The bromination of isatoic anhydride

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

Preparation of isatoates from isatoic anhydride

A wide variety of alkyl isatoates can be prepared in good yield from the high temperature reaction of isatoic anhydride with alcohols. Isatoates were found to undergo an apparent high temperature rearrangement reaction. Proposed reaction schemes are presented for the formation of isatoates and the subsequent rearrangement reaction.     

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.     

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.     

Selectivity and energetics in the MPD of isomeric fluoropentanes

The multiphoton gas-phase HF elimination from 1-, 2- and 3-fluoropentanes (1FP, 2FP and 3FP) has been studied; 1FP does not react. The conversion per flash for 3FP is 1000 times greater than that for 2FP. The average excitation energies for 3FP and 2FP are 125 and 110 kcal/mole, respectively; the 3FP undergoes secondary reaction. The difference in photophysical properties of 2FP and 3FP can be used as the basis for a purification technique.     

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.     

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.     

The mass spectra of isomeric hydrocarbons—I: Norbornene and nortricyclene; The mechanisms and energetics of their fragmentations

The mass spectra of norbornene, nortricyclene and deuterium labeled derivatives thereof have been studied. The appearance potentials of the ions [C₇H₁₀]^+·, [C₇H₉]⁺, [C₆H₇]⁺ and [C₅H₆]^+· have been determined for both compounds and heats of formation of the hydrocarbons have been estimated. Detailed fragmentation schemes are proposed for the molecular ions and it is concluded that they dissociate by essentially different mechanisms which do not involve common intermediates. The structures and energy contents of the primary fragment ions are discussed in detail by comparing energetics, labeling experiments and metastable ion abundances.     

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) 3. One step synthesis of 2,3-dihydro-4,1,6-benzoxadiazonine-5,7-(1H,6H)diones

Reactions of N-haloalkylisatoic anhydrides with amines to produce piperidinobenzamides ( 2 ), pyrrolidinobenzamides ( 4 and 5 ), and 2,3-dihydro-6-methyl-4,1,6-benzoxadiazonine-5,7-(1H,6H)diones ( 10 ) are described. Spectral data are also discussed.     

Molecular energetics of cytosine revisited: a joint computational and experimental study

A static bomb calorimeter has been used to measure the standard molar energy of combustion, in oxygen, at T = 298.15 K, of a commercial sample of cytosine. From this energy, the standard (p degrees = 0.1 MPa) molar enthalpy of formation in the crystalline state was derived as -(221.9 +/- 1.7) kJ.mol(-1). This value confirms one experimental value already published in the literature but differs from another literature value by 13.5 kJ.mol(-1). Using the present standard molar enthalpy of formation in the condensed phase and the enthalpy of sublimation due to Burkinshaw and Mortimer [J. Chem. Soc., Dalton Trans. 1984, 75], (155.0 +/- 3.0) kJ.mol(-1), results in a value for the gas-phase standard molar enthalpy of formation for cytosine of -66.9 kJ.mol(-1). A similar value, -65.1 kJ.mol(-1), has been estimated after G3MP2B3 calculations combined with the reaction of atomization on three different tautomers of cytosine. In agreement with experimental evidence, the hydroxy-amino tautomer is the most stable form of cytosine in the gas phase. The enthalpies of formation of the other two tautomers were also estimated as -60.7 kJ.mol(-1) and -57.2 kJ.mol(-1) for the oxo-amino and oxo-imino tautomers, respectively. The same composite approach was also used to compute other thermochemical data, which is difficult to be measured experimentally, such as C-H, N-H, and O-H bond dissociation enthalpies, gas-phase acidities, and ionization enthalpies.     

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.     

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.     

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.     

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).     

The chemistry of 2H-3,1-benzoxazine-2,4(1H)-dione (isatoic anhydride). 9. Synthesis of 2-arylquinoline alkaloids

A one-step synthesis of N-methyl-2-aryl-4-quinolone alkaloids is described. These compounds are readily prepared from the reaction of an N-methylisatoic anhydride with the lithium enolate of an acetophenone. By this method, the reaction of N-methylisatoic anhydride ( 5 ) or 5-methoxy-N-methylisatoic anhydride ( 7 ) with acetophenone produces the alkaloids N-methyl-2-phenyl-4-quinolone ( 1 ) and eduline ( 2 ) in 81% and 70% yield, respectively. An analogous reaction of 5 with 3,4-methylenedioxyacetophenone gives graveoline ( 3 ) in 63% yield whereas 7 and α-methoxyacetophenone affords japonine ( 4 ) in 61% yield.