772-33-8

Basic information

• Product Name: 2-HYDROXY-5-NITROBENZYL BROMIDE
• Synonyms: KOSHLAND I;KOSHLAND REAGENT;KOSHLAND'S REAGENT;KOSHLAND'S REAGENT I;ALPHA-BROMO-4-NITRO-2-CRESOL;ALPHA-BROMO-4-NITRO-O-CRESOL;2-BROMOMETHYL-4-NITROPHENOL;2-HYDROXY-5-NITROBENZYL BROMIDE
• CAS NO: 772-33-8
• Molecular Formula: C₇H₆BrNO₃
• Molecular Weight: 232.03
• EINECS: 212-248-9
• Product Categories: Building Blocks;C6 to C8;Chemical Synthesis;Organic Building Blocks;Oxygen Compounds;Phenols
• Mol File: 772-33-8.mol
• Article Data: 1

Chemical Properties

• Melting Point: 144-149 °C(lit.)
• Boiling Point: 383 °C at 760 mmHg
• Flash Point: 185.5 °C
• Appearance: Beige to light brown/Crystalline Powder
• Density: 1.795
• Vapor Pressure: 2.05E-06mmHg at 25°C
• Refractive Index: 1.6090 (estimate)
• Storage Temp.: 2-8°C
• Solubility: chloroform: soluble25mg/mL, clear, yellow
• PKA: 6.16±0.30(Predicted)
• BRN: 1868798
• CAS DataBase Reference: 2-HYDROXY-5-NITROBENZYL BROMIDE(CAS DataBase Reference)
• NIST Chemistry Reference: 2-HYDROXY-5-NITROBENZYL BROMIDE(772-33-8)
• EPA Substance Registry System: 2-HYDROXY-5-NITROBENZYL BROMIDE(772-33-8)

Safety Data

• Hazard Codes: C
• Statements: 34
• Safety Statements: 26-36/37/39-45
• RIDADR: UN 3261 8/PG 2
• WGK Germany: 3
• TSCA: Yes
• HazardClass: 8
• PackingGroup: III
• Hazardous Substances Data: 772-33-8(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 772-33-8 differently. You can refer to the following data:
1. Reagent for sulfhydryl modification.1
2. 2-Hydroxy-5-nitrobenzyl bromide is a chemical reagent that reacts with and modifies chemically the tryptophan portion of protein molecules..
3. 2-Hydroxy-5-nitrobenzyl bromide was used in covalent modification of tryptophan and tryptophan residues in monoclonal immunoglobulin. It was also used as reagent for sulfhydryl modification

Synthesis Reference(s)

Journal of the American Chemical Society, 86, p. 1448, 1964 DOI: 10.1021/ja01061a045

General Description

2-Hydroxy-5-nitrobenzyl bromide is a protein modifying reagent.

Purification Methods

Crystallise the bromide from *benzene or *benzene/ligroin. It is slightly soluble in EtOH, soluble in *C6H6 and AcOH, and very soluble in ligroin. [Beilstein 6 H 367.]

InChI:InChI=1/C7H6BrNO3/c8-4-5-3-6(9(11)12)1-2-7(5)10/h1-3,10H,4H2/p-1

Synthetic route

2-hydroxy-5-nitrobenzyl chloride (2973-19-5) → Koshlands reagent I (772-33-8)

Conditions	Yield
With hydrogen bromide; acetic acid at 70 - 80℃;

5-nitro-2-oxy-benzyl acetate → Koshlands reagent I (772-33-8)

Conditions	Yield
With hydrogen bromide; acetic acid at 70 - 80℃;

2-(2-methyl-4-nitrophenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (883715-40-0) → Koshlands reagent I (772-33-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / acetonitrile / 2 h / 90 °C / Inert atmosphere 2: dihydrogen peroxide; water / 20 °C View Scheme

2-(2-(bromomethyl)-4-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1030832-68-8) → 2,3-dimethyl-2,3-butane diol (76-09-5) + Koshlands reagent I (772-33-8) + boric acid (11113-50-1)

Conditions	Yield
With water; dihydrogen peroxide at 20℃; Kinetics;

2-bromo-5-nitrotoluene (7149-70-4) → Koshlands reagent I (772-33-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / N,N-dimethyl-formamide / 48 h / 85 °C / Inert atmosphere 2: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / acetonitrile / 2 h / 90 °C / Inert atmosphere 3: dihydrogen peroxide; water / 20 °C View Scheme

Koshlands reagent I (772-33-8) → 2-Hydroxy-5-nitro-benzyl hexamethylenetetramine Hydrobromide

Conditions	Yield
With hexamethylenetetramine In chloroform	100%

(+/-)-2-methyl-1-phenylpyrrolidine (33342-99-3, 160751-58-6, 160751-59-7) + Koshlands reagent I (772-33-8) → 2-(4-(2-methylpyrrolidin-1-yl)benzyl)-4-nitrophenol

Conditions	Yield
With dipotassium hydrogenphosphate In dichloromethane at 20℃; for 24h; Inert atmosphere;	99%

N-phenyl piperidine (4096-20-2) + Koshlands reagent I (772-33-8) → 4-nitro-2-(4-(piperidin-1-yl)benzyl)phenol

Conditions	Yield
With dipotassium hydrogenphosphate In dichloromethane at 20℃; for 24h; Inert atmosphere;	99%

julolidine (479-59-4) + Koshlands reagent I (772-33-8) → 4-nitro-2-((2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-9-yl)methyl)phenol

Conditions	Yield
With dipotassium hydrogenphosphate In dichloromethane at 20℃; for 24h; Inert atmosphere;	99%

Koshlands reagent I (772-33-8) + N,N-diethylaniline (91-66-7) → 2-(4-(diethylamino)benzyl)-4-nitrophenol

Conditions	Yield
With dipotassium hydrogenphosphate In dichloromethane at 20℃; for 24h; Inert atmosphere;	99%

Koshlands reagent I (772-33-8) + N,N-dipropylaniline (2217-07-4) → 2-(4-(dipropylamino)benzyl)-4-nitrophenol

Conditions	Yield
With dipotassium hydrogenphosphate In dichloromethane at 20℃; for 24h; Inert atmosphere;	99%

1-p-tolylpyrrolidine (54104-82-4) + Koshlands reagent I (772-33-8) → 2-(5-methyl-2-(pyrrolidin-1-yl)benzyl)-4-nitrophenol

Conditions	Yield
With dipotassium hydrogenphosphate In dichloromethane at 20℃; for 24h; Inert atmosphere;	99%

Koshlands reagent I (772-33-8) + N-(2,4,6-trimethylphenyl)imidazole (25364-44-7) → 3-(2-methylene-4-nitrophenol)-1-(2,4,6-trimethylphenyl)imidazolium bromide (950595-40-1)

Conditions	Yield
In toluene for 18h; Reflux;	98.5%
In toluene for 18h; Reflux; Inert atmosphere;	91%

trimethylsilyl isothiocyanate (2290-65-5) + Koshlands reagent I (772-33-8) → 4-nitro-2-thiocyanatomethyl-phenol

Conditions	Yield
With tetrabutyl ammonium fluoride In tetrahydrofuran at 20℃; for 1h;	98%

Koshlands reagent I (772-33-8) → 2-(azidomethyl)-4-nitrophenol

Conditions	Yield
With sodium azide In water; acetonitrile at 0 - 20℃; for 3h; Inert atmosphere;	98%
With triethylamine In acetonitrile for 3h; Heating;	64%
With sodium azide In N,N-dimethyl-formamide at 0 - 20℃; for 16h;
With sodium azide In water; acetone at 20℃; for 1h;

1-(2-methoxyphenyl)pyrrolidine (4787-76-2) + Koshlands reagent I (772-33-8) → 2-(3-methoxy-4-(pyrrolidin-1-yl)benzyl)-4-nitrophenol

Conditions	Yield
With dipotassium hydrogenphosphate In dichloromethane at 20℃; for 24h; Inert atmosphere;	96%

Koshlands reagent I (772-33-8) + diphenyl (prop-2-yn-1-yl)phosphine oxide (104856-81-7) → ((1-(2-hydroxy-5-nitrobenzyl)-1H-1,2,3-triazol-4-yl)methyl)diphenylphosphine oxide

Conditions	Yield
With sodium azide; bromotris(triphenylphosphine)copper(I) In water; dimethyl sulfoxide at 110℃; under 760.051 Torr; for 0.183333h; Huisgen Cycloaddition; Microwave irradiation; Green chemistry; regioselective reaction;	95.2%

Koshlands reagent I (772-33-8) + trimethylamine (75-50-3) → (2-hydroxy-5-nitrobenzyl)trimethylquaternary ammonium bromide

Conditions	Yield
In acetone at 20℃; for 1h;	95%

Koshlands reagent I (772-33-8) + trimellitic anhydride acid chloride (1204-28-0) → 1,3-dioxo-1,2-dihydro-2-benzofuran-5-carboxylic acid 2-bromomethyl-4-nitrophenyl ester

Conditions	Yield
With pyridine at 0 - 20℃; for 4h;	94%

Koshlands reagent I (772-33-8) + n-valeryl chloride (638-29-9) → 2-(n-butyl)-5-nitrobenzofuran (133238-87-6)

Conditions	Yield
Stage #1: Koshlands reagent I With triphenylphosphine In dichloromethane for 1h; Reflux; Stage #2: n-valeryl chloride With triethylamine In dichloromethane for 3h; Reflux;	94%

Koshlands reagent I (772-33-8) + ethylene glycol (107-21-1) → 2-(2-hydroxy-5-nirtobenzyloxy)ethanol

Conditions	Yield
at 60℃; for 5h;	93%

Koshlands reagent I (772-33-8) + 4,13-diazadibenzo-18-crown-6 (36080-67-8) → N,N'-bis(2-hydroxy-5-nitrobenzyl)-4,13-diazadibenzo-18-crown-6

Conditions	Yield
With triethylamine In tetrahydrofuran 1.) 0 deg C, 8 h, 2.) reflux, 4 h;	93%

N-phenylpyrrolidine (4096-21-3) + Koshlands reagent I (772-33-8) → 4-nitro-2-(4-(pyrrolidin-1-yl)benzyl)phenol

Conditions	Yield
With dipotassium hydrogenphosphate In dichloromethane at 20℃; for 24h; Reagent/catalyst; Solvent; Inert atmosphere;	93%

1-(2-methylphenyl)pyrrolidine (41378-30-7) + Koshlands reagent I (772-33-8) → 2-(3-methyl-4-(pyrrolidin-1-yl)benzyl)-4-nitrophenol

Conditions	Yield
With dipotassium hydrogenphosphate In dichloromethane at 20℃; for 24h; Inert atmosphere;	93%

Koshlands reagent I (772-33-8) + 1-indene (95-13-6) → 8-nitro-4b,10,10a,11-tetrahydroindeno[1,2-b]chromene

Conditions	Yield
With dipotassium hydrogenphosphate In dichloromethane at 20℃; for 24h;	92%

Koshlands reagent I (772-33-8) + N-(2-pyridylmethyl)-N’-(2-hydroxyethyl)ethylenediamine (62402-15-7) → C24H27N5O7

Conditions	Yield
With triethylamine In tetrahydrofuran for 24h; Inert atmosphere;	91.4%

Koshlands reagent I (772-33-8) + 1,4,7,10-tetraoxa-15-azacyclopentadecane (66943-05-3) → N-(2-hydroxy-5-nitrobenzyl)-aza-15-crown-5 (79566-00-0)

Conditions	Yield
	91%

Koshlands reagent I (772-33-8) + C18H16N2 → (+)-N-(2-hydroxy-5-nitro-benzyl)-1,2,3,4-tetrahydro-1,1'-bisisoquinoline

Conditions	Yield
With potassium carbonate In acetonitrile at 50℃;	91%

Koshlands reagent I (772-33-8) + C18H16N2 → C25H21N3O3

Conditions	Yield
With potassium carbonate In acetonitrile at 50℃; Inert atmosphere;	91%

Koshlands reagent I (772-33-8) + phosphorous acid trimethyl ester (121-45-9) → (2-Hydroxy-5-nitro-benzyl)-phosphonic acid dimethyl ester (84713-52-0)

Conditions	Yield
In acetone for 0.25h;	90%
at 80 - 100℃; for 0.5h;

Koshlands reagent I (772-33-8) + 1-isopropoxyoctahydro-[1,3,2]diazaphospholo[1,5-a]pyridine → 1-(2-hydroxy-5-nitrobenzyl)octahydro-[1,3,2]diazaphospholo[1,5-a]pyridine-1-oxide

Conditions	Yield
With cerium(III) chloride heptahydrate In tetrahydrofuran at 20 - 60℃; for 3.25h; Michaelis-Arbuzov Synthesis; Inert atmosphere; Green chemistry;	90%

Koshlands reagent I (772-33-8) + N,N-dimethyl-aniline (121-69-7) → 2-(4-(dimethylamino)benzyl)-4-nitrophenol

Conditions	Yield
With dipotassium hydrogenphosphate In dichloromethane at 20℃; for 24h; Inert atmosphere;	90%

1-aza-18-crown-6 (33941-15-0) + Koshlands reagent I (772-33-8) → N-(2-hydroxy-5-nitrobenzyl)-aza-18-crown-6 (79592-90-8)

Conditions	Yield
	89%

Koshlands reagent I (772-33-8) + thiourea (17356-08-0) → 2-[(2-hydroxy-5-nitrophenyl)methyl]isothiourea (129426-10-4)

Conditions	Yield
In ethanol at 20℃; for 2h;	89%

N-methylindoline (824-21-5) + Koshlands reagent I (772-33-8) → 2-((1-methylindolin-5-yl)methyl)-4-nitrophenol

Conditions	Yield
With dipotassium hydrogenphosphate In dichloromethane at 20℃; for 24h; Inert atmosphere;	89%

Upstream product

• 883715-40-0 2-(2-methyl-4-nitrophenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane 
• 7149-70-4 2-bromo-5-nitrotoluene 
• 1030832-68-8 2-(2-(bromomethyl)-4-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 
• 2973-19-5 2-hydroxy-5-nitrobenzyl chloride 

Downstream Products

• 79592-90-8 N-(2-hydroxy-5-nitrobenzyl)-aza-18-crown-6 
• 84713-52-0 (2-Hydroxy-5-nitro-benzyl)-phosphonic acid dimethyl ester 
• 950595-40-1 3-(2-methylene-4-nitrophenol)-1-(2,4,6-trimethylphenyl)imidazolium bromide 
• 1446319-81-8 C₂₂H₂₇N₃O₃Si 
• 1446319-88-5 C₁₉H₁₈N₃O₃^(1-)*C₁₆H₃₆N⁽¹⁺⁾ 
• 1446319-72-7 6,10b-dimethyl-2-nitro-5a-phenyl-5a,6,10b,11-tetrahydrochromeno[2,3-b]indole 
• 1446319-73-8 9-fluoro-6,10b-dimethyl-2-nitro-5a-phenyl-5a,6,10b,11-tetrahydrochromeno[2,3-b]indole