Benzylidene derivative

Benzaldehyde reacts (J59) with D-glucose and with methyl a- and )8-d-glucopyranosides to form the 4,6-0-benzylidene derivatives. In the 0-ben-zylidene and related compounds, the acetal carbon is asymmetric and should give rise to two isomers. Evidence has been evinced that such isomers exist and that some are relatively unstable 160). 

The mono-O-benzylidene-a-D-glucose, formed according to the reaction illustrated, reduces Fehling solution and forms a hydrazone and an osazone therefore, it must have carbons 1 and 2 unsubstituted. The following sequence of reactions furnishes evidence to fix the structure of the substance as 4,6-0-benzylidene-a-D-glucose 161). 

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Benzylidene derivatives. Compounds containing the. keto-methylene group (—CH CO) react with benzaldeliyde to yield benzylidene derivatives ... 

Dissolve 1 g. of the ketomethylene compound and 1 1 g. or 2 2 g. of pure benzaldehyde (according as to whether the compound may be regarded as RCOCHjR or as RCHjCOCHjR ) in about 10 ml. of rectified (or methylated) spirit, add 0 5 ml. of 5.N -sodium hydroxide solution, shake and allow the mixture to stand for about an hour at room temperature. The benzylidene derivative usually crystallises out or will do so upon scratching the walls of the vessel with a glass rod. Filter off the solid, wash it with a little cold alcohol, and recrystallise it from absolute alcohol (or absolute industrial spirit). 

The benzylidene derivative above is used, if both hydroxyl groups on C-2 and C-3 are needed in synthesis. This r/vzns-2,3-diol can be converted to the sterically more hindered a-cpoxide by tosylation of both hydroxy groups and subsequent treatment with base (N.R. Williams, 1970 J.G. Buchanan, 1976). An oxide anion is formed and displaces the sulfonyloxy group by a rearside attack. The oxirane may then be re-opened with nucleophiles, e.g. methyl lithium, and the less hindered carbon atom will react selectively. In the following sequence starting with an a-glucoside only the 2-methyl-2-deoxyaltrose is obtained (S. Hanessian, 1977). 

Scheme 97). Stepanov has thoroughly studied this nucleophilic reactivity some examples are given in Refs. 423 and 424. The formation of 5-benzylidene derivatives involves the same nucleophilic reactivity (422). 5-Benzothiazoline and 5-benzose enazoline derivatives of 2-diphenylaminothiazoline-4-one, have been obtained by nucleophilic addition of the thiazolone on the corresponding benzothiazolium or ben-zoselenazolium salts (433). 

However, benzylidene derivatives show a strong bathochromic shift in comparison with alkylidene derivatives. Thus absorption is a result of the whole conjugated system that is comparable to that of the quinoid dyes. The color of this type of compound is sensitive to acids and bases. 

The phenomenon of 5-hydroxymethylation is a standard case of electrophilic attack. Thus uracil (83 R = H) and paraformaldehyde in aqueous alkali furnish 5-hydroj(ymethyl-pyrimidine-2,4(l//,3//)-dione (83 R = CH20H) in good yield (59JA2521). Aromatic aldehydes react differentiy to yield 5-benzylidene derivatives of, for example, 1-methylbar-bituric acid (78CC764). 

There are many synthetic routes to alloxan. Probably the best is direct oxidation of barbituric acid (1004 R = H) with chromium trioxide (5208(32)6) but it may be made from barbituric acid via its benzylidene derivative by direct or indirect oxidation of uric acid from 5-chlorobarbituric acid (1004 R = C1) by nitration or from 5-nitrobarbituric acid (1004 R = N02) by chlorination, both via the intermediate (1005) (64M1057) or by permanganate oxidation of uracil (1006) under carefully controlled conditions (73BSF1167). 

Amino substituents also behave normally with electrophiles, being acylated and converted to benzylidene derivatives. A-Amino groups have also been converted to benzylidene derivatives and are removed on treatment with A-nitrosodiphenylamine (79JHC249). 

Dithiols, like diols, have been protected as 5,5 -methylene, 5,5 -isopropylidene, and 5,5 -benzylidene derivatives, formed by reaction of the dithiol with formaldehyde, acetone, or benzaldehyde, respectively. The methylene and benzylidene derivatives are cleaved by reduction with sodium/ammonia. The isopropylidene and benzylidene derivatives are cleaved by mercury(II) chloride with sodium/ ammonia the isopropylidene derivative is converted to a monothio ether, HSCHR-CHRSCHMe2- ... 

Haines and Karntiang later adopted a somewhat more symmetrical approach in the synthesis of glycerol-based cryptands when they utilized the six-membered benzylidene derivative of glyceroP. Details of the synthesis described in Eq. (8.8), above, are also presented in this paper. The symmetrical approach is quite similar to that described in Eq. (8.8), and is outlined below in Eq. (8.9). 

Thebainol (Pschorr Dihydrometathebainone (Schopf i), CigHjgOjN, is obtained by the reduction of metothebainone, with sodium amalgam in dilute alkali. Crystallised from methyl alcohol, it melts at 54-5° and re-melts at 76-8°, but after crystallisation from dry ether it has m.p. 135-6° and [a]f ° + 67-05° (EtOH). The oxime has m.p. 217-8° and [a][, ° + 104-2° (acetic acid, 10%). The benzylidene derivative forms yellow needles, m.p. 100-2°. An amorphous dipiperonylidene derivative has been described by Gulland and Robinson.The methyl ether is amorphous, but yields a crystalline methiodide, m.p. 245°. Thebainol is represented as (L), produced by saturation of the ethylenic (C -C ) linkage in meta-thebainone (LII). 

Dihydro- -strychnine, C21H24O3N2, m.p. 240-3° (vac.), [a]D38-7/d (CHCI3), forms a methyl ether, m.p. 209° (vac.) and a benzylidene derivative, m.p. 209-215° (Leuehs and Rack, 1940). Unlike -strychnine, the dihydro-derivative can be converted, either by boiling with acetic anhydride or by condensation with malonie acid, into the corresponding 9-acetie acid, in this ease dihydrostrychnine-9-acetie acid, C23H26O4N2, m.p. 300-3° (vac. dec.), 43-0° (H2O) (Leuehs et al., 1942). 

Stryehnine-9-acetic acid yields a typical yellow benzylidene derivative, m.p. 285-8°, but dihydrostryehnine-9-aeetie acid forms a colourless compound, isolated as the perchlorate, C3(,H3(,04N2, H2O, HCIO4, m.p. 205-225° (dec.), which may be an isobenzylidene derivative, though it gives a transient blue colour with sulphuric acid and potassium diehromate. 

Formation of an 11-methoxybenzyl ether occurs in satisfactory yield during the preparation of a 17,21 -benzylidene derivative [e.ff., (26)]. The usefulness of this ether and of related mixed acetals in removing the inhibitory effect of the 11 j5-hydroxyl group on the 20-ketone reduction has been reported. ... 

A/,A/-Dimethylamino)ethylidene Derivative, 234 a-(A/,A/-Dimethylamino)benzylidene Derivative, 234... 

The / -methoxybenzylidene acetal is a versatile protective group for diols that undergoes acid hydrolysis 10 times faster than the benzylidene group. As with the benzylidene derivative, the 1,3-derivative is thermodynamically favored over the 1,2-derivative. ... 

In 1908, while working at University of Heidelberg, Auwers and Muller described the transformation of 4-methyl-2-cumaranone (3) to flavanol 6. Thus aldol condensation of 3 with benzaldehyde gave benzylidene derivative 4, which was brominated to give dibromide 5. Subsequent treatment of 5 with alcoholic KOH then furnished 2-methylflavonol 6. In the following years, Auwers published more extensively on the scope and limitations of this reaction. ... 

This structure rationalizes (a) the formation of mono- and, under more vigorous conditions, tetra-acetyl derivatives, (b) the methyla-tion to a dimethyl derivative still containing two active hydrogens, (c) the pyrolysis back to monomeric indole, (d) the formation of a benzylidene derivative containing the Ph CH=N— Ar ehromophore, (e) the failure to form a simple nitroso derivative, (f) the Zn/AcOH reduction of the dimethyl trimer to base C18H20N2, shown to be identical with the dihydro derivative of (26). 

Other substituents Alkjd of p-dialkylamino group Mp (°C) of isopropylidene derivative Mp C C) of benzylidene derivative... 

The action of ferric chloride and hydrogen peroxide on isopropyli-dene and benzylidene derivatives of 2-hydrazinoselenazole yields deeply colored compounds of the 2,2 -dioxo-A -biselenazol-5,5 -inylidene bis-hydrazone type. (Cf. Table VIII.)... 

Other substituents Bis-isopropylidene derivative, mp ( C) Bis-benzylidene derivative, mp ( C)... 

O-isopropylidene derivative (10) was then phosphorylated with phosphorous oxychloride to form the phosphate ester (11) from which the protecting groups were removed by mild acid hydrolysis. The 3-phos-phate (15) was obtained by phosphorylating the 4,6-benzylidene derivative (13) of the same glycoside with phosphorus oxychloride, followed by hydrolytic removal of the protecting groups, from the ester (14) thus obtained. 

Unlike the 4,6-O-benzylidene derivatives, methyl 2,3-O-benzylidene-5-0-methyl-/ -D-ribofuranoside (99) (9) in which the acetal spans two secondary hydroxyl groups, reacts with NBS to give (48) the isomeric bromobenzoates 100 and 101. These are formed in a ratio of 2 1, and,... 

The ready synthesis of iminophosphorane 767 from 766 and its subsequent conversion to benzylidene derivative 768 and aza-Wittig reaction... 

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