Barbituric acids alkylated

Alkyl Bound to Carbon. These compounds may be considered as being derived by the substitution of an alkyl group for hydrogen in carbon compounds. Examples are alkylate for synthetic gasoline, ethylbenzene for styrene entering into the manufacture of plastics and rubber, and hexylres-orcinol, thymol, barbital, and other barbituric acid alkyl derivatives. 

These compounds are prepared m a manner analogous to that of barbituric acid itself Diethyl malonate is alkylated twice then treated with urea... 

Section 21 8 Alkylation of diethyl malonate followed by reaction with urea gives derivatives of barbituric acid called barbiturates, which are useful sleep promoting drugs... 

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... 

Early investigators adduced various kinds of chemical evidence in support of a monohydroxy-dioxo structure for barbituric acid (112) (a) reaction with diazomethane afforded a mono-O-methyl deriva- iye,i59,i6o barbituric acid and its 5-alkyl derivatives are much stronger acids than the 5,5-dialkyl derivatives, and (c) the 5-bromo and 5,5-dibromo derivatives have different chemical properties. - The early physical evidence also appeared to substantiate the monoenol structure, this formulation having been suggested for barbituric acid in 1926 on the basis of its ultraviolet spectrum and again in 1934, In the 1940 s, ultraviolet spectroscopic studies led to the suggestion of other monohydroxy and dihydroxy structures for barbituric acid, whereas its monoanion was assigned structure 113 (a clear distinction between ionization and tautomerism was not made in these papers). 

This subsection examines the hydrolytic stability of cyclic structures containing a ureido link. Schematically, ring closure can be achieved by N-alkylation or by /V-acylation of the second N-atom of the ureido moiety. The former results in the formation of, e.g., hydantoins and dihydropyrimidines. The latter ring closure leads to, e.g., barbituric acids. Taken together, cyclic ureides can also be regarded as ring structures that contain an imido function with an adjacent N-atom. We begin our discussion with the five-membered hydantoins, to continue with six-membered structures, namely dihydropyrimidines, barbituric acids, and xanthines. 

A variety of other carbon nucleophiles have been alkylated with alcohols including malonate esters, nitroaUcanes, ketonitriles [119, 120], barbituric acid [121], cyanoesters [122], arylacetonitriles [123], 4-hydroxycoumarins [124], oxi-ndoles [125], methylpyrimidines [126], indoles [127], and esters [128]. Selected examples are given in Scheme 35. Thus, benzyl alcohol 15 could be alkylated with nitroethane 147, 1,3-dimethylbarbituric acid 148, phenylacetonitrile 149, methyl-pyrimidine 150, and even f-butyl acetate 151 to give the corresponding alkylated products 152-156. 

By using the same catalytic system, alkylations of 1,3-dimethylbarbituric acid with alcohols were also accomplished (Scheme 5.31) [68]. The Cp lr-catalyzed alkylation using 2-iodobenzyl alcohol, followed by palladium-catalyzed carbon-carbon bond formation with allene, gave spirocyclic barbituric acid derivatives in a one-pot process. 

The [Cp IrCl2]2 and [IrCl(cod)]2 catalysts have also been used in the alkylation of barbituric acid [43] and nitroalkanes [44] with primary alcohols. 

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. 

Pentobarbital Pentobarbital, 5-ethyl-5-(2-amil)barbituric acid (4.1.13), is synthesized by methods analogous to that of amobarbital, the only difference being that the alkylation of... 

The alkylated barbituric acid 286 readily undergoes dehydration in cone. H2SO4 to produce the 6-methyl compound 287 (Equation 103) <1995H(41)937>. 

Curry, K. Novel amino carboxy alkyl derivatives of barbituric acid, WO 0179185. 

Friedel-Crafts reactions are almost unknown in pyridine and azine chemistry. Direct electrophilic alkylation in the pyrimidine 5-position can be carried out on pyrimidines with at least two strongly donating groups, and more readily with three such groups. Thus, a-haloketones and a-bromocarboxylic esters can be used for direct alkylation of 6-aminouracils (118), for example in the formation of (119). The 5-position can also act as the nucleophile for Michael additions (e.g. 118 — 120, where a subsequent elimination occurs) (92AHC(55)129). For similar reactions in barbituric acids see (85AHC(38)229). 

Alkylated barbituric acids, 6-chloro-a-methylcarbazole-2-aceticacid, 1-phenylethanol, 1-phenyl-1-propanol, dimethyl, 3,4,5,6-pentafluoro-benzyl alcohol, l-(2-naphthyl)-ethanol, 1 -(p-biphenyl)-ethanol Chirasil-Dex coated column, 0.15 pm... 

Using similar chemistry l,3-diaryl-2-thiobarbituric acid is acylated with chloroacetyl chloride in the presence of triethylamine. Subsequent (9-alkylation under the mildly basic conditions of sodium acetate yields the 5-oxo derivative <91H(32)907>. It is not necessary to use barbituric acid derivatives to accomplish synthesis of furopyrimidines. Other 6-oxopyrimidines serve well in developing analogues. For example, in a reaction similar to that described above, the acylated pyrimidine (215) undergoes cyclization to a 4-(substituted)amino compound (216) (Equation (74)) <92MI 707-03). 

The introduction of a third activating substituent facilitates nitration even more. Temperatures below 50°C with mixed acids are frequently successful with various combinations of alkyl, amino, and hydroxy substituents (OICB3362 57JCS2146 61JOC455 65JOC3153), and barbituric acids react very readily indeed, even to the extent of /pso-substitution at C-5 [01LA(315)259 05LA(339)37],... 

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