Open-chain intermediates

Rumpf et al. (97) studied the ultraviolet spectra of products obtained when 2-amino-4 phenylthiazole is acylated by /3-chloropropionyl chloride and y-chlorobutyrylchloride and showed that their structures were 94 and 95, respectively (Scheme 66). The open-chain intermediate to 95, 2-(3-... 

Equal amounts of the two crowns were also formed when BU4NOH was used as base, but both rate and yield were considerably reduced. Greene noted that such a template effect would actually involve binding between the open-chained intermediates and cations and these interactions are known to be weak relative to crown-cation interactions. Nevertheless, evidence for such interactions exists (see also Chap. 7) ... 

Apparently, cyclization involves the formation of open-chain intermediates 342, 343, further closing up to imidazolidines 344 and oxazolidines 345 which eliminate the secondary amine, thus leading to imidazolines 346 and oxazolines 347. The latter exist in the solution exclusively in the enolic forms 348, 349 which are stabilized by conjugation and intramolecular hydrogen bonds. 

The Mitsunobu reaction was applied to the synthesis of pyrrolo[l,2-d [, 2,4]triazines from pyrrole derivative 71. Thus reduction of 71 gave alcohol 72, which on treatment with diethylazodicarboxylate and triphenyl phosphine gave 74 via the open chain intermediate 73. Hydrolysis of 74 gave 75 (84AG517) (Scheme 18). 

Since the additions are normally stereospecific with respect to the alkene, if an open-chain intermediate is involved it must collapse to product more rapidly than single-bond rotations that would destroy the stereoselectivity. 

Diazonium salts couple to hydroxy-substituted vicinal triazoles (101) with subsequent rearrangement of the hydroxy arylazo compounds (102) to the carbamoyl tetrazole (104).170 An open-chain intermediate (103) has been proposed.169 This rearrangement is similar to that of the benzoyl... 

Intramolecular Henry reactions of nitro sugars are usually diastereo-selective sometimes a single isomer results from an epimeric mixture, on account of the reversivility of the Henry reaction, which allows equilibration through open chain intermediates.49 A recent example involving the D-glucose derived nitro acid ester 26 is shown in Scheme 22. 

When 23 reacts in this ANRORC process, in fact two intermediates, a cyanoimidoyl chloride (24) and a dicyanoazadiene (25), can be postulated (Scheme 11.16). When the dicyano compound 25 is the transient open-chain intermediate, scrambling of the radioactive carbon over both cyano groups takes place, and consequently after ring closure (route a), incorporation of the C-label into the pyrimidine ring should be expected (Scheme 11.16). 

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... 

The reaction of l,4-diaryl-2-methylthiopyrimidinium iodide (39) with hydrazine did not lead to the corresponding 2-hydrazino compound, as expected, but to the rearranged l-amino-2-arylaminopyrimidinium salt (40) (90JHC1441). This transformation also occurs via an Sn(ANRORC) process, involving the open-chain intermediate 41 (Scheme III.22). It cannot... 

Mechanistically, analogous to what already is suggested for 5-azido- or S-diazomethyl-1,2,3-triazoles (Section II,C), the participation of open-chain intermediates 287 or 288 is proposed (Scheme 46) the subsequent hetrocyclization engaging the pivotal sulfur and the azido or diazo-methyl side-chain develops into the rearranged 285 or 290, respectively. On the other hand, a concerted electronic reorganization involving the side-chain... 

Stereochemically, even more interesting are the bis-l,3-oxathiane derivatives 98 and 99 <2005STC369>. All compounds are chiral and the chiral elements are carbons C-2/C-2 and the 1,3-oxathine moieties themselves (Equation 9). Due to the bis-structure, compounds 98 and 99 exhibit both homochiral iZR,2 R ZS,Z S) and hetero-chiral (2R,Z S) isomers (Scheme 4) and they reveal rapid equilibration in solution via open-chain intermediates, thereby preventing separation and individual analysis of the isomers in solution. In the solid state, the compounds crystallized either as unique heterochiral isomers or as a mixture of the two as a solid solution. 

The choice of alkylating agents to intercept the open-chain intermediates 8 is limited when the 3-thienyllithium derivatives are produced from 3-halothiophenes and alkyllithiums, because the corresponding haloalkanes are produced in situ. This problem is avoided if phenyllithium is used. In the presence of a proton source, ring-opening can be reversed. 

Z-Pyrans are transformed to the corresponding 7t-isoelectronic 1,4-dihy-dropyridine derivatives by ammonia,2,37,68,69 ammonium acetate,76,440,841 primary amines,37,62,68,442 hydroxylamine,37 arylhydrazines,3,3,3 urea,440 and thiourea.440 The open-chain intermediates are rarely isolated.62... 

In terms of synthetic strategy, approaches to porphyrins from open-chain tetrapyrroles are the only truly general routes. The principle is to construct, in a stepwise manner, an open-chain tetrapyrrole bearing a pre-determined arrangement of peripheral substituents. Cyclization to produce a porphyrin, or an immediate precursor, under mild conditions which do not cause redistribution of the pyrrole rings, should be accomplished after full characterization of the open-chain intermediate. 

Frequently, five-membered heterocyclic systems have provided the C(3)N(4)C(5)C(6) fragment in 1,2,4-triazine syntheses. For instance, the oxazol-5-one (586) reacts with hydrazines to give, via open-chain intermediates (587), the l,2,4-triazine-3,6-diones (588)... 

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