Carboxylates with

Carboxyl and nitrile groups are usually introduced in synthesis with commercial carboxylic acid derivatives, nitriles, or cyanide anion. Carbanions can be carboxylated with carbon dioxide (H.F. Ebel, 1970) or dialkyl carbonate (J. Schmidlin, 1957). 

Detergents are designed to be effective in hard water meaning water containing calcium salts that form insoluble calcium carboxylates with soaps These precipitates rob the soap of Its cleansing power and form an unpleasant scum The calcium salts of synthetic deter gents such as sodium lauryl sulfate however are soluble and retain their micelle forming ability even m hard water... 

Resorcinol carboxylation with carbon dioxide leads to a mixture of 2,4-dihydroxyben2oic acid [89-86-1] (26) and 2,6-dihydroxyben2oic acid [303-07-1] (27) (116). The condensation of resorcinol with chloroform under basic conditions, in the presence of cyclodextrins, leads exclusively to 2,4-dihydroxyben2aldehyde [95-01-2] (28) (117). Finally, the synthesis of l,3-bis(2-hydroxyethoxy)ben2ene [102-40-9] (29) has been described with ethylene glycol carbonate in basic medium (118), in the presence of phosphines (119). Ethylene oxide, instead of ethyl glycol carbonate, can also be used (120). 

Many of the chemical reactions used to modify lignosulfonates are also used to modify kraft lignins. These include ozonation, alkaline—air oxidation, condensation with formaldehyde and carboxylation with chloroacetic acid (100), and epoxysuccinate (101). In addition, cationic kraft lignins can be prepared by reaction with glycidjiamine (102). 

RTIX2 compounds, eg, dichlorophenyltaHium(III) [19628-33-2], can be obtained from the reaction of thaHic haHde or carboxylate with an organoboron compound (22) ... 

There are few examples of [5 + 1] cyclizations from pyrimidine intermediates. Two of these involve the chloropropionic ester (194), which gives the 5,6,7,8-tetrahydro-7-one (195) with ammonia (59JCS1849), and the cyclization of a 4-ethynylpyrimidine-5-carboxylate with ammonia to give a pyrido[4,3-. In a recent patent, 5-ethoxycarbonylpyrimidin-4-yl-j8 -alanine derivatives are cyclized with ammonia to pipemidic acid analogues (80GEP2903850). One-carbon pyrimidine [5 +1] syntheses are included in Section 2.15.5.5.1 above. 

The treatment of ethyl Af-methyl-5-oxo isoxazoline-4-carboxylate with NaOH generated ethyl Af-methylmonomalonamide. The reaction in the case of 3-unsubstituted derivatives... 

One aspect of carboxyl modification of particular interest is its replacement with other acidic functional groups. One of these, the replacement of the carboxyl with a 5-tetrazolyl group, is of particular interest because of the resultant improved antibacterial properties. This transformation is shown in Scheme 20 (78USP4115385). 

Perfluoroalkyl iodides can be directly carboxylated with zinc and carbon dioxide under ultrasonic conditions [39] (equation 45) or by the reaction of perfluoroalkyl iodides with carbon dioxide with a zinc-copper couple in DMSO [57] (equation 46) Alkylation of the intermediate carboxylate gives the corresponding ester [52]... 

Homogeneous methanol carboxylation with I /Rh catalyst (175-195°C, 30atm), this is now a leading route to acetic acid ... 

Treatment of alkyl 9-benzyloxycarbonyl-3-methyl-6-oxo-2/7,6//-pyr-ido[2,l-f ][l,3]thiazine-4-carboxylates with BBr3 in CH2CI2 at -70 °C for 0.5-1 h and at room temperature for 3h yielded 9-carboxyl derivatives. The decarboxylation of these acids was unsuccessful. Hydrolysis of diethyl cA-3,4-H-3,4-dihydro-3-methyl-6-oxo-2//,6//-pyrido[2,l-f ][l,3]thiazine-4,9-dicarboxylate in aqueous EtOH with KOH at room temperature for 3 days yielded 4-ethoxycarbonyl-3,4-dihydro-3-methyl-6-oxo-2//,6//-pyrido-[2,l-f ] [1,3]thiazine-9-carboxylic acid (00JCS(P1)4373). Alkyl 9-hydroxy-methyl-3-methyl-6-oxo-3,4-dihydro-2//,6//-pyrido[2,l-f ][l,3]thiazine-4-car-boxylates were O-acylated with AC2O and (PhC0)20 in pyridine at room temperature for 12-48h. 

Selective hydrolysis of the 3-carboxylate with 6N-HCl/AcOH was unsuccessful and instead the 4-carboxylate hydrolyzed to the corresponding acid, however, heating of 432 at 50 °C caused its hydrolysis and decarboxylation in one step. Subsequent reaction with either MnO or DDQ gave 433. The fluorine atom at 8-position could be replaced by cyclic amines to give the 8-pyrrolyl or 8-[l-methyl-4-piperazinyl] derivatives 436 which upon hydrolysis using either acidic or basic conditions afforded the... 

Treatment of ethyl 10-methylthio-9-fluoro-3-methyl-2,3-dihydro-7-oxo-7//-pyrido[l,2,3- 7e]-l,4-benzoxazine-6-carboxylate with oxone in aqueous MeOH at 0°C afforded 10-methylsulfonyl derivative (99H(51)1563). Methylthio group in a 7-(4-methylthiophenyl)-5-oxo-2,3-dihydro-5//-pyrido[l,2,3- 7e]-l,4-benzoxazine-3-carboxamide was oxidized to a sulfoxide and a sulfone group (OOMIPl). 

Reaction of 9,10-difluoro-7-oxo-2,3-dihydro-7//-pyrido[l, 2,3- e]-1,4-ben-zothiazine-6-carboxylic acid and its ethyl ester with B(OH)3 in AC2O in the presence of ZnCl2 afforded 6-[(diacetoxyboryl)oxycarbonyl] derivative 323 (R = OAc)], which was reacted with primary and cyclic amines to give 10-amino-9-fluoro-7-carboxylic acid derivatives 324 (97MI41, 98MI30). 6-[(Difluoroboryl)oxycarbonyl derivative 323 (R = F) was obtained from ethyl 9,10-difluoro-7-oxo-2,3-dihydro-7//-pyrido[l,2,3- fe]-l,4-benzothiazine-6-carboxylate with BF3-THF complex. Reaction of 323 (R = F) and 1-methylpiperazine in DMF at 50-60 °C and subsequent acidic hydrolysis afforded 7 (97MI1). 

Reaction of ethyl 7-bromo-8-fluoro-l-(2-bromo-l-methylethyl)-4-oxo-l,4-dihydroquinoline-3-carboxylate with MeNH2 yielded 10-bromo-A, 1, 3-trimethyl-7-oxo-2,3-dihydro-7//-pyrido[l,2,3-<7e]quinoxaline-3-carboxamide (OOMIPIO). 

Note that the first step in Figure 21.6—reaction of the carboxylate with ATP to give an acyl adenylate—is itself a nucleophilic acyl substitution on phosphorus. The carboxylate first adds to a P=0 bond, giving a five-coordinate phosphorus intermediate that expels diphosphate ion as leaving group. 

Carboxylic acids by carboxylation with formic acid, 46, 74 Catalyst, palladium (Lindlar), 46, 89 Chloramine, 46, 18... 

Trimethylsilyl l//-azepine-f-carboxylate (4), prepared in 71 % yield by treating methyl 17/-azepine-1 -carboxylate with iodotrimethylsilane in chloroform at 20°C, with methanol in pentane solution at — 78 °C undergoes slow hydrolysis to the bright-yellow 17/-azepine-l-carboxylic acid (5),9 which is also obtained, as the potassium salt, by the action of potassium /ert-butoxide on ethyl 17/-azepine-l-carboxylate.139 The acid is stable at —78°C for several days but in chloroform solution at 20 °C undergoes decarboxylation to 17/-azepine (6) accompanied by some decomposition. 17/-Azepine is stable for a few hours at — 78 C and has been characterized by 3H and l3CNMR spectroscopy. 

The product obtained by treating ethyl 17/-azepine-l-carboxylate with phenyllithium is 3-[hy-droxy(diphenyl)methyl]-37/-azepine, as determined by X-ray analysis.39... 

The effect of substitutents at the C3 and C6 positions of the azepine ring is much more dramatic in that they force the 1//-azepine into a competing [6 + 2] Tt-cydoaddilion at the Cl —Cl positions.6 1 In fact, at room temperature [6 + 2] cycloaddition by a kinetically controlled, non-concerted, ionic process appears to be dominant, since on treating a mixture of ethyl 3,6-dimethyl- and ethyl 2,5-dimethyl-l//-azepine-l-carboxylate with less than a molar equivalent of ethenetctracarbonitrile, only the [6 + 2] cycloadduct 10 of the 3,6-dimethyl-l//-azepine is formed. 

Attempts to effect cycloaddition of 1/7-azepines with 2//-pyran-2-one have failed however, the more electron-deficient inethyl 2-oxo-2/7-pyran-5-carboxylate undergoes slow addition with ethyl 1//-azepine-1-carboxylate to give a mixture of the [2 + 4] 32 and [6 + 4] 33 7t-cycload-ducts.260 In contrast, prolonged reaction of methyl 1 //-azepine-1 -carboxylate with the isomeric... 

In accordance with FMO theory predictions,273 C2 —C4is the preferred modeofcycloaddition of tricarbonyliron and -ruthenium complexes of methyl l//-azepine-l-carboxylate with ethenetetracarbonitrile,222,274 hexafluoroacetone,222 and 2,2-bis(trifluoromethyl)ethene-l,l-dicarbonitrile 222 however, with ethenetetracarbonitrile, tricarbonyl[f/4-l-(ethoxycarbonyl)-1/f-azepine]iron(0) (1) yields a 1 6 mixture of the predicted C2 —C4 exo-adduct 2 and the C2 — C7 [6 + 2] 7i-cycloadduct 3,222 the latter heing formed by rearrangement of the former.274 Mixtures of the two adducts are also obtained with the tricarbonyliron complexes of 3-acetyl-l//-azepine and its l-(ethoxycarbonyl) derivative.274... 

In sharp contrast to the uncomplexed l//-azepine, which yields a C4 — C5 adduct, the tricarbonyliron complex of ethyl 1 W-azepine-l-carboxylate with dimethyl l,2,4,5-tetrazine-3,6-dicar-boxylate furnishes the C2 —C3 adduct 4 in excellent yield.273 Likewise, cycloaddition with 2,3,4,5-tetrachlorothiophene 1,1-dioxide yields adduct S.131... 

Irradiation of complex 6 in the presence of ethyl acrylate provides the [6 + 2] 7t-adduct 9 as the single enrfo-diastereomer,276 which may also be obtained by heating a mixture of methyl l//-azepine-l-carboxylate with the ester in the presence of a catalytic amount of tricarbonyl(>]6-naphthalene)chromium(O).277... 

Treatment of ethyl 1 W-azepine-l-carboxylate with palladium(II) acetate in benzene, or in an aprotic solvent, results in ring contraction (see Section 3.1.2.4.) or ring opening (vide infra), respectively, however, with palladium(II) acetate in acetic acid ethyl 2,3-diacetoxy-2,3-dihydro-l//-azepine-l-carboxylate (6) is formed as the major product along with ( , )-hexa-2,4-dienedial.243... 

With Oxygen Nucleophiles Aziridine ring-opening of 111 (Scheme 3.42) with water in the presence of a catalytic amount of TsOH gave the corresponding (3-hydrox-yphenylalanine derivative 121 in 72% yield as the major isomer [74], Treatment of N-(p-tolylsulfmyl) aziridine-2-carboxylates with TFA and subsequent aqueous workup resulted in the formation of j3-substituted serine derivatives [62, 63, 101]. Under these reaction conditions, not only was the aziridine ring opened, but also the N-sulfmyl group was removed treatment of 122 (Scheme 3.43) with TFA at 73 °C, for example, afforded 123 in 75% yield [101],... 

Ring-opening of aziridine-2-carboxylates with alcohols has been reported to give (3-alkoxy-a-amino esters [16, 102]. Treatment of as-aziridine 127 (Scheme 3.45) with alcohol in the presence of a catalytic amount of boron trifluoride etherate afforded P-alkoxy-ot-amino esters 128 in 57-100% yields [16,102a], The reaction is both regio- and stereoselective, affording 128 as the only product. 

The methanol can be removed by heating gently in vacuo. Similar compounds can be made with other carboxylate groups, either by using this method or by heating the acetate with excess carboxylic acid. Treatment of the anhydrous carboxylate with various neutral ligands (L) or anionic donors (X-) forms Rh2(OCOR)4L2 and [Rh2(OCOR)4X2]2-, respectively. The colour of the adduct depends on the donor atom in L (or X) ... 

Alkanesulfonates are the petrochemically derived sulfur analogs of soaps, which are alkane carboxylates based on renewable resources. The main difference between alkanesulfonates and soaps is, however, that alkanesulfonates consist of a rather complex mixture of homologs with different carbon chain lengths and isomers with an almost statistical distribution of the functional group along the hydrophobic carbon chain (Fig. 1), whereas soap is a mixture of homologs of alkane 1-carboxylates with an even number of carbon atoms. 

A dissertation from 1943 [2] describes an interesting investigation concerning synthesis and properties of pure ether carboxylates. With metallic sodium and chloroacetic acid ethyl ester followed by saponification, ether carboxylates were made with the general formula... 

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