3481-09-2

Basic information

• Product Name: N-Chlorophthalimide
• Synonyms: 2-chloro-1h-isoindole-1,3(2h)-dione;N-CHLOROPHTHALIMIDE;ncp;Phthalimidoyl chloride;phthalimide chloride;Chlorophtalimide;N-Chlorphthalimid;2-Chloro-2H-isoindole-1,3-dione
• CAS NO: 3481-09-2
• Molecular Formula: C₈H₄ClNO₂
• Molecular Weight: 181.58
• EINECS: 222-459-8
• Product Categories: Heterocycles;Chlorination;Halogenation;N-Substituted Maleimides, Succinimides & Phthalimides;N-Substituted Phthalimides;Synthetic Organic Chemistry;Carbonyl Compounds;Cyclic Imides;Organic Building Blocks
• Mol File: 3481-09-2.mol
• Article Data: 11

Chemical Properties

• Melting Point: 188-198 °C(lit.)
• Boiling Point: 315.1 °C at 760 mmHg
• Flash Point: 144.4 °C
• Appearance: white to pale yellow powder
• Density: 1.56 g/cm³
• Vapor Pressure: 0.000447mmHg at 25°C
• Refractive Index: 1.66
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: -3.53±0.20(Predicted)
• CAS DataBase Reference: N-Chlorophthalimide(CAS DataBase Reference)
• NIST Chemistry Reference: N-Chlorophthalimide(3481-09-2)
• EPA Substance Registry System: N-Chlorophthalimide(3481-09-2)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• RIDADR: 1759
• WGK Germany: 1
• HazardClass: 8
• PackingGroup: II
• Hazardous Substances Data: 3481-09-2(Hazardous Substances Data)

Usage

Chemical Properties

White to pale yellow powder

Uses

N-Chlorophthalimide may be employed in the synthesis of:α-amino acetalα-amino nitro compoundsvicinal diamineα,β-unsaturated vicinal haloamino nitro compoundIt may also be used as a chlorination reagent for the synthesis of 3-(methylthio)oxindoles.

General Description

N-Chlorophthalimide in anhydrous acetic acid serves as a useful oxidizing reagent for use in various direct titrimetric analyses. N-Chlorophthalimide can be synthesized by reacting phthalimide, t-butyl hypochlorite, water and t-butyl alcohol. It participates in the synthesis of 2-amino-3-benzoyl-α-(methylthio)phenylacetamide.

InChI:InChI=1/C8H4ClNO2/c9-10-7(11)5-3-1-2-4-6(5)8(10)12/h1-4H

Synthetic route

phthalimide (136918-14-4) → N-chlorophthalimide (3481-09-2)

Conditions	Yield
With trichloroisocyanuric acid In water at 20℃; for 1h;	98%
With lead(IV) acetate; aluminium trichloride In acetonitrile for 3h; Heating;	88%
With aluminum (III) chloride; lead(IV) tetraacetate In acetonitrile at 20℃; for 20h; Reflux; Inert atmosphere;	71%

potassium phtalimide (1074-82-4) → N-chlorophthalimide (3481-09-2)

Conditions	Yield
With chlorine In tetrachloromethane; water	94%
With acetic acid In water	92.5%
With chlorine In water 1) 0 deg C, 2) r.t., 60 min;	63%

sodium phthalimide (33081-78-6) → N-chlorophthalimide (3481-09-2)

Conditions	Yield
In dichloromethane	90%

1,4-dimethoxyphthalazine (57315-37-4) → N-chlorophthalimide (3481-09-2) + 2-chloro-4-methoxyphthalazin-1-one

Conditions	Yield
With trichloroisocyanuric acid In acetonitrile for 48h; Solvent; Reflux; Inert atmosphere;	A 49% B n/a
With trichloroisocyanuric acid In acetonitrile for 48h; Reflux; Inert atmosphere;	A 34% B 26%

2-chloro-4-methoxyphthalazin-1-one → N-chlorophthalimide (3481-09-2)

Conditions	Yield
With trichloroisocyanuric acid; tetrabutyl-ammonium chloride In acetonitrile for 24h; Reagent/catalyst; Reflux; Inert atmosphere;	45%

N-aminophthalamide (1875-48-5) → N-chlorophthalimide (3481-09-2)

Conditions	Yield
With trichloroisocyanuric acid In acetonitrile for 48h; Reflux; Inert atmosphere;	10%

phthalimide (136918-14-4) + tert-butylhypochlorite (507-40-4) → N-chlorophthalimide (3481-09-2)

Conditions	Yield
With water; tert-butyl alcohol

phthalimide (136918-14-4) + water (7732-18-5) + hypochloric acid (13898-47-0) → N-chlorophthalimide (3481-09-2)

phthalimide sodium → N-chlorophthalimide (3481-09-2)

Conditions	Yield
With water; chlorine at 8℃;
With water; chlorine at 8℃;

chloroform (67-66-3) + sodium phthalimide (33081-78-6) + chlorine (7782-50-5) → N-chlorophthalimide (3481-09-2)

water (7732-18-5) + sodium phthalimide (33081-78-6) + chlorine (7782-50-5) → N-chlorophthalimide (3481-09-2)

potassium phtalimide (1074-82-4) → N-chlorophthalimide (3481-09-2) + potassium chloride

Conditions	Yield
With chlorine In dichloromethane; water	A 46.4 grams (95.% yield) B n/a

phthalimide (136918-14-4) + 4-vinylpyridine-divinylbenzene → N-chlorophthalimide (3481-09-2)

Conditions	Yield
With chlorine In quinoline; dichloromethane

[(difluoromethyl)thio]methylbenzene (68965-44-6) + potassium phtalimide (1074-82-4) → N-chlorophthalimide (3481-09-2) + 2-((difluoromethyl)thio)isoindoline-1,3-dione

Conditions	Yield
Stage #1: [(difluoromethyl)thio]methylbenzene With chlorine In chloroform at -30 - 23℃; Darkness; Stage #2: potassium phtalimide In chloroform at -30 - 23℃;

phthalic anhydride (85-44-9) → N-chlorophthalimide (3481-09-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: urea / 0.5 h / 140 °C 2: chlorine / 3 h / 20 °C View Scheme

phthalic anhydride (85-44-9) → N-chlorophthalimide (3481-09-2) + 2-chloro-4-methoxyphthalazin-1-one

Conditions	Yield
Multi-step reaction with 4 steps 1: hydrogenchloride; hydrazine hydrate / quinoline / 24 h / Reflux 2: trichlorophosphate / 3 h / Inert atmosphere; Reflux 3: 24 h / Reflux; Inert atmosphere 4: trichloroisocyanuric acid / acetonitrile / 48 h / Reflux; Inert atmosphere View Scheme

2,3-dihydrophthalazine-1,4-dione (1445-69-8) → N-chlorophthalimide (3481-09-2) + 2-chloro-4-methoxyphthalazin-1-one

Conditions	Yield
Multi-step reaction with 3 steps 1: trichlorophosphate / 3 h / Inert atmosphere; Reflux 2: 24 h / Reflux; Inert atmosphere 3: trichloroisocyanuric acid / acetonitrile / 48 h / Reflux; Inert atmosphere View Scheme

1,4-dichlorophthalazine (4752-10-7) → N-chlorophthalimide (3481-09-2) + 2-chloro-4-methoxyphthalazin-1-one

Conditions	Yield
Multi-step reaction with 2 steps 1: 24 h / Reflux; Inert atmosphere 2: trichloroisocyanuric acid / acetonitrile / 48 h / Reflux; Inert atmosphere View Scheme

1,4-dimethoxyphthalazine (57315-37-4) → N-chlorophthalimide (3481-09-2)

Conditions	Yield
With trichloroisocyanuric acid; tetrabutyl-ammonium chloride In acetonitrile for 48h; Reflux; Inert atmosphere;	42 %Spectr.
Multi-step reaction with 2 steps 1: trichloroisocyanuric acid / 1,2-dichloro-ethane / 24 h / Reflux; Inert atmosphere 2: trichloroisocyanuric acid; tetrabutyl-ammonium chloride / acetonitrile / 24 h / Reflux; Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: trichloroisocyanuric acid / acetonitrile / 48 h / Reflux; Inert atmosphere 2: trichloroisocyanuric acid; tetrabutyl-ammonium chloride / acetonitrile / 24 h / Reflux; Inert atmosphere View Scheme

4-[(trimethylsilyl)oxy]phthalazin-1(2H)-one → N-chlorophthalimide (3481-09-2)

Conditions	Yield
With tetrabutyl-ammonium chloride In acetonitrile at -40℃; for 1h; Temperature; Inert atmosphere;	29 mg

2,3-dihydrophthalazine-1,4-dione (1445-69-8) → N-chlorophthalimide (3481-09-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 2,6-dimethylpyridine / acetonitrile / 12 h / Reflux; Inert atmosphere 2: tetrabutyl-ammonium chloride / acetonitrile / 1 h / -40 °C / Inert atmosphere View Scheme

Upstream product

• 136918-14-4 phthalimide 
• 1074-82-4 potassium phtalimide 
• 57315-37-4 1,4-dimethoxyphthalazine 
• 1875-48-5 N-aminophthalamide 
• 1445-69-8 2,3-dihydrophthalazine-1,4-dione 
• 4752-10-7 1,4-dichlorophthalazine 
• 85-44-9 phthalic anhydride 
• 33081-78-6 sodium phthalimide 
• 7732-18-5 water 
• 7782-50-5 chlorine 
• 67-66-3 chloroform 
• 13898-47-0 hypochloric acid 
• 507-40-4 tert-butylhypochlorite 
• 68965-44-6 [(difluoromethyl)thio]methylbenzene 

Downstream Products

• 7143-42-2 methyl 2-((methoxycarbonyl)amino)benzoate 
• 27722-45-8 N-(4-methylbenzenesulphonyl)phthalimide 
• 108890-73-9 ethyl 2-((ethoxycarbonyl)amino)benzoate 
• 298-96-4 triphenyltetrazolium chloride 
• 118-92-3 anthranilic acid 
• 122845-05-0 N-(1-benzyl-1H-pyrrol-2-yl)phthalimide 
• 136918-14-4 phthalimide 
• 88-99-3 benzene-1,2-dicarboxylic acid 
• 50593-68-5 3-chloro-6-nitro-1H-indazole 
• 165669-14-7 7-nitro-3-chloro-1H-indole 
• 78183-91-2 4'-nitrobenzyl 3-methyl-2-(2-chlorosulfinyl-4-oxo-3-phenoxyacetamido-1-azetidinyl)-3-butenoate 
• 719-98-2 N-((trifluoromethyl)thio)isoindoline-1,3-dione 

Relevant articles and documents

A Two-Step, One-Pot, and Multigram-Scale Synthesis of N-Difluoromethylthiophthalimide

A new method for the 100 g scale synthesis of N-difluoromethylthiophthalimide 1 from cheap commodity chemical benzyl mercaptan and HCF2Cl or other difluorocarbene precursors was described. Reagent 1 is an excellent electrophilic difluoromethylthiolating reagent as demonstrated by the gram-scale synthesis of five difluoromethylthiolated derivatives of structurally complicated drug-like molecules and natural products.

N-Chlorination-induced, oxidative ring contraction of 1,4-dimethoxyphthalazines

A rarely explored oxidative ring contraction of electron-rich 1,2-diazine is described. Upon treatment with an electrophilic chlorinating reagent (TCICA), 1,4-dimethoxyphthalazines undergo an N-chlorination-induced ring contraction that is accompanied by the loss of one nitrogen atom. The scope of this unusual reactivity was examined with a range of 1,4-dimethoxyphthalazine derivatives. In addition, a mechanism proceeding via a bicyclic species was proposed on the basis of an isolated reaction intermediate and DFT calculations.

Synthesis method of anthranilic acid

The invention relates to a synthesis method of anthranilic acid. The synthesis method comprises the following steps: (1), putting phthalic anhydride and urea into a reaction container, raising the temperature to 140 DEG C, and stirring; (2), after reaction, adding water, and pulping; (3), adding glacial acetic acid and halogen; (4), stirring at room temperature, reacting for three hours, then filtering to obtain a solid, and putting a mother solution into the next batch of a reaction solution; (5), putting the solid into liquid caustic soda, and stirring at room temperature; (6), adding hydrochloric acid into the reaction solution to adjust the pH to 3-4, and separating out a large amount of solid; and (7), filtering and drying to obtain the product anthranilic acid. The synthesis method has the beneficial effects as follows: a halogenating reaction is directly performed on the halogen and phthalamide, and a reaction solvent can be repeatedly used, so that the halogen utilization rateis very high; use of large amounts of acid and alkali is avoided and generation of large amounts of waste salt and waste water is also avoided; and in addition, the waste water has a COD value of 2,000 or below, so that the environmental pollution is very low and the synthesis method is suitable for industrial production.