Acetic acid derivatives acidity

In brief, suitable hydrolysis of ethyl acetoacetate derivatives will give mono-or di-alkyl substituted acetones or acetic acids. Tri-substituted acetones or acetic acids cannot be obtained moreover, the di-substituted acetones must... 

D) No general reaction can be cited for the preparation of crystalline derivatives of Class (iii). Triphenylamine, when nitrated in acetic acid with fuming nitric acid, gives tri-/>-nitrophenylamine, m.p. 280°. The presence of substituents in the phenyl groups may however complicate or invalidate nitration. 

Acetylation. Heat i g. of />-nitrophenol with 5 ml. of an acetic acid-acetic anhydride mixture under reflux for 15 minutes. Pour into water the solid acetate separates. Filter, wash with water and re-crystallise from ethanol m.p. 77 5°. This treatment usually leaves o-nitrophenol unchanged. The addition, however, of about 0 5 ml. of cone. H2SO4 to the acetylating mixture gives the o-derivative, m.p. 40°. 

The above diamines can alternatively be identified as their diacetyl derivatives. Heat under reflux 0 5 g. of the diamine with 3 ml. of acetic acid—NaOH solution will cause the separation of the diacetyl derivative. Recrystallise from ethanol. M.ps. of the diacetyl derivatives of 0-, m-, and />-phenylene diamine are 185 , 191 , and 304 respectively (p. 551). 

The alkylidene dimethone (dimedone) (I) upon boiling with glacial acetic acid, acetic anhydride, hydrochloric acid and other reagents frequently loses water and passes into a substituted octahydroxanthene or the anhydride (II), which often serves as another derivative. The derivatives (I) are soluble in dilute alkali and the resulting solutions give colourations with ferric chloride solution on the other hand, the anhydrides (II) are insoluble in dilute alkali and hence can easily be distinguished from the alkylidene dimedones (I). 

Suspend 0 25 g. of 2 4-dinitrophenylhydrazine in 5 ml. of methanol and add 0-4 0-5 ml. of concentrated sulphuric acid cautiously. FUter the warm solution and add a solution of 0 1-0-2 g. of the carbonyl compound in a small volume of methanol or of ether. If no sohd separate within 10 minutes, dUute the solution carefuUy with 2N sulphuric acid. CoUect the solid by suction filtration and wash it with a little methanol. RecrystaUise the derivative from alcohol, dUute alcohol, alcohol with ethyl acetate or chloroform or acetone, acetic acid, dioxan, nitromethane, nitrobenzene or xylene. 

Xanthylamides. Dissolve 0 25 g. of xanthhydrol in 3-5 ml. of glacial acetic acid if an oil separates (as is sometimes the case with commercial material), allow to settle for a short time and decant the supernatant solution. Add 0-25 g. of the amide, shake and allow to stand. If a crystalline derivative does not separate in about 10 minutes, warm on a water bath for a period not exceeding 30 minutes, and allow to cool. Filter oflF the solid xanthylamide (9-acylamidoxanthen) and recrystallise it from dioxan - water or from acetic acid - water, dry at 80° for 15 minutes and determine the m.p. 

Alkylation of the sodio derivative affords the C-substituted cyanoacetic ester, which when heated with dilute acid gives the mono-substitut acetic acid. 

Dissolve equimolecular amounts of the hydrocarbon and styphnic acid in the minimum volume of hot acetic acid and allow to cool. Filter oflf the crystalline derivative which separates, wash it with a little acetic acid and dry in the air. Determine the m.p. Recrystallise from acetic acid and again determine the m.p. 

The best results are obtained with freshly prepared xanthhydrol (reduction of xanthone with sodium amalgam. Section VII,16). Dissolve 0 -25 g. of xanthhydrol and 0 -25g. of the primary sulphonamide in 10 ml. of glacial acetic acid. Shake for 2-3 minutes at the laboratory temperature and allow to stand for 60-90 minutes. Filter oflf the derivative, recrystallise it from dioxan-water (3 1), and dry at room temperature under water pump suction for 30 minutes. 

Acetyl derivatives of aromatic amines may be prepared either witli acetic anhydride or acetic acid or with a mixture of both reagents. Primary amines react readily upon warming with acetic anhydride to yield, in the first instance, the mono-acetyl derivative, for example ... 

Boil a mixture of 10 g. (10 ml.) of o-toluidine and 38 g. (35 ml.) of acetic anhydride in a 75 or 100 ml. Claisen flask fitted with a reflux condenser (Fig. Ill, 28, 1, but with trap replaced by a calcium chloride or cotton wool guard tube) for 1 hour. Arrange the flask for distillation under reduced pressure (compare Fig. II, 20, 1) and distil acetic acid and the excess of acetic anhydride pass over first, followed by the diacetyl derivative at 152-153°/20 mm, some mono-acetyl-o-toluidine (1-2 g.) remains in the flask. The yield of diacetyl-o-toluidine is 14-15 g, it is a colourless, somewhat unstable hquid, which slowly sohdifies to yield crystals, m.p. 18°, To prepare the (mono-) acetyl-o-toluidine, warm a mixture of 5 g. 

An alternative procedure, more suitable for the preparation of somewhat larger quantities of the bromo derivative, is the following. Dissolve 10 g, of the compovmd in 10-15 ml. of glacial acetic acid, cautiously add 3-4 ml. of hquid bromine, and allow the mixture to stand for 15-20 minutes. Pour into 50-100 ml. of water, filter off the bromo compound at the pump, and wash with a httle cold water. Recrystallise from dilute alcohol. 

By oxidation of the methyl derivative of an aromatic hydrocarbon with a solution of chromic anhydride in acetic anhydride and acetic acid. The aldehyde formed is immediately converted into the (/m-diacetate, which is stable to oxidation. The diacetate is collected and hydrolysed with sulphuric acid, for example ... 

II II, 1st 1920 152-194 Carboxylic Acids Salts and Derivatives. Formic acid, 8. Acetic acid, 96. 

Without carbon, the basis for life would be impossible. While it has been thought that silicon might take the place of carbon in forming a host of similar compounds, it is now not possible to form stable compounds with very long chains of silicon atoms. The atmosphere of Mars contains 96.2% CO2. Some of the most important compounds of carbon are carbon dioxide (CO2), carbon monoxide (CO), carbon disulfide (CS2), chloroform (CHCb), carbon tetrachloride (CCk), methane (CHr), ethylene (C2H4), acetylene (C2H2), benzene (CeHe), acetic acid (CHsCOOH), and their derivatives. 

Six protective groups for alcohols, which may be removed successively and selectively, have been listed by E.J. Corey (1972B). A hypothetical hexahydroxy compound with hydroxy groups 1 to 6 protected as (1) acetate, (2) 2,2,2-trichloroethyl carbonate, (3) benzyl ether, (4) dimethyl-t-butylsilyl ether, (5) 2-tetrahydropyranyl ether, and (6) methyl ether may be unmasked in that order by the reagents (1) KjCO, or NH, in CHjOH, (2) Zn in CHjOH or AcOH, (3) over Pd, (4) F", (5) wet acetic acid, and (6) BBrj. The groups may also be exposed to the same reagents in the order A 5, 2, 1, 3, 6. The (4-methoxyphenyl)methyl group (=MPM = p-methoxybenzyl, PMB) can be oxidized to a benzaldehyde derivative and thereby be removed at room temperature under neutral conditions (Y- Oikawa, 1982 R. Johansson, 1984 T. Fukuyama, 1985). 

Trichloro- and 2,2,2-tribromoethoxycarbonyl (Tceoc and Tbeoc) protecting groups are introduced with the commercially available 2,2,2-trihaloethyl chloroformates. These derivatives are stable towards CrOj and acids, but can smoothly be cleaved by reduction with zinc in acetic acid at 20 °C to yield 1,1-dihaloethene and CO. Several examples in lipid (F.R. Pfeiffer, 1968, 1970) and nucleotide syntheses (A.F. Cook, 1968) have been described. 

The blocking and deblocking of carboxyl groups occurs by reactions similar to those described for hydroxyl and amino groups. The most important protected derivatives are /-butyl, benzyl, and methyl esters. These may be cleaved in this order by trifluoroacetic acid, hydrogenolysis, and strong acid or base (J.F.W. McOmie, 1973). 2,2,2-Trihaloethyl esters are cleaved electro-lytically (M.F. Semmelhack, 1972) or by zinc in acetic acid like the Tbeoc- and Tceoc-protected hydroxyl and amino groups. 

Diethyl 3-oxoheptanedioate, for example, is clearly derived from giutaryl and acetic acid synthons (e.g. acetoacetic ester M. Guha, 1973 disconnection 1). Disconnection 2 leads to acrylic and acetoacetic esters as reagents. The dianion of acetoacetic ester could, in prin-ciple,be used as described for acetylacetone (p. 9f.), but the reaction with acrylic ester would inevitably yield by-products from aldol-type side-reactions. 

Although turnover of the catalyst is low, even unreactive cyclohexane[526] and its derivatives are oxidatively carbonylated to cyclohexanecarboxylic acid using KiS Og as a reoxidant in 565% yield based on Pd(II)[527]. Similarly, methane and propane are converted into acetic acid in 1520% yield based on Pd(II) and butyric acid in 5500% yield [528],... 

Silyl enol ethers are other ketone or aldehyde enolate equivalents and react with allyl carbonate to give allyl ketones or aldehydes 13,300. The transme-tallation of the 7r-allylpalladium methoxide, formed from allyl alkyl carbonate, with the silyl enol ether 464 forms the palladium enolate 465, which undergoes reductive elimination to afford the allyl ketone or aldehyde 466. For this reaction, neither fluoride anion nor a Lewis acid is necessary for the activation of silyl enol ethers. The reaction also proceed.s with metallic Pd supported on silica by a special method[301j. The ketene silyl acetal 467 derived from esters or lactones also reacts with allyl carbonates, affording allylated esters or lactones by using dppe as a ligand[302]... 

The reduction of o-nitrophenyl acetic acids or esters leads to cyclization to oxindoles. Several routes to o-nitrophenylacetic acid derivatives arc available, including nitroarylation of carbanions with o-nitroaryl halides[2l,22] or trif-late[23] and acylation of o-nitrotoluenes with diethyl oxalate followed by oxidation of the resulting 3-(u-nitrophenyl)pyruvate[24 26]. 

One of the virtues of the Fischer indole synthesis is that it can frequently be used to prepare indoles having functionalized substituents. This versatility extends beyond the range of very stable substituents such as alkoxy and halogens and includes esters, amides and hydroxy substituents. Table 7.3 gives some examples. These include cases of introduction of 3-acetic acid, 3-acetamide, 3-(2-aminoethyl)- and 3-(2-hydroxyethyl)- side-chains, all of which are of special importance in the preparation of biologically active indole derivatives. Entry 11 is an efficient synthesis of the non-steroidal anti-inflammatory drug indomethacin. A noteworthy feature of the reaction is the... 

Benzoyl chloride and derivatives acylate 2-amino-4-aryithiazoles in dioxane in yields of 80 to 90% (249, 250). The location of the acyl group on the exocyclic N has been demonstrated by the fact that the benzoyla-tion product is identical to the benzamidothiazole synthesized from benzamide and 2-bromothiazole (251). 3-Indolyl acetic acid chloride (89) acylates 2-aminothiazole in pyridine (Scheme 62) (81). 

Boiling acetic acid converts 2-aminothiazole into the 2-acetamido derivative far more easily when catalytic amounts of diketene are added to the reaction mixture (277),... 

Halogenation of 2-aminothiazole and derivatives has been reported under a wide variety of experimental conditions in water (161, 405. 406) in aqueous acids (16. 172, 407, 408) in solvents such as chloroform (27. 172), carbon disulfide (162, 166. 320. 409). benzene (165), acetic acid (410-413, 1580). or hydrochloric acid (414) or in 20% sulfuric acid (415-417). 

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