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6311-35-9 Usage

Check Digit Verification of cas no

The CAS Registry Mumber 6311-35-9 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 6,3,1 and 1 respectively; the second part has 2 digits, 3 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 6311-35:
(6*6)+(5*3)+(4*1)+(3*1)+(2*3)+(1*5)=69
69 % 10 = 9
So 6311-35-9 is a valid CAS Registry Number.
InChI:InChI=1/C6H4BrNO2/c7-5-2-1-4(3-8-5)6(9)10/h1-3H,(H,9,10)/p-1

6311-35-9 Well-known Company Product Price

  • Brand
  • (Code)Product description
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  • Detail
  • Alfa Aesar

  • (H27926)  6-Bromonicotinic acid, 97%   

  • 6311-35-9

  • 5g

  • 816.0CNY

  • Detail
  • Alfa Aesar

  • (H27926)  6-Bromonicotinic acid, 97%   

  • 6311-35-9

  • 25g

  • 2506.0CNY

  • Detail
  • Aldrich

  • (646989)  6-Bromopyridine-3-carboxylicacid  96%

  • 6311-35-9

  • 646989-1G

  • 380.25CNY

  • Detail
  • Aldrich

  • (646989)  6-Bromopyridine-3-carboxylicacid  96%

  • 6311-35-9

  • 646989-10G

  • 2,087.28CNY

  • Detail

6311-35-9SDS

SAFETY DATA SHEETS

According to Globally Harmonized System of Classification and Labelling of Chemicals (GHS) - Sixth revised edition

Version: 1.0

Creation Date: Aug 13, 2017

Revision Date: Aug 13, 2017

1.Identification

1.1 GHS Product identifier

Product name 6-Bromonicotinic acid

1.2 Other means of identification

Product number -
Other names 6-bromopyridine-3-carboxylic acid

1.3 Recommended use of the chemical and restrictions on use

Identified uses For industry use only.
Uses advised against no data available

1.4 Supplier's details

1.5 Emergency phone number

Emergency phone number -
Service hours Monday to Friday, 9am-5pm (Standard time zone: UTC/GMT +8 hours).

More Details:6311-35-9 SDS

6311-35-9Synthetic route

2-Bromo-5-methylpyridine
3510-66-5

2-Bromo-5-methylpyridine

6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

Conditions
ConditionsYield
With potassium permanganate; Aliquat 336 In water for 4.5h; Heating;50%
With potassium permanganate; Alquat-336 In water for 1.5h; Heating;50%
With potassium permanganate; Aliquat 336 In water at 110℃; for 2.5h;44%
(5-methyl-pyridin-2-yl)amine
1603-41-4

(5-methyl-pyridin-2-yl)amine

6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: 93 percent / 1.) aq. 48percent HBr, bromine; 2.) aq. sodium nitrite / 1.) -20 deg C, 90 min; 2.) 15 deg C, 1 h 45 min
2: 50 percent / potassium permanganate / aliquat-336 / H2O / 4.5 h / Heating
View Scheme
Multi-step reaction with 2 steps
1: bromine; aqueous sodium nitrite solution; aqueous hydrobromic acid
2: aqueous KMnO4
View Scheme
6-hydroxy-3-pyridinecarboxylic acid
5006-66-6

6-hydroxy-3-pyridinecarboxylic acid

6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

Conditions
ConditionsYield
With phosphorus pentabromide
With phosphorus(V) oxybromide at 170℃; for 0.166667h; Neat (no solvent);
6-bromonicotinaldehyde
149806-06-4

6-bromonicotinaldehyde

6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

Conditions
ConditionsYield
With 1,4-dithio-D,L-threitol; recombinant aldehyde dehydrogenase from Escherichia coli; water‐forming NADH oxidase from Streptococcus mutans; NAD In aq. phosphate buffer at 40℃; for 4h; pH=8.5; Reagent/catalyst; Green chemistry; Enzymatic reaction; chemoselective reaction;
methyl 6-bromonicotinate
26218-78-0

methyl 6-bromonicotinate

6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

Conditions
ConditionsYield
With water; sodium hydroxide In tetrahydrofuran at 25℃; for 16h;13.0 g
methanol
67-56-1

methanol

6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

methyl 6-bromonicotinate
26218-78-0

methyl 6-bromonicotinate

Conditions
ConditionsYield
With sulfuric acid Reflux;100%
With triphenylphosphine; diethylazodicarboxylate In diethyl ether for 1.16667h; Ambient temperature;79%
Stage #1: 6-bromonicotinic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane for 1h;
Stage #2: methanol
55%
piperidine
110-89-4

piperidine

6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

(6-bromopyridin-3-yl)(piperidin-1-yl)methanone

(6-bromopyridin-3-yl)(piperidin-1-yl)methanone

Conditions
ConditionsYield
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 18h;100%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20 - 23℃; for 15h; Inert atmosphere;75%
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 2h;60%
6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

tert-butyl 4-[6-(dimethoxyboryl)-4H-1,3-benzodioxin-2-yl]piperidine-1-carboxylate
1200575-98-9

tert-butyl 4-[6-(dimethoxyboryl)-4H-1,3-benzodioxin-2-yl]piperidine-1-carboxylate

6-{2-[1-(tert-butoxycarbonyl)piperidin-4-yl]-4H-1,3-benzodioxin-6-yl} nicotinic acid
1200576-01-7

6-{2-[1-(tert-butoxycarbonyl)piperidin-4-yl]-4H-1,3-benzodioxin-6-yl} nicotinic acid

Conditions
ConditionsYield
With potassium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In water; acetonitrile at 160℃; for 0.333333h; Irradiation;100%
6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

methyl iodide
74-88-4

methyl iodide

methyl 6-bromonicotinate
26218-78-0

methyl 6-bromonicotinate

Conditions
ConditionsYield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 12h;94%
With potassium carbonate In N,N-dimethyl-formamide at 0 - 55℃; for 4h;0.909 g
6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

(3R)-3-methyl-1,4'-bipiperidine dihydrochloride

(3R)-3-methyl-1,4'-bipiperidine dihydrochloride

(6-bromopyridin-3-yl)[(3R)-3-methyl-1,4'-bipiperidin-1'-yl]methanone

(6-bromopyridin-3-yl)[(3R)-3-methyl-1,4'-bipiperidin-1'-yl]methanone

Conditions
ConditionsYield
With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine In ethyl acetate; acetonitrile at 20℃; for 18h;93%
6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

methyl (2S)-pyrrolidine carboxylate
2577-48-2

methyl (2S)-pyrrolidine carboxylate

C12H13BrN2O3

C12H13BrN2O3

Conditions
ConditionsYield
With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 12h;93%
5-bromo-2-pyridylamine
1072-97-5

5-bromo-2-pyridylamine

6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

6-bromo-N-(5-bromopyridin-2-yl)nicotinamide
1029088-43-4

6-bromo-N-(5-bromopyridin-2-yl)nicotinamide

Conditions
ConditionsYield
With 2-chloro-1-methyl-pyridinium iodide; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 96h;91%
6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

benzene-1,2-disulfonamide
27291-96-9

benzene-1,2-disulfonamide

6-bromo-N-(2-sulfamoylphenylsulfonyl)nicotinamide
1154060-75-9

6-bromo-N-(2-sulfamoylphenylsulfonyl)nicotinamide

Conditions
ConditionsYield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃;91%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃;91%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃;91%
6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

3-methoxyphenylboronic acid
10365-98-7

3-methoxyphenylboronic acid

C13H11NO3

C13H11NO3

Conditions
ConditionsYield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate at 100℃; Inert atmosphere; Sealed tube;91%
6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

diazomethyl-trimethyl-silane
18107-18-1

diazomethyl-trimethyl-silane

methyl 6-bromonicotinate
26218-78-0

methyl 6-bromonicotinate

Conditions
ConditionsYield
In methanol; diethyl ether; hexane for 5h;90%
In methanol; ethyl acetate at 30℃; for 1h;
6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

phenylboronic acid
98-80-6

phenylboronic acid

6-phenylpyridine-3-carboxylic acid
29051-44-3

6-phenylpyridine-3-carboxylic acid

Conditions
ConditionsYield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In tetrahydrofuran; water at 100℃; for 24h; Suzuki coupling; Inert atmosphere;90%
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate at 100℃; Inert atmosphere; Sealed tube;88%
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate at 100℃; for 12h; Sealed tube;88%
6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

N,N-dimethylammonium chloride
506-59-2

N,N-dimethylammonium chloride

6-bromo-N,N-dimethylnicotinamide
869640-49-3

6-bromo-N,N-dimethylnicotinamide

Conditions
ConditionsYield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20℃; Inert atmosphere;90%
6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

o-fluorophenylboronic acid
1993-03-9

o-fluorophenylboronic acid

6-(2-fluorophenyl)pyridine-3-carboxylic acid
505082-91-7

6-(2-fluorophenyl)pyridine-3-carboxylic acid

Conditions
ConditionsYield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate at 100℃; Inert atmosphere; Sealed tube;90%
6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

6-bromopyridine-3-carboxamide
889676-37-3

6-bromopyridine-3-carboxamide

Conditions
ConditionsYield
With ammonium hydroxide; N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 1h;88%
Stage #1: 6-bromonicotinic acid With 1,1'-carbonyldiimidazole In dimethyl sulfoxide at 20℃; for 16h;
Stage #2: With ammonia In water; dimethyl sulfoxide at 0℃; for 1h;
81%
Stage #1: 6-bromonicotinic acid With 1,1'-carbonyldiimidazole In tetrahydrofuran at 20℃; for 3h;
Stage #2: With ammonium hydroxide In tetrahydrofuran at 20℃;
79%
6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

dimethyl amine
124-40-3

dimethyl amine

6-(dimethylamino)-3-pyridinecarboxylic acid
82846-28-4

6-(dimethylamino)-3-pyridinecarboxylic acid

Conditions
ConditionsYield
In methanol; N,N-dimethyl-formamide at 130℃; for 15h; Substitution; under pressure;87%
6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

(o-hydroxyphenyl)diphenylphosphine
60254-10-6

(o-hydroxyphenyl)diphenylphosphine

2-(diphenylphosphano)phenyl 6-bromonicotinate
1312717-17-1

2-(diphenylphosphano)phenyl 6-bromonicotinate

Conditions
ConditionsYield
With dmap; dicyclohexyl-carbodiimide In tetrahydrofuran at 60℃; Steglich reaction;87%
6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

C10H8BrN3O

C10H8BrN3O

6-bromo-N-(5-(4-bromophenyl)-1H-pyrazol-3-yl)nicotinamide

6-bromo-N-(5-(4-bromophenyl)-1H-pyrazol-3-yl)nicotinamide

Conditions
ConditionsYield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane Reflux;86%
6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

N,O-dimethylhydroxylamine*hydrochloride
6638-79-5

N,O-dimethylhydroxylamine*hydrochloride

6-bromo-N-methoxy-N-methylpyridine-3-carboxamide
149806-05-3

6-bromo-N-methoxy-N-methylpyridine-3-carboxamide

Conditions
ConditionsYield
With 1-hydroxybenzotriazol-hydrate; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20 - 23℃;84%
With N-ethyl-N,N-diisopropylamine; 1,1'-carbonyldiimidazole In 2-methyltetrahydrofuran at 20℃;67%
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0 - 25℃; for 16h; Concentration; Time;
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 3h;
6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

4-(4-(2-methoxyphenyl)-1,4-diazepan-1-yl)butan-1-amine
1435684-52-8

4-(4-(2-methoxyphenyl)-1,4-diazepan-1-yl)butan-1-amine

6-bromo-N-[4-[4-(2-methoxyphenyl)-1,4-diazepan-1-yl]butyl]nicotinamide
1435685-96-3

6-bromo-N-[4-[4-(2-methoxyphenyl)-1,4-diazepan-1-yl]butyl]nicotinamide

Conditions
ConditionsYield
With benzotriazol-1-ol; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃; for 15h;83%
6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

C18H19FN4O

C18H19FN4O

(6-bromopyridin-3-yl)(4-(3-(4-fluorophenyl)-7-hydroxy-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)piperidin-1-yl) methanone

(6-bromopyridin-3-yl)(4-(3-(4-fluorophenyl)-7-hydroxy-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)piperidin-1-yl) methanone

Conditions
ConditionsYield
With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;83%
6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

dimethyl amine
124-40-3

dimethyl amine

6-bromo-N,N-dimethylnicotinamide
869640-49-3

6-bromo-N,N-dimethylnicotinamide

Conditions
ConditionsYield
Stage #1: 6-bromonicotinic acid With thionyl chloride at 80℃; for 2h; Inert atmosphere;
Stage #2: dimethyl amine With triethylamine In dichloromethane at 25℃; for 16h; Inert atmosphere;
83%
6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

cyclohexylamine
108-91-8

cyclohexylamine

6-bromo-N-cyclohexylnicotinamide
443346-20-1

6-bromo-N-cyclohexylnicotinamide

Conditions
ConditionsYield
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃;82%
6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

toluene-3-thiol
108-40-7

toluene-3-thiol

C13H11NO2S
253594-30-8

C13H11NO2S

Conditions
ConditionsYield
Stage #1: toluene-3-thiol With sodium hydride In DMF (N,N-dimethyl-formamide) at 0 - 20℃; for 1h;
Stage #2: 6-bromonicotinic acid In DMF (N,N-dimethyl-formamide) for 6h; Heating / reflux;
80%
morpholine
110-91-8

morpholine

6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

(6-bromo-pyridin-3-yl)-morpholin-4-yl-methanone
1180131-60-5

(6-bromo-pyridin-3-yl)-morpholin-4-yl-methanone

Conditions
ConditionsYield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In tetrahydrofuran at 20℃; for 14h;79%
6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

N,N-diethylethylenediamine
100-36-7

N,N-diethylethylenediamine

6-bromo-N-(2-(diethylamino)ethyl)nicotinamide
1420844-65-0

6-bromo-N-(2-(diethylamino)ethyl)nicotinamide

Conditions
ConditionsYield
Stage #1: 6-bromonicotinic acid With O-(N-succinimidyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 60℃; for 3h;
Stage #2: N,N-diethylethylenediamine In N,N-dimethyl-formamide at 20℃; for 2h;
78%
pyrrolidine
123-75-1

pyrrolidine

6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

(6-bromopyridin-3-yl)pyrrolidin-1-ylmethanone
1209460-17-2

(6-bromopyridin-3-yl)pyrrolidin-1-ylmethanone

Conditions
ConditionsYield
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 18h;78%
6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

benzene
71-43-2

benzene

(6-bromopyridin-3-yl)(phenyl)methanone
80100-16-9

(6-bromopyridin-3-yl)(phenyl)methanone

Conditions
ConditionsYield
Stage #1: 6-bromonicotinic acid With thionyl chloride for 3h; Reflux;
Stage #2: benzene With aluminum (III) chloride at 5℃; Reflux;
77%
6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

(3-ethoxy-4-methoxyphenyl)boronic acid
915201-13-7

(3-ethoxy-4-methoxyphenyl)boronic acid

3'-ethoxy-4'-methoxybiphenyl-3-carboxylic acid

3'-ethoxy-4'-methoxybiphenyl-3-carboxylic acid

Conditions
ConditionsYield
Stage #1: 6-bromonicotinic acid; tetrakis(triphenylphosphine) palladium(0) In 1,2-dimethoxyethane at 20℃; for 0.25h;
Stage #2: (3-ethoxy-4-methoxyphenyl)boronic acid With sodium carbonate In 1,2-dimethoxyethane; water for 24h; Heating / reflux;
76%
6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

C12H19BrClNOSi

C12H19BrClNOSi

5-(4-bromo-2-chlorophenyl)-2-(6-bromopyridin-3-yl)-4,5-dihydrooxazole

5-(4-bromo-2-chlorophenyl)-2-(6-bromopyridin-3-yl)-4,5-dihydrooxazole

Conditions
ConditionsYield
With pyridine; ethanaminium,N-(difluoro-λ4-sulfanylidene)-N-ethyl-,tetrafluoroborate In dichloromethane at -78 - 20℃; for 2h;76%
6-bromonicotinic acid
6311-35-9

6-bromonicotinic acid

(4-acetylaminophenyl)boronic acid
101251-09-6

(4-acetylaminophenyl)boronic acid

6-(4-acetamidophenyl)nicotinic acid

6-(4-acetamidophenyl)nicotinic acid

Conditions
ConditionsYield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate at 100℃; Inert atmosphere; Sealed tube;76%

6311-35-9Relevant articles and documents

CANCER TREATMENTS TARGETING CANCER STEM CELLS

-

Paragraph 0448; 0463; 0467-0470; 01101; 01104-01106, (2021/05/15)

Disclosed are compounds, methods, compositions, uses, and kits that allow for treating cancer. In some embodiments, the compounds are used to treat diseases or disorders. The compounds may treat cancer by targeting cancer stem cells. In some embodiments, the cancer is colorectal cancer, gastric cancer, gastrointestinal stromal tumor, ovarian cancer, lung cancer, breast cancer, pancreatic cancer, prostate cancer, testicular cancer, lymphoma, liver cancer, endometrial cancer, leukemia, or multiple myeloma. Disclosed are compounds, methods, compositions, uses, and kits that may be used in regenerative medicine. The compounds utilized in the disclosure are of Formula (0) and (I).

ARYL-BIPYRIDINE AMINE DERIVATIVES AS PHOSPHATIDYLINOSITOL PHOSPHATE KINASE INHIBITORS

-

Paragraph 0475, (2019/07/13)

The invention relates to inhibitors of PI5P4K inhibitors useful in the treatment of cancers, neurodegenerative diseases, inflammatory disorders, and metabolic diseases, having the Formula (I): wherein A, X, Y, Z, Q, R1, R2, R3, R4, R5, and n are described herein.

A biocatalytic method for the chemoselective aerobic oxidation of aldehydes to carboxylic acids

Knaus, Tanja,Tseliou, Vasilis,Humphreys, Luke D.,Scrutton, Nigel S.,Mutti, Francesco G.

supporting information, p. 3931 - 3943 (2018/09/11)

Herein, we present a study on the oxidation of aldehydes to carboxylic acids using three recombinant aldehyde dehydrogenases (ALDHs). The ALDHs were used in purified form with a nicotinamide oxidase (NOx), which recycles the catalytic NAD+ at the expense of dioxygen (air at atmospheric pressure). The reaction was studied also with lyophilised whole cell as well as resting cell biocatalysts for more convenient practical application. The optimised biocatalytic oxidation runs in phosphate buffer at pH 8.5 and at 40 °C. From a set of sixty-one aliphatic, aryl-Aliphatic, benzylic, hetero-Aromatic and bicyclic aldehydes, fifty were converted with elevated yield (up to >99%). The exceptions were a few ortho-substituted benzaldehydes, bicyclic heteroaromatic aldehydes and 2-phenylpropanal. In all cases, the expected carboxylic acid was shown to be the only product (>99% chemoselectivity). Other oxidisable functionalities within the same molecule (e.g. hydroxyl, alkene, and heteroaromatic nitrogen or sulphur atoms) remained untouched. The reaction was scaled for the oxidation of 5-(hydroxymethyl)furfural (2 g), a bio-based starting material, to afford 5-(hydroxymethyl)furoic acid in 61% isolated yield. The new biocatalytic method avoids the use of toxic or unsafe oxidants, strong acids or bases, or undesired solvents. It shows applicability across a wide range of substrates, and retains perfect chemoselectivity. Alternative oxidisable groups were not converted, and other classical side-reactions (e.g. halogenation of unsaturated functionalities, Dakin-Type oxidation) did not occur. In comparison to other established enzymatic methods such as the use of oxidases (where the concomitant oxidation of alcohols and aldehydes is common), ALDHs offer greatly improved selectivity.

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