5331-43-1

Basic information

• Product Name: Carbobenzoxyhydrazide
• Synonyms: hydrazinecarboxylicacid,phenymethylester;phenymethylhydrazinecarboxylate;CARBOBENZOXYHYDRAZIDE;CARBOBENZOXYHYDRAZINE;CARBAZIC ACID BENZYL ESTER;BENZYL CARBAZATE;BENZYLOXYCARBONYL HYDRAZIDE;(BENZYLOXYCARBONYL)HYDRAZINE
• CAS NO: 5331-43-1
• Molecular Formula: C₈H₁₀N₂O₂
• Molecular Weight: 166.18
• EINECS: 226-230-3
• Product Categories: Phosgene Derivatives
• Mol File: 5331-43-1.mol
• Article Data: 10

Chemical Properties

• Melting Point: 65-68 °C(lit.)
• Boiling Point: 294.38°C (rough estimate)
• Flash Point: >230 °F
• Appearance: light beige shiny flakes
• Density: 1.2265 (rough estimate)
• Refractive Index: 1.6180 (estimate)
• Storage Temp.: 2-8°C
• Solubility: DMSO, Methanol
• PKA: 10.56±0.20(Predicted)
• Water Solubility: Soluble in water (slightly), methanol and DMSO.
• BRN: 1952982
• CAS DataBase Reference: Carbobenzoxyhydrazide(CAS DataBase Reference)
• NIST Chemistry Reference: Carbobenzoxyhydrazide(5331-43-1)
• EPA Substance Registry System: Carbobenzoxyhydrazide(5331-43-1)

Safety Data

• Hazard Codes: Xi
• Statements: 41
• Safety Statements: 26-36
• WGK Germany: 3
• RTECS: MV1724950
• TSCA: Yes
• Hazardous Substances Data: 5331-43-1(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 5331-43-1 differently. You can refer to the following data:
1. Benzyl Carbazate has been shown to prevent the occurrence of oligonucleosome-sized DNA fragmentation in the cell-free system.
2. Benzyl carbazate is used as a reagent for preparation of benzyloxycarbonyl (Z, Cbz) hydrazides of carboxylic acids, particularly N-protected amino acids. Subsequent hydrogenolysis gives the hydrazide which can be converted to the azide for coupling with a further amino acid residue by the azide method. It is also used in the preparation of simple acyl or sulfonyl hydrazides avoiding diacylation.

InChI:InChI=1/C8H10N2O2/c9-10-8(11)12-6-7-4-2-1-3-5-7/h1-5H,6,9H2,(H,10,11)

Synthetic route

C11H11Cl3N2O4 (202980-89-0) → N-benzyloxycarbonyl-hydrazine (5331-43-1)

Conditions	Yield
With chloro-trimethyl-silane; mischmetal (50 percent Ce, 25 percent La, 16 percent Nd, 6 percent Pr) In tetrahydrofuran for 3h; Heating;	99%

benzyl chloroformate (501-53-1) → N-benzyloxycarbonyl-hydrazine (5331-43-1)

Conditions	Yield
With lithium carbonate; hydrazine hydrate In ethyl acetate at 30 - 120℃; for 2.75h; Temperature; Solvent; Reagent/catalyst; Inert atmosphere;	95%
With potassium carbonate; hydrazine hydrate In tetrahydrofuran at -20℃; for 2h;	90%
With hydrazine hydrate In diethyl ether for 1h; Acylation;	82%
With chloroform; hydrazine hydrate
(i) N2H4*H2O, (ii) HCl; Multistep reaction;

N-benzyloxycarbonylimidazole (22129-07-3) → N-benzyloxycarbonyl-hydrazine (5331-43-1)

Conditions	Yield
With hydrazine hydrate In tetrahydrofuran at 20℃;	95%
With hydrazine hydrate In dichloromethane at 0 - 20℃; for 1.5h;	5.78 g

hydrazine hydrate (7803-57-8) + benzyl chloroformate (501-53-1) → N-benzyloxycarbonyl-hydrazine (5331-43-1)

Conditions	Yield
In diethyl ether at -5 - 20℃; for 2h;	58%

hydrazinecarboxylic acid methyl ester (6294-89-9) + benzyl alcohol (100-51-6) → N-benzyloxycarbonyl-hydrazine (5331-43-1)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide	39%

benzyl 4-nitrophenyl carbonate (13795-24-9) → N-benzyloxycarbonyl-hydrazine (5331-43-1)

Conditions	Yield
With hydrazine hydrate In dichloromethane at 0 - 20℃; Inert atmosphere;	24%

DBC (3459-92-5) → N-benzyloxycarbonyl-hydrazine (5331-43-1)

Conditions	Yield
With hydrazine hydrate at 110℃;
With hydrazine hydrate auf dem Dampfbad;
With hydrazine hydrate In isopropyl alcohol

(5-Ethyl-3,7,8,10-tetramethyl-2,4-dioxo-3,4,5,10-tetrahydro-2H-benzo[g]pteridin-4a-yl)-carbamic acid benzyl ester → N-benzyloxycarbonyl-hydrazine (5331-43-1) + 5-ethyl-10-methyl-2,4-dioxo-2,3,4,10-tetrahydrobenzo[g]pteridin-5-ium perchlorate

Conditions	Yield
In acetonitrile at 25℃; Equilibrium constant;

benzyl chloride (100-44-7) + sodium compound of α-naphthol → N-benzyloxycarbonyl-hydrazine (5331-43-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: (i) Na, petroleum ether, (ii) /BRN= 471308/, KI, DMF 2: N2H4*H2O / propan-2-ol View Scheme

benzyl alcohol (100-51-6) → N-benzyloxycarbonyl-hydrazine (5331-43-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: dichloromethane / 1 h / 20 °C 2: hydrazine hydrate / dichloromethane / 1.5 h / 0 - 20 °C View Scheme

N-benzyloxycarbonyl-hydrazine (5331-43-1) + trifluoroacetic anhydride (407-25-0) → benzyl 2-(trifluoroacetyl)hydrazinecarboxylate

Conditions	Yield
In dichloromethane at 0℃;	100%
With triethylamine In dichloromethane at 0 - 20℃; for 2h;	77%

2-(4-formylphenyl)pyridine (127406-56-8) + N-benzyloxycarbonyl-hydrazine (5331-43-1) → C20H17N3O2 (1003888-34-3)

Conditions	Yield
In isopropyl alcohol at 80℃; for 16h;	100%

1-(tert-butoxycarbonyl)-3-(ethoxycarbonyl)piperidine-3-carboxylic acid (1093214-91-5) + N-benzyloxycarbonyl-hydrazine (5331-43-1) → 1-tert-butyl 3-ethyl 3-({2-[(benzyloxy)carbonyl]hydrazino}carbonyl)piperidine-1,3-dicarboxylate (1186019-61-3)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 16h;	100%

N-benzyloxycarbonyl-hydrazine (5331-43-1) + N,N-Dimethylcarbamoyl chloride (79-44-7) → C11H15N3O3

Conditions	Yield
With sodium hydroxide In ethyl acetate at 50℃; for 16h; Reagent/catalyst;	100%

methyl N-{[(1,1-dimethylethyl)oxy]carbonyl}-N-(2-oxoethyl)glycinate (175211-73-1) + N-benzyloxycarbonyl-hydrazine (5331-43-1) → C18H25N3O6

Conditions	Yield
With sodium sulfate In methanol at 20℃; for 2h;	100%

Pd(t-BuNC)2Cl2 (55820-40-1, 34710-33-3, 97859-03-5) + N-benzyloxycarbonyl-hydrazine (5331-43-1) → C18H28Cl2N4O2Pd

Conditions	Yield
In tetrahydrofuran at 20℃; for 5h;	100%

di-tert-butyl dicarbonate (24424-99-5) + N-benzyloxycarbonyl-hydrazine (5331-43-1) → 1-tert-butoxycarbonyl-2-carbobenzyloxyhydrazine (57699-88-4)

Conditions	Yield
With triethylamine In dichloromethane	99%
With dmap; triethylamine In dichloromethane for 24h;	90%
With triethylamine In tetrahydrofuran at 20℃; for 16h; Inert atmosphere;	89%

N-benzyloxycarbonyl-hydrazine (5331-43-1) + acetone (67-64-1) → 2-(propan-2-yliden)hydrazinecarboxylic acid benzyl ester (3057-26-9)

Conditions	Yield
In toluene at 20 - 60℃; for 26h;	99%
With triethylamine In methanol for 2h; Heating;	97%
In toluene a.) 50 degC, 30 min, b.) room temp., 12 h;	94%

4-[4-(tert-butyl)-1,3-thiazol-2-yl]benzaldehyde + N-benzyloxycarbonyl-hydrazine (5331-43-1) → C22H23N3O2S (1003888-35-4)

Conditions	Yield
In isopropyl alcohol at 80℃; for 18h;	99%

4-tolyl iodide (624-31-7) + N-benzyloxycarbonyl-hydrazine (5331-43-1) → benzyl 1-p-tolylhydrazinecarboxylate (1197055-07-4)

Conditions	Yield
With copper(l) iodide; 1,10-Phenanthroline; caesium carbonate In N,N-dimethyl-formamide at 20 - 80℃; Inert atmosphere;	99%

1-tert-butyl-4-iodobenzene (35779-04-5) + N-benzyloxycarbonyl-hydrazine (5331-43-1) → benzyl 1-(4-tert-butylphenyl)hydrazinecarboxylate (1197055-09-6)

Conditions	Yield
With copper(l) iodide; 1,10-Phenanthroline; caesium carbonate In N,N-dimethyl-formamide at 20 - 80℃; Inert atmosphere;	99%

N-benzyloxycarbonyl-hydrazine (5331-43-1) + 4,5-diphenylocta-1,7-diyne-4,5-diol (14763-00-9, 14865-30-6) → benzyl (2,5-dimethyl-3a,6a-diphenylhexahydro-2,5-epiminofuro[3,2-b]furan-7-yl)carbamate (1252032-33-9)

Conditions	Yield
With (N'-(tbutyl)-N,N-diethylcarbamimidoyl)gold(I) chloride; silver(I) triflimide In acetonitrile at 20℃; for 16h; Inert atmosphere;	99%

N-benzyloxycarbonyl-hydrazine (5331-43-1) + isobutyraldehyde (78-84-2) → (2E)-(2-methylpropyliden)hydrazinecarboxylic acid benzyl ester (1451982-81-2)

Conditions	Yield
In toluene at 20 - 60℃; for 26h;	99%

N-benzyloxycarbonyl-hydrazine (5331-43-1) + 5-hydroxyvanillin (3934-87-0) → (E)-benzyl 2-(3,4-dihydroxy-5-methoxybenzylidene)hydrazinecarboxylate (1621252-64-9)

Conditions	Yield
In ethanol Reflux;	99%

N-benzyloxycarbonyl-hydrazine (5331-43-1) + vanillin (121-33-5) → (E)-benzyl 2-(4-hydroxy-3-methoxybenzylidene)hydrazinecarboxylate (1621252-65-0)

Conditions	Yield
In ethanol Reflux;	99%

N-benzyloxycarbonyl-hydrazine (5331-43-1) + 3,4-dihydroxybenzaldehyde (139-85-5) → (E)-benzyl 2-(3,4-dihydroxybenzylidene)hydrazinecarboxylate (1621252-66-1)

Conditions	Yield
In ethanol Reflux;	99%

2,4-dihydroxy-5-methoxybenzaldehyde (51061-83-7) + N-benzyloxycarbonyl-hydrazine (5331-43-1) → (E)-benzyl 2-(2,4-Dihydroxy-5-methoxybenzylidene)hydrazinecarboxylate (1621252-68-3)

Conditions	Yield
In ethanol Reflux;	99%

N-benzyloxycarbonyl-hydrazine (5331-43-1) + acetophenone (98-86-2) → N'-(1-phenyl-ethylidene)-hydrazinecarboxylic acid benzyl ester

Conditions	Yield
In methanol at 20℃;	98%
In hexane for 8h; Heating;	79%
In methanol at 65℃;

N-benzyloxycarbonyl-hydrazine (5331-43-1) + pentan-3-one (96-22-0) → N'-(1-ethyl-propylidene)-hydrazinecarboxylic acid benzyl ester

Conditions	Yield
In hexane for 8h; Heating;	98%

N-benzyloxycarbonyl-hydrazine (5331-43-1) → N'-((DL)-2-tert-butoxycarbonylamino-3-phenyl-propionyl)-hydrazine carboxylic acid benzyl ester (97297-40-0)

Conditions	Yield
Stage #1: 2-(tert-butoxycarbonylamino)-3-phenylpropionic acid With benzotriazol-1-ol; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 0.5h; Stage #2: N-benzyloxycarbonyl-hydrazine In dichloromethane at 20℃;	98%

3-methoxy-1-iodobenzene (766-85-8) + N-benzyloxycarbonyl-hydrazine (5331-43-1) → benzyl 1-(3-methoxyphenyl)hydrazinecarboxylate (1197055-14-3)

Conditions	Yield
With copper(l) iodide; 1,10-Phenanthroline; caesium carbonate In N,N-dimethyl-formamide at 20 - 80℃; Inert atmosphere;	98%

N-benzyloxycarbonyl-hydrazine (5331-43-1) + 3,4,5-trimethoxy-benzaldehyde (86-81-7) → (E)-benzyl 2-(3,4,5-trimethoxybenzylidene)hydrazinecarboxylate (1621252-63-8)

Conditions	Yield
In ethanol Reflux;	98%

N-benzyloxycarbonyl-hydrazine (5331-43-1) + [5-(2-ethoxy-2-oxoethyl)-1H-tetrazol-1-yl]acetic acid → benzyl 2-{[5-(2-ethoxy-2-oxoethyl)-1H-tetrazol-1-yl]acetyl}hydrazinecarboxylate

Conditions	Yield
With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 25 - 30℃; for 16h;	98%

N-benzyloxycarbonyl-hydrazine (5331-43-1) + 1-(but-3-enyl)-2-oxocyclohexanecarboxylic acid ethyl ester (61771-76-4) → C21H28N2O4

Conditions	Yield
In ethanol	98%

N-benzyloxycarbonyl-hydrazine (5331-43-1) + methyl 1-(pent-4-en-1-yl)-2,5-dioxocyclohexanecarboxylate 5-monoethylene ketal → C23H30N2O6

Conditions	Yield
In ethanol	98%

N-benzyloxycarbonyl-hydrazine (5331-43-1) + Glyoxilic acid (298-12-4) → C10H10N2O4

Conditions	Yield
In ethanol; water at 80℃; for 4h;	98%

N-benzyloxycarbonyl-hydrazine (5331-43-1) + salicylaldehyde (90-02-8) → benzyl (E)-2-(2-hydroxybenzylidene)hydrazine-1-carboxylate (1621252-67-2)

Conditions	Yield
In ethanol at 20℃; for 0.666667h;	97.8%
In ethanol Reflux;	91.5%

para-iodoanisole (696-62-8) + N-benzyloxycarbonyl-hydrazine (5331-43-1) → benzyl 1-(4-methoxyphenyl)hydrazinecarboxylate (40093-52-5)

Conditions	Yield
With copper(l) iodide; 1,10-Phenanthroline; caesium carbonate In N,N-dimethyl-formamide at 20 - 80℃; Inert atmosphere;	97%
With copper(l) iodide; 1,10-Phenanthroline; caesium carbonate In N,N-dimethyl-formamide at 80℃; for 1h; Inert atmosphere;	51%

2-methyltetrahydrofuran-3-one (3188-00-9) + N-benzyloxycarbonyl-hydrazine (5331-43-1) → benzyl 2-(2-methyldihydrofuran-3(2H)-ylidene)hydrazine-1-carboxylate

Conditions	Yield
at 15℃; for 16h;	97%

Upstream product

• 501-53-1 benzyl chloroformate 
• 100-44-7 benzyl chloride 
• 13795-24-9 benzyl 4-nitrophenyl carbonate 
• 100-51-6 benzyl alcohol 
• 7803-57-8 hydrazine hydrate 
• 202980-89-0 C₁₁H₁₁Cl₃N₂O₄ 
• 3459-92-5 DBC 
• 22129-07-3 N-benzyloxycarbonylimidazole 
• 6294-89-9 hydrazinecarboxylic acid methyl ester 

Downstream Products

• 102956-12-7 3,3'-p-xylylene-bis-carbazic acid dibenzyl ester 
• 46742-14-7 glycine-(N'-benzyloxycarbonyl-hydrazide) 
• 287728-91-0 N-benzyloxycarbonylaminophthalimide 
• 111411-69-9 N,N-phthaloyl-glycine-(N'-benzyloxycarbonyl-hydrazide) 
• 59105-30-5 N'-benzoyl-hydrazinecarboxylic acid benzyl ester 
• 100381-25-7 N-trifluoroacetyl-alanine-(N'-benzyloxycarbonyl-hydrazide) 
• 101938-64-1 benzyl (2,5-dimethyl-1H-pyrrol-1-yl)carbamate 
• 122725-86-4 adipic acid bis-(N'-benzyloxycarbonyl-hydrazide) 
• 101282-24-0 (2-chloro-1-phenyl-ethylidene)-carbazic acid benzyl ester 
• 101118-63-2 [2-bromo-1-(4-bromo-phenyl)-ethylidene]-carbazic acid benzyl ester 
• 119641-48-4 benzil-bis-(benzyloxycarbonyl-hydrazone) 
• 131868-09-2 3-(N'-benzyloxycarbonyl-hydrazino)-phthalide 
• 4046-51-9 β-Benzyloxycarbonyl-hydrazin-carbonsaeure-p-nitro-phenylester, 'Z-Azaglycin'-p-nitro-phenylester 
• 57699-88-4 1-tert-butoxycarbonyl-2-carbobenzyloxyhydrazine 

Relevant articles and documents

Method for preparing benzyl carbazate

The invention provides a method for preparing benzyl carbazate. The method comprises the following steps: (1) adding a dichloromethane solvent and hydrazine hydrate into a reaction kettle, stirring until the dichloromethane solvent and hydrazine hydrate are dissolved, adding a catalyst, and stirring for at least 5 minutes; (2) slowly dropwise adding benzyl chloroformate into the reaction kettle, and carrying out heat preservation reaction for 2 hours; (3) carrying out heat preservation and water separation on the obtained reaction liquid through a liquid separation device, and recycling hydrazine hydrate after water separation; (4) adding hydrochloric acid into an organic phase obtained after water separation, and carrying out acidification refining; (5) adding a sodium carbonate aqueous solution into the acidified and refined solution for neutralization, carrying out cooling crystallization on the neutralized solution, centrifuging, separating the filtrate to remove water, recycling the organic phase, and collecting the crystallized solid for later use; and (6) recrystallizing the collected crystal solid with water to obtain benzyl carbazate. The benzyl carbazate with higher purity is obtained by adding a cooling crystallization method, and the cooling crystallization method is simple, easy to operate and safer for operators.

Synthesis and application of a novel asymmetric azo reagent: 1-(tert-butyl)-2-(4-chlorobenzyl) azodicarboxylate (tBCAD)

A series of novel asymmetric azo reagents, 1-(tert-butyl)-2-(4-substituted benzyl) azodicarboxylate, were prepared. The synthetic process has the advantage of simpleness, easy operation, mild reaction condition and high yield. The 1-(tert-butyl)-2-(4-chlorobenzyl) azodicarboxylate (tBCAD) was selected for its stability and convenience to handle, and its precursor can be recycled by recrystallization with toluene. The tBCAD and DIAD were applied to a wide variety of Mitsunobu reactions. The experimental results showed that the performance of tBCAD in Mitsunobu reaction was comparable to that of DIAD, while the stability of tBCAD was much better than DIAD. Thus, tBCAD can be a novel, stable, effective azo-reagent for the Mitsunobu reaction.

Gold-catalyzed three-component spirocyclization: A one-pot approach to functionalized pyrazolidines

An efficient, highly atom economic synthesis of hitherto unknown spirocyclic pyrazolidines in a one-pot process was developed. The gold-catalyzed three-component coupling of alkynols, hydrazines and aldehydes or ketones likely proceeds via cycloisomerization of the alkynol to an exocyclic enol ether and subsequent [3 + 2]-cycloaddition of an azomethine ylide. A library of 29 derivatives with a wide range of functional groups was synthesized in up to 97% yield. With this new method, every position in the final product can be substituted which renders the method ideal for applications in combinatorial or medicinal chemistry.