14166-21-3

Basic information

• Product Name: (+/-)-TRANS-1,2-CYCLOHEXANEDICARBOXYLIC ANHYDRIDE
• Synonyms: (+/-)-TRANS-1,2-CYCLOHEXANEDICARBOXYLIC ANHYDRIDE;TRANS-1,2-CYCLOHEXANEDICARBOXYLIC ANHYDRIDE;TRANS-HEXAHYDROPHTHALIC ANHYDRIDE;1,3-Isobenzofurandione, hexahydro-, trans-;trans-cyclohexane-1,2-dicarboxylic anhydride;Einecs 238-009-9;cis-1.2-Cyclohexane dicarboxylic anhydride 1g [14166-21-3];trans-1,2-Cyclohexanedicarboxylic anhydride,trans-Hexahydrophthalic anhydride
• CAS NO: 14166-21-3
• Molecular Formula: C₈H₁₀O₃
• Molecular Weight: 154.16
• EINECS: 238-009-9
• Mol File: 14166-21-3.mol
• Article Data: 11

Chemical Properties

• Melting Point: 145-147 °C(lit.)
• Boiling Point: 283.4°Cat760mmHg
• Flash Point: 143.9°C
• Appearance: /
• Density: 1.235g/cm³
• Refractive Index: 1.536
• Storage Temp.: 2-8°C
• Solubility: Acetone (Sparingly), Chloroform (Slightly), DMSO (Slightly)
• Stability: Moisture Sensitive
• CAS DataBase Reference: (+/-)-TRANS-1,2-CYCLOHEXANEDICARBOXYLIC ANHYDRIDE(CAS DataBase Reference)
• NIST Chemistry Reference: (+/-)-TRANS-1,2-CYCLOHEXANEDICARBOXYLIC ANHYDRIDE(14166-21-3)
• EPA Substance Registry System: (+/-)-TRANS-1,2-CYCLOHEXANEDICARBOXYLIC ANHYDRIDE(14166-21-3)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22-42/43-41
• Safety Statements: 26-27-36/37/39-37/39-24-23
• WGK Germany: 3
• Hazardous Substances Data: 14166-21-3(Hazardous Substances Data)

Usage

Description

(+/-)-TRANS-1,2-CYCLOHEXANEDICARBOXYLIC ANHYDRIDE is an organic compound that is characterized by its anhydride structure, which is derived from the cyclohexane ring with two carboxyl groups. It is known for its potential applications in the pharmaceutical and chemical industries due to its unique chemical properties.

Uses

Used in Pharmaceutical Industry:
(+/-)-TRANS-1,2-CYCLOHEXANEDICARBOXYLIC ANHYDRIDE is used as a reagent for the preparation of inhibitors targeting specific biological molecules. Its application in this industry is primarily due to its ability to interact with and inhibit the activity of proteins and enzymes, which can be beneficial in the development of new drugs.
1. Hepatitis C Virus (HCV) Inhibitors:
(+/-)-TRANS-1,2-CYCLOHEXANEDICARBOXYLIC ANHYDRIDE is used as a reagent for the synthesis of HCV inhibitors. These inhibitors are designed to target and block the replication of the hepatitis C virus, thereby helping to treat and manage the infection.
2. Granzyme B Inhibitors:
(+/-)-TRANS-1,2-CYCLOHEXANEDICARBOXYLIC ANHYDRIDE is also used in the development of granzyme B inhibitors. Granzyme B is a serine protease involved in the immune system's response to infection and is a potential therapeutic target for various diseases, including cancer.
3. Protein Kinase C Inhibitors:
(+/-)-TRANS-1,2-CYCLOHEXANEDICARBOXYLIC ANHYDRIDE has been employed in studies related to the development of protein kinase C inhibitors. Protein kinase C is a family of enzymes that play a crucial role in various cellular processes, and its inhibition can have therapeutic implications in treating diseases such as cancer and neurological disorders.

Purification Methods

Crystallise the anhydride from *C6H6/Et2O. It has been obtained by heating the cis-acid or anhydride with HCl at 180o for 3hours. It can be obtained from the acid by heating in Ac2O. It sublimes at 125-135o/0.02mm. [Kohler & Jansen J Am Chem Soc 60 2145 1938, Fichter & Simon Helv Chim Acta 17 1218 1934, Beilstein 9 IV 2802.]

InChI:InChI=1/C16H22O7/c17-13(18)9-5-1-3-7-11(9)15(21)23-16(22)12-8-4-2-6-10(12)14(19)20/h9-12H,1-8H2,(H,17,18)(H,19,20)/t9-,10+,11-,12+

Synthetic route

trans-1,2-cyclohexanedicarboxylic acid (2305-32-0) → (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3)

Conditions	Yield
With acetyl chloride for 4h; Heating;	76%
With acetic anhydride
With 4-methyl-morpholine; methyl chloroformate In tetrahydrofuran at 20℃; for 0.25h;

trans-4-Cylohexene-1,2-dicarboxylic anhydride (85-43-8, 935-79-5, 13149-03-6, 51268-23-6) → (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3)

Conditions	Yield
With chloroform; palladium Hydrogenation;

dimethyl cis-1,2,3,6-tetrahydrophthalate (4841-84-3) → (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: methanol. sodium methylate 2: acetyl chloride 3: palladium; chloroform / Hydrogenation View Scheme

trans-cyclohex-4-ene-1,2-dicarboxylic acid (88-98-2, 2305-26-2, 15573-40-7, 50987-15-0, 51096-07-2, 51096-08-3) → (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetyl chloride 2: palladium; chloroform / Hydrogenation View Scheme

dimethyl trans-cyclohex-4-ene-1,2-dicarboxylate (17673-68-6) → (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: aqueous KOH 2: acetyl chloride 3: palladium; chloroform / Hydrogenation View Scheme

ethyl N-ethyl-glycinate (3183-20-8) + (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) → trans-2-<<(2-ethoxy-2-oxoethyl)ethylamino>carbonyl>cyclohexanecarboxylic acid

Conditions	Yield
With triethylamine In dichloromethane for 20h; Ambient temperature;	99%

(+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) → (+/-)-trans-2-(hydroxymethyl)cyclohexylmethanol (76155-27-6)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; for 2h; Inert atmosphere; Reflux;	98%
With lithium aluminium tetrahydride In tetrahydrofuran for 2h; Heating;	93%
With lithium aluminium tetrahydride In tetrahydrofuran	90%
With lithium aluminium tetrahydride In tetrahydrofuran for 24h; Heating;	75.1%
With lithium aluminium tetrahydride; Celite; sodium sulfate 1) THF, 0,5 h, rt; 2h, reflux, 2) THF, 0 deg C; Yield given. Multistep reaction;

benzylamine (100-46-9) + (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) → trans-2-benzylhexahydroisoindole-1,3-dione

Conditions	Yield
With 1,1,1,3,3,3-hexamethyl-disilazane; zinc(II) chloride In benzene Heating;	97%

Pro-Ala-NH2*HCl + (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) → 2-[2-(1-carbamoyl-ethylcarbamoyl)-pyrrolidine-1-carbonyl]-cyclohexanecarboxylic acid

Conditions	Yield
With 4 A molecular sieve; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide	96%

p-(ethoxycarbonyl)phenyl triflate (125261-30-5) + (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) → trans-2-(4-(ethoxycarbonyl)benzoyl)cyclohexane-1-carboxylic acid

Conditions	Yield
With [2,2]bipyridinyl; bis(1,5-cyclooctadiene)nickel (0); chloro-trimethyl-silane; zinc(II) iodide; zinc In N,N-dimethyl acetamide at 80℃; for 12h; Inert atmosphere; Sealed tube;	94%

trifluoromethanesulfonic acid 3,5-dimethylphenyl ester (219667-41-1) + (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) → trans-2-(3,5-dimethylbenzoyl)cyclohexane-1-carboxylic acid

Conditions	Yield
With [2,2]bipyridinyl; bis(1,5-cyclooctadiene)nickel (0); chloro-trimethyl-silane; zinc(II) iodide; zinc In N,N-dimethyl acetamide at 80℃; for 12h; Inert atmosphere; Sealed tube;	91%

(+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) + 4-[4-(2-methoxyphenyl)piperazin-1-yl]butylamine (21103-33-3) → 4-{4-[trans-1,2-cyclohexanedicarboxyimido]butyl}-1-(2-methoxyphenyl)piperazine

Conditions	Yield
In xylene for 3h; Heating;	90%

diethylzinc (557-20-0) + (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) → (1RS,2RS)-2-propionylcyclohexanecarboxylic acid

Conditions	Yield
With [2,2]bipyridinyl; bis(1,5-cyclooctadiene)nickel (0); para-fluorostyrene In tetrahydrofuran at 0℃; for 4h;	87%
With bis(1,5-cyclooctadiene)nickel (0); 1-trifluoromethyl-4-vinyl-benzene; (2-diphenylphosphino)ethylpyridine In tetrahydrofuran; hexane at 0℃; for 4.5h;	86%

3,5-Dichloroaniline (626-43-7) + (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) → (1SR,2SR)-2-((3,5-dichlorophenyl)carbamoyl)cyclohexanecarboxylic acid

Conditions	Yield
In tetrahydrofuran at 65℃;	85%

6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole hydrochloride (84163-13-3) + (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) → (1R,2R)-2-[4-(6-Fluoro-benzo[d]isoxazol-3-yl)-piperidine-1-carbonyl]-cyclohexanecarboxylic acid

Conditions	Yield
With triethylamine In tetrahydrofuran for 24h; Heating;	79%

4-(1,2,3,4-tetrahydroisoquinolin-2-yl)butylamine (174643-96-0) + (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) → 2-{4-[trans-1,2-cyclohexanedicarboxyimido]butyl}-1,2,3,4-tetrahydroisoquinoline

Conditions	Yield
In xylene for 3h; Heating;	79%

9-Decen-1-ol (13019-22-2) + (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) → (1S,2S)-Cyclohexane-1,2-dicarboxylic acid monodec-9-enyl ester

Conditions	Yield
With pyridine In dichloromethane at 20℃; for 72h;	79%

diphenylzinc (1078-58-6) + (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) → trans-2-phenyl-cyclohexanecarboxylic acid (24905-74-6, 24905-75-7, 37982-24-4, 64396-70-9, 64396-71-0, 97906-58-6, 113215-84-2, 113215-85-3)

Conditions	Yield
Stage #1: (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride With bis(1,5-cyclooctadiene)nickel (0); 2.9-dimethyl-1,10-phenanthroline; bis(diphenylphosphino)butane In tetrahydrofuran at 45℃; for 3h; Stage #2: diphenylzinc With para-fluorostyrene In tetrahydrofuran at 66℃; for 5h;	77%

tert.-butylhydroperoxide (75-91-2) + (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) → E-2-carbo-tert-perbutoxy cyclohexanecarboxylic acid (29516-56-1, 82435-77-6, 82435-78-7)

Conditions	Yield
With sodium hydride In diethyl ether at 25℃; for 1h;	76%

Sorbyl alcohol (17102-64-6) + (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) → (+/-)-(E,E)-2,4-hexadienyl trans-cyclohexane-1,2-dicarboxylate

Conditions	Yield
With pyridine; dmap In dichloromethane at 45℃; for 16h; Esterification;	75%
With pyridine; dmap In dichloromethane for 18h; Heating;

ethene (74-85-1) + (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) → trans-2-(1-oxo-2-propenyl)cyclohexanecarboxylic acid (71550-73-7, 71550-76-0)

Conditions	Yield
With aluminium trichloride In 1,2-dichloro-ethane for 4.5h;	70%

(+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) → trans-2-(hydroxymethyl)cyclohexanecarboxylic acid (57280-65-6, 65376-04-7, 80795-84-2, 93379-40-9)

Conditions	Yield
With sodium tetrahydroborate In tetrahydrofuran at 0 - 15℃; for 3h;	65%

1-amino-3-(dimethylamino)propane (109-55-7) + (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) → N-(3-(dimethylamino)propyl)-trans-cyclohexane-1,2-dicarbonic acid imide

Conditions	Yield
With toluene-4-sulfonic acid In toluene for 5h; Heating;	64%
Condensation;

(+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) → 3a,7a-trans-3a,4,5,6,7,7a-Hexahydro-1H-isobenzofuran-3-one (7702-72-9)

Conditions	Yield
With lithium aluminium tetrahydride	63%
With sodium tetrahydroborate In tetrahydrofuran for 48h; Ambient temperature;	46%
With lithium aluminium tetrahydride; diethyl ether

6-nitroveratryl alcohol (1016-58-6) + (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) → trans-cyclohexane-1,2-dicarboxylic acid mono(4,5-dimethoxy-2-nitrobenzyl) ester

Conditions	Yield
With pyridine; dmap In chloroform at 50℃; for 24h;	63%

ethanol (64-17-5) + (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) → ethyl-(trans-2-amino-1-cyclohexanecarboxylate)hydrochloride (1127-99-7, 28250-14-8, 90950-07-5)

Conditions	Yield
Stage #1: (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride With trimethylsilylazide In 1,4-dioxane at 70 - 80℃; Curtius Rearrangement; Heating; Stage #2: With water In 1,4-dioxane at 0℃; for 0.166667h; Reflux; Stage #3: ethanol With hydrogenchloride In 1,4-dioxane; water for 2h; Reflux;	57%

(+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) → trans-1,2-cyclohexanedicarboxylic acid (2305-32-0)

Conditions	Yield
With potassium superoxide; tetraethylammonium bromide In N,N-dimethyl-formamide at 25℃; for 12h; Ring cleavage;	41%

1,2-dimethoxybenzene (91-16-7) + (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) → trans-2-(3,4-dimethoxybenzoyl)cyclohexanecarboxylic acid

Conditions	Yield
With aluminium trichloride In dichloromethane Friedel-Crafts acylation; Heating;	40%

3-(3-isopropyl-1,2,4-oxadiazol-5-yl)-5,7-dihydro-4H-thieno[2,3-c]pyran-2-amine + (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) → (1SR,2SR)-2-[3-(3-isopropyl[1,2,4]oxadiazol-5-yl)-4,7-dihydro-5H-thieno[2,3-c]pyran-2-ylcarbamoyl]cyclohexanecarboxylic acid

Conditions	Yield
In diethyl ether at 20℃; for 68h; Inert atmosphere;	33%

(+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) + 1-(benzyloxy)-4-bromo-3-fluorobenzene (185346-79-6) → trans-2-[4-(benzyloxy)-2-fluorobenzoyl]cyclohexane-1-carboxylic acid

Conditions	Yield
Stage #1: 4-(benzyloxy)-1-bromo-2-fluorobenzene With n-butyllithium In diethyl ether; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride In tetrahydrofuran; diethyl ether; hexane at -78℃; for 1h;	32%

2-methyl-4-bromoiodobenzene (116632-39-4) + (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) → trans-2-(4-bromo-2-methylbenzoyl)cyclohexane-1-carboxylic acid

Conditions	Yield
Stage #1: 2-methyl-4-bromoiodobenzene With n-butyllithium In tetrahydrofuran at -78℃; for 1.5h; Inert atmosphere; Stage #2: (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride In tetrahydrofuran; diethyl ether at -78℃; for 2.25h;	20%

N-methylhomoveratrylamine (3490-06-0) + (+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) → (+/-)-trans-2-[(3,4-dimethoxy-phenethyl)-methyl-carbamoyl]-cyclohexanecarboxylic acid

Conditions	Yield
With benzene

(+/-)-trans-1,2-cyclohexanedicarboxylic anhydride (14166-21-3) + benzene (71-43-2) → (1R*,2R*)-2-benzoylcyclohexane-1-carboxylic acid (86528-43-0)

Conditions	Yield
With aluminium trichloride

Upstream product

• 4841-84-3 dimethyl cis-1,2,3,6-tetrahydrophthalate 
• 610-10-6 (1S,2S)-cyclohexane-1,2-dicarboxylic acid 
• 46022-05-3 (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid 
• 17673-68-6 dimethyl trans-cyclohex-4-ene-1,2-dicarboxylate 
• 88-98-2 trans-cyclohex-4-ene-1,2-dicarboxylic acid 
• 85-43-8 trans-4-Cylohexene-1,2-dicarboxylic anhydride 
• 2305-32-0 trans-1,2-cyclohexanedicarboxylic acid 

Downstream Products

• 113301-23-8 (1R,2R)-Cyclohexane-1,2-dicarboxylic acid 1-((R)-2-methoxy-1-phenyl-ethyl) ester 2-methyl ester 
• 29516-56-1 E-2-carbo-tert-perbutoxy cyclohexanecarboxylic acid 
• 71550-73-7 trans-2-(1-oxo-2-propenyl)cyclohexanecarboxylic acid 
• 34314-73-3 C₁₁H₁₉NO₃Si 
• 119518-16-0 trans-2-<3-(4-Chlorophenyl)-1,3-dioxopropyl>cyclohexanoic acid 
• 76155-27-6 (+/-)-trans-2-(hydroxymethyl)cyclohexylmethanol 
• 2305-32-0 trans-1,2-cyclohexanedicarboxylic acid 

Relevant articles and documents

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RECYCLABLE POLYMERS BASED ON RING-FUSED GAMMA-BUTYROLACTONES

The invention discloses a class of new polymers, trans-ring-fused poly(4-hydroxybutyrate)s (RF-P4HB) that exhibit a unique set of properties, including robust thermal stability and mechanical strength, quantitative recyclability to the building block monomers via thermolysis and/or chemical catalysis, and convenient production from the chemical ring-opening polymerization under ambient temperature and pressure. Another unique property is the formation of crystalline stereocomplexed polymers with high melting temperature upon mixing the two enantiomeric RF-P4HB chains via stereocomplexing co-crystallization. This invention also provides the corresponding ring-fused lactone monomer structures that enable the synthesis of the RF-P4HB polymers, through trans-fusing of rings to the parent γ-butyrolactone ring. Furthermore, a polymerization or copolymerization process for the synthesis of RF-P4HB polymers and copolymers is disclosed.

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