 3-oxo-5-hydroxy-6-cyanohexanoic acid tert-butyl ester. According to the method, by using lithium metal and diisopropylamine as raw materials, reaction isinitiated under the action of styrene to prepare an intermediate product LDA, thereby solving the problem of overlow reaction temperature in the prior art, and the intermediate is directly mixed witha raw material tert-butyl acetate without further treatment to prepare an intermediate tert-butyl lithioacetate in a micro-channel reactor, and then the intermediate tert-butyl lithioacetate and ethyl 4-cyano-3-hydroxybutyrate are used for preparing the target product 3-oxo-5-hydroxy-6-cyanohexanoic acid tert-butyl ester in the micro-channel reactor. The reaction time is greatly shortened, the pollution is small, the pollutant emission is less, the cost is low, and the post-treatment is simple; and the yield reaches 99%, the purity is 99% or above, and the method is especially suitable for industrial large-scale production.