Imides from amines

The phthaloyl (Phth) derivatives of amines, formed from amines and N-ethoxy-carbonylphthalimide (G.H.L. Nefkens, 1960), are acid-resistant imides, which can be easily deblocked by nucleophilic reagents, most conveniently by hydrazine. 

The choice of these derivatives, namely, those formed from amines of moderate strength, appears to be the best compromise for the synthesis to be effective. Although the susceptibility of phosphor-amidates to attack by nucleophiles increases with enhancement of the basic strength of the parent amine,279 280 the reverse trend is observed for the yields of nucleoside 5 -phosphoramidates when they are prepared from nucleoside 5 -phosphates by condensation with the appropriate amines through the action of N,N -dicyclohexylcarbodi-imide.279... 

The application of antibiotics as chiral selectors has resulted in the successful resolution of almost all types of neutral, acidic, and basic racemic molecule. These antibiotics have been used for the enantiomeric resolution of amino acids, their derivatives, peptides, alcohols, and other pharmaceuticals. The selectivities of the most commonly used antibiotic-based (vancomycin, teicoplanin, and ristocetin A) CSPs varied from one racemate to another and are given in Table 1. Vancomycin was used for the chiral resolution of amino acids, amines, amides, imides, cyclic amines, amino alcohols, hydantoins, barbiturates, oxazolidinones, acids, profens, and other pharmaceuticals. Teicoplanin was found to be excellent chiral selector for the enantiomeric resolution of amino acids, amino alcohols, imides, peptides, hydantoins, a-hydroxy and halo acids, and oxazolidinones, whereas ristocetin A is capable of chiral resolution of amino acids, imides, amino... 

Interaction of 258 with anilines or five-membered nitrogen heterocycles produced 265 and 266 via an aminoalkylation . Bicyclic derivatives 267-271 with an aminal structure resulted from the interaction of 258 with amides, urethanes, imides, ureas, amines or hydrazines. Finally, 272 was formed with carbon acids and a reduction to 273 occurred with the sodium salt of formic acid " . It is not yet totally clear whether an iminium ion is involved in the formation of 259-273. The yields of isolated products varied from 45 to 95 %. 

Benzo[Z>]thiophen 5-Oxides. - Mild methods for the oxidation of 2,3-dihydrobenzo[Z>] thiophens to the sulphoxide have been developed. The photochemical reactions of various 2- and 3-substituted benzo[ ]-thiophen 1-oxides led to different photodimers. From 3-chlorobenzo[b]-thiophen-2-carboxylic acid 1,1-dioxide, 1,3-oxazinones of biological interest were obtained through cyclization reactions with cyanamides and carbodi-imides. Secondary amines add to 2-phenylbenzo [b] thiophen 1,1-dioxide to give 3-amino-substituted 2,3-dihydro-2-phenylbenzo[b]thiophen 1,1-dioxides. " ... 

If 44 reacts with benzyl bromide, the product is AT-benzylphthalimide (45) via a straightforward Sn2 displacement. To generate the amine, the imide can be hydrolyzed by acid-base reactions (1. aqueous base 2. aqueous acid) to give the amine (46) and phthalic acid (47). The reaction of 45 with aqueous hydroxide is an example of an acyl substitution reaction that will be introduced in Chapter 16 (Section 16.8). For several reasons, it will not be discussed at this time. A better procedure has been developed that treats 45 with hydrazine (NH2NH2) to generate amine 46 and a molecule known as a hydrazide, 48. Hydrazide 48 is easily separated from amine 46. A hydrazide is one of those specialized chemicals encountered from time to time, but not discussed in detail. 

Radovic et al. (1996) investigated the effects of nitriding the surface on adsorption from solution. Reacting with ammonia at elevated temperatures introduced pyridine functional groups on carbon. Reaction at 200 °C forms amides, imides, imines, amines, and nitriles while reaction at 250 °C results in bonding of ammonia to the carbon double bonds (Vinke et al., 1994). The effects of nitriding (at 250 °C) were similar to that of oxidation. Nitriding also hindered the adsorption of benzoate and aliphatic anions, oxalate, and fumarate. 

Another oxidative Ugi-3CR was reported by Xie et al. for the synthesis of a-amino imides from tertiary amines by direct activation of sp C—Hs adjacent to nitrogen using an oxidant (tert-butyl hydroperoxide (TBHP)) and a copper salt [23]. Notably, the reaction could be conducted under mild... 

X. Ye, C. Xie, Y. Pan, L. Han, T. Xie, Org. Lett. 2010, 12, 4240 243. Copper-catalyzed synthesis of a-amino imides from tertiary amines Ugi-type three-component assemblies involving direct functionalization of sp C-Hs adjacent to nitrogen atoms. 

A useful synthesis of symmetrical diaryl carbodi-imides from iminophosphoranes (readily available from amines and triphenylphosphine) and carbon disulphide has been described (Scheme 50). ... 

Continuation of the work reported last year on the conversion of 2,4,6-triphenylpyrylium salts into the corresponding 2,4,6-triphenylpyridiniums has yielded additional synthetically useful procedures. Examples are the conversion of alkyl, aryl, and heteroaryl primary amines into iodides,esters, " and thiocyanates and the production of carbodi-imides from amidrazones, as outlined in Scheme 34. ... 

X Aminosulf onylammoniosulf ony 1 imides from tert. amines... 

To avoid these problems, refiners commonly use additives called detergents" (Hall et al., 1976), (Bert et al., 1983). These are in reality surfactants made from molecules having hydrocarbon chains long enough to ensure their solubility in the fuel and a polar group that enables them to be absorbed on the walls and prevent deposits from sticking. The most effective chemical structures are succinimides, imides, and fatty acid amines. The required dosages are between 500 and 1000 ppm of active material. 

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 ... 

Finally, when polyamides containing four or five carbon diacids, ie, succinic acid [110-15-6] and glutaric acid [110-94-1], respectively, are heated, they form cychc imides that cap the amine ends and prevent high molecular weights from being achieved (84). For nylon-x,4, n = 1 and for nylon-x,5, n = 2. 

To minimize the formation of fuhninating silver, these complexes should not be prepared from strongly basic suspensions of silver oxide. Highly explosive fuhninating silver, beheved to consist of either silver nitride or silver imide, may detonate spontaneously when silver oxide is heated with ammonia or when alkaline solutions of a silver—amine complex are stored. Addition of appropriate amounts of HCl to a solution of fuhninating silver renders it harmless. Stable silver complexes are also formed from many ahphatic and aromatic amines, eg, ethylamine, aniline, and pyridine. 

Another alternative for preparing a primary amine from an alkyl halide is the Gabriel amine synthesis, which uses a phthalimide alkylation. An imide (—CONHCO—) is similar to a /3-keto ester in that the acidic N-H hydrogen is flanked by two carbonyl groups. Thus, imides are deprotonated by such bases as KOH, and the resultant anions are readily alkylated in a reaction similar to the acetoacetic ester synthesis (Section 22.7). Basic hydrolysis of the N-alkylated imide then yields a primary amine product. The imide hydrolysis step is analogous to the hydrolysis of an amide (Section 21.7). 

Alicyclic dianhydrides are interesting for electronic applications. The polyimides obtained from them are colorless with high transparency in the visible range, exhibit low birefringence,125 and have a low dielectric constant.126 The reactivity of the polycyclic aliphatic dianhydride has been investigated. For example, bicyclo-[2,2,2]-oct-7-ene tetracarboxylic dianhydride reacts quickly with an aromatic amine because the bicyclo-imide is less strained than the corresponding dianhydride.127... 

Imide-terminated telechelics are also synthesized by metathesis depolymerization, and it is found that phthalimide-substituted olefins allow for productive depolymerization when only one methylene spacer separates the nitrogen atom and the olefin (Fig. 8.21). This combination of steric hindrance around the nitrogen lone pair and decreased electron donation from resonance prevents the negative neighboring group effect. However, secondary acyclic amines are unable to produce telechelics through metathesis depolymerization because of unfavorable catalyst-amine interactions. 

As in 10-55 hydrazides and hydroxamic acids can be prepared from carboxylic esters, with hydrazine and hydroxylamine, respectively. Both hydrazine and hydroxylamine react more rapidly than ammonia or primary amines (the alpha effect, p. 445). Imidates, RC(=NH)OR, give amidines, RC(=NH)NH2. Lactones, when treated with ammonia or primary amines, give lactams. Lactams are also produced from y- and 5-amino esters in an internal example of this reaction. 

A mechanistic proposal, which is based on the mthenium-catalyzed dehydration reaction reported by Nagashima and coworkers [146], is shown in Scheme 44. Reaction of a primary amine with hydrosilane in the presence of the iron catalyst affords the bis(silyl)amine a and 2 equiv. of H2. Subsequently, the isomerization of a gives the A,0-bis(silyl)imidate b and then elimination of the disiloxane from b produces the corresponding nitrile. Although the disiloxane and its monohydrolysis product were observed by and Si NMR spectroscopy and by GC-Mass-analysis, intermediates a and b were not detected. 

A series of N-substituted narceine amides (Section III,D,1) was prepared from 101 under the action of primary amines (100). Acid-catalyzed dehydration transformed these amides to corresponding imides (ene lactams) of the ( )-narceine imide (117) type (100). Similar transformations were performed in the hydrastine series (101). JV-Methylhydrastine (98) when treated with dilute ammonium hydroxide gave hydroxy lactam 127, which was dehydrated to (Z)-fumaridine (113) (5). Sodium borohydride was able to reduce the stilbene double bond in 98 to produce saturated lactone 132 (5). 

The hydroxy lactams are postulated to be intermediates in transformations of enol lactones to ene lactams. This hypothesis was proved by synthesis. For example, treatment of N-methylhydrastine (98) with dilute ammonium hydroxide resulted in hydroxy lactam 148, which by the action of hydrochloric acid underwent dehydration to produce fumaridine (113) (5). Similarily, fumschleicherine (120) in reaction with trifluoroacetic acid gave fumaramine (111) 121). Narceine amide (149) was prepared from (Z)-narceine enol lactone (101) in likewise fashion 100,122) and dehydrated to narceine imide (116). A large number of N-alkylated narceine amides was synthesized from (Z)-narceine enol lactone (101) and primary amines by Czech investigators for... 

We have now adjusted our molecular systems to provide a model in which both forces can operate simultaneously. The U-shaped relationship that exists between the imide function and amides of aryl amines creates a hydrogen bonding edge and a planar stacking surface that converge from perpendicular directions as in 44 to provide a microenvironment complementary to nucleic acid components. A large number of aromatic rings can be functionalized with this simple scaffold, and spacers (R) can also be incorporated. The imide function is a mimic of the thymine residues. 

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