5445-51-2

Basic information

• Product Name: 1,1-Cyclobutanedicarboxylic acid
• Synonyms: 1,1-Cyclobutanedicar;1-Cyclobutanedicarboxylic acid;1,1-Cyclobutanedicarboxylic acid, 99% 25GR;1,1-Cyclobutanedicarboxylic acid, 99% 5GR;Caboplatin IMpurity B (Cyclobutane-1,1-dicarboxylic acid);1,1-Dicarboxylic acid cyclobutane;1,1-cyclobutanetwo forMic acid;Cyclobutane-1,1-dicarboxylic acid 99%
• CAS NO: 5445-51-2
• Molecular Formula: C₆H₈O₄
• Molecular Weight: 144.13
• EINECS: 226-651-2
• Product Categories: Carboxylic Acids;Organic acids;Cyclobutanes & Cyclobutenes;Simple 4-Membered Ring Compounds;Carboxylic Acids;Ring Systems;Cycloalkanes;C6;Carbonyl Compounds
• Mol File: 5445-51-2.mol

Chemical Properties

• Melting Point: 158 °C(lit.)
• Boiling Point: 222.71°C (rough estimate)
• Flash Point: 189.6 °C
• Appearance: White/Fine Crystalline Powder
• Density: 1.3217 (rough estimate)
• Vapor Pressure: 2.27E-06mmHg at 25°C
• Refractive Index: 1.5800 (estimate)
• Storage Temp.: Store below +30°C.
• PKA: pK1:3.13 ;pK2:5.88 (25°C)
• BRN: 2046031
• CAS DataBase Reference: 1,1-Cyclobutanedicarboxylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 1,1-Cyclobutanedicarboxylic acid(5445-51-2)
• EPA Substance Registry System: 1,1-Cyclobutanedicarboxylic acid(5445-51-2)

Safety Data

• Hazard Codes: C
• Statements: 34
• Safety Statements: 26-36/37/39-45-28A
• RIDADR: UN 3261 8/PG 2
• WGK Germany: 3
• TSCA: T
• HazardClass: 8
• PackingGroup: III
• Hazardous Substances Data: 5445-51-2(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
1,1-Cyclobutanedicarboxylic acid is used as a key component in the design, studies, and structural model of antitumor dicycloplatin, a clinical cancer drug. Its chemical properties contribute to the development of effective cancer treatments.
Additionally, 1,1-Cyclobutanedicarboxylic acid is used in understanding the hydrolysis mechanism of carboplatin, a second-generation anticancer drug. This knowledge aids in improving the drug's efficacy and minimizing side effects for patients undergoing cancer treatment.

InChI:InChI=1/C6H8O4/c7-4(8)6(5(9)10)2-1-3-6/h1-3H2,(H,7,8)(H,9,10)/p-2

Synthetic route

1,3-dibromo-propane (109-64-8) + diethyl malonate (105-53-3) → cyclobutane-1,1'-dicarboxylic acid (5445-51-2)

Conditions	Yield
With sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride for 2h; Ambient temperature;	23%

ethyl 1-cyano-1-cyclobutanecarboxylate (28246-87-9) → malonic acid (141-82-2) + cyclobutane-1,1'-dicarboxylic acid (5445-51-2)

Conditions	Yield
Hydrolysis;

diethyl cyclobutane-1,1-dicarboxylate (3779-29-1) → cyclobutane-1,1'-dicarboxylic acid (5445-51-2)

Conditions	Yield
With potassium carbonate
With oxonium
With sodium hydroxide; water at 20℃; for 48h; Hydrolysis;

1-cyanocyclobutane-1-carboxylic acid (30491-91-9) → cyclobutane-1,1'-dicarboxylic acid (5445-51-2)

Conditions	Yield
With potassium hydroxide

1,3-dibromo-propane (109-64-8) + diethyl malonate (105-53-3) → Cyclobutanecarboxylic acid (3721-95-7) + cyclobutane-1,1'-dicarboxylic acid (5445-51-2)

Conditions	Yield
With sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride for 1h; Ambient temperature; other subst. 1,3-dibromo compounds, other phase transfer catalysts;
With sodium hydroxide; tetrabutyl-ammonium chloride for 1h; Ambient temperature; Yield given. Yields of byproduct given;

(3-iodo-propyl)-malonic acid diethyl ester (300687-20-1) + toluene (108-88-3) + sodium phenylmalonic acid ester → phenylacetic acid (103-82-2) + cyclobutane-1,1'-dicarboxylic acid (5445-51-2)

diethyl ether (60-29-7) + (3-iodo-propyl)-malonic acid diethyl ester (300687-20-1) + sodium compound of phenylacetonitrile → cyclobutane-1,1'-dicarboxylic acid (5445-51-2) + 2-phenyl-pimelic acid

Conditions	Yield
Hydrolyse mit alkoh. KOH und Decarboxylierung;

sulfuric acid (7664-93-9) + 3-(1-ethoxycarbonyl-cyclobutyl)-3-amino-2-cyano-acrylic acid ethyl ester → malonic acid (141-82-2) + cyclobutane-1,1'-dicarboxylic acid (5445-51-2)

cyclobutane-1,1'-dicarboxylic acid (5445-51-2) → dipotassium cyclobutane-1,1-dicarboxylic acid

Conditions	Yield
With potassium hydroxide pH=7; Inert atmosphere; Schlenk technique;	100%
With potassium hydroxide In water
With potassium hydroxide In water

carboplatinum (41575-94-4) + cyclobutane-1,1'-dicarboxylic acid (5445-51-2) → 2C6H12N2O4Pt*3C6H8O4

Conditions	Yield
In water at 20℃; for 5h;	99.6%

carboplatinum (41575-94-4) + cyclobutane-1,1'-dicarboxylic acid (5445-51-2) → C6H12N2O4Pt*3C6H8O4

Conditions	Yield
In water at 20℃; for 5h;	99.6%

carboplatinum (41575-94-4) + cyclobutane-1,1'-dicarboxylic acid (5445-51-2) → C6H12N2O4Pt*5C6H8O4

Conditions	Yield
In water at 20℃; for 5h;	99.4%

carboplatinum (41575-94-4) + cyclobutane-1,1'-dicarboxylic acid (5445-51-2) → 2C6H12N2O4Pt*C6H8O4

Conditions	Yield
In water at 20℃; for 5h;	99.3%

carboplatinum (41575-94-4) + cyclobutane-1,1'-dicarboxylic acid (5445-51-2) → 2C6H12N2O4Pt*2C6H8O4

Conditions	Yield
In water at 20℃; for 5h;	99.2%

carboplatinum (41575-94-4) + cyclobutane-1,1'-dicarboxylic acid (5445-51-2) → C6H12N2O4Pt*4C6H8O4

Conditions	Yield
In water at 20℃; for 5h;	99.2%

carboplatinum (41575-94-4) + cyclobutane-1,1'-dicarboxylic acid (5445-51-2) → C6H12N2O4Pt*2C6H8O4

Conditions	Yield
In water at 20℃; for 5h;	99.1%

cyclobutane-1,1'-dicarboxylic acid (5445-51-2) + dicycloplatin → C6H12N2O4Pt*4C6H8O4

Conditions	Yield
In water at 20℃; for 5h;	99%

cyclobutane-1,1'-dicarboxylic acid (5445-51-2) + 5,5-difluoro-10-mesityl-1,3,7,9-tetramethyl-5H-4λ4,5λ4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinine (1308671-66-0) → C28H31BN2O4

Conditions	Yield
With chloro-trimethyl-silane In acetonitrile at 120℃; for 0.5h; Microwave irradiation;	98%

cyclobutane-1,1'-dicarboxylic acid (5445-51-2) → [1-(hydroxymethyl)cyclobutyl]methanol (4415-73-0)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran at -20 - 20℃; for 4h; Inert atmosphere;	95%
In tetrahydrofuran	92%
With lithium aluminium tetrahydride In tetrahydrofuran for 12h; Heating;	88%

cyclobutane-1,1'-dicarboxylic acid (5445-51-2) + zinc(II) oxide + ammonia (7664-41-7) → cyclobutane-1,1-dicarboxylatodiammine zinc(II)

Conditions	Yield
Stage #1: cyclobutane-1,1'-dicarboxylic acid; zinc(II) oxide In water at 20℃; for 0.5h; Stage #2: ammonia In water	95%

carboplatinum (41575-94-4) + cyclobutane-1,1'-dicarboxylic acid (5445-51-2) → dicycloplatin

Conditions	Yield
In water at 5℃; for 20h; Temperature; Time;	93.2%
In water at 30℃; for 0.15h; Temperature; Microwave irradiation;	90%
In water at 20℃;

dichloro(2,2'-bipyridine)palladium(II) (14871-92-2) + cyclobutane-1,1'-dicarboxylic acid (5445-51-2) → (2,2'-bipyridine-κ2N,N')(1,1-cyclobutanedicarboxylato-κ2O,O')palladium(II) (214846-23-8)

Conditions	Yield
With silver nitrate In water byproducts: AgCl; stirring the Pd complex and AgNO3 in H2O at 60°C for 2, filtration, addn. of the org. acid, adjustment of pH to 5; vac. filtration, washing (H2O; EtOH; Et2O), drying (vac.); elem. anal.;	93%

cis-dichlorobis(dimethylsulfoxide)platinum(II) (75992-73-3, 25794-47-2, 30729-25-0, 15274-33-6, 22840-91-1, 14568-13-9) + cyclobutane-1,1'-dicarboxylic acid (5445-51-2) → {1,1-cyclobutanedicarboxylato(2-)-O,O'}bis{sulfinylbis{methane}-S-}platinum(II) (187224-67-5, 119759-73-8)

Conditions	Yield
Stage #1: cyclobutane-1,1'-dicarboxylic acid With silver(l) oxide In water at 20℃; for 0.333333h; Darkness; Stage #2: cis-dichlorobis(dimethylsulfoxide)platinum(II) In water at 70℃; for 0.166667h; Darkness; Stage #3: In water at 20℃; for 24h; Darkness;	90%

cis-diaminediiodoplatinum(II) + cyclobutane-1,1'-dicarboxylic acid (5445-51-2) → carboplatinum (41575-94-4)

Conditions	Yield
With barium dihydroxide; silver sulfate In water byproducts: AgI, BaSO4; addn. of Ag2SO4 to slight excess of Pt-complex, stirring (4 h), filtration off of AgI, concn., addn. of soln. of ligand (neutralized with Ba(OH)2); filtration off of BaSO4, concn. (crystn.), washing (EtOH, Et2O), drying(vac.); elem. anal.;	88%
Stage #1: cis-diaminediiodoplatinum(II) With silver sulfate In water for 4h; Stage #2: cyclobutane-1,1'-dicarboxylic acid With barium hydroxide octahydrate In water	85%
Stage #1: cis-diaminediiodoplatinum(II) With silver nitrate In water Darkness; Stage #2: cyclobutane-1,1'-dicarboxylic acid With potassium hydroxide for 3h; pH=5;	50.3%
With potassium hydroxide In water; N,N-dimethyl-formamide Pt-compd. dissolved in DMF with heating, addn. of the acid and aq. KOH, heated in an unstoppered flask at 60°C for 20 h; cooled, filtered, addn. of ether;	40%

thallium(I) nitrate + cyclobutane-1,1'-dicarboxylic acid (5445-51-2) → cyclobutane-1,1-dicarboxylic acid, monothallium(I) salt

Conditions	Yield
In water (inert atmosphere); addn. of the Tl salt in hot H2O to the org. diacid in boiling H2O; pptn. by concn.; elem. anal.;	86%

cyclobutane-1,1'-dicarboxylic acid (5445-51-2) + formamide (77287-34-4, 77287-35-5, 60100-09-6) + manganese(ll) chloride → CH5N2(1+)*3CHO2(1-)*Mn(2+)

Conditions	Yield
at 130℃; for 24h; Autoclave; Microwave irradiation;	85%

cyclobutane-1,1'-dicarboxylic acid (5445-51-2) + formamide (77287-34-4, 77287-35-5, 60100-09-6) + cobalt(II) chloride (7646-79-9) → [NH2-CH-NH2][Co(HCOO)3]

Conditions	Yield
at 130℃; for 24h; Autoclave;	85%
at 130℃; for 24h; Autoclave; Microwave irradiation;	85%

cyclobutane-1,1'-dicarboxylic acid (5445-51-2) + silver nitrate → 1,1-cyclobutanedicarboxylic acid disilver salt

Conditions	Yield
Stage #1: cyclobutane-1,1'-dicarboxylic acid With sodium hydroxide In water Stage #2: silver nitrate In water at 20℃; for 1h; Darkness;	82%
With NaOH In water aq. soln. of NaOH added to dicarboxylic acid in water, AgNO3 added in dark, stirred for 15-30 min; ppt. filtered, washed with water, dried in air;
With sodium hydroxide In water

methanol (67-56-1) + cyclobutane-1,1'-dicarboxylic acid (5445-51-2) → dimethyl cyclobutane-1,1-dicarboxylate (10224-72-3)

Conditions	Yield
With sulfuric acid In dichloromethane for 15h; Heating;	81%

cyclobutane-1,1'-dicarboxylic acid (5445-51-2) + [Pd(1,4-bis(2-hydroxyethyl)piperazine)Cl2] → C14H24N2O6Pd

Conditions	Yield
Stage #1: [Pd(1,4-bis(2-hydroxyethyl)piperazine)Cl2] With silver nitrate In water for 24h; Darkness; Stage #2: cyclobutane-1,1'-dicarboxylic acid With silver(I) chloride; sodium hydroxide In water at 60℃; for 2h; pH=5-6;	81%

cisplatin (15663-27-1) + cyclobutane-1,1'-dicarboxylic acid (5445-51-2) → diammino(1,1-cyclobutanedicarboxylate)platinum(II)*DMF

Conditions	Yield
With potassium hydroxide In water; N,N-dimethyl-formamide Pt-compd. dissolved in DMF with heating, addn. of the acid and aq. KOH, heated in an unstoppered flask at 60°C for 20 h; cooled, filtered, concn. in vac.;	80%

cis-dichloro(ethylenediamine)palladium(II) (15020-99-2) + cyclobutane-1,1'-dicarboxylic acid (5445-51-2) → (1,2-ethylenediamine)(1,1-cyclobutanedicaboxylato)palladium(II) monohydrate (214846-19-2)

Conditions	Yield
With sodium hydroxide; silver nitrate In water byproducts: AgCl; stirring the Pd complex and AgNO3 in H2O at 20°C in darkness overnight, filtration, addn. of the org. acid, adjustment of pH to 5 with NaOH; vac. filtration, washing (H2O; EtOH; Et2O), drying (vac.); elem. anal.;	80%
With AgNO3; NaHCO3 In water byproducts: AgCl, CO2; AgNO3 was added to a suspn. of complex in water in the dark with stirring and heating at 60°C for 1 h, refrigerated, AlCl was filtered, dicarboxylic acid was added, NaHCO3 was added dropwise with heating and stirring (CO2), left at room temp.; solid was filtered, washed with water, air-dried; elem. anal.;	78%

copper carbonate hydroxide + cyclobutane-1,1'-dicarboxylic acid (5445-51-2) + water (7732-18-5) → {(C4H6(COO)2) copper(II)}*H2O (151840-51-6, 879282-32-3)

Conditions	Yield
In water soln. of ligand in H2O added dropwise to warm aq. suspn. of Cu salt under stirring and heating below 70°C (water bath); heated for 2 h; filtered; filtrate evapd. for a few d; filtered; ppt. washed with EtOH and ether; air dried; elem. anal.;	80%

cyclobutane-1,1'-dicarboxylic acid (5445-51-2) → spirocyclobutyl-malonyl peroxide (34867-87-3)

Conditions	Yield
With methanesulfonic acid; urea hydrogen peroxide adduct at 22℃; for 18h;	80%
With methanesulfonic acid; urea hydrogen peroxide adduct at 20℃; for 18h;	80%

di(pyridin-2-yl)amine (1202-34-2) + cyclobutane-1,1'-dicarboxylic acid (5445-51-2) + water (7732-18-5) + cobalt(II) chloride (7646-79-9) → cylobutane-1,1-dicarboxylato dipyridylamine cobalt(II)* hydrate

Conditions	Yield
With sodium carbonate for 2h; Thermodynamic data; Heating;	80%

cyclobutanemethanol (4415-82-1) + cyclobutane-1,1'-dicarboxylic acid (5445-51-2) → bis(cyclobutylmethyl)cyclobutane-1,1-dicarboxylate

Conditions	Yield
With toluene-4-sulfonic acid In tetrahydrofuran; benzene at 80℃; for 4h; Dean-Stark;	80%

terbium(III) nitrate hexahydrate + cyclobutane-1,1'-dicarboxylic acid (5445-51-2) + formamide (77287-34-4, 77287-35-5, 60100-09-6) → [Tb(HCOO)4](1-)[NH2CHNH2](1+)

Conditions	Yield
In formamide High Pressure; Tb(NO3)3*6H2O, cyclobutane-1,1'-dicarboxylic acid dissolved in formamideplaced in autoclave, heated at 130°C for 24 h, slowly cooled ove rnight; collected, washed with EtOH, petroleum ether, dried under N2 at room temp.; elem. anal.;	77%

gadolinium(III) nitrate hexahydrate + cyclobutane-1,1'-dicarboxylic acid (5445-51-2) + formamide (77287-34-4, 77287-35-5, 60100-09-6) → [Gd(HCOO)4](1-)[NH2CHNH2](1+)

Conditions	Yield
In formamide High Pressure; Gd(NO3)3*6H2O, cyclobutane-1,1'-dicarboxylic acid dissolved in formamideplaced in autoclave, heated at 130°C for 24 h, slowly cooled ove rnight; collected, washed with EtOH, petroleum ether, dried under N2 at room temp.; elem. anal.;	77%

Upstream product

• 28246-87-9 ethyl 1-cyano-1-cyclobutanecarboxylate 
• 3779-29-1 diethyl cyclobutane-1,1-dicarboxylate 
• 30491-91-9 1-cyanocyclobutane-1-carboxylic acid 
• 109-64-8 1,3-dibromo-propane 
• 105-53-3 diethyl malonate 
• 300687-20-1 (3-iodo-propyl)-malonic acid diethyl ester 
• 108-88-3 toluene 
• 60-29-7 diethyl ether 
• 7664-93-9 sulfuric acid 

Downstream Products

• 3721-95-7 Cyclobutanecarboxylic acid 
• 3019-25-8 1-cyclobutylethanone 
• 3779-29-1 diethyl cyclobutane-1,1-dicarboxylate 
• 10224-72-3 dimethyl cyclobutane-1,1-dicarboxylate 
• 98899-26-4 cyclobutane-1,1-dicarboxylic acid dibutyl ester 
• 33582-68-2 cyclobutane-1,1-dicarboxylic acid diamide 
• 51816-01-4 cyclobutane-1,1-dicarboxylic acid dichloride 
• 35207-71-7 3-chlorocyclobutane-1-carboxylic acid 
• 124-38-9 carbon dioxide 
• 277756-42-0 1-trifluoromethyl-cyclobutanecarbonyl fluoride 
• 277756-45-3 (1-trifluoromethyl)cyclobutanecarboxylic acid 
• 419571-31-6 dibenzyl cyclobutane-1,1-dicarboxylate 
• 30494-32-7 3-chlorocyclobutane carboxylic acid chloride 
• 15963-47-0 3-chlorocyclobutanemethanol 

Relevant articles and documents

Selective reactions of 1,1-cycloalkanedicarboxylic acids with SF4. a route to 1,1-bis(trifluoromethyl)cycloalkanes, 1-fluoroformyl-1-(trifluoromethyl)cycloalkanes and 1-(trifluoromethyl)-1-cycloalkanecarboxylic acids

Six-, five-, four- and three-membered 1,1-cycloalkanedicarboxylic acid (2a-d) were synthesized by alkaline hydrolysis of the corresponding diesters (1a-d) and the reactions of the formers with SF4 were investigated. 1,1-Bis(trifluoromethyl)cycloalkanes (3a-d) were the products of the reactions conducted at 120-150°C while at 30°C 1-fluoroformyl-1-(trifluoromethyl)cycloalkanes (4a-d) were exclusively formed. The latter were isolated as pure compounds or converted in situ into 1-(trifluoromethyl)-1-cycloalkanecarboxylic acids (5a-d).

General Synthesis of Methyl- and Dimethyl-cyclobutanes from Simple 1,3-Diols by Phase Transfer Catalysis

A general method is described for the preparation of methyl- and dimethyl-cyclobutanes from simple 1,3-diols.The key steps of the procedure are a phase transfer catalysed ring closure and the transformation of a carboxyl group to a methyl group.Phase transfer catalysis provides good yields in the synthesis of the cyclobutane skeleton.

ANALYSE STRUCTURALE EN SERIE CYCLOBUTANIQUE. Partie 1. Derives monosubstitues et gem disubstitues du cyclobutane

Methylene bending mode analysis of some cyclobutane-d2 molecules reveals that in the dissolved state (solvent CCl4), bromocyclobutane occurs exclusively in a pseudo-equatorial form, whereas, under the same conditions, cyclobutanol and 1-bromocyclobutane carbonitrile exist both in pseudo-axial and pseudo-equatorial conformations.NMR spectroscopy confirms the results obtained for bromocyclobutane and leads to the conclusion that the pseudo-equatorial conformer is predominant in the case of cyclobutanol as well as in that of cyclobutane carbonitrile.A theoretical study of cyclobutanol in the gaseous state by the P.C.I.L.O. method gives results which are consistent with a pseudo-equatorial conformer.

DOUBLE HUNSDIECKER REACTIONS. CONVENIENT PREPARATION OF 1,1-DIBROMOCYCLOPROPANE AND 1,1-DIBROMOCYCLOBUTANE

A convenient procedure for effecting the conversion of small-ring gem-dicarboxylic acids to their dibromides is described.