Dimethylamino fulvene

N-Dimeihyljormamide-dimelhyl sulfate complex. In a 500-ml. four-necked flask equipped with mechanical stirrer, reflux condenser with calcium chloride drying tube, dropping funnel, and thermometer is placed 73 g. (1.0 mole) of dimethyl-formamide, and 126 g. (1.0 mole) of dimethyl sulfate is added dropwise with stirring at 50-60° (Note 1). After the addition is complete, the mixture is heated for another 2 hours at 70-80°. The dimethylformamide complex forms as a viscous, colorless or pale yellow ether-insoluble oil. 

6-(Dimetkylamino)fulvene. A 1-1. four-necked flask is equipped with mechanical stirrer, dropping funnel with calcium 

The crude product is crystallized after treatment with activated carbon from ca. 1.5 1. of petroleum ether (b.p. 60-80°) or 800 ml. of cyclohexane. From the orange-yellow solution 84 g. (69%) of 6-(dimethylamino)fulvene separates in yellow leaflets, m.p. 67-68° (Note 4). Concentration of the filtrate and further recrystallization of the residue from petroleum ether or cyclohexane gives an additional 8 g. of product. The combined yield is 92 g. (76%). 

The nitrogen delivery apparatus has been completely described.2 

Air and moisture must be carefully excluded from the reactants during the course of this preparation. 

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Oxidation of thiophene with peracid under carefully controlled conditions gives a mixture of thiophene sulfoxide and 2-hydroxythiophene sulfoxide. These compounds are trapped by addition to benzoquinone to give ultimately naphthoquinone (225) and its 5-hydroxy derivative (226) (76ACS(B)353). The further oxidation of the sulfoxide yields the sulfone, which may function as a diene or dienophile in the Diels-Alder reaction (Scheme 88). An azulene synthesis involves the addition of 6-(A,A-dimethylamino)fulvene (227) to a thiophene sulfone (77TL639, 77JA4199). 

Fulvene-type enamines, which possess some nonbenzenoid aromatic character, have been synthesized by treating cyclopentadienylsodium with an amide-dimethyl sulfate eomplex (117aJ17b) or quaternary pyridinium salts (117c). One of the simplest ones produced is 6-(dimethylamino)fulvene (117a,117d). 

Dimethylamino)fulvene is light-sensitive and is stored in brown bottles. 

This procedure illustrates formylation by N,N-dimethylamino-methoxymethylium methyl sulfate, a compound which can be produced readily by reaction of easily available materials. 6-(Dimethylamino)fulvene is a useful intermediate for the synthesis of various f used-ring nonbenzenoid aromatic compounds. 

Dimethylamine, reaction with phosphorus trichloride, 46, 42 f-Dimethylami nobenzaldehyde, conversion to 0,/9-dichloro- -dimethyl-aminostyrene, 46, 34 tn-Dimethylaminobenzoic acid, 47, 71 /5-Dimethylaminobenzoic acid, 47, 71 6.(Dimethylamino)fulvene, 47, 52 -Dimethylaminophenylacetic acid, 47, 71... 

Phenylcyclopent[c]azcpine (33a) and 6,7-fused cyclopentazepines 33b-d are formed in moderate yields in a one-pot, two-stage process involving initial condensation of triphenyl-[(l-phenylvinyl)imino]phosphoranes 32 with 6-(dimethylamino)fulvene-2-carbaldehyde (30), followed by an intramolecular aza-Wittig reaction of the iminophosphorane with the pendant aldehyde function.5 The method fails with the unsubstituted vinylphosphorane 32 (R1 = R2 = H). 

Kato et al. (151,152) explored the chemistry of 2-ferf-butylMvenes with isomiinchnones, as well as with several other mesoionic compounds, in a novel approach to pseudo-hetero-azulenes. Thus, isomtinchnone 51a, generated as before in situ from A-benzoylphenylglyoxyanilide 253 with triethylphosphite, reacts with 2-ferf-butyl-6-(dimethylamino)fulvene to give the [47i+6ti] adduct diphenylcyclo-penta[c]pyran in low yield. Likewise, reaction of 51a with dimethylfulvene gave a mixture of two adducts, one of which arises from a [47i+2ti] cycloaddition. 

An azulene synthesis involves the addition of 6-(iV,iV-dimethylamino)fulvene (208) to a thiophene sulfone (77TL639, 77JA4199). 

The radical cations of fulvene systems are of interest, because steric and electronic factors might favor a perpendicular structure and because the energy difference between the respective cis and trans isomers are expected to be small. However, the chloranil photosensitized reaction resulted in CIDNP effects, indicating planar or slightly twisted structures. The Z- and E-2-tert-butyl-6-(dimethylamino)fulvene [20, R = — N(CH3)2] radical cations rearrange readily whereas di-/er/-butylfulvene [20, R = — C(CH3)3] showed no interconversion under comparable experimental conditions [160]. 

Cyclopentadienyl-SMA have been obtained through addition of triphenylsilylithium reagent to 6-(dimethylamino)fulvenes, hydrolysis and final treatment of the residue with methyl iodide.196... 

A first series was reported on the reaction of simple aryl lithium species with 6-(V,(V-dimethylamino fulvene and subsequent transmetallation. Thereby, it was possible to synthesise para-methoxy phenyl (15), /V./V-di methyI -pheny I (16) and benzo[l,3]dioxole phenyl-substituted (17) dimethylamino-functionalised titanocene dichlorides, which show IC50 values in the range of 54 pM [22]. This represents a significant improvement in cytotoxicity compared with the benzyl-substituted titanocenes by a factor of 3 for titanocene 16 (IC50 for the benzyl-substituted analogue 120 pM) and even 10 for titanocene 17 (IC50 for the benzyl-substituted analogue 280 pM). The sole decrease in cytotoxic activity was... 

Unfortunately, the carbolithiation reaction of lithium species with 6-/V, /V-dimethylamino fulvene and subsequent transmetallation reaction leads to titano-cenes with stereoisomers, as an equimolar mixture of the R and S form of the substituted lithium cyclopentadienide is formed. Subsequently, this equimolar mixture of R and S configured substituted lithium cyclopentadienide is used for the transmetallation reaction and therefore, a mixture of the 25% of RJt, 25% of the S,S and 50% of the R.S form of the chiral titanocene dichloride is obtained. 

Stoichiometric lithium naphthalenide has been used for the lithiation of 6,6-bis(dimethylamino)fulvene 687, generating at —78 °C the lithioenamine 688, which has been used for the preparation of 6-aminofulvenes in moderate yields993 (Scheme 178). 

Thiophene 1,1-dioxide did not undergo cycloaddition with electron-deficient dienophiles. In most of the cases the dihydrobenzothiophene derivative 109 was obtained as the major product. This shows that self-dimerization is faster than cycloaddition with a different molecule. In the case of dimethyl acetylenedicarboxylate (DMAD) and 4-phenyl-3//-l,2,4-triazole-3,5(4//)-dione (PTAD), the Diels-Alder adducts 111 and 112 of 109 were obtained <1997JA9077>. However, cyclopentadiene gave the Diels-Alder adduct 113 with thiophene 1,1-dioxide. The DMAD adduct 111 on thermolysis undergoes a retro-Diels-Alder reaction to give dimethyl phthalate and thiophene 1,1-dioxide. Azulene was isolated in the thermolysis of 108 in the presence of 6-(dimethylamino)-fulvene this was the result of a [4-1-6] cycloaddition of the thiophene 1,1-dioxide formed in the reaction followed by elimination of SO2 and dimethylamine (Scheme 28) <1999BCJ1919>. 

The rate constants for protonation at the metal of (6-dimethylamino-fulvene)M(CO)3 increase in the order Cr < Mo < W quantitative results are given but they appear unreliable. Proton transfer between protonated and unprotonated forms of (arene)Cr(CO)j is fast on the NMR time scale and occurs by rate-determining proton removal by the conjugate base ([FSOj] ) of the acid employed" (FSOjH). 

Condensation with active-methylene compounds. The acetal condenses with cyclopentadiene without solvent at the reflux temperature to give 6-dimethylamino-fulvene (4, m.p. 67°). Similar condensations are reported with acetophenone, malononitrile, nitromethane, ethylacetoacetate. 

The donor-acceptor-substituted calicene 8 undergoes an interesting cycloaddition with 6,6-bis(dimethylamino)fulvene (9) to give the fulvene-annulated azulene 10 besides the substitution product 11. ... 

The amino group of 6-(dimethylamino]fulvene is itself readily replaced by nucleophilic attack. The following reactions serve as examples [73,247] ... 

Reaction of 6-(dimethylamino)fulvene with lithium aluminium hydride or with organolithium compounds has provided a route for the preparation of fulvene itself and its 6-substituted derivatives [248] ... 

Monoformylation of 6-(dimethylamino)fulvene followed by hydrolysis gives 2-formyl-6-hydroxyfulvene [73] ... 

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