Amide, sodium from amines

Pentafluoroaniline. Pentafluoroaniline [771 -60-8] i2is been prepared from amination of hexafluoroben2ene with sodium amide inbquid ammonia or with ammonium hydroxide in ethanol (or water) at 167—180°C for 12—18 h. It is weakly basic (p = 0.28) and dissolves only in concentrated acids. Liquid crystals have been prepared from Schiff bases derived from pentafluoroaniline (230). 

Caubere et al. [63, 64] treated 32a with sodium amide-sodium tert-butoxide (NaNH2-NaOtBu) in tetrahydrofuran (THF) in the presence of secondary amines and obtained enamines. Analogously, the corresponding thioenol ethers were formed from 32a and sodium amide-sodium thiolate in the presence or absence of NaOtBu. It was shown, however, that cyclohexyne rather than 6 is the decisive intermediate en route to the enamines as well as the thioenol ethers [63b, 64], As already mentioned above, the enol ether 41 arises inter alia from 32b and KOtBu in DMSO. The best yield (47%) was obtained in refluxing THF (Scheme 6.11) [60],... 

Reduction of amides to aldehydes was accomplished mainly by complex hydrides. Not every amide is suitable for reduction to aldehyde. Good yields were obtained only with some tertiary amides and lithium aluminum hydride, lithium triethoxyaluminohydride or sodium bis 2-methoxyethoxy)aluminum hydride. The nature of the substituents on nitrogen plays a key role. Amides derived from aromatic amines such as JV-methylaniline [1103] and especially pyrrole, indole and carbazole were found most suitable for the preparation of aldehydes. By adding 0.25 mol of lithium aluminum hydride in ether to 1 mol of the amide in ethereal solution cooled to —10° to —15°, 37-60% yields of benzaldehyde were obtained from the benzoyl derivatives of the above heterocycles [1104] and 68% yield from N-methylbenzanilide [1103]. Similarly 4,4,4-trifluorobutanol was prepared in 83% yield by reduction of N-(4,4,4-trifluorobutanoyl)carbazole in ether at —10° [1105]. 

Since acetic acid and acetic anhydride mixtures are excellent solvents for amides derived from primary carbinamines and cyclohexylamines, A-nitroso derivatives can be prepared in this solvent medium with sodium nitrite. The method appears to be somewhat more rapid than that carried in an aqueous medium, but fails when amides derived from secondary carbinamines are to be nitrosated. As the reaction medium is one which will also acetylate primary amines, appropriate amines may be dissolved in the reaction medium and, in turn, acetylated and nitrosated without the isolation of the intermediate amide. 

The Hofmann rearrangement is the conversion of primary amides into primary amines by the action of sodium hypohalite (usually generated in situ from halogen and sodium hydroxide). The most important feature of the rearrangement is that the amine formed has... 

The most recent source of these iminium ion precursors is the amide derived from 3-chloropropionyl chloride. Using the procedure reported by Ruhlmann for the preparation of 1-methoxy-l-trimethylsilyloxycyclopropane, Wasserman and Dion " converted the piperidide (58) to the 1-piperidino-l-trimethylsilyloxycyclopropane (59) by treatment with sodium metal in dry ether at 0°C. This reaction, which takes place smoothly and in high yield, serves as a short, inexpensive way to form the stable cyclopropanone equivalent. Further reaction of the silyl derivative (59) with tetrabutylam-monium fluoride in THF yields the corresponding carbinol amine (60). 

Reactions with sodium amide-sodium r butoxide Ar. amines from ar. bromides... 

Sodium hypochlorite Amines from carboxylic acid amides CONH2 -... 

These rearranged aziactones can be easily converted into quaternary a-aUcylated a-amino acid derivatives, either by ring opening with a primary amine or by reduction with sodium borohydride (Scheme 40.4). X-Ray diffraction analysis of an amide derived from a chiral amine allowed assignment of the absolute configuration of the rearrangement products as that arising from electrophilic attack at the C4-Si-face. 

The reaction is applicable to the preparation of amines from amides of aliphatic aromatic, aryl-aliphatic and heterocyclic acids. A further example is given in Section IV,170 in connexion with the preparation of anthranilic acid from phthal-imide. It may be mentioned that for aliphatic monoamides containing more than eight carbon atoms aqueous alkaline hypohalite gives poor yields of the amines. Good results are obtained by treatment of the amide (C > 8) in methanol with sodium methoxide and bromine, followed by hydrolysis of the resulting N-alkyl methyl carbamate ... 

A suspension of sodium amide in 500 ml of anhydrous liquid artmonia was prepared from 18 g of sodium (see Chapter II, Exp. 11). To the suspension was added in 10 min with swirling a mixture of 0.30 mol of 1-chloro-l-ethynylcyclohexane (see VIII-2, Exp. 27) and 50 ml of diethyl ether. The reaction was very vigorous and a thick suspension was formed. The greater part of the ammonia was evaporated by placing the flask in a water bath at 50°C. After addition of 500 ml of ice-water the product was extracted three times with diethyl ether. The ethereal extracts were dried over anhydrous KjCOj and subsequently concentrated in a water-pum vacuum. Distillation of the residue afforded the amine, b.p. 54°C/15 mmHg, n 1.4345, in 87% yield. 

Refluxing linoleic acid and a primary or secondary alkyl amine with -toluenesulfonic acid in toluene for 8—18 h also yields the substituted amides (32—34). The reaction of methyl esters with primary or secondary amines to make substituted amides is catalyzed with sodium methoxide. Reactions are rapid at 30°C under anhydrous conditions (35). Acid chlorides can also be used. Ai,A/-dibutyloleamide [5831-80-17 has been prepared from oleoyl chloride and dibutyl amine (36). 

Pyridine and its methyl derivatives, (2), (3), and (4), undergo amination with sodium amide at the 2-position eg, 2-anTino-3-methylpyridine [1603-40-3] and 2-anTino-5-methylpyridine [1603-41 -4] from (3) (eq. 3). This Chichibabin reactionis most important for introduction of a 2-amino substituent, which may be replaced readily by many other groups (18). 

Sulfonamides (R2NSO2R ) are prepared from an amine and sulfonyl chloride in the presence of pyridine or aqueous base. The sulfonamide is one of the most stable nitrogen protective groups. Arylsulfonamides are stable to alkaline hydrolysis, and to catalytic reduction they are cleaved by Na/NH3, Na/butanol, sodium naphthalenide, or sodium anthracenide, and by refluxing in acid (48% HBr/cat. phenol). Sulfonamides of less basic amines such as pyrroles and indoles are much easier to cleave than are those of the more basic alkyl amines. In fact, sulfonamides of the less basic amines (pyrroles, indoles, and imidazoles) can be cleaved by basic hydrolysis, which is almost impossible for the alkyl amines. Because of the inherent differences between the aromatic — NH group and simple aliphatic amines, the protection of these compounds (pyrroles, indoles, and imidazoles) will be described in a separate section. One appealing proj>erty of sulfonamides is that the derivatives are more crystalline than amides or carbamates. 

The first amination of a halogenopyridine involving a rearrangement was carried out by Levine and Leake in 1955 in an attempt to prepare 3-phenacylpyridine. When 3-bromopyridine (27, X = Br) was allowed to react with sodium amide in liquid ammonia in the presence of sodio-acetophenone, the reaction mixture obtained consisted chiefly of amorphous nitrogenous material from which only 10% of 4-aminopyridine (34, Y = NH2) and 13.5% of 4-phenacylpyridine were isolated. 

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