Sodium substituted derivatives

In general, condensation takes place at the a-carbon atom, leading to simple cinnamic acids or to their a-substituted derivatives. When possible, the anhydride corresponding to the sodium sail should be the condensing agent. 

Substitution Derivatives of Ethyl Malonate, Ethyl malonate resembles ethyl acetoacetate in that it gives rise to mono- and di-substituted derivatives in precisely similar circumstances. Thus when ethanolic solutions of ethyl malonate and of sodium ethoxide are mixed, the sodium derivative (A) of the enol form is produced in solution. On boiling this solution with an alkyl halide, e.g, methyl iodide, the methyl derivative (B) of the keto form is obtained. When this is treated again in ethanolic solution with sodium ethoxide, the... 

Barbituric acid and 2-thiobarbituric acid are readily prepared by the condensation of diethylmalonate with urea and thiourea respectively, in the presence of sodium ethoxide. The use of substituted derivatives of urea and thiourea and of diethyl malonate will clearly lead to a wide range of barbituric and thiobarbituric acids having substituents in the i, 3, or 5 positions. 

The mono-alkyl C-substituted derivatives of ethyl acetoacetate upon treatment with sodium ethoxide and another molecule of alkyl halide afford the di-alkyl C-substituted products... 

Alkylation of A-4-thiazoline-2-one may yield O-R or N-R derivatives according to experimental conditions. With diazomethane in ethanol O-raethylation takes place (29. 36. 214). N-Methylation is reported when a basic solution of A-4-thiazoline-2-one reacts with methyl iodide or dimethylsulfate (21, 29, 215, 216), Reaction of l-chloro-2-dimethyl-aminoethane with the sodium salt of 4 R-A-4-thiazoline-2-one (91) in alcohol, first claimed to yield the aminoalkylether (217, 218), was shown after infrared investigation to give the N-substituted derivative (92) (107), even when R Ph (Scheme 45). More probably the site of reaction in... 

The imide proton N-3—H is more acidic than N-1—H and hence this position is more reactive toward electrophiles in a basic medium. Thus hydantoins can be selectively monoalkylated at N-3 by treatment with alkyl haUdes in the presence of alkoxides (2,4). The mono-A/-substituted derivatives (5) can be alkylated at N-1 under harsher conditions, involving the use of sodium hydride in dimethylform amide (35) to yield derivatives (6). Preparation of N-1 monoalkylated derivatives requires previous protection of the imide nitrogen as an aminomethyl derivative (36). Hydantoins with an increased acidity at N-1—H, such as 5-arylmethylene derivatives, can be easily monoalkylated at N-3, but dialkylation is also possible under mild conditions. 

Predict the products formed when each of the following isotopically substituted derivatives of chlorobenzene is treated with sodium amide in liquid ammonia. Estimate as quantitatively as possible the composition of the product mixture. The asterisk ( ) in part (a) designates C, and D in part (b) is H. 

Alkylation at the ind-N of l,2,3,4-tetrahydro-j8-carbolines has been carried out with alkyl halide after treatment with sodamide in the usual manner. Cyanoethylation of a p /r-V-substituted tetrahydro-jS-carboline in the presence of Triton B yields the corresponding 9-cyanoethyl derivative. Similarly, treatment of p / -V-methyl-l,2,3,4,4a,9b-hexahydro-y-carboline with sodamide, followed by benzyl chloride, leads to the ind-A -benzyl-substituted derivatives. l-Oxo-l,2,3,4-tetrahydro-j8-carboline yields the ind-A -methyl derivative directly with dimethyl sulfate.Prolonged treatment with sodium hydride, followed by methyl iodide, yields the 2,9-dimethyl derivative. Heating with sodium hydride in acetone followed by the addition of dimethyl sulfate gives rise to the ind-V-methyl derivative. ... 

Detailed investigations of the chemical reactivity of the diketiminato-stabilized phosphenium cations like 28 (Scheme 17) are to date rare and include only two reports dealing with the substitution and reduction of P-halogen-derivatives. Thus, reaction of 28 (X=Br) with sodium hydroxide in toluene was reported to proceed with displacement of the halide substituent at phosphorus and conservation of the heterocyclic ring to give a mixture of bromide and triflate salts containing a P-hydroxy-substituted cation, both of which were isolated in small yields [89], The products are remarkable as they represent one of very few examples of a stable phosphinous acid which does not rearrange to the tautomeric secondary phosphine oxide. Potassium reduction of the P-chloro-substituted derivative 34 produced the... 

Reaction of compound 37 with bromine in chloroform results in mono-bromination a to the sulfur. Treatment of this brominated derivative with NaBH3CN in AcOH gives a mixture of products resulting from reduction of the C=N double bond and of elimination of HBr. Reaction of 44 with sodium ethoxide results in the ethoxy-substituted derivative 45, whereas reaction with pyridine gives the dehydrobrominated derivative 46. Reaction of either 44 or 46 with sodium cyanide in dimethyl sulfoxide (DMSO) gives the cyano-derivative 47 <1983HCA971> (Scheme 13). 

The most efficient synthesis is based on the reaction of phthalic anhydride with the sodium salt of the pyrrole the intermediate acid after cyclization generally provides high yields of 206 and/or its substituted derivatives. Tetrachloro derivative 212 was prepared from tetrachlo-rophthalic anhydride via acid 211 by this procedure [90JCS(P 1) 1463 ]. 

Cyclocondensation of 2-aroylbenzoic acid 223 with hydrazine gave the phthalazine derivative 224, which was alkylated with ethyl chloroacetate in aqueous sodium hydroxide or pyridine to give the N-substituted derivative 225. Condensation of the latter with hydrazine afforded the hydra-zide 226, which could be cyclized to give the 2//[l,2,4]triazino[3,4-a]phthalazin-3(4tf)-one 227 (91MI3). 

Methyl a-D-glucopyranoside may be converted,271 in a remarkably selective reaction, into its 2,4,6-tribenzyl ether (in 62% yield) on treatment with three molar equivalents of sodium hydride in benzyl chloride at 110°, a substitution pattern that might have been predicted in view of the low, relative reactivity of HO-3 towards alkylation in the mechanistically related, Haworth procedure.268 Similar, selective benzylations have also been achieved on partially substituted derivatives of methyl a- and /3-D-galactopyranoside272 and on methyl 6-deoxy-a-L-galactopyranoside62 in all of these, an unexpectedly high relative-reactivity of HO-4 (ax) compared to that of HO-3 (eq) was noted, indicating that steric factors are not the sole influence on reactivity in these cases. Nevertheless, the primary hydroxyl... 

The coupling of Naphtol AS or its phenyl-substituted derivatives with diazonium salts from variously substituted anilines in aqueous alkaline solution (section 4-11) gave incomplete reactions and impure products in some instances, probably because these coupling components have inadequate solubility in aqueous media. Pure dyes in ca. 90% yields were obtained by reaction in dimethylformamide in the presence of sodium acetate. Metallisation of these o,o -dihydroxyazo ligands with sodium chromium salicylate or a cobalt(II) salt gave metal-complex dyes in 80-100% yields [22]. Specific structural isomers of these complexes were identified by i.r., n.m.r., Raman and UV/visible spectroscopy [23]. 

Thiourea and its /V-substituted derivatives readily reacted with EMME in hot ethanolic sodium ethoxide to yield 2-thiopyrimidine-5-carboxylates (219) (42JA794 56JA5294), With N-substituted thiourea, as in the case of -substituted urea, the primary amino group was first involved in the reaction. 

TPPS (sodium salt) was obtained from Strem Chemicals and used as received. TTAP and some of its metal-substituted derivatives were kindly by Dr. E. Ojadi of Brandeis University. The other porphyrins used in this study were synthesized following published procedures (14,U). 

Curiously, however, reaction of the dialdehyde (94b) with ethyl nitroacetate under practically identical conditions — aqueous ethanol in the presence of sodium acetate and sodium carbonate at pH 8.6 — takes a different course. The compound, isolated in 34% yield, constitutes a monoaddition product to one aldehyde group, as evidenced by the formation of a triacetate after hydrogenation and acetylation. It has been assigned structure (95) 5 ) and, as such, is a C-substituted derivative of the hemialdal form (94a) of the dialdehyde. Though some NMR data were cited as proof of this formulation 58) two alternatives, (96) and (97) respectively, cannot be ruled out. Of these, structure (97) derived from... 

The 2-aminoquinazolines 259 were prepared in two independent ways. The 2-quinazolinone 258 was transformed to 2-aminoquinazoline 259 by treatment with phosphorus oxychloride and subsequently with sodium amide in liquid ammonia, or with phosphorus pentachloride under carefully controlled conditions [75JCS(P1)1471]. Attempts to prepare the N-substituted derivatives failed, but the reaction was successful with the unsubstituted cis cyclopentane-fused homolog [76JCS(P1)1415]. 

Mononitrogen-substituted derivatives are obtained from sodium uracil and sulfenyl halides CF Cl3 SCl (w = 0, 1, 2) 49, 96) ... 

Reaction of sodium triazolide or 3-aminotriazolide with the bicyclic amine derivatives (48a) and (48b) gave the N(l) substituted derivatives (49a) and (49b) (Equation (17)) <92JMC2392>. 

From the above discussion it is evident that alkylation of 1,2,3-benzotriazin-4-one results almost entirely in substitution at Nj and/or Nj, and that alkylation on oxygen is at most a minor reaction. Alkylation of l,2,3-benzotriazine-4(3//)-thione (39, R = H), on the other hand, leads to predominant or exclusive substitution on sulfur, presumably as a result of the greater nucleophilicity of sulfur compared to oxygen. This difference in reactivity between the oxygen (10, R = H) and sulfur (39, R = H) compounds has been elegantly demonstrated by Murray and Vaughan. Treatment of the sodium salt of 10, R = H, with phenacyl bromide gives the Nj-substituted derivative 127, which, on... 

Azetidin-2-one can be synthesized by treating 1-ethoxy-1-hydroxycy-clopropane with aqueous sodium azide at pH 5.5 (Scheme 8.7a). This type of construction has wider applications and A-substituted derivatives are formed from 1-amino-1-hydroxycyclopropanes in two steps first A-chlorination with tert- miy hypochlorite [2-methylpropan-2-yl chlo-rate(I)], and then treatment with silver ion in acetonitrile (ethanenitrile) to release chloride ion and trigger ring expansion of the tricycle (Scheme 8.7b). 

The use of soluble metal catalysts makes it possible to react 8 and its substituted derivatives with aryl bromides and triflates at 100 °C. The catalyst systems that have been used are Pd2(dba>3 and ( )BINAP with calcium carbonate as base (dba = dibenz[ ,. ]anthracene, BINAP = 2,2-bis(diphenyl-phosphanyl)-l,l-binaphthyl)<2000JA2178>, and 2-(di-r-butylphosphino)biphenyltris(dibenzylideneacetone)palladium with sodium yt-butoxide as base <2003T3109>. 

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