Nitrogen heterocycles esters with

It melts at 39°C and may be purified by vacuum sublimation. The Hquid boils at 233°C to give a monomeric vapor in which the Ti—Br distance is 231 pm. Titanium tetrabromide is soluble in dry chloroform, carbon tetrachloride, ether, and alcohol. Like titanium tetrachloride, TiBr forms a range of adducts with molecules such as ammonia, amines, nitrogen heterocycles, esters, and ethers. 

Nitrogen heterocycles, reactions with acetylenecarboxylic acids and esters R. M, Acheson and N. F. Elmore, Adv. Heterocycl. Chem. 23, 263-482 (1978) R. M. Acheson, ibid. 1, 125-165 (1963). 

The chiral diol moiety is only rarely present as such in the final compound to be synthesized. Usually, the 1,2-diol unit is further functionalized and sometimes, can be quite difficult to find in the end-product. Nevertheless, a few natural products possess, embedded in their complex structures, an optically active vicinal diol function which has been created using the AD reaction. Such is the case for the alkaloids indicine 2 and intermedine 1, which were obtained by condensation of the nitrogen heterocycle 4 with (-1-)- and (-)-trachelanthic acid 3 and 5 respectively (Scheme 12) [79]. The desired optically active esters 8 and 9 were rapidly accessed by the AD reaction of the trisubstituted alkene 6. Dihydroxyla-tion using the AD-mix-P generated ester 7 in 83% yield and 85% ee whilst AD-mix-a gave the antipode 8 with slightly better enantioselectivity (90% ee). Hydrolysis and recrystallization furnished the optically pure acids 3 and 4 which were further transformed into the desired natural products. 

Their Esters with Nitrogen-Containing Heterocyclic Compounds... 

Dimethyl acetylenedicarboxylate gave first a similar adduct (2) which then added further molecules of furan yielding (3) and subsequently (4). Between 1931 and 1940 the reactions of acetylenedi-carboxylic acid and its dimethyl ester with a number of nitrogen containing heterocyclic compounds were examined, and structures were proposed for the products. Apart from an unpublished investigation of the products from pyridine and dimethyl acetylenedicar-... 

III. Reactions of Acetylenic Acids and Esters with Individual Nitrogen-Containing Heterocyclic Compounds... 

Reactions of Acetylenecarboxylic Acids and Their Esters with Nitrogen-Containing Heterocyclic Compounds R, M. Achbson... 

Protonated nitrogen heterocycles can be carbalkoxylated" by treatment with esters of a-keto acids and Fenton s reagent. Pyridine is carbalkoxylated at C-2 and C-4, for example. The attack is by "COOR radicals generated from the esters ... 

The recently reported (757) conversion of 5-pyrazolones directly to a,j8-acetylenic esters by treatment with TTN in methanol appears to be an example of thallation of a heterocyclic enamine the suggested mechanism involves initial electrophilic thallation of the 3-pyrazolin-5-one tautomer of the 5-pyrazolone to give an intermediate organothallium compound which undergoes a subsequent oxidation by a second equivalent of TTN to give a diazacyclopentadienone. Solvolysis by methanol, with concomitant elimination of nitrogen and thallium(I), yields the a,)S-acetylenic ester in excellent (78-95%) yield (Scheme 35). Since 5-pyrazolones may be prepared in quantitative yield by the reaction of /3-keto esters with hydrazine (168), this conversion represents in a formal sense the dehydration of /3-keto esters. In fact, the direct conversion of /3-keto esters to a,jS-acetylenic esters without isolation of the intermediate 5-pyrazolones can be achieved by treatment in methanol solution first with hydrazine and then with TTN. 

In Table IV some physical data and spectral characteristics of 6,7-secoberbines are listed. Only methyl corydalate (55) is optically active. Formula 55 presents the spatial structure of this compound, deduced by Nonaka et al. (65) and confirmed by Cushman et al. by both correlation with (+)-mesotetrahydrocorysamine (72) (<5S) and total synthesis (69). It is difficult to find common characteristic features in both the mass and H-NMR spectra of these alkaloids because they differ significantly from each other in their structures. On one hand, corydalic acid methyl ester (55) incorporates a saturated nitrogen heterocycle, while the three aromatic bases (56-58) differ in the character of the side chain nitrogen. For example, in mass fragmentation, ions of the following structures may be ascribed to the most intensive bands in the spectrum of 55 ... 

During studies on the use of amidines as azomethine ylide sources, Jones et al. (67-69) reported in a series of papers the application of their general strategy to an asymmetric process. Quatemization of the dihydroimidazole 214 with an a-halo ester followed by DBU-induced ylide formation and subsequent cyclization furnished a range of nitrogen heterocycles in a one pot generation and cyclization protocol (70) (Scheme 3.73). 

The carboxylic acid is then converted to its ester with ethanol in the presence of an acid. Carboxylic esters are not, in the normal course of events, reduced by sodium borohydride. The presence of an adjacent imine nitrogen apparently changes the resistance to that reagent. Thus, treatment of (71-7) with sodium borohydride leads to a selective reduction of the ester on the heterocyclic ring to an alcohol while leaving that on the benzene ring unaffected. There is thus obtained oxagrelate (71-8) [80]. 

Protonated nitrogen heterocycles can be carbalkoxylated351 by treatment with esters of at-keto acids and Fenton s reagent ... 

Reactions of Acetylenecarboxylic Esters with Nitrogen-containing Heterocycles R. M. 

Reactions of Acetylenecarboxylic Acids and Their Esters with Nitrogen-containing Heterocyclic Compounds R. M. Acheson, Adv. Heterocycl. Chem., 1963,1, 125-165. The Reactions of Diazomethane with Heterocyclic Compounds R. Gompper, Adv. Heterocycl. Chem., 1963, 2, 245-286. 

This volume contains two articles which bring up to date older reviews in the Series. Progress in the chemistry of the 1,3-oxazines since they were covered by Eckstein and Urbanski in Volume 2 (1963) is described by the same authors. Acheson and Elmore review reactions of acetylenecarboxylic esters with nitrogen heterocycles, which have been the subject of much concentrated research in the years since Acheson s article in Volume 1. The review on indolizines (Swinboume, Hunt, and Klinkert) also concentrates on the advances of the last IS years and up-dates reviews published elsewhere. Anastassiou and Kasmai provide a critical account of the V-excessive heteroannulenes, and Fletcher and Siegrist deal authoritatively with the olefin-forming condensations of anils with methyl groups, the Anil Synthesis. ... 

Nitrogen heterocycles covalent hydration in, 20, 117 reactions of acetylenecarboxylic esters with, 23, 263... 

Substitution of chloride in a variety of heterocyclic chlorides by esters, lactones, amides and lactams has been shown to occur in toluene in the presence of hexam-ethyldisilazide (NaHMDS) acting as a base.52 An example using a chlorothiadiazole derivative is shown in Scheme 6. There has been a report53 of a mild and convenient method for the introduction of tetrafluoroethyl substituents into nitrogen heterocycles using the reaction of hexafluoropropane with azine and azole A-oxidcs. 

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