The bromination of isatoic anhydride

Bromination of isatoic anhydride in acetic acid gives N-dibromoacetyl-3,5-dibromoanthranilic acid. Three new anthranils are described.     

Microwave-assisted addition of azomethines to isatoic anhydride

Diels-Alder addition of azomethines to isatoic anhydride in a solvent-free and eco-friendly condition is investigated using a microwave oven. The product is exclusively 2,3-diaryl-2,3-dihydroquinazolin-4(1H)-ones 4a-d. HOMO-LUMO energy of the iminoketene and the dienophiles were calculated using semi-empirical AM1 calculations.     

Preparation of novel heterocyclic systems from isatoic anhydrides

Isatoic anhydride ( 1a ) and 5-chloroisatoic anhydride ( 1b ) were treated with 2-(1-methylhydrazino)ethanol ( 2 ) to produce 2-aminobenzoic acid 2-(2-hydroxyethyl)-2-methylhydrazide ( 3a ) and its 5-chloro analog 3b , respectively. Treatment of 3a and 3b with carbon disulfide gave, respectively, 2,3-dihydro-3-[(2-hydroxyethyl)methylamino]-2-thioxo-4-(1H)quinazolinone ( 4a ) and its 6-chloro analog 4b . Compounds 4a and 4b afforded 5,6-dihydro-5-methyl-2-thioxo-4H,8H-[1,3,5,6]oxathiadiazocino[4,5-b]quinazolin-8-one ( 5a ) and its 10-chloro analog 5b , respectively, upon treatment with thiophosgene. Compound 5a could be produced directly from 3a and thiophosgene. Treatment of 4a and 4b with trifluoroacetic anhydride followed by potassium carbonate gave 3,4-dihydro-4-methyl-2H,6H-[1,3,4]thiadiazino[2,3-b]quinazolin-6-one ( 7a ) and its 8-chloro analog 7b , respectively. Treatment of 4a with thionyl chloride also gave 7a , but 4b and thionyl chloride afforded a mixture of 7b and 8-chloro-3,4-dihydro-4-methyl-2H,6H-[1,3,4]oxadiazino[2,3-b]quinazolin-6-one ( 10 ). The dimethyl analogs of 4a and 4b ( 13a and 13b ) upon treatment with thiophosgene afforded 3,4-dihydro-2,2,4-trimethyl-2H,6H-[1,3,4]oxadiazino[2,3-b]quinazolin-6-one ( 14a ) and its 8-chloro analog 14b , respectively.     

The energetics of isomeric benzoxazine diones: isatoic anhydride revisited

The standard (p(o) = 0.1 MPa) molar enthalpy of formation of crystalline 2H-1,3-benzoxazine-2,4(3H)dione was measured, at T= 298.15 K, by static bomb calorimetry and the standard molar enthalpy of sublimation, at T= 298.15 K, was obtained using Calvet microcalorimetry. These values were used to derive the standard molar enthalpy of formation in the gaseous phase, T= 298.15 K, of -(401.0 +/- 3.5) kJ mol(-1). The standard molar enthalpy of sublimation of isatoic anhydride was recalculated, and our recommended experimental value for the standard molar enthalpy of formation in the gaseous phase, T= 298.15 K, is -(406.2 +/- 3.4) kJ mol(-1). Density functional calculations for the two isomers 2H-1,3-benzoxazine-2,4(3H)dione and isatoic anhydride, in which the ring nitrogen and oxygen have been transposed, confirm the experimental evidence of nearly identical thermochemical stability for these isomers.     

Application of isatoic anhydride chemistry to the synthesis of racemic paraensine

The alkaloid paraensine was obtained in racemic form in 84% overall yield by a two step reaction sequence which involves a hetero ring opening of N-methylisatoic anhydride with the lithium enolate of 4,5-di-hydro-4,5,5-trimethyl-2(3H)-furanone followed by a thermal cyclization.     

Facile synthesis of reactive benzoazetinone by flash vacuum pyrolysis of isatoic anhydride

Pyrolysis of isatoic anhydride (3) at 550°C and ca. 1×10⁻² torr gave benzoazetinone (1, 80%) as the only product. The existence of 1 was confirmed by low-temperature NMR spectroscopy at −90°C. Above −20°C, 1 was converted to dimer (4, 50%), trimer (5, 22%), and anthranilic acid (6, 12%). Pyrolysis of 3 at 800°C and ca. 1×10⁻² torr gave 1-cyanocyclopentadiene (7) in 38% yield.     

A tandem synthesis of N-(4-hydroxyquinolin-2-yl)sulfonamides from sulfonoketenimides and isatoic anhydride

The one-pot synthesis of a novel class of N-(4-hydroxyquinolin-2-yl)sulfonamide derivatives is achieved in moderate to good yields by the sequential copper-catalyzed reaction between sulfonyl azides, terminal alkynes, and isatoic anhydride in N,N-dimethylformamide.     

Utilization of isatoic anhydride in the syntheses of various types of quinazoline and quinazolinone derivatives

Isatoic anhydride has attracted a great deal of attention in recent decades. A review of the methods of preparation of all known quinazoline and quinazolinone derivatives is given herein. Isatoic anhydrides react with some nitrogen nucleophiles, followed by cyclocondensation by electrophiles, to produce several quinazoline and quinazolinone derivatives. These compounds find use as medicinal and pharmacological substances.     

1,2-Dihydro-2-thioxo-4H-3,1-benzothiazin-4-one: formation from carbon disulfide and isatoic anhydride

The reaction of isatoic anhydride (1) with carbon disulfide at room temperature unexpectedly afforded 1,2-dihydro-2-thioxo-4H-3,1-benzothiazin-4-one (2). The use of ¹³C-labeled carbon disulfide elucidated that CS₂ was entirely incorporated into the product.     

The synthesis of o-Amino-N-substituted benzamides and 3-substituted 2,4 (1H,3H)-quinazolinediones from isatoic anhydride

The reaction of isatoic anhydride with sterically hindered amines in DMF or DMSO, and subsequent treatment of the o-amino-N-substituted benzamides thus produced with phosgene, gives high yields of 2,4(1H,3H)-quinazolinediones with branched alkyl groups in the 3-position.     

The chemistry of 2H-3,1-benzoxazine-2,4(1H)-dione (isatoic anhydride). 11. Reaction of N-methylisatoic anhydride with 1-cyanoacetylpiperidine

The reaction of N-methylisatoic anhydride with 1-cyanoacetylpiperidine in the presence of sodium hydride produces a tautomeric mixture of 4a and 4b , with 4b predominating. When heated in xylene, 4 is converted to the piperidine adduct 5 whereas heating in dimethylsulfoxide furnishes 3 . Spectral data for 4 and 5 are also discussed.     

Sensitive detection of proteins in polyacrylamide gel via isatoic anhydride derivatization: Introduction of a low‐cost fluorescent prelabeling procedure

Here, we introduce isatoic anhydride as a sensitive and commodious fluorescent prelabel for detection of proteins in one‐dimensional polyacrylamide gels. High reactivity of isatoic anhydride with nucleophiles in mild alkaline environments makes it an appropriate tag for labeling of biomolecules. In this study, we show that preelectrophoresis labeling of proteins with isatoic anhydride for few minutes at room temperature allows detection of 2–4 ng of standard proteins, BSA and lysozyme, per band. Proteins were successfully labeled in the presence of a wide range of common biological reagents and in crude cell extract. The labeled proteins have the same electrophoretic migration in comparison to unlabeled proteins; however the application of saturation labeling method results in slight band broadening. Compatibility of the method with downstream processes was assessed by tryptic digestion of labeled proteins and study of peptide mixture using gel electrophoresis which revealed partial digestion of labeled proteins due to lysine modification. The present procedure is sensitive, rapid, and inexpensive and is a promising alternative for current protein staining procedures, where downstream processes are not desired.     

Preparation of epoxy-silica composites cured with iso-methyltetrahydrophthalic anhydride

The possibility of preparing epoxy-silica composites using iso-methyltetrahydrophthalic anhydride as curing agent was examined; the composition of the composites and conditions of their preparation were determined. The effect exerted by the concentration of precursors, tetraethoxysilane and epoxypropxypropyltriethoxysilane, on the glass transition point, sol fraction yield, heat resistance, and adhesion properties of the hybrid materials obtained was studied.     

2H-3,1-benzoxazine-2,4-(1H)-dione (isatoic anhydride). 15. Reactions with lactone enolates

The reaction of N-methylisatoic anhydride, 1 , with the lithium enolates derived from various butyrolactones or δ-valerolactone produces stable anthranoyl lactone derivatives 4 . Heating these products in toluene results in a cyclization to afford 4-hydroxy-3-(2-hydroxyalkyl)-1-methyl-2(1H)-quinolinones, 8 and 14 , in good yields.     

A phosgene and peroxide-free one-pot tandem synthesis of isatoic anhydrides involving anthranilic acid,Boc anhydride,and 2-chloro-N-methyl pyridinium iodide

A phosgene and peroxide-free approach for the synthesis of isatoic anhydrides has been described. The synthesis involves the carbamate formation with Boc anhydride followed by in situ cyclization to afford the isatoic anhydride. The importance of this synthetic strategy is in the ease of operation, scalability, and preparation from readily available raw materials.     

The chemistry of 2H-3,1-benzoxazine-2,4(1H)-dione (isatoic anhydride). 12. Synthesis of araliopsine and isoplatydesmine

N-Methylisatoic anhydride reacts with the lithium enolate derived from 3,3-dimethyloxiranepropanoic acid ethyl ester (7) to initially produce the acyclic β-ketoester 8 . Under neutral conditions, 8 spontaneously cyclizes to the alkaloid araliopsine ( 1a ). In the presence of acid, 8 cyclizes to a mixture of 1a and its leanear isomer isoplatydesmine (2a).