Open chain amides

Regioselectivity becomes important, if unsymmetric difunctional nitrogen components are used. In such cases two different reactions of the nitrogen nucleophile with the open-chain educt may be possible, one of which must be faster than the other. Hydrazone formation, for example, occurs more readily than hydrazinoLysis of an ester. In the second example, on the other hand, the amide is formed very rapidly from the acyl chloride, and only one cyclization product is observed. 

Macrocyclic peptides and depsipeptides ( macrocyciic peptides with amide and ester linkages) are important natural compounds. They have been synthesized in low yield from open-chain precursors by DCC treatment at high dilution (E. SchrSder, 1963 M.M. Shemyakin,... 

In solution 1550-1510 Amide II found in open-chain amides only... 

An investigation of acylaziridines was carried out by comparison of IR, NMR and MS data and included some 1,2-dibenzoylaziridines as well as 2-p-nitrobenzoyl-3-phenyl-oxaziridine (68IZV1530). Amide conjugation in acylated nitrogen-containing three-membered rings is weaker than in open chain acid amides. 

Bis(tnfluoromethyl)-subsntuted hetero-1,3-dienes and acetylenes react to give open-chain tnfluoromethyl-substituted N-propargylic amides, 4//-1.3 oxazines, and 2-oxazohnes [42,144] The formation of 2-oxazolmes is an example of pathway 2 (equabon 25), where only one carbon atom of the acetylene moiety IS incorporated into the new nng system The selectivity of this reaction can be controlled efficiently in favor of the five-membered nng system by altering the reaction conditions In the presence of 4-dimethylaminopyndine, the five-mem-... 

Lipoic acid exists as a mixture of two structures a closed-ring disulfide form and an open-chain reduced form (Figure 18.33). Oxidation-reduction cycles interconvert these two species. As is the case for biotin, lipoic acid does not often occur free in nature, but rather is covalently attached in amide linkage with lysine residues on enzymes. The enzyme that catalyzes the formation of the lipoamide nk.2Lg c requires ATP and produces lipoamide-enzyme conjugates, AMP, and pyrophosphate as products of the reaction. 

Most heterocycles have the same chemistry as their open-chain counterparts. Lactones and acyclic esters behave similarly, lactams and acyclic amides behave similarly, and cyclic and acyclic ethers behave similarly. In certain cases, however, particularly when the ring is unsat lira ted, heterocycles have unique and interesting properties. 

The broadband at 3270 cm-1 is due to the O-H stretching vibration of the hydroxyl group. Moreover, the N-H stretching vibration absorption for open-chain amides occurs near 3270 cm-1 in the niclosamide solid state. 

Phenyl-[l,3]dioxane 32 has been reported to bind the 0X2 receptor with a pX of 8.3 and a pXb of 7.9, and is 600-fold selective for 0X2 over 0X1 [85,86]. JNJ-10268752 (no specific structure has been disclosed) has been described as a selective 0X2 receptor antagonist (X, 0X1 /OX2 = 18/2, 500 nM, respectively) [87]. Compounds exemplified by 33 have been reported as 0X2 receptor antagonists (IC5o = 9nM) selective versus 0X1 (IC50 = 1870 nM) [88]. Recently, open chain amide 34, sulfonamide compound 35 [89,82], and spirocyclic sulfonamide 36 [90]... 

The recently synthesized phosphatriazolo[l,5- ]pyridines 4 can also participate in reactions involving the ring opening of the five-membered ring <1995ZNB558>. When the unsubstituted phospha-heterocycle is treated with aqueous acetonitrile, a hydrolysis occurs and the open-chained phosphenic amide 47 can be obtained in acceptable yield (Scheme 13). 

Similarly, open chain C-nucleosides of adenine have been prepared by condensing 4,5,6-triaminopyrimidine with aldonic acids (or aldonolac-tones) of various chain-lengths. The amides (102) first formed were thermally cyclized, affording the 8-(hydroxyalkyl)adenines (103) in rather low yields (119). 

The sensitivity of position 2 in 4-chloroquinazoline for nucleophilic addition was also demonstrated in the reaction with lithium piperidide (73RTC460). Whereas in the amination with potassium amide/liquid ammonia no open-chain intermediate could be isolated, with lithium piperi-dide/piperidine the open-chain compound ort/z6>-(piperidinomethy-leneamino)benzonitrile (78,60%) was obtained, in addition to 4-piperidino-quinazoline (80,19%) (Scheme 11.35). The formation of 80 from 78 involves... 

Scheme 11.51). Some of these reactions are even initiated by the addition of nucleophilic species, being formed by fragmentation of open-chain compounds, which are originally derived from C-5 adducts (see Section II,C,l,b). Thus, the number of molecules that react by addition of the amide ion to C-5 is certainly higher than can be derived from the percentage of the molecules given in Table II.IO. 

The simplest conjugated system involving nitrogen and oxygen atoms in an open chain is the amide group [108]. The site of... 

In contrast with the oxocarboxylic acids, which readily participate in tautomeric equilibria in solution, their open-chain and cyclic N-unsubsti-tuted and A-monosubstituted amide isomers are more stable. In most cases, the tautomeric equilibrium (Scheme 3) is not observed in neutral aprotic solvents at ambient temperature. In protic solvents, e.g., CD3OD, intercon-... 

A -Unsubstituted and A-mono-n-alkyl-substituted 3-(3-trifluoromethyl-benzoyl)propionamides were obtained in the cyclic form 20B (R = H, Me, Et, Pr, Bu). Amides containing branched alkyl substituents on the nitrogen atom and A,N-dimethylhydrazide exist (85JMC28) as the open-chain isomers 20A (R = f-Pr, ec-Bu, f-Bu, cyclo-C n, NMea). For the open-chain isomers 20A, a typical aroyl C = 0 signal at 190 5 ppm was observed in the - C-NMR spectrum, while the cyclic isomers gave the carbinolamine [C(OH)NR] signal at 90 2 ppm. 

N-Benzylamides 22 and 23 (R = PhCH2) are isolated as stable cyclic isomers 22B and 23B, whereas N-r-butylamides possess open-chain structures 22A and 23A (R = f-Bu) in the solid state (86KGS80). The hydrochloride of the amide 22A (R = r-Bu) retains the open-chain structure in the... 

P. A. S. Smith, Esters and Amides of Nitrogen Oxy-acids, Open Chain Nitrogen Compounds, Vol. 2., Benjamin, New York, Chapter 15,455-513 (1966). 

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