Alkoxycarbonyl preparation

Olah s original preparative nitrations were carried out with mixtures of the aromatic compound and nitronium salt alone or in ether, and later with sulpholan as the solvent. High yields of nitro-compounds were obtained from a wide range of aromatic compounds, and the anhydrous conditions have obvious advantages when functional groups such as cyano, alkoxycarbonyl, or halogenocarbonyl are present. The presence of basic fimctions raises difficulties with pyridine no C-nitration occurs, i-nitropyridinium being formed. ... 

The preparation and spectroscopic properties (infrared, ultraviolet, NMR) of iV-alkoxycarbonyl-N -(2-thiazolyl)thioureas (268) have been studied by the Nagano group (78, 264). These compounds react with bromine in acetic acid or chloroform to give 2--alkoxycarbonylimino-thiazolo[3,2-h]thiadiazolines (Scheme 162), whose structures were established by mass spectroscopy, infrared, NMR, and reactivity patterns (481). 

Pyridazinecarbohydrazides are prepared in the normal way from an ester or acid chloride and hydrazine or a substituted hydrazine, generally in good yields. Pyridazines with two ortho alkoxycarbonyl groups give cyclic hydrazides with hydrazine, which are pyridazinopyridazines. 

Problems arise in the preparation of substituted l//-azepines with (alkoxycarbonyl)nitrenes as nitrene attack on a mono- or disubstituted benzene ring is not generally regioselective, and with toluene, 04 34-136139 144 o- and p-xy ienes,134-139 p-cresoi,134 chlorobenzene104-134 136 and biphenyl,104 136 mixtures of 1//-azepine-1-carboxylates of undetermined composition are produced. 

Other Alkoxycarbonylating Reagents Prepared from 2-Hydroxyimino-2-phenylacetonitrile... 

A few hydrazides and thiohydrazides prepared with the aid of alkoxycarbonyl-imidazoles or thiocarbonylimidazoles are shown below 12261,12271... 

A rich family of 2-alkoxycarbonyl-l,3,2-oxazaphospholidine-2-oxides 179-181 was prepared from the reaction of camphor derived aminoalcohols 177 and 178 with either methoxycarbonyl phosphonic dichloride or ethyl dichlorophosphite followed by the reaction with methyl bromoacetate. The reaction with aminoalcohol 177a afforded the phosphorus epimers 179 and 180, in ratios from 1/1 to 12/1 depending on the iV-substituent which could be separated easily by column chromatography. The reaction with aminoalcohols 178a-c, however, gave a single epimer 181a-c in each case (Scheme 50) [81]. 

Hydroxycarbonylation and alkoxycarbonylation of alkenes catalyzed by metal catalyst have been studied for the synthesis of acids, esters, and related derivatives. Palladium systems in particular have been popular and their use in hydroxycarbonylation and alkoxycarbonylation reactions has been reviewed.625,626 The catalysts were mainly designed for the carbonylation of alkenes in the presence of alcohols in order to prepare carboxylic esters, but they also work well for synthesizing carboxylic acids or anhydrides.137 627 They have also been used as catalysts in many other carbonyl-based processes that are of interest to industry. The hydroxycarbonylation of butadiene, the dicarboxylation of alkenes, the carbonylation of alkenes, the carbonylation of benzyl- and aryl-halide compounds, and oxidative carbonylations have been reviewed.6 8 The Pd-catalyzed hydroxycarbonylation of alkenes has attracted considerable interest in recent years as a way of obtaining carboxylic acids. In general, in acidic media, palladium salts in the presence of mono- or bidentate phosphines afford a mixture of linear and branched acids (see Scheme 9). 

When Wacker-type reactions are performed under a CO atmosphere, the (3-H elimination pathway can be suppressed in favor of CO insertion and subsequent nucleophilic cleavage of the acyl metal species.399 This alkoxycarbonylation process has found widespread utility, particularly in the synthesis of five- and six-membered oxacyclic natural products. For example, the THF core of tetronomycin was prepared by the Pd-catalyzed alkoxycarbonylation of 4-alkenol derivatives (Equations (117) and (118)), where stereocontrol was achieved by utilizing either the directing ability of a free hydroxyl or the conformational bias imposed by a bulky silyl ether.420 Additional examples making... 

The alkoxycarbonylation reaction is also feasible with 6-exo-nng closure for the preparation of stereodefined THP rings. Using this process, the integral THP moieties of frenolicin B,428 leucascandrolide A,429 and phorboxazole A (Equation (119))430 431 have been prepared. All of these reactions occur with 2,6-m-selectivity, a rationale for which has been advanced by an analysis of chair-like transition states.431... 

Pd-catalyzed carbonylation of heteroaryl halides provides a quick entry to heteroaryl carbonyl compounds such as heteroaryl aldehydes, carboxylic acids, ketones, esters, amides, a-keto esters and a-keto amides. In addition, Pd-catalyzed alkoxycarbonylation and aminocarbonylation are compatible with many functional groups, and therefore, are more advantageous than conventional methods for preparing esters and amides [78],... 

Pd-catalyzed alkoxycarbonylation enables synthesis of a variety of heterocyclic esters that are otherwise not easily prepared. 5-Bromopyrimidine was transformed into 5-ethoxycarbonyl-pyrimidine in quantitative yield employing the Pd-catalyzed alkoxycarbonylation. The alkoxycarbonylation of 2-chloro-4,6-dimethoxypyrimidine, in turn, led to benzyl 4,6-dimethoxypyrimidine-2-carboxylate (112), whereas alkoxycarbonylation of 2-(chloromethyl)-4,6-dimethoxypyrimidine provided pyrimidinyl-2-acetate 113 [79]. 4,6-Dimethoxypyrimidines 112 and 113 are both important intermediates for the preparation of antihypertensive and antithrombotic drugs. 

A larger blue shift in fluorescence was observed for alkoxycarbonyl-substituted PTs 400 and 401. The polymers were prepared from 2,5-dibromo-substituted monomers by two methods (i) Ullmann reaction with Cu powder and (ii) Ni(0)-mediated polymerization (Scheme 2.63) [485]. Both polymers have similar molecular weights (Mn 3000), although the Cu-prepared polymers showed higher quality and lower polydispersity. PL emission maxima for the Cu-prepared polymers 400 and 401 were red-shifted, compared to the Ni-prepared polymers (by 13-15 nm ( 0.05 0.06 eV) in solution and 25-30 nm ( 0.08 O.lOcV) in films, Table 2.4). This demonstrates that the properties of the polymer depend on the preparation method and, consequently conclusions from small shifts of 0.05-0.1 eV in PL EL energies of the materials, prepared by different methods, should be made with care. 

Amino(alkoxycarbonyl)methylenemalonates (314) were also prepared in good yields in the reactions of dialkyl cyanoformate and bromo- or chloromalonates in the presence of SnCl2 or TiCl3 in benzene, or in the presence of zinc activated by copper in THF, [81JAP(K)71049, 81JAP(K)87542]. 

The first example of biphasic catalysis was actually described for an ionic liquid system. In 1972, one year before Manassen proposed aqueous-organic biphasic catalysis [1], Par shall reported that the hydrogenation and alkoxycarbonylation of alkenes could be catalysed by PtCh when dissolved in tetraalkylammonium chloride/tin dichloride at temperatures of less than 100 °C [2], It was even noted that the product could be separated by decantation or distillation. Since this nascent study, synthetic chemistry in ionic liquids has developed at an incredible rate. In this chapter, we explore the different types of ionic liquids available and assess the factors that give rise to their low melting points. This is followed by an evaluation of synthetic methods used to prepare ionic liquids and the problems associated with these methods. The physical properties of ionic liquids are then described and a summary of the properties of ionic liquids that are attractive to clean synthesis is then given. The techniques that have been developed to improve catalyst solubility in ionic liquids to prevent leaching into the organic phase are also covered. 

An interesting degenerate rearrangement was observed when in attempts to prepare the 5-diazomethyl-4-alkoxycarbonyl-l,2,3-thiadiazole (167) from its precursor, the tosylhydrazone 165 or the oxime 166, not 167 but the rearranged 5-(o -alkoxycarbonyldiazomethyl)-l,2,3-thiadiazole (168) was obtained (Scheme IV.65) [82TL1103 83JCS(CC)588]. 

The reaction between a phosphoramidothioate and N-chlorosulfenylcarbamate described in Figure 2 has been applied to methamidophos. In Figure 2, the reaction was used to derivatize a toxic me thyIcarhamate ester by a non-toxic phosphora-midothioate however, in the case of methamidophos the reaction was used to derivatize a toxic phosphoramidothioate with a nontoxic carbamate moiety. The IJ-alkoxycarbonyl-IJ -alkylamino-sulfenyl derivatives of methamidophos thus prepared, where R... 

However, the real breakthrough came with the drastically facilitated preparation of 1-cyclopropylcyclopropanol (15) from methyl cyclopropanecarboxylate (19) applying the transformation of an alkoxycarbonyl group into a cyclopropanol fragment with ethylmagnesium bromide in the presence of Ti(zPrO)4 as developed by Kulinkovich et al. [13]. The optimized conversion of the alcohol 15 to the bromide 16 and its dehydrobromination makes the alkene 1 available in synthetically useful quantities of 40 -55 g within one week (Scheme 3) [ 14]. This sequence is also applicable to prepare substituted, especially spirocyclopropane-annelated, bicyclopropylidenes [ 14a]. 

Al-(Alkoxycarbonyl) 0-(arenesulfonyl)hydroxylamines [alkyl Af-(arenesulfonyloxy) carbamates] 3i-o can be easily obtained by sulfonylation of commercially available iV-(alkoxycarbonyl)hydroxylamines (alkyl V-hydroxy carbamates). Af-(Alkoxycarbonyl) hydroxylamines can be also prepared from hydroxylamine and alkyl chloroformate . ... 

N-Acylation and 3-alkoxycarbonylation reactions may be achieved by conventional acylation procedures. A variety of 3-acyl derivatives 157 can be prepared most conveniently by the treatment of DPPOx 266 with carboxylic acids in the presence of a tertiary amine. tert-Butoxycarbonyl (Boc-Ox, 236) and benzyloxy carbonyl (Cbz-Ox, 267) (Cbz = benzyloxycarbonyl) compounds are of practical use for introduction of nitrogen protecting groups. ... 

Finally, cationic ring-opening polymerization of 2-aIkoxy-5(4//)-oxazolones has been used to prepare poly iV-alkoxycarbonyl amino acids. The polymerization was found to be dependent on the nature of the amino acid side chain and the substituent on C-2. 

A Pd-catalyzed alkoxycarbonylation of 2-chloropyridine 117 to ester 118 was reported in the synthesis of camptothecin analogs <97JOC6588>. Another Pd-catalyzed alkoxycarbonylation was the central feature in Hibino s total synthesis of oxopropaline G (121), a P-carboline isolated from Streptomyces sp G324 <98TL2341>. Triflate 119 was prepared from 2-foimyl-3-iodoindole in seven steps. The Pd-catalyzed alkoxycarbonylation of 119 provided the key intermediate, l-methoxycarbonyl-4-methylcarboline 120, which was then transformed to oxopropaline G (121) in four additional steps. 

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