Synthesis barbiturates

Any combination of two carbonyl or other electron-withdrawing groups will do this reaction. Compound 69 was needed for a barbiturate synthesis. As cyanide is very anion-stabilising, disconnection gives the ketone 70, whose synthesis will be discussed in chapter 30, and the nitrile 71. The synthesis was straightforward once the right conditions had been found.12... 

Diethyl malonate has uses other than m the synthesis of carboxylic acids One particu larly valuable application lies m the preparation of barbituric acid by nucleophilic acyl substitution with urea... 

Beryllium, calcium, boron, and aluminum act in a similar manner. Malonic acid is made from monochloroacetic acid by reaction with potassium cyanide followed by hydrolysis. The acid and the intermediate cyanoacetic acid are used for the synthesis of polymethine dyes, synthetic caffeine, and for the manufacture of diethyl malonate, which is used in the synthesis of barbiturates. Most metals dissolve in aqueous potassium cyanide solutions in the presence of oxygen to form complex cyanides (see Coordination compounds). 

Barbituric acid — see also Pyrimidine-2,4,6-trione, perhydro-acidic pK, 3, 60 bromination, 3, 70 fluorination, 3, 70 structure, 3, 68 tautomerism, 2, 27 in thermography, 1, 392 Barbituric acid, iV-alkyl-chlorination, 3, 70 Barbituric acid, 5-aminomethylene-synthesis, 3, 524 Barbituric acid, 5-arylidene-pyridopyrimidines from, 3, 227 Barbituric acid, 1,3-dicyclohexyl-synthesis, 3, 113 Barbituric acid, 2-thio-sensitizing dye... 

The final step in the synthesis of all barbiturates consists in either condensation of a suitably substituted malonic or cyano-acetic ester with urea by means of sodium ethoxide (scheme a) or... 

Cyclization of the two pendant alkyl side chains on barbiturates to form a spiran is consistent with sedative-hypnotic activity. The synthesis of this most complex barbiturate starts by alkylation of ethyl acetoacetate with 2-chloropentan-3-one to give 152. Hydrolysis and decarboxylation under acidic conditions gives the diketone, 153. This intermediate is then reduced to the diol (154), and that is converted to the dibromide (155) by means of hydrogen bromide. Double Internal alkylation of ethyl... 

The one-pot MCR of methylene active nitriles 47 has been used in the synthesis of both pyrano- and pyrido[2,3-d]pyrimidine-2,4-diones in a single-mode microwave reactor [90]. Microwave irradiation of either barbituric acids 61 or 6-amino- or 6-(hydroxyamino)uracils 62 with triethyl-orthoformate and nitriles 47 (Z = CN, C02Et) with acetic anhydride at 75 °C for 2-8 min gave pyrano- and pyrido[2,3-d]pyrimidines in excellent yield and also provided a direct route to pyrido[2,3-d]pyrimidine N-oxides (Scheme 27). 

The synthesis of bis(triazine) molecules capable of acting as synthetic receptors for barbiturate guest molecules has been described <06EJO1444>. 

The manufacture of P.Y.139 may serve as an example for the synthesis of a me-thine pigment. P.Y.139 is the condensation product of diiminoisoindoline with 2 moles of barbituric acid [18]. 

Bassani has reported the substrate-templated photochemical synthesis of barbituric acid receptors by irradiating a solution of olefin 104 in the presence of template 105 (see Scheme 49) [122]. In the absence of such template, the major cycloadducts formed are the head-to-head (106) and head-to-tail dimers (107) (see Scheme 49). However, in the presence of barbituric acid, the distribution of products changes and the head-to-head cycloadduct is formed in higher proportions than the rest. 

Synthesis of Immunogen (Hapten) The barbiturate, 5-ally 1-5-(1-carboxyisopropyl) barbituric acid (I) is first converted to 5-allyl-5-(1 -p-n i trophenyloxycarbonylisopropyl) barbituric acid (II) by the interaction of the base with /7-nitrophenol in N, N-dimethylformamide (DMF) as shown below ... 

It would be extremely tedious for you to read the synthesis of all the barbituric acid derivatives that exist today, so I will limit you to the more widely used and important ones. I have grouped the listed barbiturates by their clinical action and the duration of that action. 

These are made from urea much like the barbiturates. The formula for urea (given below) can be used to make any of the drugs requiring it for their synthesis. However, it must be dried for those formulas requiring dry or anhydrous urea. This can be accomplished by distillation and shaking with a drying agent. It can also be purchased, but the DBA will be notified. 

The first positive results in the synthesis of these heterocyclic compounds by MCR of aminoazoles, aldehydes, and barbituric acids were published in 2008 by Shi et al. [111]. They also used green chemistry methodology and carried out treatment of the starting materials in water under microwave irradiation. The temperature optimization procedure and search for the best catalytic system allowed selecting one equivalent of p-TSA and 140°C as optimum conditions for the synthesis. With application of the procedure elaborated 24 novel pyrazolopyr-idopyrimidines 76 were generated (Scheme 33). 

Interestingly enough, a closely related protocol was successfully proposed for the synthesis of spirooxindoles-containing tetrahydrochromene skeletons when aromatic aldehydes were switched for isatin derivatives. This high-yielded reaction was performed with dimedone, 4-hydroxycoumarin, or barbituric acids in water using triethylbenzylammonium chloride (TEBA) as catalyst (Scheme 36) [125]. A Knoevenagel condensation occurred first between isatin and malonitrile derivative, followed by Michael addition of 1,3-dicarbonyl substrates and cyclization to the cyano moiety. 

An interesting entry to functionalized dihydropyrans has been intensively studied by Tietze in the 1990s using a three-component domino-Knoevenagel Hetero-Diels-Alder sequence. The overall transformation involves the transient formation of an activated heterodienophile by condensation of simple aldehydes with 1,3-dicarbonyls such as barbituric acids [127], Meldrum s acid [128], or activated carbonyls. In situ cycloaddition with electron-rich alkenes furnished the expected functionalized dihydropyrans. Two recent examples concern the reactivity of 1,4-benzoquinones and pyrazolones as 1,3-dicarbonyl equivalents under microwave irradiation. In the first case, a new three-component catalyst-free efficient one-pot transformation was proposed for the synthesis of pyrano-1,4-benzoquinone scaffolds [129]. In this synthetic method, 2,5-dihydroxy-3-undecyl-1,4-benzoquinone, paraformaldehyde, and alkenes were suspended in ethanol and placed under microwave irradiations to lead regioselectively the corresponding pyrano-l,4-benzoquinone derivatives (Scheme 38). The total regioselectivity was... 

Muravyova EA, Shishkina SV, Musatov VI, Knyazeva IV, Shishkin OV, Desenko SM, Chebanov VA (2009) Chemoselectivity of multicomponent condensations of barbituric acids, 5-aminopyrazoles, and aldehydes. Synthesis 1375-1385... 

Bamiphylline, 426 Bamipine, 51 Barbital, 267, 268 Barbiturates, listing, 268, 269 Baroreceptors, 54 Bayer-Villiger lactone synthesis, 28, 31... 

The barbiturates were widely used as sedative-hypnotic drugs. Barbital was introduced as a drug in 1903. The method of synthesis for thousands of its analogs has undergone little change. Urea reacts with various derivatives of malonic acid, usually a diethyl ester of a dialkyl substituted malonic acid. This is a classic example of a nucleophilic acyl substitution. A derivative of ammonia reacts with esters to form an amide, only in this case a cyclization to a strainless six-membered ring results because of the proximity of the bifunctionality. 

Barbiturates generally increase the synthesis of porphyrin and intermittent porphyria is therefore an absolute contraindication for their use. 

Diesters are malonates, and are often used for the synthesis of barbiturates. Malonyl dichlorides can be used in place of a malonyl diesters, in which case the reaction can be performed at room temperature, as demonstrated by the synthesis of A-phenyl and A -pyridyl 2-thiobarbituric acids 666 from malonyl dichloride 664 and A, iV -diarylureas 665 <2002AJC287>. 

Humanity s centuries-old, avid search for substances that would relieve these conditions has resulted in a progression from alcohol to opiates to the synthesis of bromides and barbiturates. Each of these, however, shares treatment-limiting and potentially life-threatening disadvantages, including the following ... 

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