85-40-5

Basic information

• Product Name: Tetrahydrophthalimide
• Synonyms: 3a,4,7,7a-tetrahydro-1h-isoindole-3(2h)-dione;3a,4,7,7a-tetrahydro-isoindole-3-dione;3-alpha,4,7,7-alpha-tetrahydro-1h-isoindole-3(2h)-dione;delta(4)-tetrahydrophthalimide;delta(sup4)-tetrahydrophthalimide;TETRAHYDROPHTHALIMIDE;4-CYCLOHEXENE-1,2-DICARBOXIMIDE;1,2,3,6-TETRAHYDROPHTHALIMIDE
• CAS NO: 85-40-5
• Molecular Formula: C₈H₉NO₂
• Molecular Weight: 151.16
• EINECS: 201-602-8
• Mol File: 85-40-5.mol

Chemical Properties

• Melting Point: 132-140°C
• Boiling Point: 337°C
• Flash Point: 165°C
• Appearance: white crystalline powder
• Density: 1.228
• Vapor Pressure: 0.00011mmHg at 25°C
• Refractive Index: 1.5810 (estimate)
• Storage Temp.: Store below +30°C.
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 11.69±0.20(Predicted)
• Water Solubility: 12.2g/L at 20℃
• Stability: Light Sensitive
• CAS DataBase Reference: Tetrahydrophthalimide(CAS DataBase Reference)
• NIST Chemistry Reference: Tetrahydrophthalimide(85-40-5)
• EPA Substance Registry System: Tetrahydrophthalimide(85-40-5)

Safety Data

• Hazardous Substances Data: 85-40-5(Hazardous Substances Data)

Usage

Uses

Used in Environmental and Toxicological Studies:
Tetrahydrophthalimide is used as a biomarker for the exposure to the fungicide Captan, helping to assess the levels of Captan in the environment and its potential impact on human and animal health. This information is crucial for understanding the risks associated with Captan exposure and for developing strategies to minimize its harmful effects.

Flammability and Explosibility

Nonflammable

InChI:InChI=1/C8H9NO2/c10-7-5-3-1-2-4-6(5)8(11)9-7/h1-2,5-6H,3-4H2,(H,9,10,11)/t5-,6+

Synthetic route

4-cyclohexene 1-carboxylic acid 2-carboxamide (2028-12-8) → 1,2,3,6-tertahydrophthalimide (85-40-5)

Conditions	Yield
In 1,3,5-trimethyl-benzene at 170℃; for 2.5h; Temperature; Solvent; Large scale;	95%

1,2,3,6-Tetrahydrophthalic anhydride (85-43-8) → 1,2,3,6-tertahydrophthalimide (85-40-5)

Conditions	Yield
With choline chloride; urea at 140℃; for 1h; Green chemistry;	81%
With complex<3THF*Mg2Cl2O*TiNCO>6 In pyridine Heating; Yield given;

anhydride or dicarboxylic acid → 1,2,3,6-tertahydrophthalimide (85-40-5)

Conditions	Yield
With ammonia at 180℃;	74%

N-Hydroxymethyl-cis-4-cyclohexene-1,2-dicarboximide (42027-93-0) → 1,2,3,6-tertahydrophthalimide (85-40-5)

Conditions	Yield
at 100℃; Substitution; Thermolysis;

1,2,3,6-tertahydrophthalimide (85-40-5) + 1,10-bis(methoxymethyl)-1,10-diaza-18-crown-6 (83809-94-3) → C30H44N4O8 (91043-68-4)

Conditions	Yield
In benzene reflux; 20 deg C, 2 h;	99%

1,2,3,6-tertahydrophthalimide (85-40-5) + chloral (75-87-6) → N-(1-Hydroxy-2,2,2-trichloroethyl)-cis-4-cyclohexene-1,2-dicarboximide

Conditions	Yield
In ethanol for 2.5h; Addition; Heating;	99%

1-bromo-butane (109-65-9) + 1,2,3,6-tertahydrophthalimide (85-40-5) → 2-butyl-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione (2021-19-4)

Conditions	Yield
With 18-crown-6 ether; potassium carbonate In acetone for 24h; Ambient temperature;	97%

1,2,3,6-tertahydrophthalimide (85-40-5) → octahydro-1H-isoindol-1-one (2555-11-5)

Conditions	Yield
With [Ru4H6(p-cumene)4]Cl2; hydrogen In water at 90℃; under 45003.6 Torr; for 22h;	97%

1,2,3,6-tertahydrophthalimide (85-40-5) + 1-bromo-5-chloropentane (54512-75-3) → 2-(5-chloropentyl)-3a,4,7,7a-tetrahydro-isoindole-1,3-dione (929224-25-9)

Conditions	Yield
With potassium carbonate In acetone at 20℃; for 60h;	92%

1,2,3,6-tertahydrophthalimide (85-40-5) + (Z)-3-Hexen-1-ol (928-96-1) → ((Z)-2-Hex-3-enyl)-3a,4,7,7a-tetrahydro-isoindole-1,3-dione (82478-58-8)

Conditions	Yield
With dimethyl azodicarboxylate; triphenylphosphine In tetrahydrofuran Ambient temperature; overnight;	90%

1,2,3,6-tertahydrophthalimide (85-40-5) + acrylic acid n-butyl ester (141-32-2) → butyl 3-(3a,4,7,7a-tetrahydro-1,3-dioxo-1H-isoindol-2(3H)-yl)propanoate (1252935-87-7)

Conditions	Yield
With 1,4-diaza-bicyclo[2.2.2]octane; tetrabutylammomium bromide at 100℃; for 1.5h; aza-Michael addition; Neat (no solvent);	90%

4-chlorobutyl bromide (6940-78-9) + 1,2,3,6-tertahydrophthalimide (85-40-5) → 2-(4-chlorobutyl)-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 0 - 20℃;	87%

1,2,3,6-tertahydrophthalimide (85-40-5) + diethyl Fumarate (623-91-6) → diethyl 2-(3a,4,7,7a-tetrahydro-1,3-dioxo-1H-isoindol-2(3H)-yl)succinate (1252935-79-7)

Conditions	Yield
With 1,4-diaza-bicyclo[2.2.2]octane; tetrabutylammomium bromide at 100℃; for 2.5h; aza-Michael addition; Neat (no solvent);	85%

1,2,3,6-tertahydrophthalimide (85-40-5) + 11-bromomethyl-tricosane (732276-63-0) → C32H57NO2 (1266676-35-0)

Conditions	Yield
With tetrabutylammomium bromide; potassium carbonate In N,N-dimethyl-formamide at 50℃; Inert atmosphere;	85%

1,2,3,6-tertahydrophthalimide (85-40-5) + ethyl 2-(p-tolylamino)acetate (21911-68-2) → C19H22N2O4

Conditions	Yield
With oxygen; copper(l) chloride In acetonitrile at 50℃; for 24h; Green chemistry; regioselective reaction;	85%

1,2,3,6-tertahydrophthalimide (85-40-5) + chloroformic acid ethyl ester (541-41-3) → N-ethoxycarbonyl-1,2,3,6-tetrahydrophthalimide

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 4h;	82%

2-methyl-1-buten-4-ol (763-32-6) + 1,2,3,6-tertahydrophthalimide (85-40-5) → 2-(3-Methyl-but-3-enyl)-3a,4,7,7a-tetrahydro-isoindole-1,3-dione (82478-57-7)

Conditions	Yield
With dimethyl azodicarboxylate; triphenylphosphine In tetrahydrofuran Ambient temperature; overnight;	81%

3-(1,2,4,4a,5,6-hexahydro-pyrazino[1,2-a]quinolin-3-yl)-propylamine (182208-57-7) + 1,2,3,6-tertahydrophthalimide (85-40-5) → 2-[3-(1,2,4,4a,5,6-hexahydro-pyrazino[1,2-a]quinolin-3-yl)-propyl]-3a,4,7,7a-tetrahydro-isoindole-1,3-dione

Conditions	Yield
In toluene Heating / reflux;	80%

1,2,3,6-tertahydrophthalimide (85-40-5) + 1-butyn-4-ol (927-74-2) → 2-But-3-ynyl-3a,4,7,7a-tetrahydro-isoindole-1,3-dione (82478-59-9)

Conditions	Yield
With dimethyl azodicarboxylate; triphenylphosphine In tetrahydrofuran Ambient temperature; overnight;	78%

1,2,3,6-tertahydrophthalimide (85-40-5) + (Z)-2-fluoro-3-phenylprop-2-enyl acetate (62360-00-3) + phenol (108-95-2) → (Z)-2-(2-phenoxy-3-phenylallyl)-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione

Conditions	Yield
With 1,1'-bis-(diphenylphosphino)ferrocene; bis(η3-allyl-μ-chloropalladium(II)); caesium carbonate In toluene at 80℃; for 16h; Inert atmosphere; regioselective reaction;	78%

1,2,3,6-tertahydrophthalimide (85-40-5) + di-tert-butyl dicarbonate (24424-99-5) → 3a,4,7,7a-tetrahydro-1H-isoindol-2(3H)-carboxylic acid tert-butylester

Conditions	Yield
Stage #1: 1,2,3,6-tertahydrophthalimide With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 60℃; for 18h; Stage #2: di-tert-butyl dicarbonate With triethylamine In dichloromethane at 0 - 20℃; for 21.5h;	77.3%

methyl 2-(m-tolylamino)acetate (126689-79-0) + 1,2,3,6-tertahydrophthalimide (85-40-5) → C18H20N2O4

Conditions	Yield
With oxygen; copper(l) chloride In acetonitrile at 50℃; for 24h; Green chemistry; regioselective reaction;	77%

1,2,3,6-tertahydrophthalimide (85-40-5) + di-n-propyl fumarate (14595-35-8) → dipropyl 2-(3a,4,7,7a-tetrahydro-1,3-dioxo-1H-isoindol-2(3H)-yl)succinate (1252935-80-0)

Conditions	Yield
With 1,4-diaza-bicyclo[2.2.2]octane; tetrabutylammomium bromide at 100℃; for 3.5h; aza-Michael addition; Neat (no solvent);	76%

1,2,3,6-tertahydrophthalimide (85-40-5) + di-tert-butyl dicarbonate (24424-99-5) → (3aH,7aS)-tert-butyl 3a,4,7,7a-tetrahydro-1H-isoindole-2(3H)-carboxylate (474925-37-6)

Conditions	Yield
Stage #1: 1,2,3,6-tertahydrophthalimide With lithium aluminium tetrahydride In tetrahydrofuran for 24h; Heating; Stage #2: di-tert-butyl dicarbonate In dichloromethane for 1h; Further stages.;	73%

1,2,3,6-tertahydrophthalimide (85-40-5) + 1,3-dibromo-propane (109-64-8) → 2-(3-bromopropyl)-3a,4.7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione (56401-24-2)

Conditions	Yield
With tetra-(n-butyl)ammonium iodide; potassium carbonate In acetone at 40℃; for 8h;	72%

1,2,3,6-tertahydrophthalimide (85-40-5) + dibutyl fumarate (105-75-9) → dibutyl 2-(3a,4,7,7a-tetrahydro-1,3-dioxo-1H-isoindol-2(3H)-yl)succinate (1252935-81-1)

Conditions	Yield
With 1,4-diaza-bicyclo[2.2.2]octane; tetrabutylammomium bromide at 100℃; for 3.5h; aza-Michael addition; Neat (no solvent);	72%

1,2,3,6-tertahydrophthalimide (85-40-5) + fumaric acid dipentyl ester (20314-74-3) → dipentyl 2-(3a,4,7,7a-tetrahydro-1,3-dioxo-1H-isoindol-2(3H)-yl)succinate (1252935-82-2)

Conditions	Yield
With 1,4-diaza-bicyclo[2.2.2]octane; tetrabutylammomium bromide at 100℃; for 4h; aza-Michael addition; Neat (no solvent);	70%

1,2,3,6-tertahydrophthalimide (85-40-5) + pent-3-yn-2-one (7299-55-0) → 2-((E)-4-Oxo-pent-2-enyl)-3a,4,7,7a-tetrahydro-isoindole-1,3-dione

Conditions	Yield
With triphenylphosphine	69%

1,2,3,6-tertahydrophthalimide (85-40-5) + dihexyl fumarate (19139-31-2) → dihexyl 2-(3a,4,7,7a-tetrahydro-1,3-dioxo-1H-isoindol-2(3H)-yl)succinate (1252935-83-3)

Conditions	Yield
With 1,4-diaza-bicyclo[2.2.2]octane; tetrabutylammomium bromide at 100℃; for 4.5h; aza-Michael addition; Neat (no solvent);	68%

1,2,3,6-tertahydrophthalimide (85-40-5) + 1-bromoacetone (598-31-2) → 1-(Δ4-tetrahydrophthalimido)propan-2-one (54399-02-9)

Conditions	Yield
With sodium ethanolate In ethanol for 2h; Heating;	64%

1,2,3,6-tertahydrophthalimide (85-40-5) + diheptyl fumarate (20314-73-2) → diheptyl 2-(3a,4,7,7a-tetrahydro-1,3-dioxo-1H-isoindol-2(3H)-yl)succinate (1252935-84-4)

Conditions	Yield
With 1,4-diaza-bicyclo[2.2.2]octane; tetrabutylammomium bromide at 100℃; for 5h; aza-Michael addition; Neat (no solvent);	63%

Upstream product

• 85-43-8 1,2,3,6-Tetrahydrophthalic anhydride 
• 2028-12-8 4-cyclohexene 1-carboxylic acid 2-carboxamide 
• 42027-93-0 N-Hydroxymethyl-cis-4-cyclohexene-1,2-dicarboximide 

Downstream Products

• 95316-76-0 2-(4r-methyl-5t-phenyl-oxazolidin-3-ylmethyl)-3a,4,7,7a-tetrahydro-isoindole-1,3-dione 
• 95316-76-0 2-(4r-methyl-5c-phenyl-oxazolidin-3-ylmethyl)-3a,4,7,7a-tetrahydro-isoindole-1,3-dione 
• 2021-19-4 2-butyl-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione 
• 474925-37-6 (3aR,7aS)-tert-butyl 3a,4,7,7a-tetrahydro-1H-isoindole-2(3H)-carboxylate 
• 17620-38-1 2-oxiranylmethyl-3a,4,7,7a-tetrahydro-isoindole-1,3-dione 
• 10533-30-9 2,3,3a,4,7,7a-hexahydro-1H-isoindole 
• 1446021-66-4 tert-butyl 5-(methylamino)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate 
• 203661-68-1 tert-butyl 5-oxohexahydro-1H-isoindole-2(3H)-carboxylate 
• 1031335-28-0 5-aminohexahydrocyclopenta[c]pyrrole-2(1H)-carboxylic acid tert-butyl ester 
• 54399-03-0 2-prop-2-ynyl-3a,4,7,7a-tetrahydro-isoindole-1,3-dione 

Relevant articles and documents

Synthesis of N-unsubstituted cyclic imides from anhydride with urea in deep eutectic solvent (DES) choline chloride/urea

N-Unsubstituted cyclic imides were readily synthesized in deep eutectic solvent (DES) choline chloride (ChCl)/urea from anhydrides with urea. Urea serves as both a DES component and a nitrogen source, which endows the protocol with advantages of smooth reaction, easy separation of products, simple recovery and recycling of ChCl/urea.

Preparation method of 1,2,3,6-tetrahydrophthalimide

The invention provides a preparation method of 1,2,3,6-tetrahydrophthalimide. The preparation method comprises the following steps: a) mixing 1,2,3,6-tetrahydrophthalic anhydride with an ammonia source, and carrying out a low-temperature reaction to obtain a reaction intermediate, wherein the temperature of the low-temperature reaction is 0-30 DEG C; and b) carrying out a dehydration ring-closurereaction on the reaction intermediate obtained in the step a) in the presence of a solvent, carrying out cooling and recrystallizing to obtain the 1,2,3,6-tetrahydrophthalimide. According to the preparation method provided by the invention, a step-by-step method is adopted, a ring-opening reaction and a ring-closure reaction are separated to reduce side reactions, and a conventional heating process is not carried out in the whole process, so the generation of viscous colloidal byproducts in a temperature range of 80-110 DEG C can be effectively avoided, and high selectivity is realized, thereby improving product purity; meanwhile, reaction operation in a solvent is simple, conditions are easy to control, and environment friendliness is achieved; the overall two-step yield can reach 95% orhigher; moreover, no waste gas is generated in the reaction process, and redundant ammonia gas can be recycled, so environmental production cost is greatly saved.

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.

Diels-Alder reactions of hexachlorocyclopentadiene with N-hydroxy- and N-hydroxyalkyl-cis-4-cyclohexene-1,2-dicarboximides

The Diels-Alder reaction of hexachlorocyclopentadiene with N-hydroxymethyl-cis-4-cyclohexene-1,2-dicarboximide is accompanied by partial or complete elimination of formaldehyde molecule. The desired stable polychlorinated Diels-Alder adducts are obtained from substrates in which the hydroxy group is protected by acetylation and those containing a trichloromethyl group in the α-position or lacking the methylene group.

INCORPORATION OF MOLECULAR NITROGEN INTO AMIDES AND IMIDES BY USE OF TITANIUM-NITROGEN COMPLEXES

Molecular nitrogen was incorporated into amides and imides by the reaction of titanium-nitrogen complex 1 prepared from TiCl3 and Mg under N2 in THF with acyl chlorides 3.The cyclic imides 10, 12, 14 and quinazoline 16 were obtained by the reaction of isocyanate complex 6 generated by fixation of CO2 into titanium complex 1 with the corresponding cyclic anhydrides 9, 11, 13 and benzoxazone 15.

OLEFIN CYCLISATIONS OF HINDERED α-ACYLIMINIUM IONS

Stereocontrolled NaBH4/H+-reduction of 3,4-cis-disubstituted N-alkenyl imides 1-5 leads to secondary hydroxylactams.Tertiary hydroxylactams are formed via addition of MeMgCl to imides 2 and 4.HCOOH-Cyclisation of the hydroxylactams affords polycyclic piperidines through stereoselective α-acyliminium ring closure.Concomitant synchronous and stepwise cyclisation pathways are operative in the anti-periplanar addition of tertiary α-acyliminium ions to Me substituted olefins 8c and 11c.