33184-16-6

Basic information

• Product Name: 5-Fluoro-2-methylbenzoic acid
• Synonyms: RARECHEM AL BO 0443;2-METHYL-5-FLUOROBENZOIC ACID;5-FLUORO-2-METHYLBENZOIC ACID;5-FLUORO-O-TOLUIC ACID;5-Fluoro-2-Methyl Benzoic Acid 2-Methyl-5-Fluorobenzoic Acid;5-Fluoro-2-methylbenzoic acid 99%;5-Fluoro-2-methylbenzoicacid99%;Benzoic acid, 5-fluoro-2-Methyl-
• CAS NO: 33184-16-6
• Molecular Formula: C₈H₇FO₂
• Molecular Weight: 154.14
• EINECS: 1312995-182-4
• Product Categories: Aromatic Carboxylic Acids, Amides, Anilides, Anhydrides & Salts;Benzene series;Benzoic acid;C8;Carbonyl Compounds;Carboxylic Acids;Aromatics
• Mol File: 33184-16-6.mol
• Article Data: 3

Chemical Properties

• Melting Point: 130-132 °C(lit.)
• Boiling Point: 262.1 °C at 760 mmHg
• Flash Point: 112.3 °C
• Appearance: Beige to light gray/Crystalline Powder
• Density: 1.258 g/cm³
• Vapor Pressure: 0.00563mmHg at 25°C
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: soluble in Methanol
• PKA: 3.53±0.25(Predicted)
• BRN: 2249813
• CAS DataBase Reference: 5-Fluoro-2-methylbenzoic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 5-Fluoro-2-methylbenzoic acid(33184-16-6)
• EPA Substance Registry System: 5-Fluoro-2-methylbenzoic acid(33184-16-6)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-37/39-36
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 33184-16-6(Hazardous Substances Data)

Usage

Chemical Properties

white to light yellow crystal powder

Uses

Different sources of media describe the Uses of 33184-16-6 differently. You can refer to the following data:
1. 5-Fluoro-2-methylbenzoic acid is used in preparation of novel iminothiazole derivatives as cannabinoid receptor ligands.
2. 5-Fluoro-2-methylbenzoic acid may be used in the preparation of:5-fluoro-3-hydroxy-2-methylbenzoic acid5-fluoro-2-methyl-3-nitrobenzoic acid methyl ester5-fluoro-N,2-dimethylbenzamide

InChI:InChI=1/C8H7FO2/c1-5-2-3-6(9)4-7(5)8(10)11/h2-4H,1H3,(H,10,11)/p-1

Synthetic route

carbon dioxide (124-38-9) → 5-fluoro-2-methylbenzoic acid (33184-16-6)

Conditions	Yield
Stage #1: 2-bromo-4-fluorotoluene With magnesium In diethyl ether for 2h; Grignard Reaction; Heating / reflux; Stage #2: carbon dioxide In diethyl ether Grignard Reaction; Stage #3: With hydrogenchloride In water; ethyl acetate Grignard Reaction;	59%

carbon dioxide (124-38-9) + 2-chloro-4-fluorotoluene (452-73-3) → 5-fluoro-2-methylbenzoic acid (33184-16-6)

Conditions	Yield
Stage #1: 2-chloro-4-fluorotoluene With magnesium at 55℃; for 11h; Inert atmosphere; Stage #2: carbon dioxide With hydrogenchloride In water at 0 - 10℃; pH=1 - 2;

2-bromo-4-fluorotoluene (1422-53-3) + carbon dioxide (124-38-9) → 5-fluoro-2-methylbenzoic acid (33184-16-6)

Conditions	Yield
Stage #1: 2-bromo-4-fluorotoluene With magnesium In tetrahydrofuran at 25℃; for 4h; Inert atmosphere; Reflux; Stage #2: carbon dioxide With hydrogenchloride In water at 0 - 10℃; pH=1 - 2;

carbon dioxide (124-38-9) + 4-fluoro-2-iodotoluene (13194-67-7) → 5-fluoro-2-methylbenzoic acid (33184-16-6)

Conditions	Yield
Stage #1: 4-fluoro-2-iodotoluene With magnesium In tetrahydrofuran at 25 - 50℃; for 4h; Inert atmosphere; Reflux; Stage #2: carbon dioxide With hydrogenchloride In water at 0 - 10℃; pH=1 - 2;

5-fluoro-2-methylbenzoic acid (33184-16-6) + methyl iodide (74-88-4) → 5-fluoro-2-methylbenzoic acid methyl ester (175278-29-2)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 16h;	99%
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 2h;	90%

5-fluoro-2-methylbenzoic acid (33184-16-6) + 1-bromo-2-(triisopropylsilyl)acetylene (111409-79-1) → 3-fluoro-6-methyl-2-((triisopropylsilyl)ethynyl)benzoic acid

Conditions	Yield
With bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; potassium hydrogencarbonate In tert-Amyl alcohol at 30℃; for 24h;	96%
With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; potassium carbonate In tert-Amyl alcohol at 80℃; for 24h; Sealed tube; Schlenk technique;	86%

5-fluoro-2-methylbenzoic acid (33184-16-6) → 3-fluoro-2-iodo-6-methylbenzoic acid (1417190-24-9)

Conditions	Yield
With N-iodo-succinimide; palladium diacetate In N,N-dimethyl-formamide	89.7%
With [bis(acetoxy)iodo]benzene; iodine; palladium diacetate In N,N-dimethyl-formamide at 100℃; for 18h; Inert atmosphere;
With [bis(acetoxy)iodo]benzene; iodine; palladium diacetate In N,N-dimethyl-formamide at 100℃; for 16h;	80 g
With N-iodo-succinimide; palladium diacetate In N,N-dimethyl-formamide at 110℃; for 15h;	25 g

methanol (67-56-1) + 5-fluoro-2-methylbenzoic acid (33184-16-6) → 5-fluoro-2-methylbenzoic acid methyl ester (175278-29-2)

Conditions	Yield
With sulfuric acid at 60℃;	89%
With sulfuric acid for 24h; Heating;
With thionyl chloride for 4h; Heating;

5-fluoro-2-methylbenzoic acid (33184-16-6) → 5-fluoro-2-methylbenzaldehyde (22062-53-9)

Conditions	Yield
With dipotassium hydrogenphosphate; fac-tris(2-phenylpyridinato-N,C2')iridium(III); tris-(trimethylsilyl)silane; dimethyl dicarbonate In acetonitrile at 20℃; for 6h; Schlenk technique; Inert atmosphere; Sealed tube; Irradiation;	85%

oct-1-en-3-one (4312-99-6) + 5-fluoro-2-methylbenzoic acid (33184-16-6) → 4-fluoro-7-methyl-2-(3-oxooctyl)-2,3-dihydro-1H-inden-1-one

Conditions	Yield
With manganese(II)carbonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2 In water; acetonitrile at 150℃; for 20h; Inert atmosphere;	83%

5-fluoro-2-methylbenzoic acid (33184-16-6) + methylamine (74-89-5) → 5-fluoro-N,2-dimethylbenzamide (1332325-17-3)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 6.5h; Inert atmosphere;	82%

2-methyl-4-(2-(2R)-methyl-[1,3'(3'S)]bipyrrolidinyl-1'-yl)-phenylamine (1146415-75-9) + 5-fluoro-2-methylbenzoic acid (33184-16-6) → (2R,3'S)-5-fluoro-2-methyl-N-[2-methyl-4-(2-methyl[1,3']bipyrrolidinyl-1'-yl) phenyl]benzamide (1146699-80-0)

Conditions	Yield
With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃;	82%

2-methyl-4-(2-(2S)-methyl-[1,3'(3'R)]bipyrrolidinyl-1'-yl)-phenylamine (1146415-72-6) + 5-fluoro-2-methylbenzoic acid (33184-16-6) → (2S,3'R)-5-fluoro-2-methyl-N-[2-methyl-4-(2-methyl[1,3']bipyrrolidinyl-1'-yl) phenyl]benzamide

Conditions	Yield
With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃;	82%

2-methyl-4-(2-(2S)-methyl-[1,3'(3'S)]bipyrrolidinyl-1'-yl)-phenylamine (1056623-62-1) + 5-fluoro-2-methylbenzoic acid (33184-16-6) → (2S,3'S)-5-fluoro-2-methyl-N-[2-methyl-4-(2-methyl[1,3']bipyrrolidinyl-1'-yl) phenyl]benzamide (1146699-86-6)

Conditions	Yield
With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃;	82%

2-methyl-4-(2(2R)-methyl-[1,3'(3'R)]bipyrrolidinyl-1'-yl)-phenylamine (1146415-77-1) + 5-fluoro-2-methylbenzoic acid (33184-16-6) → (2R,3'R)-5-fluoro-2-methyl-N-[2-methyl-4-(2-methyl[1,3']bipyrrolidinyl-1'-yl) phenyl]benzamide (1146852-39-2)

Conditions	Yield
With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃;	82%

5-fluoro-2-methylbenzoic acid (33184-16-6) + 5-phenyl-1-penten-3-one (53931-59-2) → 4-fluoro-7-methyl-2-(3-oxo-5-phenylpentyl)-2,3-dihydro-1Hinden-1-one

Conditions	Yield
With manganese(II)carbonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2 In water; acetonitrile at 150℃; for 20h; Inert atmosphere;	82%

5-fluoro-2-methylbenzoic acid (33184-16-6) + triphenylantimony dichloride (594-31-0, 34716-91-1, 20265-29-6) → bis(5-fluoro-2-methylbenzoato)triphenylantimony(V)

Conditions	Yield
With sodium ethoxide In methanol under N2, Schlenk techniques; soln. of benzoic acid deriv. and EtONa in MeOH stirred for 30 min, Ph3SbCl2 added, mixt. stirred at room temp. for12 h; evapn. under vac., recrystd. from CH2Cl2/ether (1/1); elem. anal.;	80%

5-fluoro-2-methylbenzoic acid (33184-16-6) + tetraphenylantimony(V) bromide (16894-69-2) → (5-fluoro-2-methylbenzoato)tetraphenylantimony(V)

Conditions	Yield
With sodium ethoxide In methanol under N2, Schlenk techniques; soln. of benzoic acid deriv. and EtONa in MeOH stirred for 30 min, Ph4SbBr added, mixt. stirred at room temp. for 12 h; evapn. under vac., recrystd. from CH2Cl2/petroleum ether (1/1); elem. anal.;	80%

ethanol (64-17-5) + 5-fluoro-2-methylbenzoic acid (33184-16-6) → ethyl 2-methyl-5-fluorobenzoate

Conditions	Yield
With sulfuric acid at 100℃; for 12h; Sealed tube;	80%

5-fluoro-2-methylbenzoic acid (33184-16-6) → 5-fluoro-2-methylbenzoic acid methyl ester (175278-29-2)

Conditions	Yield
With sulfuric acid In methanol	78%

4-penten-3-one (1629-58-9) + 5-fluoro-2-methylbenzoic acid (33184-16-6) → 3-fluoro-6-methyl-2-(3-oxopentyl)benzoic acid

Conditions	Yield
With [RhCl2(p-cymene)]2 In water at 95℃; for 12h; Sealed tube;	78%

dec-1-en-3-one (56606-79-2) + 5-fluoro-2-methylbenzoic acid (33184-16-6) → 4-fluoro-7-methyl-2-(3-oxodecyl)-2,3-dihydro-1H-inden-1-one

Conditions	Yield
With manganese(II)carbonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2 In water; acetonitrile at 150℃; for 20h; Inert atmosphere;	78%

5-fluoro-2-methylbenzoic acid (33184-16-6) + 1,1'-carbonyldiimidazole (530-62-1) → 2-methyl-5-fluorobenzamide

Conditions	Yield
Stage #1: 5-fluoro-2-methylbenzoic acid; 1,1'-carbonyldiimidazole In dichloromethane at 35℃; for 1h; Stage #2: With ammonia In dichloromethane at 35℃; for 2h;	77.6%

5-fluoro-2-methylbenzoic acid (33184-16-6) → 5-fluoro-2-methylbenzoyl chloride (21900-39-0)

Conditions	Yield
With thionyl chloride for 3h; Reflux;	77%
With thionyl chloride
With thionyl chloride In toluene

non-1-en-3-one (24415-26-7) + 5-fluoro-2-methylbenzoic acid (33184-16-6) → 4-fluoro-7-methyl-2-(3-oxononyl)-2,3-dihydro-1H-inden-1-one

Conditions	Yield
With manganese(II)carbonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2 In water; acetonitrile at 150℃; for 20h; Inert atmosphere;	77%

dodec-1-en-3-one (58879-39-3) + 5-fluoro-2-methylbenzoic acid (33184-16-6) → 4-fluoro-7-methyl-2-(3-oxododecyl)-2,3-dihydro-1H-inden-1-one

Conditions	Yield
With manganese(II)carbonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2 In water; acetonitrile at 150℃; for 20h; Inert atmosphere;	77%

5-fluoro-2-methylbenzoic acid (33184-16-6) + Phenyl vinyl ketone (768-03-6) → 4-fluoro-7-methyl-2-(3-oxo-3-phenylpropyl)-2,3-dihydro-1Hinden-1-one

Conditions	Yield
With manganese(II)carbonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2 In water; acetonitrile at 150℃; for 20h; Inert atmosphere;	76%

octyl vinyl ketone (42832-47-3) + 5-fluoro-2-methylbenzoic acid (33184-16-6) → 4-fluoro-7-methyl-2-(3-oxoundecyl)-2,3-dihydro-1H-inden-1-one

Conditions	Yield
With manganese(II)carbonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2 In water; acetonitrile at 150℃; for 20h; Inert atmosphere;	74%

tetradec-1-en-3-one (26496-24-2) + 5-fluoro-2-methylbenzoic acid (33184-16-6) → 4-fluoro-7-methyl-2-(3-oxotetradecyl)-2,3-dihydro-1H-inden-1-one

Conditions	Yield
With manganese(II)carbonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2 In water; acetonitrile at 150℃; for 20h; Inert atmosphere;	72%

5-fluoro-2-methylbenzoic acid (33184-16-6) → 2-methyl-3-nitro-5-fluorobenzoic acid (850462-64-5)

Conditions	Yield
With sulfuric acid; nitric acid In dichloromethane at 30 - 40℃; for 3h; Temperature; Reagent/catalyst;	70.5%
With sulfuric acid; nitric acid at -110 - -15℃; for 4.5h;	45.1%
With sulfuric acid; nitric acid at 0℃; for 0.5h; Nitration;

5-fluoro-2-methylbenzoic acid (33184-16-6) + acetonitrile (75-05-8) → 2-acetyl-6-fluoroisoindolin-1-one

Conditions	Yield
With iron(III)-acetylacetonate; copper(II) nitrate; Selectfluor at 80℃; for 8h; Schlenk technique; Inert atmosphere;	70%

N-methylmaleimide (930-88-1) + 5-fluoro-2-methylbenzoic acid (33184-16-6) → C12H12FNO2

Conditions	Yield
With sodium dihydrogenphosphate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; water at 85℃; for 16h; Green chemistry; chemoselective reaction;	70%

5-fluoro-2-methylbenzoic acid (33184-16-6) → 2-bromo-5-fluorobenzamide (1006-34-4)

Conditions	Yield
Stage #1: 5-fluoro-2-methylbenzoic acid With thionyl chloride at 70℃; for 20h; Stage #2: With ammonium hydroxide In water at 20℃; for 1h;	69%

2-aminopyridine (504-29-0) + 5-fluoro-2-methylbenzoic acid (33184-16-6) → C13H11FN2O

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃;	68%

Upstream product

• 22062-54-0 (5-fluoro-2-methylphenyl)methanol 
• 124-38-9 carbon dioxide 
• 13194-67-7 4-fluoro-2-iodotoluene 
• 1422-53-3 2-bromo-4-fluorotoluene 
• 452-73-3 2-chloro-4-fluorotoluene 

Downstream Products

• 697739-03-0 5-fluoro-2-methyl-3-nitrobenzoic acid methyl ester 
• 33184-59-7 4-fluoro-2-(phenylcarbonyl)benzoic acid 
• 138786-63-7 2-(5-{3-[(E)-2-(7-Chloro-quinolin-2-yl)-vinyl]-phenyl}-tetrazol-2-ylmethyl)-5-fluoro-benzoic acid 
• 138786-65-9 methyl 2-(bromomethyl)-5-fluorobenzoate 
• 246877-30-5 5-fluoro-2-methyl-3-nitrobenzoic acid benzyl ester 
• 246877-29-2 5-fluoro-3-hydroxy-2-methylbenzoic acid 
• 246877-31-6 3-amino-5-fluoro-2-methylbenzoic acid 
• 850462-64-5 5-fluoro-2-methyl-3-nitrobenzoic acid 
• 33184-52-0 (5-fluoro-2-methylphenyl)(phenyl)methanone 
• 21900-39-0 5-fluoro-2-methylbenzoyl chloride 
• 175278-29-2 5-fluoro-2-methylbenzoic acid methyl ester 
• 1408282-26-7 6-fluoro-3,10-diazatricyclo[6.4.1.0^4,13]trideca-1,4⁽¹³⁾,5,7-tetraen-9-one 
• 1408282-25-6 3-(2-(phthalimido)ethyl)-6-fluoro-1H-indole-4-carboxylic acid methyl ester 

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