Chloro-derivatives, reactions

A new synthesis of 6-azacytidine was reported recently. Treatment of 6-azauridine tribenzoate with dimethylchlormethylammonium chloride gave the 4-chloro derivative. Reaction with ammonia and removal of the protecting groups yielded 6-azacytidine. ... 

Derivatives of the pyrimido[4,5-e][l,2,4]triazines at the 7-position were prepared (75JOC2329) by displacement of the respective chloro derivatives. Reaction of pyrimidotriazines 291 or 294 (R = S02Me) with acetylenic alcohols or amines gave azalumazines 292 or azapterins 295, respectively, with dienophilic side chains (88JOC800). Compounds 292 or 295 underwent intramolecular Diels-Alder reaction to give 6,7-annulated 5-deazapteridines 293 and 296, respectively (88JOC3568). 

Alkoxy acids" and esters" have been prepared from the corresponding chloro derivatives. Reaction of the hydroxyl group of methyl lactate with methyl iodide is brought about by silver oxide (65%). Alkylation of the isomeric hydroxy benzoic acids is readily accomplished. ... 

Carbon-Halogen Bonds. Carbon-halogen bonds may be prepared directly via the lithio intermediate or a second intermediate prepared from the lithio intermediate. For example, reaction of hexachloroethane with 2-lithiodimethylaminomethylferrocene gave the chloro derivative (Reaction 16) (23). However, preparation of other halogen derivatives via lithio intermediates has not been successful. A better and more versatile method for preparing the chloro, bromo, and iodo derivatives involves isolating a boronic acid intermediate as in Reaction 17 (24). 

With R = 2,4,6 ter-butylphenyl in the chloro derivative, reactions (7.526) are possible. 

Formic acid behaves differently. The expected octadienyl formate is not formed. The reaction of butadiene carried out in formic acid and triethylamine affords 1,7-octadiene (41) as the major product and 1,6-octadiene as a minor product[41-43], Formic acid is a hydride source. It is known that the Pd hydride formed from palladium formate attacks the substituted side of tt-allylpalladium to form the terminal alkene[44] (see Section 2.8). The reductive dimerization of isoprene in formic acid in the presence of Et3N using tri(i)-tolyl)phosphine at room temperature afforded a mixture of dimers in 87% yield, which contained 71% of the head-to-tail dimers 42a and 42b. The mixture was treated with concentrated HCl to give an easily separable chloro derivative 43. By this means, a- and d-citronellol (44 and 45) were pre-pared[45]. 

Pyrrohdinone forms alkaU metal salts by direct reaction with alkaU metals or their alkoxides or with their hydroxides under conditions in which the water of reaction is removed. The potassium salt prepared in situ serves as the catalyst for the vinylation of 2-pyrrohdinone in the commercial production of A/-vinylpyrrohdinone. The mercury salt has also been described, as have the N-bromo and N-chloro derivatives (61,62). 

Aminotria2ines also form A/-chloro derivatives, eg, sodium tricbloroammelide (25), tetrachloroammeUde (26) and bexacbloromelamine (27). Reaction of aminotria2ines with excess HOCl or CI2O produces TCCA the exocycHc amino groups are converted to NCl (28). TCCA is decomposed to... 

Generally, the reactions of halopyrazines and haloquinoxalines with nucleophiles are believed to proceed by way of addition/elimination sequences, although there are clear-cut examples where this is not the case (see Section 2.14.2.2) and, consistent with a mechanism which involves bond forming, rather than bond breaking, reactions in the rate-determining step, fluoro derivatives are considerably more reactive ca. xlO ) than the corresponding chloro derivatives. 

MgBr reagent by an exchange reaction, while the 4-chloro derivative undergoes reductive cleavage (Scheme 90) (63AHC(2)365). 

The chloro-derivative [ClAs Mn(CO)2-(/j -C5H5) 2] (shiny black crystals, mp 124°) can now be much more readily obtained by direct reaction of AsCb with [Mn(CO)2-... 

In the chloro series, the compounds to be considered are N=S-C1, cyc/o-N3S3Cl3, cyclo-N3S3CI3O3, and cyc/o-N4S4Cl2 the ionic compounds [S4N3]" "C1 and [cyc/o-N2S3Cl]+Cl and [c<2/ <2-N(SCl)2] [BCl4] together with various isomeric oxo- and fluoro-chloro derivatives. Thi-azyl chloride, NSCl, is best obtained by pyrolysis of the trimer in vacuum at 100°. It can also be made by the reaction of CI2 on NSF (note that... 

HN(S02F)2 melts at 17°, boils at 170° and can be further fluorinated with elemental F2 at room temperature to give FN(S02F)2, mp —79.9°, bp 60°. The chloro derivative HN(S02C1)2 is a white crystalline compound, mp 37° it is made in better yield from sulfamic acid by the following reaction sequence ... 

Direct bromination readily yields the 6-bromo derivative (111), just as with uracil. Analogous chlorination and iodination requires the presence of alkalies and even then proceeds in low yield. The 6-chloro derivative (113) was also obtained by partial hydrolysis of the postulated 3,5,6-trichloro-l,2,4-triazine (e.g.. Section II,B,6). The 6-bromo derivative (5-bromo-6-azauracil) served as the starting substance for several other derivatives. It was converted to the amino derivative (114) by ammonium acetate which, by means of sodium nitrite in hydrochloric acid, yielded a mixture of 6-chloro and 6-hydroxy derivatives. A modified Schiemann reaction was not suitable for preparing the 6-fluoro derivative. The 6-hydroxy derivative (115) (an isomer of cyanuric acid and the most acidic substance of this group, pKa — 2.95) was more conveniently prepared by alkaline hydrolysis of the 6-amino derivative. Further the bromo derivative was reacted with ethanolamine to prepare the 6-(2-hydroxyethyl) derivative however, this could not be converted to the corresponding 2-chloroethyl derivative. Similarly, the dimethylamino, morpholino, and hydrazino derivatives were prepared from the 6-bromo com-pound. ... 

Reaction of 2,4-dichloro-l,5-naphthyridine with ammonia (170°, 20 hr), hydrazine (100°, 16 hr), or aqueous hydrochloric acid (100°, 3 hr) was shown to yield the 2-amino- (47% yield) and 2-hydroxy-4-chloro derivatives (66% yield), but 2-hydrazino substitution (68% yield) was assumed. Disubstitution with ammonia (190°, 4 hr), hydrazine (100°, 48 hr), and ammonia-phenol (180°, 6 hr) occurred in high yield. Displacement of the 4-oxo group in 2,4-dioxo-l,5-naphthyridine occurs with aniline plus its hydrochloride (180°, 12 hr, 88% yield) to yield 429. Oxo groups in the 2- or 4-positions were... 

Tile chloro derivative 33a (not isolated) interacts with pyridine-2,3-diamine in dichloromethane at room temperature to yield 73 (85%) (93BSB357). A further example deals with the reaction between the salt 39 and benzene-1,2-diamine, which gives an imine 74 (80%) under special experimental conditions (93BSB357). In order for the reaction to work, the salt 39 must be isolated prior to its employment (Section IV,C,8). No traces of the diimines were detected for both cases. However, the experimental conditions were not optimized for this purpose since no more than three equivalents of the diamines were used (Scheme 23). 

Reaction of 2-hydroxy-4//-pyrido[l,2-u]pyrimidin-4-ones 168 and 2-chloromethylsaccharins 169 in the presence of a base gave 2-<9-alkylated products 170 (94EUP626378, 95JMC4687, 95USP5378720). From the reaction mixture of 3-chloro derivative 168 (R = H, R = Cl) and... 

When methylene chloride was used as a solvent, it was found that 28 are obtained in minor amounts, while the dominating product is the -coordinated chloro-carbyne species [(> -Tp )Mo(CO)2(=CCl)], whose yield increases abruptly with substitution in the pyrazol-l-yl fragments (3-methyl-, 3,4,5-trimethyl-, and 3,5-dimethyl-4-chloro derivatives) [90AX(C)59,95JCS(D) 1709]. The tungsten analog can be prepared similarly. The chlorocarbyne molybdenum complex follows also from the reaction of the parent anion with triphenylsulfonium cation but conducted in dichloromethane. The bromo- and iodocarbyne derivatives are made similarly. 

Aryloxy-9,10-dimethoxy-6,7-dihydro-4//-pyrimido[6,1 -a]isoquinolin-4-ones formed in the reaction of 2-chloro derivative and phenols in the presence of K2CO3 in DMF at 90 °C for 2. 5 h or in boiling 2-PrOH for 6-24 h (00MIP20). When 2-isobutylphenol was used the reaction was carried out in the presence of BuLi in THF at —78 °C. 

Halogenation of steroid 3-ketones can lead to complicated mixtures by virtue of the fact that the kinetic enol leads to 3 halo products, whereas the thermodynamic product is that halogenated at the 4 position. Carefully controlled reaction of the 5a-androstanolone with chlorine thus leads to the 2a-chloro derivative (29). Reaction of that intermediate with O(p-nitrophenyl)-hydroxylamine affords the androgenic agent ni stremine acetate (30). ... 

Though the great majority of antiinflammatory agents contain some form of acidic proton, occasional compounds devoid of such a function do show that activity. Thus the nonacidic pyrazolylpyrimidine epi razole (47) is described as a nonsteroid antiinflammatory agent. Reaction of pyrimidinone 42 with phosphorus oxychloride leads to the chloro derivative Replacement of halogen with hydrazine gives... 

An alternate scheme for preparing these compounds starts with a prefabricated pyrimidone ring. Aldol condensation of that compound (95), which contains an eneamide function, with pyridine-3-aldehyde (80), gives the product 96. Catalytic hydrogenation gives the product of 1,4 reduction. The resulting pyrimidinedione, of course exists in the usual tautomeric keto (97a) and enol (97b) forms. Reaction with phosphorus oxyxchloride leads to the chloro derivative 98. Displacement with methoxide gives 99. Reaction of this last intermediate with the furylalkylamine derivative 92 leads to the H-2 blocker lupitidine (100) [22]. 

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