Phthalaldehydes

The most widely appHed colorimetric assay for amino acids rehes upon ninhydrin-mediated color formation (129). Fluorescamine [38183-12-9] and (9-phthalaldehyde [643-79-8] are popular as fluorescence reagents. The latter reagent, ia conjunction with 2-mercaptoethanol, is most often used ia post-column detection of amino acids separated by conventional automated amino acid analysis. More recently, determiaation by capillary 2one electrophoresis has been developed and it is possible to determine attomole quantities of amino acids (130). 

Dich1oromethy1)-2-(trichioromethy1)henzene [2741-57-3] the end product of exhaustive side-chain chlorination of o-xylene (80) is an iatermediate ia the manufacture of phthalaldehydic acid [119-67-5]. 

In a similar manner, phthalazine or its alkyl- or aryl-substituted derivatives are obtainable from 1,2-diacylarenes (Scheme 76). Phthalaldehydic acid and its analogs are transformed by hydrazines into the corresponding phthalazin-l(2//)-ones. Phthalazin-l(2iT)-one itself is prepared from naphthalene by oxidation, subsequent treatment with hydrazine and decarboxylation as shown in Scheme 77 (55YZ1423,64FRP1335759). 4-Substituted phthalazin-l(2iT)-ones are prepared in a similar way from 2-acylbenzoic acids. 3-Hydroxyphthalides,... 

Phthalaldehyde [643-79-8] M 134.1, m 54-56°, 55.5-56°, 58°, b 83-84°/0.8mm. Purified by steam distillation better by using super heated steam (at 175-180°) and efficient cooling. The distillate is saturated with Na2S04 extracted exhaustively with EtOAc, dried (Na2S04), filtered and evaporated. The residue... 

Phthalaldehydic acid (o-formylbenzoic acid) gives the NMR spectra set 32. In what form does the compound actually exist ... 

Note If netilmicin is to be chromatographed alone it is recommended that the methanol content of the mobile phase be increased (e.g. to 23 -I- 7), in order to increase the value of the hRf. The detection limit for the substances in the application tested was more sensitive using DOOB reagent on RP layers than when NBD chloride, fluorescamine or o-phthalaldehyde were employed. The derivatives so formed were stable and still fluoresced after several weeks if they were stored in the dark. 

Dipping solution Make 0.1 g o-phthalaldehyde (phthaldialdehyde, OPA) and 0.1 ml 2-mercaptoethanol (2-hydroxy-l-ethanethiol) up to 100 ml with acetone. 

In the presence of 2-mercaptoethanol o-phthalaldehyde reacts with primary amines to yield fluorescent isoindole derivatives [20] ... 

For the detection of the ergot alkaloids 0.2 g o-phthalaldehyde in 100 ml cone, sulfuric acid ( ) [15] or buffer solution is employed as spray solution. Cysteine [11, 12, 15, 19] or sulfurous acid [17] is occasionally substituted for mercapto-ethanol. 

The reaction of ort/io-phthalaldehyde and a thiol compound with an amino acid to form an isoindole derivative can be used to enhance the detection sensitivity for the normally only weakly UV-detectable amino acid compounds, and to introduce an... 

The reaction of phthalaldehyde and diethyl oxydiacetate in the presence of potassium tert-butoxide gives, with hydrolysis of the ester function, 3-benzoxepin-2,4-dicarboxylic acid (2a).89 The reaction of the dimethyl ester lb gives dimethyl 3-benzoxepin-2,4-dicarboxylate (2 b) when... 

Methylenedioxy)phthalaldehyde was converted with dimethyl oxydiacetate to the corresponding 3-benzoxepin derivative 3.92... 

Benzoxepin (4) was obtained in 55% yield by the reaction of phthalaldehyde with the bis-ylide generated from the bis(triphenylphosphonium) salt prepared from bis(bromomethyl) ether and triphenylphosphane.93,94... 

Intermolecular Condensation of Phthalaldehyde with a-Activated Sulfides... 

Benzothiepins 2 can be synthesized by a double Knoevenagel condensation starting from phthalaldehydes I and diesters of thiodiglycolic acid, or diphenacyl sulfide.33-63 " 66 In principle, this is an extension of Hinsberg s synthesis of thiophenes (see Houben-Weyl, Vol. E6a, p 282) which employs 1,4-dialdehydes rather than 1,2-dicarbonyl compounds. 

The thermolabile, unsubstituted 3-benzothiepin (3) can be synthesized by a double Wittig reaction, in analogy to the Knoevenagel condensation (vide supra). This is achieved by condensation of phthalaldehyde with the bis(triphenylphosphonium) salt of bis(bromomethyl) sulfide in the presence of lithium methoxide as base at — 30"C.68... 

Base-catalyzed condensation of 2-iminoindane-2-carbonitrile (62) with phthalaldehyde affords indeno[2,l-c]-2-benzazepine-5-carbonitrile (63) in excellent yield (95%),97 which is identical to an uncharacterizcd byproduct obtained earlier98 by condensing benzene-1,2-diacetonitrile with phthalaldehyde in the presence of sodium methoxide. The naphthalene analog 64 is prepared by condensing naphthalene-2,3-dicarbaldehyde with the indanecarbonitrile 62 under similar conditions. 

The first synthesis of a 3//-3-benzazepine, e.g. 65 (R1 = R2 = Me), was achieved by the condensation of phthalaldehyde with a bis[(alkoxycarbonyl)methyl]methylamine.24"25 With sodium methoxide as the base, A%V-bis[(methoxycarbonyl)methyl]pheiiylaniine condenses with the dialdehyde in a similar manner to give dimethyl 3-phenyl-3//-3-benzazepine-2,4-dicar-boxy late (65, Rl — Ph R2 — Me).99 However, replacement of methoxide by potassium tert-butoxide results in formation of 3-phenyl-3//-3-benzazepine-2,4-dicarboxylic acid (65, R1 = Ph R2 = H).25... 

Phthalaldehyde Acid (16, 68) By chlorination of phthalide, followe by hydrolysis with boiling water and crystallization from benzene. Austin and Bousquet, U. S. pat. 2,047,946 [C. A. 30,6on (rg36)]. 

Another reagent that readily forms fluorescent derivatives with primary amines is o-phthalaldehyde (trade name "Fluoropa"). The reaction proceeds in aqueous solution in the presence of a mercaptan at a pH of 9-11 producing an isoindole. 

The derivatives have an optimum fluorescence at an excitation wavelength of 340 nm and an emission wavelength of 455 nm. The adduct is relatively stable at a pH of 9-11 but it rapidly degrades to a non-fluorescent residue at low pH values. Consequently, when used as a pre-column derivatizing reagent the pH of the mobile phase should be kept fairly high, o-phthalaldehyde has been employed for derivatization in the analysis of dopamine (29), catecholamines (30) and histamines (31). 

The initial discoveries of the extension of the aromatic ring of the ortho-phthalaldehyde (OPA) to a naphthalene-2,3-dicarboxaldehyde (NBA) and the substitution of cyanide (CN ) for 2-ME as the nucleophile have provided the Center with a much more versatile reagent system (5,11), which maintains the sensitivity for primary aliphatic amines and amino acids, and now is known to form fluorescent products with oligopeptides, proteins, and other related analytes that possess a primary amine function (Equation 1). 

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