6282-02-6

Basic information

• Product Name: N-(Hydroxymethyl)benzamide
• Synonyms: N-(HYDROXYMETHYL)BENZAMIDE;BENZAMIDOMETHANOL;Benzamide, N-(hydroxymethyl)-;N-Methylolbenzamide;N-(Hydroxymethyl)benzamide,98%;N-(Hydroxymethyl)benzamid;N-(Hydroxymethyl)ben
• CAS NO: 6282-02-6
• Molecular Formula: C₈H₉NO₂
• Molecular Weight: 151.16
• EINECS: 228-495-0
• Product Categories: Intermediates of Dyes and Pigments;Aromatic Carboxylic Acids, Amides, Anilides, Anhydrides & Salts;Amides;Building Blocks;Carbonyl Compounds;Chemical Synthesis;Organic Building Blocks
• Mol File: 6282-02-6.mol
• Article Data: 14

Chemical Properties

• Melting Point: 95-100 °C
• Boiling Point: 273.17°C (rough estimate)
• Flash Point: 184.2 °C
• Appearance: white crystalline powder
• Density: 1.2023 (rough estimate)
• Vapor Pressure: 1.74E-06mmHg at 25°C
• Refractive Index: 1.5810 (estimate)
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: DMSO (Slightly), Water (Slightly)
• PKA: 13.25±0.46(Predicted)
• BRN: 2045129
• CAS DataBase Reference: N-(Hydroxymethyl)benzamide(CAS DataBase Reference)
• NIST Chemistry Reference: N-(Hydroxymethyl)benzamide(6282-02-6)
• EPA Substance Registry System: N-(Hydroxymethyl)benzamide(6282-02-6)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 22-36-36/37/38
• Safety Statements: 26-37/39-37
• WGK Germany: 1
• Hazardous Substances Data: 6282-02-6(Hazardous Substances Data)

Usage

Chemical Properties

white crystalline powder

Uses

N-(Hydroxymethyl)benzamide (CAS# 6282-02-6) can be used to prepare high-dispersibilty disperse acidic dyes.

InChI:InChI=1/C8H9NO2/c10-6-9-8(11)7-4-2-1-3-5-7/h1-5,10H,6H2,(H,9,11)

Synthetic route

formaldehyd (50-00-0) + benzamide (55-21-0) → N-(hydroxymethyl)benzamide (6282-02-6)

Conditions	Yield
With NaY zeolite In water at 100℃; for 1h; Reagent/catalyst; Time;	96%
With water at 100℃; for 1h; Reagent/catalyst;	96%
With aluminum oxide; water at 60 - 65℃; for 0.133333h; microwave irradiation;	75%

benzamide (55-21-0) → N-(hydroxymethyl)benzamide (6282-02-6)

Conditions	Yield
With formaldehyd	84%

formaldehyd (50-00-0) + benzamide (55-21-0) + m-xylene (108-38-3) → N-(hydroxymethyl)benzamide (6282-02-6)

Conditions	Yield
With water at 100℃; for 10h; Reagent/catalyst; Sealed tube;	62%

formaldehyd (50-00-0) + benzamide (55-21-0) → N-(hydroxymethyl)benzamide (6282-02-6) + N,N'-methylenebisbenzamide (1575-94-6) + bis-N-benzamidomethyl ether (113660-19-8)

Conditions	Yield
With potassium carbonate In water Heating;	A 57% B n/a C n/a

N-<(phenylsulfenyl)methyl>benzamide (58379-67-2) → 1-Benzamido-1-methoxymethane (13156-28-0) + N-(hydroxymethyl)benzamide (6282-02-6) + N-<(phenylsulfonyl)methyl>benzamide (76965-50-9) + N-<(phenylsulfinyl)methyl>benzamide (110682-76-3)

Conditions	Yield
With sodium periodate In methanol for 60h; Ambient temperature;	A 8 % Spectr. B 4 % Spectr. C 40% D 8 % Spectr.

formaldehyd (50-00-0) + benzamide (55-21-0) → N-(hydroxymethyl)benzamide (6282-02-6) + N,N'-methylenebisbenzamide (1575-94-6)

Conditions	Yield
With HY zeolite In water at 100℃; for 12h; Reagent/catalyst;	A 28% B 35%
In 1,4-dioxane; water at 40 - 60℃; Thermodynamic data; Kinetics; Mechanism; activation energy, pH 3.5-4.0;

formaldehyd (50-00-0) + benzamide (55-21-0) + m-xylene (108-38-3) → N-(2,4-dimethylbenzyl)benzamide (84359-55-7) + N-(hydroxymethyl)benzamide (6282-02-6)

Conditions	Yield
With water at 100℃; for 10h; Sealed tube;	A 20% B 35%
With water at 100℃; for 10h; Concentration; Reagent/catalyst; Sealed tube;	A n/a B 10%

formaldehyd (50-00-0) + benzamide (55-21-0) + triethylamine (121-44-8) → N-(hydroxymethyl)benzamide (6282-02-6)

benzamidomethyl benzoate (61652-83-3) → N-(hydroxymethyl)benzamide (6282-02-6) + benzoic acid (65-85-0)

Conditions	Yield
With water In acetonitrile at 25℃; Rate constant;
With water; acetic acid In acetonitrile at 25℃; Rate constant; various buffer concentrations;
With sulfuric acid; water In acetonitrile at -258.2℃; Kinetics; Thermodynamic data; ΔS(excit.) ΔH(excit.), var. temp., var. acid concentrations;

formaldehyd (50-00-0) + benzamide (55-21-0) + acid aqueous solution → N-(hydroxymethyl)benzamide (6282-02-6)

Conditions	Yield
at 25℃; Rate constant; sowie bei 50grad und 70grad;

formaldehyd (50-00-0) + benzamide (55-21-0) + alkaline aqueous solution → N-(hydroxymethyl)benzamide (6282-02-6)

Conditions	Yield
at 15℃; Equilibrium constant; sowie bei 20grad, 25grad und 30grad;
at 25℃;

formaldehyd (50-00-0) + benzamide (55-21-0) + potassium carbonate → N-(hydroxymethyl)benzamide (6282-02-6)

N-(hydroxymethyl)benzamide (6282-02-6) + Benzeneselenol (645-96-5) → N-<(phenylselenyl)methyl>benzamide (110682-74-1)

Conditions	Yield
With hydrogenchloride at 60 - 70℃; for 0.75h;	95%

conc. aqueous HCl + diethyl ether (60-29-7) + N-(2-mercaptopropionyl)glycine (1953-02-2) + N-(hydroxymethyl)benzamide (6282-02-6) → N-[2-(S-benzamidomethyl)mercaptopropionyl]glycine

Conditions	Yield
In water	94.4%

d(4)-methanol (811-98-3) + N-(hydroxymethyl)benzamide (6282-02-6) → C8H8(2)HNO

Conditions	Yield
With C54H43ClN3P2Ru(1+)*F6P(1-); caesium carbonate In toluene at 140℃; for 72h; Inert atmosphere; Glovebox; Green chemistry;	92%
With tris(2-diphenylphosphinoethyl)phosphine; potassium tert-butylate; water; caesium carbonate; cobalt(II) bromide In m-xylene at 140℃; for 30h; Green chemistry;

GLUTATHIONE (70-18-8) + N-(hydroxymethyl)benzamide (6282-02-6) + trifluoroacetic acid (76-05-1) → S-benzamidomethylglutathione trifluoroacetate salt hydrate (96236-83-8)

Conditions	Yield
for 0.0833333h;	90%

N-(hydroxymethyl)benzamide (6282-02-6) + 2-(4-tert-Butyl-phenyl)-6-chloro-imidazo[1,2-a]pyridine → 3-benzamidomethyl-2-(4'-t-butylphenyl)-6-chloroimidazo<1,2-a>pyridine

Conditions	Yield
With sulfuric acid In acetic acid for 14h; Heating;	90%

N-(hydroxymethyl)benzamide (6282-02-6) + β-naphthol (135-19-3) → N-((2-hydroxynaphthalen-1-yl)methyl)benzamide (69025-33-8)

Conditions	Yield
With sulfuric acid In ethanol for 7h; Friedel-Crafts Acylation; Heating; Green chemistry;	89%
With sulfuric acid In ethanol at 50℃; for 7h;	71%
With hydrogenchloride; ethanol
With hydrogenchloride In ethanol for 4h; Heating; Yield given;
With hydrogenchloride; ethanol

N-(hydroxymethyl)benzamide (6282-02-6) + tert-butyldichlorophosphine (25979-07-1) → aminomethyl-P-t-butyl-phosphinic acid (119930-52-8)

Conditions	Yield
With hydrogenchloride In acetic acid 1.) 60 min, 25 deg C then reflux, 60 min; 2.) reflux;	89%
With hydrogenchloride 1.) glacial acetic acid, reflux, 30 min, 2.) reflux, 6 h; Yield given. Multistep reaction;

2-phenyl-indole (948-65-2) + N-(hydroxymethyl)benzamide (6282-02-6) → N-[(2-phenyl-1H-indol-4-yl)methyl]benzamide

Conditions	Yield
With sulfuric acid In ethanol at 35℃; for 120h; Friedel-Crafts Alkylation;	88.9%

2,4-dihydroxybenzophenone (131-56-6) + N-(hydroxymethyl)benzamide (6282-02-6) → C29H24N2O5

Conditions	Yield
With sulfuric acid In ethanol at 35℃; for 72h; Reagent/catalyst; Friedel-Crafts Acylation;	87%

N-(hydroxymethyl)benzamide (6282-02-6) + trichloroacetonitrile (545-06-2) → N-(trichloroacetamidomethyl)benzamide

Conditions	Yield
With sodium hydride In dichloromethane at 20℃;	86.5%

N-(hydroxymethyl)benzamide (6282-02-6) + thiophenol (108-98-5) → N-<(phenylsulfenyl)methyl>benzamide (58379-67-2)

Conditions	Yield
With hydrogenchloride 1.) 60-70 deg C, 1h, 2.) RT, 2h;	86%

N-(hydroxymethyl)benzamide (6282-02-6) → N-(chloromethyl)benzamide (38792-42-6)

Conditions	Yield
With phosphorus pentachloride In diethyl ether at 5 - 20℃; for 2.5h;	85%
With thionyl chloride In dichloromethane	77%
With thionyl chloride In dichloromethane	45%

N-(hydroxymethyl)benzamide (6282-02-6) + p-Chlorothiophenol (106-54-7) → N-(4-chlorophenylthiomethyl)benzamide (92290-67-0)

Conditions	Yield
With hydrogenchloride; ethanol Ambient temperature;	85%

N-(hydroxymethyl)benzamide (6282-02-6) → C8H8(2)HNO

Conditions	Yield
With d(4)-methanol; C54H43ClN3P2Ru(1+)*F6P(1-); caesium carbonate In toluene at 140℃; for 72h; Inert atmosphere; Sealed tube; Green chemistry;	85%

2,6-di-tert-butylphenol (128-39-2) + N-(hydroxymethyl)benzamide (6282-02-6) → N-[(4-hydroxy-3,5-di-tert-butyl)methyl]benzamide

Conditions	Yield
With sulfuric acid In ethanol at 35℃; for 120h; Friedel-Crafts Alkylation;	83.3%

N-(hydroxymethyl)benzamide (6282-02-6) + para-thiocresol (106-45-6) → N-(4-methylphenylthiomethyl)benzamide (103603-53-8)

Conditions	Yield
With hydrogenchloride In ethanol	83.2%

N-(hydroxymethyl)benzamide (6282-02-6) + 1-mercapto-2-hydroxybutane (25807-94-7) → 1-<(benzamidomethyl)thio>-2-butanol (96228-47-6)

Conditions	Yield
With sulfuric acid In water for 48h;	83%

N-(hydroxymethyl)benzamide (6282-02-6) + 6-Phenoxy-2-phenyl-imidazo[1,2-b]pyridazine (180901-13-7) → N-(6-Phenoxy-2-phenyl-imidazo[1,2-b]pyridazin-3-ylmethyl)-benzamide

Conditions	Yield
With sulfuric acid In acetic acid for 14h; Heating;	83%

N-(hydroxymethyl)benzamide (6282-02-6) + 2-(4'-t-butylphenyl)-6-chloroimidazo<1,2-b>pyridazine (180901-27-3) → 3-benzamidomethyl-2-(4'-t-butylphenyl)-6-chloroimidazo<1,2-b>pyridazine

Conditions	Yield
With sulfuric acid In acetic acid at 120℃;	82%

N-(hydroxymethyl)benzamide (6282-02-6) + 2-(4-tert-Butyl-phenyl)-6-methylsulfanyl-imidazo[1,2-b]pyridazine → N-[2-(4-tert-Butyl-phenyl)-6-methylsulfanyl-imidazo[1,2-b]pyridazin-3-ylmethyl]-benzamide

Conditions	Yield
With sulfuric acid In acetic acid for 14h; Heating;	82%

2-acetylpropanoic acid ethyl ester (609-14-3) + N-(hydroxymethyl)benzamide (6282-02-6) → 2-(benzoylamino-methyl)-2-methyl-acetoacetic acid ethyl ester (101105-75-3)

Conditions	Yield
With boron trifluoride diethyl etherate at 0 - 20℃; for 2h;	82%

N-(hydroxymethyl)benzamide (6282-02-6) + ethyl (4-chlorobenzoyl)acetate (2881-63-2) → ethyl 2-(benzamidomethyl)-3-(4-chlorophenyl)-3-oxopropanoate

Conditions	Yield
With boron trifluoride diethyl etherate at 0 - 20℃; for 2h;	81%

N-(hydroxymethyl)benzamide (6282-02-6) + mercaptoacetic acid (68-11-1) → Benzamidomethyl-thioessigsaeure (55843-15-7)

Conditions	Yield
With hydrogenchloride at 0℃; for 0.5h;	80%

N-(hydroxymethyl)benzamide (6282-02-6) + 2-Naphthalen-2-yl-6-phenylsulfanyl-imidazo[1,2-b]pyridazine (180900-91-8) → N-(2-Naphthalen-2-yl-6-phenylsulfanyl-imidazo[1,2-b]pyridazin-3-ylmethyl)-benzamide

Conditions	Yield
With sulfuric acid In acetic acid for 14h; Heating;	79%

N-(hydroxymethyl)benzamide (6282-02-6) + 2-(4-tert-Butyl-phenyl)-6-iodo-imidazo[1,2-a]pyridine (188692-68-4) → N-[2-(4-tert-Butyl-phenyl)-6-iodo-imidazo[1,2-a]pyridin-3-ylmethyl]-benzamide

Conditions	Yield
With sulfuric acid In acetic acid for 14h; Heating;	79%

4-hydroxy[1]benzopyran-2-one (1076-38-6) + N-(hydroxymethyl)benzamide (6282-02-6) → N-[(4-hydroxy-2-oxo-2H-chromen-8-yl)methyl]benzamide

Conditions	Yield
With sulfuric acid In ethanol at 35℃; for 120h; Friedel-Crafts Alkylation;	76.5%

N-(hydroxymethyl)benzamide (6282-02-6) + phosphorisocyanatidic acid dimethyl ester (867-04-9) → dimethyl (N-benzamidomethyl)amidophosphate (125376-12-7)

Conditions	Yield
With triethylamine In benzene at 40 - 50℃; for 3h;	75%

N-(hydroxymethyl)benzamide (6282-02-6) + 6-methylthio-2-styrylimidazo<1,2-b>pyridazine → 3-benzamidomethyl-6-methylthio-2-styrylimidazo<1,2-b>pyridazine

Conditions	Yield
With sulfuric acid In acetic acid at 120℃;	74%

Upstream product

• 50-00-0 formaldehyd 
• 55-21-0 benzamide 
• 108-38-3 m-xylene 
• 61652-83-3 benzamidomethyl benzoate 
• 58379-67-2 N-<(phenylsulfenyl)methyl>benzamide 
• 121-44-8 triethylamine 

Downstream Products

• 4380-83-0 N-(piperidinomethyl)benzamide 
• 108993-93-7 N-(5-methyl-selenophen-2-ylmethyl)-benzamide 
• 115037-52-0 2,3-bis-(benzoylamino-methyl)-5-methyl-selenophene 
• 115037-51-9 2,5-bis-(benzoylamino-methyl)-3-methyl-selenophene 
• 115120-84-8 2,5-bis-(benzoylamino-methyl)-3,4-dimethyl-selenophene 
• 858796-23-3 5-(benzoylamino-methyl)-furan-2-carboxylic acid 
• 857999-82-7 4-(benzoylamino-methyl)-thiophene-2-carboxylic acid 
• 33858-93-4 N-(3,4-dimethoxyphenylthiomethyl)benzamide 
• 57894-15-2 N-(3,4-dihydroxy-benzyl)-benzamide 
• 105026-89-9 N-(4-hydroxy-3-methoxybenzyl)benzamide 
• 65608-94-8 N-(p-methylbenzyl)benzamide 

Relevant articles and documents

Preparation method of 4AA

The invention discloses a preparation method of 4AA. The preparation method comprises the following steps: S1, preparing a first intermediate from benzamide and a formaldehyde aqueous solution; S2, preparing a second intermediate from the first intermediate, thionyl chloride, toluene and n-heptane; S3, preparing a third intermediate from the second intermediate, methyl acetoacetate, sodium methoxide, toluene, diluted hydrochloric acid and isopropanol; S4, preparing a fourth intermediate from the third intermediate, reductase, ethyl acetate, saturated sodium bicarbonate and saturated salt water; S5, preparing a fifth intermediate from the fourth intermediate, imidazole, TBSCL and methylbenzene; S6, preparing a sixth intermediate from the fifth intermediate, ethanolamine, methanol and n-heptane; S7, preparing a seventh intermediate by using the sixth intermediate, a Grignard reagent and n-heptane; and S8, preparing 4AA from the seventh intermediate, ruthenium trichloride, potassium acetate, ethyl acetate, acetic acid and a peracetic acid solution.

A convenient and clean synthesis of methylenebisamides and carbinolamides over zeolites in aqueous media

A simple, efficient and environmentally benign protocol for the synthesis of methylenebisamides and carbinolamides in high yields from aromatic amides and formaldehyde in the presence of heterogeneous catalysts (Hβ and NaY zeolites) using water as a solvent is demonstrated. Moreover, the catalyst is recyclable and can be reused without significant loss in its catalytic activity.

Rate of formation of N-(hydroxymethyl)benzamide derivatives in water as a function of pH and their equilibrium constants

The third-order rate constants for the pH-dependent formation of the carbinolamides generated from the reaction of formaldehyde and benzamide, 4-chloro, 4-nitro, 4-methyl and 4-methoxybenzamide, are reported. The acid-catalyzed reaction was found to occur via rate-limiting proton transfer, whereas the hydroxide-dependent reaction occurred via a specific-base process. Coupling the rate constants for carbinolamide formation reported herein with the previously established rates for carbinolamide breakdown yielded equilibrium constants for the carbinolamides studied in water.