Ammonia benzylic compounds

The benzylideneoxazolone (189) reacts with amines to give a-benzamidocinnamides, which can be induced to cyclize in different ways by a choice of conditions (Scheme 19). The N-benzyl compound (203), for instance, yields an imidazolinone under the influence of bases, whereas the action of perchloric acid produces the oxazole derivative (204). The latter gives the stable oxazoleimine (205) on deprotonation. Treatment of the ternary imonium perchlorate (206) with ammonia, followed by sodium hydroxide, affords the orange diazafulvene shown (72JCS(P1)1140). 

Thio-D-xylopyranose has been the sugar of this type most thoroughly investigated. Its synthesis was reported in 1961, independently and simultaneously from three different laboratories. With sodium thiocyanate, l,2-0-isopropylidene-5-0-p-tolylsulfonyl-a-D-xylofuranose (211) gives a thiocyanate that reacts with sodium sulfide to give l,2-0-isopropylidene-5-thio-a-D-xylofuranose (212). A better synthesis is the treatment of 211 with sodium thiosulfate, followed by reduction of the resultant Bunte salt with sodium boro-hydride. The same compound 212 is obtained by nucleophilic replacement of the 5-sulfonyloxy group in 211 by treatment with potassium thioacetate followed by deacetylation to 212, or by the reaction of 211 with sodium a-toluenethioxide, followed by scission of the resultant S-benzyl compound with sodium in liquid ammonia. 

An interesting alternate synthesis for this agent starts with the chlorination of the benzylic carbon of 8 by means of N ( li lorosuccinimide. Treatment of the chloro compound (9) with M)Jium amide in liquid ammonia serves to remove remaining proton I ll that carbon. This carbanion (10) then performs an alkylation iiMCtlon on unreacted starting chloride. The product of this iilkylation (11) still contains a fairly acidic benzylic proton ... 

In the former Soviet Union much use is made of industrial by-products to prepare acid inhibitors. The PB class is obtained by treating technical butyraldehyde with ammonia and polymerising the resulting aldehyde-ammonia. PB-5, for example, with O-Ol-O-15% of an arsenic salt is used in 20-25% HCl. A mixture of urotropine (hexamethyleneimine, hexamine) with potassium iodide, a regulator and a foaming agent is the ChM inhibitor. BA-6 is prepared from the condensation product of hexamine with aniline. A more recent development is the Katapin series which consists of /7-alkyl benzyl pyridine chlorides Katapin A, for example, is the /7-dodecyl compound. 

The first clue to the existence of the SrnI mechanism came from product studies both in aliphatic and aromatic cases. It was noticed that in the reaction of benzyl and substituted benzyl chlorides with the 2-nitropropane anion, oxygen alkylation, yielding the oxime and then the aldehyde, occurs exclusively in the case of benzyl chloride and 3-nitrobenzyl chloride, whereas, with 4-nitrobenzyl chloride, the yield of aldehyde is only 6% and the carbon-alkylated (104) product is obtained in 92% yield (Kornblum, 1975). This was interpreted as the result of a competition between 8, 2 (O-alkylation) and S l (C-alkylation) reactions. In the aromatic case, it was observed that the reaction of 5- and 6-halopseudocumenes with KNHj in liquid ammonia (Kim and Bunnett, 1970) forms the 5- and 6-pseudocumi-dines in a ratio which is the same whether the starting compound is the 5- or 6-isomer in the case of the chloro- and bromo-derivatives, as expected from an aryne mechanism (Scheme 9), whereas much more non-rearranged... 

The preparation of 2-benzylcyclopentanone from 2-benzyl-2-carbomethoxycyclopentanone has not been previously reported. Starting with the ethyl ester, however, the compound has been prepared by heating the ester for many hours with concentrated hydrochloric acid. - The direct alkylation of cyclopentanone with benzyl chloride in the presence of sodium amide in liquid ammonia goes only in a poor yield. ... 

In addition to amino-methylamine exchanges, amino-benzylamine exchanges were found. When iv-benzyl salts of pyrimidine, 4,6-dimethyl-pyrimidine, and 4-t-butylpyrimidine react with liquid ammonia, the respective debenzylated compounds were isolated (Scheme III.9) (82JHC3739). 

Dibenzopyrrocolines have been prepared by intramolecular addition of benzyne intermediates and by nucleophilic substitutions, as shown in Scheme 6 with the synthesis of ( )-cryptowoline (2) and the related dehydro base 39 by Bennington and Morin (7). ( )-6 -Bromotetrahydroisoquinoline 37, prepared by standard procedures, when heated with copper powder in dimethylformamide afforded dibenzopyrrocoline 38 in low yield, and 39 was formed when 37 was allowed to react with potassium amide in liquid ammonia. Compound 39 was converted to ( )-cryptowoline iodide (2) by hydrogenolysis of O-benzyl ether 39 and quartemization with methyl iodide. 

All nuclear nucleophilic substitutions on derivatives of compound 4 have involved the replacement of a substituent at position 7 (the equivalent of the y -position in pyridine). In the 7-chloro derivative 244, replacement is possible by methoxide ion,151 by ammonia (with some rearrangement)192 and by amines,151 and by thiourea to give the sulfide (245).151 Substituted 7-chloro derivatives undergo replacement by benzyl oxide ion to give a 7-benzyloxy derivative155,220 and by azide,153 hydrazine,216 hydrosulfide (to give the 7-thione166), and methyl thiolate.220 Some of these compounds carry D-ribofuranosyl benzoate substituents on N-2 or N-3, and methoxide ion... 

Removal of N-benzyl substituents from the compounds 373,38 374a,38 374b,4008 and 375205 was successfully achieved using sodium in liquid ammonia, but an attempt to debenzylate 376 by catalytic hydrogenation failed. 78... 

The pyridazine dioxide derivative (108) was made by intramolecular nitroso compound dimerization as shown (Scheme 23). 1,2-Oxathiin 2,2-dioxides are obtained by the addition of sulfuric acid to a,(3-unsaturated ketones, e.g. (109) — (110) (66HC(21-2)774). 1,2-Dithiins are synthesized from conjugated diynes using benzyl thiol reductive debenzylation of intermediate (111) by sodium in liquid ammonia at - 70°C gives, after aerial oxidation, the 1,2-dithiin (112) (67AG(E)698). 

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