Hydroxy amines from ammonia

Pyrones, which are the ring-oxygen equivalents of pyridones, are simply a- and y-hydroxy-pyrylium salts from which an 0-proton has been removed. There is little to recommend that 2- and 4-pyrones be viewed as aromatic they are perhaps best seen as cyclic unsaturated lactones and cyclic p-oxy-a,P-unsaturated-ketones, respectively, for example 2-pyrones are hydrolysed by alkali, just like simpler esters (lactones). It is instructive that, whereas the pyrones are converted into pyridones by reaction with amines or ammonia, the reverse is not the case - pyridones are not transformed into pyrones by water or hydroxide. Some electrophilic C-substitutions are known for pyrones and benzopyrenes, the oxygen guiding the electrophile ortho or para, however there is a tendency for electrophihe addition to the C-C double bond of the heterocyclic ring, again reflecting their non-aromatic nature. Easy Diels-Alder additions to 2-pyrones are further evidence for diene, rather than aromatic, character. 

When /8-propiolactone is heated under pressure with anhydrous ammonia, /3-hydroxypropionamide is obtained. A mole of /3-propiolactone (72 g) is heated under pressure with 5.87 moles (100 g) of ammonia for 16 hr at 100 C to obtain a 50 per cent yield of crude /3-hydrox5rpropionamide, which can be purified by vacuum distillation. By a dehydration reaction, the amination of the lactone of a y-hydroxycarboxylic acid yields a stable cyclic amide or lactam, as is the case when y-butyrolactone is converted to a-pyrrolidone. However, owing to the instability of the four-membered ring, a lactam cannot be formed from ammonia and the lactone of a /8-hydroxycarboxylic acid, such as -propiolactone. When hydroxy-propionamide is dehydrated, no lactam is formed. Only unsaturated acid derivatives can be obtained, as shown in the equation below. 

In some cases, up to 3% racemization has been observed when using the HOSu-DCC method, which renders it unsuitable for some types of peptide synthesis." Esters derived from HOSu are relatively reactive, as shown by a kinetic study of their rates of hydrolysis in aqueous buffers although, in some examples, endo-lV-hydroxy-5-norbornene-2,3-dicarboximide has proven superior to HOSu in peptide bond formation. Of course, the HOSu-DCC method is not limited to peptide synthesis and is well suited to the preparation of amides in general, both from ammonia and primary amines (e.g. eq 2). ... 

Telomers 422 (n = 2) and other 4-halogeno-l,3-dioxolan-2-ones were shown288 to react readily with ammonia or primary aliphatic amines, with formation of 4-hydroxy-2-oxazolidones (460). The latter, for which the trans arrangement of the hydrogen atoms of the oxazoli-done ring was deduced from H-n.m.r. data, readily underwent replacement of the hydroxyl group by a phenyl group on reaction with... 

The reduction of 2, either catalytically or with zinc in acetic acid, leads to 3-amino-4-hydroxy-2-quinolone 20 [72TH000], These amino compounds are rather unstable they dimerize with loss of ammonia to "bis-amines", which in turn are readily oxidized to dyes similar to those obtained from ninhydrin and primary amines [68M1205] [68M1543], The amino derivatives 20 are therefore conveniently converted into 0,N-diacetyl derivatives, the N-acetyl derivative 21, or its dehydrated form, the oxazolo derivative 22 [95MI000], The variety of biological activity of oxazolo-quinolines of type 22 has been detected only in recent years [94JHC1647],... 

Also, the primary amine moities of polar lipids catalyze the aldol condensation of Cm-Cig aldehydes resulting from plasmalogen hydrolysis, thus forming a,3-unsaturated aldehydes (l2t). Phosphatidyl ethanolamine reacted with propanal and n-hexanal forming phosphatidyl l-(2-hydroxyethyl)-2-ethyl-3,5-dimethyl pyridinium, and phosphatidyl-1-(2-hydroxy ethyl)-2-hexyl-3,5-dipentyl pyridinium, respectively (125). The peridinium ring is formed by the reaction between one mole of amino-N of phosphatidyl ethanolamine and three moles of n-alkanals. The same reaction took place in the synthesis of substituted pyridines by condensation of carbonyl compounds with ammonia (126, 127). 

The original Kabachnik-Fields procedure employing ammonia as the amine component used ammonia in ethanol and the reactions were performed in sealed vessels at circa 100°C.90,123 This method avoids such conditions by using ammonium acetate as the source of ammonia, and it is also thought to act as an acid catalyst for imine formation other ammonium salts were unsatisfactory. Addition of water to produce a homogeneous reaction mixture resulted in diethyl 1-hydroxy-1-benzylphosphonate formation (i.e. from direct attack of diethyl phosphite 25 on benzaldehye, a common side reaction in the Kabachnik-Fields reaction). The yields of this reaction are serviceable, and better for aromatic than aliphatic aldehydes. The product 58 may be further purified by crystallization as the hydrochloride salt by treatment of 58 with hydrogen chloride in ethanol/diethyl ether.122... 

To remove the water, which is formed on dimerization of trimethylsilanol, at least one additional equivalent of a silylating agent such as HMDS [boiling point = 126°C] must be used. Excess HMDS can then react with trimethylsilanol or water to give hexamethyidisiloxane and ammonia, but will also reconvert any hydrolyzed hydroxy-N-heterocycle into the corresponding activated 0-silylated intermediates. Thus, sufficient HMDS should be used to silylate the hydroxy-N-heterocycle and all the alcoholic, phenolic, or other acidic hydroxy groups present in the heterocyclic or amine moiety. It should also be used to convert trimethylsilanol and water (or intruded humidity) from the reaction into hexamethyidisiloxane and ammonia (Eqs. 1-3). 

The synthesis of the fluoroketone that combines the retroamide type bond (76) is shown in Scheme 5. The 2,2-difluoro-3-hydroxyester 11 from a Reformatsky reaction was converted to the primary amide 12 by treatment with ammonia in diethyl ether. Reduction of the amide with borane dimethyl sulfide and protection of the resulting amine gave the protected intermediate 13. For the preparation of peptides XIV and XV, the hydroxy function was oxidized to the corresponding ketone using pyridinium dichromate. 

The reaction would have to be run such that a minimum of water would need to be removed by reverse osmosis or by evaporation. Carbon dioxide under pressure has been used to free 6-hydroxy-2-naphthoic acid from its potassium salt, to recover the acid and recycle potassium carbonate.49 Ammonia or tertiary amines can be used to separate carboxylic acids. The ammonia or amine can be recovered by heating under a vacuum. This type of reaction is used in some floor polishes. The polymer containing the carboxylic acid groups is soluble in aqueous ammonia until applied. It loses its solubility in water when the ammonia evaporates. However, the polish can be stripped from the floor by the use of... 

Recently, Leuck et al. [282] have described an acyl-type anchor for the fast and efficient preparation of 3 -aminoalkyl oligonucleotides based on the 2-hydroxy-methyl-6-nitrobenzoyl group (Figure 19.12). The linker is prepared from 6-nitroph-thalide by acylation of the respective aminoalcohol and attachment to LCAA-CPG through the benzylic hydroxyl via the succinyl group. Cleavage is achieved under conditions of basic hydrolysis by the intramolecular attack of the liberated hydroxyl onto the amide carbonyl with the expulsion of the amine. Complete detachment of the oligomer requires 2 h at 55 °C in concentrated ammonia or 30 min at 65 °C in 40% aqueous methylamine-concentrated aqueous ammonia (l lv/v), or can be accomplished at room temperature within 24 h in concentrated ammonia. The new anchor was shown to be superior to the phthalimido support [279] in terms of product yield and deprotection time. 

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