1075-89-4

Basic information

• Product Name: 3,3-Tetramethyleneglutarimide
• Synonyms: TETRAMETHYLENE GLUTARIMIDE;BETA,BETA-TETRAMETHYLENEGLUTARIMIDE;LABOTEST-BB LT00233142;3,3-TETRAMETHYLENEGLUTARIMIDE;8-AZASPIRO[4,5]DECANE-7,9-DIONE;1,1-cyclopentanediacetimide;1,1-cyclopentanedlacetimide;AZA-8
• CAS NO: 1075-89-4
• Molecular Formula: C₉H₁₃NO₂
• Molecular Weight: 167.21
• EINECS: 427-770-4
• Product Categories: BUILDING BLOCKS;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 1075-89-4.mol
• Article Data: 2

Chemical Properties

• Melting Point: 153-155 °C
• Boiling Point: 295.79°C (rough estimate)
• Flash Point: 162.6 °C
• Appearance: white to off-white crystalline powder
• Density: 1.1222 (rough estimate)
• Vapor Pressure: 4.31E-05mmHg at 25°C
• Refractive Index: 1.4760 (estimate)
• Storage Temp.: Poison room
• PKA: 11.71±0.20(Predicted)
• BRN: 383702
• CAS DataBase Reference: 3,3-Tetramethyleneglutarimide(CAS DataBase Reference)
• NIST Chemistry Reference: 3,3-Tetramethyleneglutarimide(1075-89-4)
• EPA Substance Registry System: 3,3-Tetramethyleneglutarimide(1075-89-4)

Safety Data

• Hazard Codes: T+
• Statements: 28
• Safety Statements: 45-36/37/39
• RIDADR: UN 2811 6.1 / PGIII
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 1075-89-4(Hazardous Substances Data)

Usage

Chemical Properties

white to off-white crystalline powder

Uses

Buspirone intermediate.

InChI:InChI=1/C9H13NO2/c11-7-5-9(3-1-2-4-9)6-8(12)10-7/h1-6H2,(H,10,11,12)

Synthetic route

3,3-tetramethylene glutaric anhydride (5662-95-3) → tetramethylene glutarimide (1075-89-4)

Conditions	Yield
With ammonium hydroxide In tetrahydrofuran at 190℃;	92%

ammonium salt of/the/ cyclopentane-diacetic acid-(1.1) → tetramethylene glutarimide (1075-89-4)

cyclopentane-dimalonic acid-(1.1)-monoamide → tetramethylene glutarimide (1075-89-4)

Conditions	Yield
ueber den Schmelzpunkt;

tetramethylene glutarimide (1075-89-4) + propargyl bromide (106-96-7) → 8-Propargyl-8-azaspiro<4.5>decane-7,9-dione (25032-23-9)

Conditions	Yield
With potassium carbonate In acetone for 10h; Heating;	100%
With potassium carbonate In acetone Heating;	100%

1,4-dibromo-butane (110-52-1) + N-(2-pyridinyl)piperazine (20980-22-7) + tetramethylene glutarimide (1075-89-4) → BUSPIRONE (36505-84-7)

Conditions	Yield
With potassium carbonate; benzyltriethylammonium bromide Product distribution; 1.) xylene, reflux, 3 h, 2.) reflux, 5 h; other imides and catalysts, variation of reaction time, also in toluene; also 1-(2-quinolinyl)piperazine;	97%
With potassium carbonate; benzyltriethylammonium bromide 1.) xylene, reflux, 3 h, 2.) reflux, 5 h; Yield given. Multistep reaction;

4-chlorobutanal dimethyl acetal (29882-07-3) + tetramethylene glutarimide (1075-89-4) → 8-(4,4-dimethoxybutyl)-8-azaspiro[4.5]decane-7,9-dione (1359159-58-2)

Conditions	Yield
With tetrabutylammomium bromide; potassium carbonate In dimethyl sulfoxide at 80℃; for 4h;	96%

tetramethylene glutarimide (1075-89-4) + benzyl bromide (100-39-0) → 8-benzyl-8-azaspiro[4.5]decane-7,9-dione (77261-38-2)

Conditions	Yield
Stage #1: tetramethylene glutarimide With potassium carbonate for 1h; Stage #2: benzyl bromide In acetone for 2h; Reflux; Inert atmosphere;	96%

di-tert-butyl dicarbonate (24424-99-5) + tetramethylene glutarimide (1075-89-4) → 8-(tert-butoxycarbonyl)-7,9-dioxo-8-azaspiro[4.5]decane (854280-06-1)

Conditions	Yield
With dmap In acetonitrile at 20℃; for 15h;	95%

tetramethylene glutarimide (1075-89-4) → 3-azaspiro[5.5]undecane (180-44-9)

Conditions	Yield
In tetrahydrofuran	94%

tetramethylene glutarimide (1075-89-4) + benzoyl chloride (98-88-4) → 8-benzoyl-8-azaspiro[4.5]decane-7,9-dione

Conditions	Yield
With dmap; triethylamine In dichloromethane at 0 - 20℃; for 15h; Schlenk technique; Inert atmosphere;	94%

4-chlorobutyl bromide (6940-78-9) + tetramethylene glutarimide (1075-89-4) → 8-(4-chlorobutyl)-8-azaspiro<4.5>decane-7,9-dione (21098-11-3)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 0 - 20℃;	93%
In N-methyl-acetamide

tetramethylene glutarimide (1075-89-4) + 4-bromobutanenitrile (5332-06-9) → 4-(7,9-dioxo-8-aza-spiro[4.5]dec-8-yl)butyronitrile (1236066-79-7)

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile at 60℃; for 20h; Inert atmosphere;	93%

tetramethylene glutarimide (1075-89-4) + 8-(2-quinolinyl)-8-aza-5-azoniaspiro<4.5>decane bromide (142415-01-8) → Kaspar (142336-21-8)

Conditions	Yield
With potassium carbonate; 18-crown-6 ether In xylene for 6h; Heating;	89%

tetramethylene glutarimide (1075-89-4) + 8-(1,2-benzisothiazol-3-yl)-8-aza-5-azoniaspiro[4.5]decane bromide (87691-94-9) → tiospirone (87691-91-6)

Conditions	Yield
With 18-crown-6 ether; potassium carbonate In toluene for 22h; Heating;	88%

bromopropionitrile (2417-90-5) + tetramethylene glutarimide (1075-89-4) → 3-(7,9-dioxo-8-aza-spiro[4.5]dec-8-yl)propionitrile (1236066-78-6)

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile at 60℃; for 20h; Inert atmosphere;	87%

(E)-1,1-Difluorodec-3-en-2-yl Diethyl Phosphate + tetramethylene glutarimide (1075-89-4) → (E)-8-(1,1-difluorodec-2-en-4-yl)-8-azaspiro[4.5]decane-7,9-dione

Conditions	Yield
With bis(η3-allyl-μ-chloropalladium(II)); caesium carbonate In dimethyl sulfoxide at 30℃; for 1h; Inert atmosphere;	87%

tetramethylene glutarimide (1075-89-4) + 6-methyl-4-bromomethylcoumarin (79344-41-5) → 8-[(6-methyl-2-oxo-2H-chromen-4-yl)methyl]-8-azaspiro[4.5]decane-7,9-dione

Conditions	Yield
Stage #1: tetramethylene glutarimide With potassium carbonate In acetone at 20℃; for 0.666667h; Stage #2: 6-methyl-4-bromomethylcoumarin In acetone at 55 - 60℃; for 10h;	85%

tetramethylene glutarimide (1075-89-4) + 6-chloro-4-bromomethylcoumarin (79344-40-4) → 8-[(6-chloro-2-oxo-2H-chromen-4-yl)methyl]-8-azaspiro[4.5]decane-7,9-dione

Conditions	Yield
Stage #1: tetramethylene glutarimide With potassium carbonate In acetone at 20℃; for 0.666667h; Stage #2: 6-chloro-4-bromomethylcoumarin In acetone at 55 - 60℃; for 10h;	85%

tetramethylene glutarimide (1075-89-4) + 4-(bromomethyl)-7-chloro-2H-chromen-2-one (79344-39-1) → 8-[(7-chloro-2-oxo-2H-chromen-4-yl)methyl]-8-azaspiro[4.5]decane-7,9-dione

Conditions	Yield
Stage #1: tetramethylene glutarimide With potassium carbonate In acetone at 20℃; for 0.666667h; Stage #2: 4-(bromomethyl)-7-chloro-2H-chromen-2-one In acetone at 55 - 60℃; for 10h;	85%

4-(bromomethyl)-7,8-dimethyl-2H-chromen-2-one (1252026-46-2) + tetramethylene glutarimide (1075-89-4) → 8-[(7,8-dimethyl-2-oxo-2H-chromen-4-yl)methyl]-8-azaspiro[4.5]decane-7,9-dione

Conditions	Yield
Stage #1: tetramethylene glutarimide With potassium carbonate In acetone at 20℃; for 0.666667h; Stage #2: 4-(bromomethyl)-7,8-dimethyl-2H-chromen-2-one In acetone at 55 - 60℃; for 10h;	85%

tetramethylene glutarimide (1075-89-4) + 4-bromomethyl-6-methoxycoumarin (82156-57-8) → 8-[(6-methoxy-2-oxo-2H-chromen-4-yl)methyl]-8-azaspiro[4.5]decane-7,9-dione

Conditions	Yield
Stage #1: tetramethylene glutarimide With potassium carbonate In acetone at 20℃; for 0.666667h; Stage #2: 4-bromomethyl-6-methoxycoumarin In acetone at 55 - 60℃; for 10h;	85%

4-(bromomethyl)-7-methoxycoumarin (35231-44-8) + tetramethylene glutarimide (1075-89-4) → 8-[(7-methoxy-2-oxo-2H-chromen-4-yl)methyl]-8-azaspiro[4.5]decane-7,9-dione

Conditions	Yield
Stage #1: tetramethylene glutarimide With potassium carbonate In acetone at 20℃; for 0.666667h; Stage #2: 4-(bromomethyl)-7-methoxycoumarin In acetone at 55 - 60℃; for 10h;	85%

6-bromo-4-(bromomethyl)–2H-chromen-2-one + tetramethylene glutarimide (1075-89-4) → 8-[(6-bromo-2-oxo-2H-chromen-4-yl)methyl]-8-azaspiro[4.5]decan-7,9-dione

Conditions	Yield
Stage #1: tetramethylene glutarimide With potassium carbonate In acetone at 20℃; for 0.666667h; Stage #2: 6-bromo-4-(bromomethyl)–2H-chromen-2-one In acetone at 55 - 60℃; for 10h;	85%

4-(bromomethyl)-2H-naphthol[1,2-b]pyran-2-one (87317-83-7) + tetramethylene glutarimide (1075-89-4) → 8-[(2-oxo-2H-benzo[h]chromen-4-yl)methyl]-8-azaspiro[4.5]decane-7,9-dione

Conditions	Yield
Stage #1: tetramethylene glutarimide With potassium carbonate In acetone at 20℃; for 0.666667h; Stage #2: 4-(bromomethyl)-2H-naphthol[1,2-b]pyran-2-one In acetone at 55 - 60℃; for 10h;	85%

(4aS,8aR)-2-(1-(2-chloroacetyl)azetidin-3-yl)-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one + tetramethylene glutarimide (1075-89-4) → 8-(2-(3-((4aS,8aR)-4-(3,4-dimethoxyphenyl)-1-oxo-4a,5,8,8a-tetrahydrophthalazin-2(1H)-yl)azetidin-1-yl)-2-oxoethyl)-8-azaspiro[4.5]decane-7,9-dione

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 3h;	80%

4-bromomethyl-7-methyl-coumarin (41321-75-9) + tetramethylene glutarimide (1075-89-4) → 8-[(7-methyl-2-oxo-2H-chromen-4-yl)methyl]-8-azaspiro[4.5]decane-7,9-dione

Conditions	Yield
Stage #1: tetramethylene glutarimide With potassium carbonate In acetone at 20℃; for 0.666667h; Stage #2: 4-bromomethyl-7-methyl-coumarin In acetone at 55 - 60℃; for 10h;	80%

4-(bromomethyl)-5,7-dimethyl-2H-chromen-2-one (41295-53-8) + tetramethylene glutarimide (1075-89-4) → 8-[(5,7-dimethyl-2-oxo-2H-chromen-4-yl)methyl]-8-azaspiro[4.5]decane-7,9-dione

Conditions	Yield
Stage #1: tetramethylene glutarimide With potassium carbonate In acetone at 20℃; for 0.666667h; Stage #2: 4-(bromomethyl)-5,7-dimethyl-2H-chromen-2-one In acetone at 55 - 60℃; for 10h;	80%

6-tert-butyl-4-(bromomethyl)-2H-chromen-2-one + tetramethylene glutarimide (1075-89-4) → 8-[(6-tert-butyl-2-oxo-2H-chromen-4-yl)methyl]-8-azaspiro[4.5]decane-7,9-dione

Conditions	Yield
Stage #1: tetramethylene glutarimide With potassium carbonate In acetone at 20℃; for 0.666667h; Stage #2: 6-tert-butyl-4-(bromomethyl)-2H-chromen-2-one In acetone at 55 - 60℃; for 10h;	80%

5,6-benzo-4-bromomethylcoumarin (101553-94-0) + tetramethylene glutarimide (1075-89-4) → 8-[(3-oxo-3H-benzo[f]chromen-1-yl)methyl]-8-azaspiro[4.5]decane-7,9-dione

Conditions	Yield
Stage #1: tetramethylene glutarimide With potassium carbonate In acetone at 20℃; for 0.666667h; Stage #2: 5,6-benzo-4-bromomethylcoumarin In acetone at 55 - 60℃; for 10h;	80%

1,4-dibromo-2,2,3,3-tetradeuteriobutane (52089-63-1) + tetramethylene glutarimide (1075-89-4) → 8-(4-bromobutyl-2,2,3,3-d4)-8-azaspiro[4,5]decane-7,9-dione

Conditions	Yield
With potassium carbonate In acetonitrile for 14h; Alkylation; Heating;	77.92%

1,4-dibromo-butane (110-52-1) + tetramethylene glutarimide (1075-89-4) → 8-(4-bromobutyl)-8-azaspiro[4.5]decane-7,9-dione (80827-62-9)

Conditions	Yield
With 18-crown-6 ether; potassium carbonate In toluene at 111℃; for 24h; Inert atmosphere;	75%
With potassium carbonate; potassium iodide In acetonitrile at 60℃; for 6h;	69%

1-bromo-4-butene (5162-44-7) + tetramethylene glutarimide (1075-89-4) → 8-(3-butenyl)-8-azaspiro<4.5>decane-7,9-dione (131779-51-6)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide Heating;	74%

Upstream product

• 5662-95-3 3,3-tetramethylene glutaric anhydride 

Downstream Products

• 80827-62-9 8-(4-bromobutyl)-8-azaspiro[4.5]decane-7,9-dione 
• 36505-84-7 BUSPIRONE 
• 87691-91-6 tiospirone 
• 77261-61-1 8-[(Dibenzylamino)-methyl]-8-aza-spiro[4.5]decane-7,9-dione 
• 78503-16-9 N-[2-(4-diphenylmethoxy-piperidino)-ethyl]-β,β-tetramethylene-glutarimide hydrochloride 
• 176-64-7 8-azaspiro[4.5]decane 
• 77261-38-2 8-benzyl-8-azaspiro[4.5]decane-7,9-dione 
• 33386-08-2 buspirone hydrochloride 
• 21098-11-3 8-(4-chlorobutyl)-8-azaspiro<4.5>decane-7,9-dione 
• 180-44-9 3-azaspiro[5.5]undecane 
• 138277-78-8 S 20244 

Relevant articles and documents

AMIDOALKYLPIPERAZINYL DERIVATIVES FOR THE TREATMENT OF CENTRAL NERVOUS SYSTEM DISEASES

The invention relates to novel amidoalkylpiperazinyl derivatives of tricyclic heterocyclic systems of general formula (I), wherein Z represents -NH- and X represents -S-, or Z represents -S- and X represents >C=C1 represents H or -CH3, R6 and R7 both represent H, n is an integer from 0 to 4 inclusive, G represents a cyclic amide or imide moiety, and optical isomers, geometric isomers, and pharmaceutically acceptable salts thereof. The compounds may be useful for the treatment and/or prevention of the central nervous system disorders.