Aryliden derivatives

Alkylidene or 4-arylidene derivatives of A-2-thiazolin-5-one have been used as 4-alkyl-A-2-thiazoline-5-one precursors. Thus reduction of... 

Dioxopiperazines have been converted into the corresponding dihydroxypyrazines by base catalyzed isomerization of the corresponding arylidene derivatives (Scheme 64) (70JCS(C)980), although this reaction appears to be limited to the synthesis of benzyl- or aryl-substituted benzylpyrazines. 

The pvnmido[2,l-7][l,3]thiazine 296 reacted with aromatic aldehydes in AcOH to form the 3-arylidene derivatives <1996PS(113)67>. 

With sodium methoxide, arylidene derivatives 209 undergo a rearrangement into photochromic dihetaryl-substituted cyclopentenediones 211. They are easily alkylated to form geminally substituted products 212 in 91-94% yields (07MC301). Their photochemical properties were investigated (07OS975, 08IZV853). 

In general RuO - normally likely to be the active species in most Ru-assisted carbohydrate oxidations - is an excellent oxidant for aUcylidene and arylidene derivatives [311,317]. 

A novel approach to the synthesis of a 1,5-naphthyridine starts from quinuclidin-3-one (143), which is first converted to the 2-arylidene derivative and then reacted with phenacyl-pyridinium bromides and ammonium acetate to give l,4-ethano-3,4-dihydro-2//-l,5-naph-thyridines (144) (82S27). 

Earlier work had revealed [70JCS(C)980] that the 3-arylidene derivatives possess the Z-configuration. Gallina and Liberatori have confirmed this. In addition, they have isolated both Z and E alkylidene derivatives from condensation with aliphatic aldehydes. In the H-NMR spectrum, the vinylic proton is deshielded by 0.65 ppm in the Z isomer (88) compared to the E isomer (89). Other workers have confirmed these observations [80JCS(P1)419],... 

It has been reported that KF/alumina is a useful catalyst for the condensation of l,4-diacetylpiperazine-2,5-dione with aldehydes under micro-wave irradiation (90SC3325). High yields of the mono- or bis-arylidene derivatives having the Z-configuration have been obtained. 

Reaction of 2-acyl-l,2,3,4,ll,lla-6H-hexahydropyrazino[l,2-fr]isoqui-noline-l,4-diones with aromatic aldehydes in the presence of KOfBu in CH2CI2 afforded 2-unsubstituted-3-arylidene derivatives (09T2201). From a similar reaction of czs-6H,llaH-6-benzyloxymethyl-9-methyl-7,8,10-trimethoxy-2-pivaloyl-l, 2,3,4,11,11 a-6H-hexahydropyrazino[l, 2-b] isoquinoline-1,4-dione and 3-methyl-2,4,5-benzaldehyde 2-unsubsti-tuted-3-(3-methyl-2,4,5-trimethoxyphenyl)methylene and 2-pivaloyl-3,3-dihydroxy derivatives were isolated in 20% and 39% yields, respectively. 

The fixed geometry of a, 3-unsaturated ketones in the S-cis form, as observed in arylidene alkanones, influences their reactivity. For example, the reaction of arylhydrazines with 3,5-diarylidene-4-piperidones, 2-arylidene-l-tetralones, 2,6-diarylidenecyclohexanones and 2-arylideneindan-l,3-diones requires stronger conditions than for the case of their noncyclic analogues [76, 77, 78, 79, 80, 81, 82, 83, 84]. However, arylidene derivatives of cyclohexanone, 1-indanone, 4-chromanone, 4-thiochromanone and TV-methyl-4-piperidone hydrochloride react with hydrazines more easily [85,86,87,88], It is interesting to note that the more complicated and sterically hindered unsaturated ketones of the spiro type 64 react with hydrazine and phenylhydrazine very easily in the presence of piperidine, leading to pyrazoles 65 in high yields [89] (Scheme 2.16). 

Condensation of monochloroacetic acid with an arylthiourethan (41) in glacial acetic acid leads to 42 [Eq. (12)].76 With alkylthiourethans, reaction temperatures must be maintained at 160°-170°.77 Simultaneous reaction of the starting materials or 42 with aromatic aldehydes affords high yields of the 5-arylidene derivatives.76 Similarly, arylamides of arylsulfonylcyano-thioacetic acids condense with a-halocarboxy compounds to afford 2-substituted 4-thiazolidinones.78... 

A convenient synthesis [Eq. (13)] of 2-ary lidenehydrazono-4-thia-zolidinone (43) from ethyl thiocyanoacetate (44), arylideneazines (45), and hydrazine hydrate (46) has been reported.79 Presumably, the reaction proceeds via the intermediary hydrazone, which condenses with 44 to give 43. Subsequently, condensation of 43 with the aromatic aldehyde, generated in situ from disproportionation of the azine with hydrazine, affords the 5-arylidene derivative. The reaction of 44 with ammonium acetate and an aromatic aldehyde gives 5-arylidene-2-imino-4-thiazolidinones.80... 

Pyridylethyl derivatives of 2 are formed by reaction of a- or y-vinyl-pyridine with 2.107 Treatment of 1 or 2, as well as the 5-arylidene derivatives, with acrylonitrile in the presence of pyridine results in formation of 84 by cyanoethylation on the ring nitrogen (Scheme 2) however, cyanoethyla-tion of 5-aryl-2-iminothiazolidinones involves the exocyclic nitrogen.108 Aminoalkylation (Mannich reaction) of 2 or 2-aryl-4-thiazolidinones with formaldehyde and amines in warm alcoholic solvents affords the desired 3-alkylated product 85 (Scheme 2),109,110 whereas 3-aryl-2-iminothiazoli-dinones react with substituted anilines and aliphatic amines and formaldehyde to give the 2-arylaminomethyl derivatives 86 [Eq. (25)].111... 

The 5-arylidene derivatives (e.g.,96) react with Grignard reagents via 1,4-conjugate addition to the exocyclic double bond to afford 97 [Eq. (28)] heterocyclic ring opening does not occur under these conditions.121 126,134,138 Other nucleophiles, such as p-thiocresol and piperidine, add 1,4 to exocyclic double bonds to give the simple adducts 97 (R = SAr and NR 2, respectively). 134 5-Methyl-3-phenyl-2-phenylimino-4-thiazolidinone undergoes... 

Phenylhydrazono-4-thiazolidinones (124) and their 5-substituted derivatives are cyclized upon treatment with formaldehyde or aromatic aldehydes to give the bicyclic structure 125.169 5-Arylidene derivatives of 126 have been cyclized to 127 by initial treatment with chloroacetic acid, followed by hot acetic anhydride or concentrated sulfuric acid.170... 

Cyclization of the 4-phenylhydrazono derivatives of 2-thiazolidinone with formaldehyde or aromatic aldehydes gives 2-phenyl-2,3-dihydro-thiazolo[4,3-c]l,2,4-triazol-5-ones (131) [Eq. (39)] subsequent condensation with aldehydes affords the corresponding 7-arylidene derivatives.171... 

The most fruitful and general route to (13) and its derivatives seems to be via oxidative ring closure (using bromine or lead tetraacetate) of the alkylidene or arylidene derivatives of the corresponding 3-hydrazinopyridazine (Scheme 41) (66T2073). Alternatively, thermal... 

Due to the rapid rearrangement of the [4,3-a] series into the [1,5-a] series (see Section 4.15.4.5.2) uncontaminated [l,2,4]triazolo[4,3-a]pyrimidines are difficult to prepare. The only useful methods available (Scheme 45) seem to be treatment of an appropriate 2-hydrazinopyrimidine with a low boiling ortho ester (for 3-H, 3-Me, 3-Et and 3-Pr) or oxidative ring closure of an arylidene derivative of 2-hydrazinopyrimidine to form the 3-aryl compounds (77AJC2515). 

Trimethyl-l,6-dihydropyrimidine-2-thione (113), on condensation with aromatic aldehydes in ethanolic KOH, gives arylidene derivatives 114 which react with chloroacetic acid in the presence of anhydrous sodium acetate in acetic anhydride to afford a cyclized product formulated as 115 (81 Mil) that can also be represented by the alternate structure 116 (Scheme 25). Similarly, the thione 113 reacts with chloroacetic acid and aromatic aldehydes in the presence of anhydrous sodium acetate in acetic acid and acetic anhydride to furnish a cyclized product for which structure 117 has been assigned without any evidence (81 Mil). The cyclized product can also be represented by the other isomeric structure 118. The bicyclic compound (115 or 116) condenses with aromatic aldehydes to give arylidene derivatives that are also obtained in a single-step synthesis involving the reaction of 114 with chloroacetic acid and aromatic aldehydes in the presence of anhydrous sodium acetate in acetic acid and acetic anhydride. 

Dihydropyridazine-3,6-diones have reactive methylene groups, and they react with aromatic aldehydes to give 4,5-bis-arylidene derivatives (86JPR932 87JPR525). Pyridazines have been shown to undergo 1,3-dipolar cycloaddition with diazomethane [82H(I8)I75 88HI43I],... 

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