Barbituric acid amination

The ZwKKER reaction involving Co salts is frequently used for the detection of barbituric acid derivatives [31-35], but some purine, pyridine and piperidine derivatives and heterocyclic sulfonamides also yield colored derivatives. The Zwkker reaction is particularly sensitive when it is possible to form a tetrahedral complex [Co(Barb)2 Xj] (X = donor ligand, e.g. amine) [4]. 

Alkyl and 1-aralkyl-5,6-dihydrouracils (LXXIX), prepared by condensation of A -(2-carbamoylalkyl)aralkylamines with urea or by treating a suitable primary amine with an ester of acrylic acid followed by cyanic acid, are CNS depressants and anticonvulsants [639, 640], as well as anti-inflammatory agents [641]. Such compounds are to be compared with the corresponding barbituric acid derivatives in which not more than one hydrogen in the 5-position is substituted, and also with barbiturates in which the 5,5-substituents are similar to the R and groups of the 5,6-positions here. 

The Knoevenagel reaction consists in the condensation of aldehydes or ketones with active methylene compounds usually performed in the presence of a weakly basic amine (Scheme 29) [116], It is well-known that aldehydes are much more reactive than ketones, and active methylene substrates employed are essentially those bearing two electron-withdrawing groups. Among them, 1,3-dicarbonyl derivatives are particularly common substrates, and substances such as malonates, acetoacetates, acyclic and cyclic 1,3-diketones, Meldrum s acid, barbituric acids, quinines, or 4-hydroxycoumarins are frequently involved. If Z and Z groups are different, the Knoevenagel adduct can be obtained as a mixture of isomers, but the reaction is thermodynamically controlled and the major product is usually the more stable one. 

More sensitive, and most frequently used, is the periodic acid-thio-barbituric acid assay devised by Warren22 and modified by Amin-off.107 122 In a reaction sequence initiated by periodate oxidation, the... 

The application of antibiotics as chiral selectors has resulted in the successful resolution of almost all types of neutral, acidic, and basic racemic molecule. These antibiotics have been used for the enantiomeric resolution of amino acids, their derivatives, peptides, alcohols, and other pharmaceuticals. The selectivities of the most commonly used antibiotic-based (vancomycin, teicoplanin, and ristocetin A) CSPs varied from one racemate to another and are given in Table 1. Vancomycin was used for the chiral resolution of amino acids, amines, amides, imides, cyclic amines, amino alcohols, hydantoins, barbiturates, oxazolidinones, acids, profens, and other pharmaceuticals. Teicoplanin was found to be excellent chiral selector for the enantiomeric resolution of amino acids, amino alcohols, imides, peptides, hydantoins, a-hydroxy and halo acids, and oxazolidinones, whereas ristocetin A is capable of chiral resolution of amino acids, imides, amino... 

The applications of re-acidic chiral stationary phases include the resolution of a-blockers and /1-blockers, amines, arylacetamine, alkylcarbinols, hydantoins, barbiturates, naphthols, benzodiazapines, carboxylic acids, lactams, lactones, phthaldehydes selenoids, and phosphorus compounds. Hyun et al. [16] achieved a chiral resolution of a homologous series of iV-acyl-x-(l-naphthyl )cthylaminc on AA(3,5-dinitrobenzoyl-(i )-phenylglycine and N-(3,5 - dini tr o ben zoy I)-(,S ) -1 c u c ine CSPs. The authors used hexane-2-propanol (80 20, v/v) as the mobile phase. Similarly, the scope of re-basic CSPs comprises the chiral resolution of / -blockers, amino acids, amines, diamines, amino phosphonates, naphthols, benza-diazapines, carboxylic acids, hydroxy acids, dipeptides, tripeptides, diols,... 

Tu and co-workers [101] reported the synthesis of a series of novel pyrimido [5,4-6][4, 7]phenanthroline-9,11(7/7,8/7,10/7,12//)-diones 55 via a microwave-assisted three-component reaction of barbituric acid, an aldehyde and quinolin-6-amine in DMF without any catalyst. The results suggest that aldehydes bearing electron-withdrawing groups have higher reactivity providing higher yields in shorter reaction times (Scheme 41). 

A one-pot efficient method for the synthesis of derivatives 67 and 68 by condensation reaction of barbituric acids, lH-pyrazol-5-amines and aldehydes under solvent-free conditions has been reported (Scheme 16) [39]. These products were evaluated in vitro for their antibacterial activities against E. coli (ATCC 25922), P. aeruginosa (ATCC 85327), Enterococcus faecalis (ATCC 29737), Bacillus subtilis (ATCC 465), Bacillus pumilus (PTCC 1114), Micrococcus luteus... 

Variations of the ketene aminal structure were also screened as extender candidates. Ketene acetals 7 give barbituric acid derivatives 8 in less than quantitative yields. (51 Additionally, the instability of ketene acetals in the presence of primary alcohols would limit their RIM utility. (6)... 

Treatment of 3-bromoethyl-l,3,4-oxadiazol-2(3//)-ones with primary amines gives 2-imi-dazolidinones <92JHC1081>. Benzofuroxan iV-oxide is transformed into benzimidazole. /V-oxide on treatment in basic medium with acetoacetic ester or barbituric acid (Scheme 189) <87JHC165,... 

Danielsson and Dolby280 showed that aminomethylation in the 1- and 3-positions was possible in both 5,5-diethyl- and 5-ethyl-5-phenylbarbituric acids when formaldehyde and morpholine were used as the reagents. Furthermore, Werner and Fritzsche281 found that 1-aminomethylated 5,5-disubstituted barbituric acids 105 [R = piperidinyl bis(2-chloroethyl)amine] have nonchelated NH groups and that a second aminomethylation is possible at the N-3 atom. 

Dialkylacetals of DMF react instantaneously and quantitatively with acids, amines, amides, barbiturates either in solution or directly by on-column derivatisation using a mixture of the analyte and reagent. Methyl and butyl derivatives can be prepared. There is a considerable range of derivatisation reagents available and the reader is referred to the literature and the reference texts quoted [47-49]. In addition, many suppliers of... 

DeaUylation. Amines are denuded of one or more allyl group(s) by the catalytic transfer to barbituric acid, which is a known allyl group scavenger. 

Ultraviolet speotroscopic studies with 5,5-disubstituted barbituric acids (44) indicated that in aqueous solutions, the dominant forms are either the dioxo tautomeric form (i.e., monolaotam in alkaline medium) or the trioxo tautomerio form (barbituric acid structure in acid medium). The acidity of barbiturates in aqueous solution depends on the number of substituents attached to barbituric acid. The 5,5-disubstituted barbituric acids, 5,5-disubstituted thiobarbituric acids, and 1,5,5-trisubstituted barbituric acids are relatively weak acids, and salts of these barbiturates are easily formed by treatment with bases. The pKa of 5,5-disubstituted barbituric acids ranges from 7.1 to 8.1 (44). The 5,5-disubstituted barbiturio aoids can undergo a second ionization, having pKa values in the range of 11.7 to 1 2.7. The alkali metal salts of the barbiturates coupled with their highly lipophilic character will cause chemical incompatibility reactions (precipitation) when these compounds are mixed with acid salts of weakly basic amines. 

The color intensity of the complex (Figure 3.10.4) is much smaller than the color intensity of complex (Figure 3.10.3), so in most assays based on the Parri methodology, an amine is added. Other structures of the complexes have been suggested, for example one in which one of the carbonyl groups adjacent to the nitrogen in the barbituric acid ring coordinates to the cobalt ion. 

Bult, A., The cobaltous amine reaction 1. The behaviour of the 5,5-disubsti-tuted barbituric acids, Pharmaceutisch Weekblad, 111, 157, 1976. 

Siegmund Gabriel (Berlin ii November 1851-22 March 1924), professor in Berlin, synthesised isoquinoline, discovered a preparation of primary amines by the action of potassium phthalimide on halides and acid hydrolysis of the resulting ester of phthalylglycocoll, synthesised pyrrolidine from S-chlorobutylamine and piperidine from co-chloramylamine, pyrimidine from barbituric acid, and quinazoline. ... 

Xylidine is used as a raw material in the production of riboflavin (vitamin B2), the synthesis of which is based on the condensation of 3,4-dimethylaniline with D-ribose to give the Schiff s base. By hydrogenation with Raney nickel and coupling the amine with benzenediazonium chloride followed by condensation with barbituric acid, riboflavin is obtained. 

Wang et al. [56] developed a one-pot iodine-catalyzed synthesis of benzo[/] pyrimido[4,5-6]quinoline derivatives 29 via a three-component reaction of benzal-dehydes, naphthalen-2-amine, and barbituric acid at room temperature in aqueous media (Scheme 10.22). The reaction was carried out in water at room temperature to avoid a ring-opening reaction. It was observed that no reaction occurred without using the catalyst. Then, reaction was attempted by changing the mol% of I2. The results showed that 5 mol% at room temperature in water was sufficient to push the reaction forward. Increas loading of the catalyst did not improve the yield to a great extent. 

These methods are highly sensitive and specific for cyanide determination. These methods are based on the formation of polymethine dyes, for the example benzidine-pyridine method is used. Also, the barbituric acid method can be recommended. One general procedure of determining CN with bromine-pyridine-aromatic amine is described below. 

Next, BrCN reacts with pyridine to yield glutaconic aldehyde. This aldehyde is condensed with an aromatic amine such as p-phenylenediamine [9,10], benzidine [11,12], barbituric acid, 2,4-quinolinediol, 2,5-piperazinedione and hydantoin [9-13] to form a red polymethine dye. The molar absorptivities at An x = 530 nm are 6.0 x 10 and 3.1 x 10 for benzidine and p-phenylenediamine, respectively. The probable mechanism of the reaction with p-phenylenediamine is explained by Botto et al. [10] ... 

Next, CNCl reacts with a pyridine-pyrazolone reagent to yield a color product. This product is condensed with another aromatic amine such as in the pyridine-barbituric acid, the pyridine-benzidine, or in the pyridine-p-phenylenediamine method. In the pyridine-pyrazolone method, the measured absorbance corresponds to the amoimt of cyanogen chloride produced in the reactions. 

---