85-42-7

Basic information

• Product Name: Hexahydrophthalic anhydride
• Synonyms: 1,2-Cyclohexanedicarboxylic Acid anhydride;1,3-Isobenzofurandione, hexahydro-;3-Isobenzofurandione,hexahydro-1;Araldite HT 907;hexahydro-3-isobenzofurandione;Lekutherm Hardener H;NT 907;1,2-CYCLOHEXANEDICARBOXYLIC ANHYDRIDE
• CAS NO: 85-42-7
• Molecular Formula: C₈H₁₀O₃
• Molecular Weight: 154.16
• EINECS: 201-604-9
• Product Categories: Diels-Alder Adducts;Organics
• Mol File: 85-42-7.mol
• Article Data: 17

Chemical Properties

• Melting Point: 32-34 °C(lit.)
• Boiling Point: 158 °C17 mm Hg(lit.)
• Flash Point: >230 °F
• Appearance: Colorless and clear viscous liquid
• Density: 1.18
• Vapor Pressure: 0.003mmHg at 25°C
• Refractive Index: 1.4620 (estimate)
• Storage Temp.: Store at room temperature.
• Solubility: Chloroform, Methanol (Slightly)
• PKA: 4.14[at 20 ℃]
• Water Solubility: 4.2g/L at 20℃
• Sensitive: Moisture Sensitive
• Stability: Moisture Sensitive
• BRN: 83213
• CAS DataBase Reference: Hexahydrophthalic anhydride(CAS DataBase Reference)
• NIST Chemistry Reference: Hexahydrophthalic anhydride(85-42-7)
• EPA Substance Registry System: Hexahydrophthalic anhydride(85-42-7)

Safety Data

• Hazard Codes: Xn
• Statements: 41-42/43
• Safety Statements: 23-24-26-37/39
• RIDADR: 3335
• WGK Germany: 1
• RTECS: NP6895168
• TSCA: Yes
• Hazardous Substances Data: 85-42-7(Hazardous Substances Data)

Usage

Description

Hexahydrophthalic anhydride (HHPA) is widely used for electronics applications, e.g. HHPA cured epoxy resins have excellent dielectric properties, high-temperature stability, and high glass transition temperatures. HHPA is used as a curing agent in adhesive coatings and sealant materials, e.g. for the second-generation two-part epoxy adhesive synthesis. Hexahydrophthalic anhydride is also used in the manufacture of alkyd and polyester resins, insecticides, and rust preventives.

References

[1] Guy Rabilloud, High Performance Polymers. Vol. 1 Conductive Adhesives, 1997 [2] John Burke Sullivan and Gary R. Krieger, Clinical Environmental Health and Toxic Exposures, 2001 [3] B. A. G. J?nsson, H. Welinder, C. Hansson and B. St?hlbom, Occupational exposure to hexahydrophthalic anhydride: air analysis, percutaneous absorption, and biological monitoring, International Archives of Occupational and Environmental Health 1993, vol. 65, 43-47

Chemical Properties

White crystalline powder

Uses

Different sources of media describe the Uses of 85-42-7 differently. You can refer to the following data:
1. Intermediate for alkyds, plasticizers, insect repellents, and rust inhibitors; hardener in epoxy resins.
2. HPPA, in combination with triethaylamine (TEA), can be used as a polymerization initiator in the preparation of polyester based resins. It can also be used as a hardener to cure 1,4-butanediol diglycidyl ether which can be used as an epoxy based system for electronic devices.

Application

Predominantly cis 1,2-cyclohexanedicarboxylic anhydride (HHPA) is a cyclic anhydride that can be used for a variety of applications such as: plasticizer, rust inhibitor, and a curing agent for epoxy based resins.HPPA, in combination with triethaylamine (TEA), can be used as a polymerization initiator in the preparation of polyester based resins. It can also be used as a hardener to cure 1,4-butanediol diglycidyl ether which can be used as an epoxy based system for electronic devices.

Definition

ChEBI: A cyclic dicarboxylic anhydride that is the cyclic anhydride of hexahydrophthalic acid.

General Description

Predominantly cis 1,2-cyclohexanedicarboxylic anhydride (HHPA) is a cyclic anhydride that can be used for a variety of applications such as: plasticizer, rust inhibitor, and a curing agent for epoxy based resins.

Hazard

Toxic by inhalation, strong irritant to eyes and skin.

Flammability and Explosibility

Nonflammable

Synthesis

Hexahydrophthalic anhydride is obtained by reacting ciscyclohexane-1, 2-dicarboxylic acid with oxalyl chloride.Combine ciscyclohexane-1, 2-dicarboxylic acid (1 mmol, 172 mg) and oxalyl chloride (1.2 mmol, 152 mg, 0.103 ml) in dry toluene (5 mL) and add a drop of freshly distilled DMF. Purge the reaction vessel with argon and heat the reaction under stirring for 3 h. Stop the stirring, decant the toluene solution and filter. Evaporate the volatiles. Transform into crystalline form by trituration with diethyl ether. 1H NMR (400 MHz, CDCl3) δ 3.18 - 3.12 (m, 2H 2CH) 1.96 - 1.83 (m, 4H 2CH2) 1.57 - 1.49 (m, 4H 2CH2). HRMS (ESI), calcd for C8H10NaO3 [M+Na]+ 175.0522, found 175.0527; calcd for C9H14NaO4 [M+CH3 OH+Na]+ 209.0784, found 209.0788.Fig The synthetic method of Hexahydrophthalic anhydride.

InChI:InChI=1/C8H10O3/c9-7-5-3-1-2-4-6(5)8(10)11-7/h5-6H,1-4H2/t5-,6+

Synthetic route

3,4,5,6-Tetrahydrophthalic anhydride (2426-02-0) → 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7)

Conditions	Yield
With hydrogen; nickel In N,N-dimethyl-formamide at 95℃; under 33752.7 Torr; for 3h; Product distribution; Further Variations:; Catalysts; Pressures; Temperatures; Solvents; Catalytic hydrogenation;	88%
With sodium amalgam Erhitzen des entstehenden Gemisches der stereoisomeren Hexahydrophthalsaeuren im Vakuum auf 210-220grad; anhydride of/the/ cis-hexahydrophthalic acid;

(1R,2S)-cyclohexane-1,2-dicarboxylic acid (610-09-3) → 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7)

Conditions	Yield
beim Schmelzen; anhydride of/the/ cis-hexahydrophthalic acid;

cyclohexane-1,2-dicarboxylic acid (1687-30-5) → 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7)

Conditions	Yield
With acetic anhydride Dehydration;

anhydride of/the/ inactive trans-hexahydrophthalic acid → 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7)

Conditions	Yield
at 210 - 220℃; anhydride of/the/ cis-hexahydrophthalic acid;

dextrorotatory trans-hexahydrophthalic acid → 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7)

Conditions	Yield
With acetyl chloride anhydride of/the/ dextrorotatory trans-hexahydrophthalic acid;

benzene-1,2-dicarboxylic acid (88-99-3) → phthalic anhydride (85-44-9) + 2-methyl-1-cyclohexanecarboxylic acid (7077-04-5, 10479-51-3, 56586-13-1) + 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7)

Conditions	Yield
With 5%-palladium/activated carbon; hydrogen In 1,4-dioxane at 219.84℃; under 51680.2 Torr; for 12h;

4-methoxy-benzylamine (2393-23-9) + 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) → 2-(4-methoxybenzyl)hexahydro-1H-isoindole-1,3(2H)-dione

Conditions	Yield
With acetic acid for 18h; Reflux;	100%

4-chlorodiphenyl ether (7005-72-3) + 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) → 2-[4-(4-Chloro-phenoxy)-benzoyl]-cyclohexanecarboxylic acid

Conditions	Yield
With aluminium trichloride In dichloromethane 1.) 30 min, 0 deg C, 2.) 1 h, RT;	99%

tert-butyl 4-[4-amino-6-(pyrazin-2-ylamino)-2,4'-bipyridin-2'-yl]piperazine-1-carboxylate (1370453-11-4) + 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) → 2-({[2'-[4-(tert-butoxycarbonyl)piperazin-1-yl]-6-(pyrazin-2-ylamino)-2,4'-bipyridin-4-yl]amino}carbonyl)cyclohexanecarboxylic acid (1370456-54-4)

Conditions	Yield
With pyridine; dmap In N,N-dimethyl-formamide at 100℃; for 48h;	99%
With pyridine; dmap In N,N-dimethyl-formamide at 100℃; for 48h;	99%

1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) + potassium trifluoro(prop-1-en-2-yl)borate → 3,3-diallylhexahydroisobenzofuran-1(3H)-one (1418757-97-7)

Conditions	Yield
With boron trifluoride diethyl etherate In dichloromethane at 20℃; for 2h; Inert atmosphere; chemoselective reaction;	99%

6-methylheptanol (1653-40-3) + 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) → diisooctyl cyclohexane-1,2-dicarboxylate (1028279-92-6)

Conditions	Yield
With C9H21NO3S*H2O4S at 160 - 180℃; for 2.5h; Temperature;	98.8%

7-methyl-1-octanol (2430-22-0) + 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) → 1,2-cyclohexane dicarboxylic acid di-isononylester (318292-43-2)

Conditions	Yield
With acetic anhydride at 180 - 230℃; under 760.051 Torr; for 3h; Temperature;	98.5%
at 180 - 200℃; for 2h; Temperature;	98.7%
titanium(IV) isopropylate at 250℃; under 3.75038 - 570.057 Torr; for 5h; Product distribution / selectivity;

Tetraethylene glycol (112-60-7) + 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) → C24H38O11

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; for 9h;	98%

tryptamine (61-54-1) + 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) → C18H22N2O3 (713111-32-1)

Conditions	Yield
In dichloromethane at 20℃; for 18h;	98%

2,4-Dimethoxybenzylamine (20781-20-8) + 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) → 2-(2,4-dimethoxybenzyl)hexahydro-1H-isoindole-1,3(2H)-dione

Conditions	Yield
With acetic acid for 4h; Reflux;	98%

methanol (67-56-1) + 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) → (1S,2R)-2-(methoxycarbonyl)cyclohexanecarboxylic acid (88335-92-6)

Conditions	Yield
With N-((1R,2R)-2-(dimethylamino)-1-(4-nitrophenyl)-3-(trityloxy)propyl)-3,5-bis-(trifluoromethyl)benzamide In tert-butyl methyl ether at 20℃; for 60h; Inert atmosphere; enantioselective reaction;	97%

1,4-butenediol (6117-80-2) + 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) → C20H28O8

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; for 9h;	96%

2-bromo-4-fluoroaniline (1003-98-1) + 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) → 2-(2-bromo-4-fluorophenyl)hexahydro-2H-isoindole-1,3-dione

Conditions	Yield
With acetic acid for 3h; Reflux;	96%

2,2,5,5-Tetramethyl-2,5-dihydro-1H-pyrrole-3-carboxylic acid (3-amino-propyl)-amide (93799-49-6) + 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) → 2-{3-[(2,2,5,5-Tetramethyl-2,5-dihydro-1H-pyrrole-3-carbonyl)-amino]-propylcarbamoyl}-cyclohexanecarboxylic acid (93799-08-7)

Conditions	Yield
In tetrahydrofuran; diethyl ether at 25℃; for 48h;	94%

1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) + 2,2'-[1,2-ethanediylbis(oxy)]bisethanol (112-27-6) → C22H34O10 (123683-15-8)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; for 9h;	94%
With base at 0 - 20℃; for 9h;

1-(3-(chloromethyl)phenyl)-2-hydroxy-2-methylpropan-1-one (1308332-52-6) + 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) → C19H24O6 (1399155-46-4)

Conditions	Yield
With dmap; triethylamine In dichloromethane at 20℃; for 2h; Inert atmosphere;	94%
With dmap; triethylamine In dichloromethane at 20℃; for 2h; Inert atmosphere;	94%

tryptamine (61-54-1) + 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) → 2-(2-(1H-indol-3-yl)ethyl)-octahydro-1H-isoindole-1,3(2H)-dione (66224-74-6)

Conditions	Yield
With triethylamine In toluene for 36h; Inert atmosphere; Dean-Stark; Reflux;	94%

1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) → 1,2-bis(hydroxymethyl)cyclohexane (3971-29-7)

Conditions	Yield
With [Zn(BH4)2(py)] In tetrahydrofuran for 0.8h; Heating;	93%
With lithium aluminium tetrahydride	90%
With potassium borohydride; magnesium chloride In tetrahydrofuran; toluene at 100℃; for 24h;	84.3%
Stage #1: 1,2-Cyclohexanedicarboxylic acid-anhydride With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 60℃; Stage #2: With water In tetrahydrofuran	75%
With lithium aluminium tetrahydride In tetrahydrofuran 1.) 0 deg C, 1 h, 2.) r. t. overnight;	55%

1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) + L-Tryptophan (73-22-3) → (S)-2-(1,3-dioxooctahydroisoindol-2-yl)-3-(1H-indol-3-yl)propionic acid

Conditions	Yield
With pyridine for 12h; Heating;	93%

1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) + Trp (54-12-6) → 2-(1,3-dioxooctahydroisoindol-2-yl)-3-(1H-indol-3-yl)propionic acid

Conditions	Yield
With pyridine for 12h; Heating;	92%

1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) + D-tryptophan (153-94-6) → (R)-2-(1,3-dioxooctahydroisoindol-2-yl)-3-(1H-indol-3-yl)propionic acid

Conditions	Yield
With pyridine for 12h; Heating;	92%

4-aminophenylacetic acid (1197-55-3) + 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) → 4-(1,3-dioxo-hexahydro-2-isoindolinyl)phenylacetic acid (62971-19-1)

Conditions	Yield
With acetic acid at 120℃; for 2h;	91.5%

meta-aminobenzoic acid (99-05-8) + 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) → C15H15NO4

Conditions	Yield
With acetic acid at 120℃; for 2h;	91.5%

1-amino-2-azidoethane (87156-40-9) + 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) → C10H16N4O3

Conditions	Yield
In chloroform at 20℃; for 3h;	90.9%

2,2,5,5-Tetramethyl-2,5-dihydro-1H-pyrrole-3-carboxylic acid (2-amino-ethyl)-amide (93799-56-5) + 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) → 2-{2-[(2,2,5,5-Tetramethyl-2,5-dihydro-1H-pyrrole-3-carbonyl)-amino]-ethylcarbamoyl}-cyclohexanecarboxylic acid (93799-07-6)

Conditions	Yield
In tetrahydrofuran; diethyl ether at 25℃; for 48h;	90%

rac-Ala-OH (302-72-7) + 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) → 2-(1,3-dioxooctahydroisoindol-2-yl)propionic acid

Conditions	Yield
With pyridine for 10h; Heating;	90%
With acetic acid at 120℃; for 12h; Reflux;
With acetic acid for 4h; Reflux;

1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) → cis-hexahydrophthalimide (7506-66-3)

Conditions	Yield
With ammonium acetate for 0.0125h; microwave heating;	90%

2,6-bis(4-amino-2-trifluoromethylphenoxy)anthraquinone + 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) → 2,6-bis[4-(1,2-cyclohexanedicarboximido)-2-trifluoromethylphenoxy]anthraquinone

Conditions	Yield
With acetic acid at 140℃; for 3h;	90%

Upstream product

• 2426-02-0 3,4,5,6-Tetrahydrophthalic anhydride 
• 635-08-5 cyclohex-1-ene-1,2-dicarboxylic acid 
• 46022-05-3 (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid 
• 610-10-6 (1S,2S)-cyclohexane-1,2-dicarboxylic acid 
• 88-99-3 benzene-1,2-dicarboxylic acid 
• 1687-30-5 cyclohexane-1,2-dicarboxylic acid 
• 85-43-8 1,2,3,6-Tetrahydrophthalic anhydride 
• 38765-78-5 cyclohex-2-ene-1,2-dicarboxylic acid 
• 85-44-9 phthalic anhydride 
• 610-09-3 (1R,2S)-cyclohexane-1,2-dicarboxylic acid 

Downstream Products

• 92377-27-0 2-(2-diethylamino-ethyl)-(3ar,7ac)-hexahydro-isoindole-1,3-dione 
• 68260-70-8 cis-2-allylhexahydroisoindole-1,3-dione 
• 84-65-1 9,10-phenanthrenequinone 
• 16132-02-8 N-(2-Thiazolyl)cyclohexan-1,2-dicarbonsaeureimid 
• 19692-01-4 2-thiazol-2-ylcarbamoyl-cyclohexanecarboxylic acid 
• 34314-73-3 C₁₁H₁₉NO₃Si 
• 33440-90-3 2-(5-nitro-thiazol-2-ylcarbamoyl)-cyclohexanecarboxylic acid 
• 56415-48-6 (1S,2R)-Cyclohexane-1,2-dicarboxylic acid 1-hydroxyamide 2-{[(R)-2-methyl-1-(pyrrolidine-1-carbonyl)-propyl]-amide} 
• 67643-20-3 5-(2-carboxy-cyclohexyl)-oxazole-4-carboxylic acid methyl ester 
• 38300-68-4 cis-1,2-Bis(chloromethyl)cyclohexan 
• 15753-50-1 cis-1,2-cyclohexanedimethanol 
• 147201-75-0 (1R,2R)-2-[(Benzyloxycarbamoyl-methyl)-methyl-carbamoyl]-cyclohexanecarboxylic acid 
• 332394-38-4 (1S,2R)-2-Diisobutylcarbamoyl-cyclohexanecarboxylic acid 
• 129760-95-8 5,10-Dihydro-4-ethyl-2-phenylpyrazolo<1,5-a><1,3>-7-cyclohexandiazepin-5,10-dione 

Relevant articles and documents

Synthesis method of trans 1 and 2 - cyclohexane dicarboxylic acid monomethylester

The invention provides a synthesis method of trans 1 and 2 - cyclohexane dicarboxylic acid monomethylester, and belongs to the field of organic synthesis. The trans 1-2 -cyclohexane dicarboxylic acid monomethylester synthesis method comprises the following steps: trans-cyclohexane -1 and 2 -dicarboxylic acid anhydride. The methanol and solvent is added to the reaction vessel, stirred and purified to obtain the target product trans 1, 2 - cyclohexanedicarboxylate, wherein the solvent is any one or more of tetrahydrofuran, 2 - methyltetrahydrofuran, benzene, toluene, methylene chloride, chloroform, ethyl acetate, methyl acetate or diethyl ether. Since a specific solvent is selected for the reaction solvent, racemization does not occur in the process of synthesizing trans 1 and 2 - cyclohexane dicarboxylic acid monomethyl ester, and the trans ee and 1 cyclohexane dicarboxylic acid monomethyl ester with higher 2 - value can be finally obtained.

Catalytic hydrogenation products of aromatic and aliphatic dicarboxylic acids

Hydrogenation of aromatic dicarboxylic acids gave 100 % selectivity to respective cyclohexane dicarboxylic acid with 5 % Pd/C catalyst. 5 % Ru/C catalyst was observed to give over hydrogenation products at 493 K and at lower temperature (453 K) the selectivity for cyclohexane dicarboxylic acids was increased. Hydrogenation of phthalic acid with Ru-Sn/Al2O3 catalyst was observed to give phthalide instead of 1,2-benzene dimethanol or 2-hydroxy methyl benzoic acid. Ru-Sn/Al2O3 catalyst selectively hydrogenated the carboxylic group of cyclohexane dicarboxylic acids to give cyclohexane dimethanol. Use of proper catalysts and reaction conditions resulted in desired products.

NOVEL HEPATITIS C VIRUS INHIBITORS

The invention provides compounds of formula (I): wherein Rings A and A' are independently 5-membered optionally substituted aromatic heterocycles; Q is C(=O)NR1R1' or formula U is C(R4)2, O, S, S(=O)2, C(R4)2C(R4)2, CH2O, OCH2, CH2S, SCH2, CH2S(=O)2, S(=O)CH2 or C=C(Ru )2; X is CH2, CHR12, CR12R12, O, S, S(=O)2 or NRx; m is 0, 1, 2 or 3; n is 0, 1, 2 or 3; the other variables are as defined in the claims, which are of use in the treatment or prophylaxis of hepatitis C virus infection, and related aspects.