Diene anhydride

Functionalization of paraffins to the corresponding olefins, dienes, anhydrides, unsaturated acids and nitriles is of industrial interest [1] since paraffins are much more abundant and less expensive than the corresponding olefins. For this reason research interests have recently shifted away from olefins and towards paraffins as starting feeds for the production of petrochemicals and industrial intermediates. Oxydehydrogenation of paraffins is a viable approach towards this goal. 

E,4E)-Hexa- Maleic Endo-major product 2,4-diene anhydride (plus enantiomer)... 

The photocycloaddition of cis-1,2-dihydrophthalic anhydride to benzene, naphthalene, or anthracene affords in each case products arising from ( 4j + 4J reaction, a type of addition unknown for cyclohexa-1,3-diene itself. Energy transfer from benzene to the diene anhydride still provided the main reaction pathway, namely electrocyclic closure to give the cis-dihydroDewarbenzene anhydride. The naphthalene photo-adduct (393) on xanthone-photosensitized irradition gave the cage compound (394) similar reaction also occurs with the benzene photo-adduct. 

The Diels-Alder Reaction consists in the direct combination of a compound containing a conjugated diene system u ith a reagent which possesses a double or triple bond activated bj suitable adjacent groups. Examples of such reagents are maleic anhydride, p-benzoquinone, acraldehyde and acetylene dicarboxylic esters. Combination always occurs at the 1,4 positions of the diene system ... 

The mechanism of the diene synthesis appears to involve an electron transfer from the diene to the dienophile, .e., it is initiated by an ionic reaction. The following scheme may represent the addition of 2 3-dimethylbutadiene to maleic anhydride ... 

The product of a Diels-Alder cycloaddition always contains one more ring than was present m the reactants The dienophile maleic anhydride contains one ring so the product of Its addition to a diene contains two... 

P4ALEIC ANHYDRIDE, MALEIC ACID AND FUMARIC ACID] (Vol 15) 9a,21-dichloro-17-[(2-furanyl-carbonyl)oxyl]-llb-hydroxy-16a-methyl-pregna-l,4-diene-3,20-dione. See Mometasone fluroate. 

The balance between aromatic and aUphatic reactivity is affected by the type of substituents on the ring. Furan functions as a diene in the Diels-Alder reaction. With maleic anhydride, furan readily forms 7-oxabicyclo [2.2.1]hept-5-ene-2,3-dicarboxyhc anhydride in excellent yield [5426-09-5] (4). 

Maleic anhydride has been used in many Diels-Alder reactions (29), and the kinetics of its reaction with isoprene have been taken as proof of the essentially transoid stmcture of isoprene monomer (30). The Diels-Alder reaction of isoprene with chloromaleic anhydride has been analy2ed using gas chromatography (31). Reactions with other reactive hydrocarbons have been studied, eg, the reaction with cyclopentadiene yields 2-isopropenylbicyclo[2.2.1]hept-5-ene (32). Isoprene may function both as diene and dienophile in Diels-Alder reactions to form dimers. 

Concerted Nonpolar Reactions. Maleic anhydride exemplifies the model dienophile for cycloaddition with dienes such as 1,3-butadiene... 

The success of the cycloaddition reaction of maleic anhydride varies gready depending on which heterocyclic diene is used. The cycloaddition of maleic anhydride to furan [110-00-9] occurs ia a few seconds under ambient conditions (42,43). Although the endo adduct (14) is favored kiaeticaHy, the exo adduct (13) is isolated. 

Endo adducts are usually favored by iateractions between the double bonds of the diene and the carbonyl groups of the dienophile. As was mentioned ia the section on alkylation, the reaction of pyrrole compounds and maleic anhydride results ia a substitution at the 2-position of the pyrrole ring (34,44). Thiophene [110-02-1] forms a cycloaddition adduct with maleic anhydride but only under severe pressures and around 100°C (45). Addition of electron-withdrawiag substituents about the double bond of maleic anhydride increases rates of cycloaddition. Both a-(carbomethoxy)maleic anhydride [69327-00-0] and a-(phenylsulfonyl) maleic anhydride [120789-76-6] react with 1,3-dienes, styrenes, and vinyl ethers much faster than tetracyanoethylene [670-54-2] (46). 

Diels-Alder Reactions. The important dimerization between 1,3-dienes and a wide variety of dienoplules to produce cyclohexene derivatives was discovered in 1928 by Otto Diels and Kurt Alder. In 1950 they won the Nobel prize for their pioneering work. Butadiene has to be in the j -cis form in order to participate in these concerted reactions. Typical examples of reaction products from the reaction between butadiene and maleic anhydride (1), or cyclopentadiene (2), or itself (3), are <7 -1,2,3,6-tetrahydrophthaHc anhydride [27813-21 -4] 5-vinyl-2-norbomene [3048-64-4], and 4-vinyl-1-cyclohexene [100-40-3], respectively. 

In a study of the relative rates of addition of 20 dienophiles to cyclopentadiene, TCNE was at the head of the Hst, eg, it added 7700 times as rapidly as maleic anhydride (15). Reaction with most 1,3-dienes takes place rapidly and in high yield at room temperature. TCNE has often been used to characterize 1,3-dienes, including those that are unstable and difficult to isolate (16). 

Cyclopentadiene contains conjugated double bonds and an active methylene group and can thus undergo a Diels-Alder diene addition reaction with almost any unsaturated compound, eg, olefins, acetylene, maleic anhydride, etc. The number of its derivatives is extensive only the reactions and derivatives considered most important are discussed. 

The diene addition is stereochemically specific (22). Although two stereoisomers are possible, the endo and the exo forms, in the addition of maleic anhydride to CPD the endo adduct is the exclusive product (23). 

In the case of vinylfurans and vinylpyrroles there is the possibility of cycloaddition involving either the cyclic diene system or the diene system including the double bond. 2-Vinylfuran reacts in high yield with maleic anhydride in ether at room temperature to form the adduct involving the exocyclic double bond. Similarly, 2- and 3-vinylpyrroles react with 7T-electron-deficient alkenes and alkynes under relatively mild conditions to give the corresponding tetrahydro- and dihydro-indoles (Scheme 51) (80JOC4515). 

Benzo[Z)]furans and indoles do not take part in Diels-Alder reactions but 2-vinyl-benzo[Z)]furan and 2- and 3-vinylindoles give adducts involving the exocyclic double bond. In contrast, the benzo[c]-fused heterocycles function as highly reactive dienes in [4 + 2] cycloaddition reactions. Thus benzo[c]furan, isoindole (benzo[c]pyrrole) and benzo[c]thiophene all yield Diels-Alder adducts (137) with maleic anhydride. Adducts of this type are used to characterize these unstable molecules and in a similar way benzo[c]selenophene, which polymerizes on attempted isolation, was characterized by formation of an adduct with tetracyanoethylene (76JA867). 

Benzo[c]furan, generated in situ in boiling xylene in the presence of dimethylmaleic anhydride, gives mainly the exo adduct furan itself fails to react with this dienophile (Scheme 53) (82JOC4011. l,3-Diphenylbenzo[c]furan is also a reactive diene but the corresponding 1,3-dimesityl derivative is inert to several dienophiles, even under forcing conditions (82CC766). 

The anhydride of thiophene-2,3-dlcarboxylic acid is of interest as a precursor of 2,3-didehydrothiophene. Evidence for the generation of this elusive intermediate is obtained by the isolation of [4-1-2] and [2-1-2] cycloaddition products with dienes (81T4151). 

Initial materials of this super-tough type were blends of nylon 66 with an ionomer resin (see Chapter 11). More recent materials are understood to be blends of nylon 66 with a modified ethylene-propylene-diene terpolymer rubber (EPDM rubber—also see Chapter 11). One such modification involves treatment of the rubber with maleic anhydride, this reacting by a Diels—Alder or other... 

At room temperature, the diene 1 and maleic anhydride react to give A and B. When the reaction mixture is heated to 160°C, C and D are formed, and as heating is continued, the C D ratio decreases. Explain the reason for the different products at the two reaction temperatures and the reason for the change of produet ratio with time at the higher temeprature. 

A -Dien-3-ol esters e.g., acetates) have greater utility as reaction intermediates than as protecting groups. They are prepared from A" -3-ketones by reaction with the acetic anhydride"" or by exchange with isopropenyl acetate. 

Preparation of /m -3) -Acetoxypregna-5,17(20)-dien-21-aI A solution of 12.2 g of 17a-ethynylandrost-5-ene-3/ ,17jS-diol diacetate and 0.5 g of silver acetate in 250 ml acetic acid and 100 ml of acetic anhydride is refluxed under... 

The Boekelheide reaction has found utility in other synthetic methodology. An approach to 2,3-pyridynes made use of this chemistry in the preparation of the key intermediate 30. Treatment of 28 with acetic anhydride produced the desired pyridone 29. Lithiation was followed by trapping with trimethylsilyl chloride and exposure to triflic anhydride gave the pyridyne precursor 30. Fluoride initiated the cascade of reactions that resulted in the formation of 2,3-pyridyne 31 that could be trapped with appropriate dienes in Diels-Alder reactions. 

Soon after the discovery of the addition reaction between diene-ophiles and dienes which now bears their names, Diels and Alder extended their investigations to include potential heterocyclic dienes. In 1929 the first compound investigated, furan, was observed to combine with maleic anhydride, like butadiene in a typical Diels-Alder reaction, across the 2,5-positions yielding a 1 1 molar adduct... 

The Diels-Alder reaction,is a cycloaddition reaction of a conjugated diene with a double or triple bond (the dienophile) it is one of the most important reactions in organic chemistry. For instance an electron-rich diene 1 reacts with an electron-poor dienophile 2 (e.g. an alkene bearing an electron-withdrawing substituent Z) to yield the unsaturated six-membered ring product 3. An illustrative example is the reaction of butadiene 1 with maleic anhydride 4 ... 

For the ordinary Diels-Alder reaction the dienophile preferentially is of the electron-poor type electron-withdrawing substituents have a rate enhancing effect. Ethylene and simple alkenes are less reactive. Substituent Z in 2 can be e.g. CHO, COR, COOH, COOR, CN, Ar, NO2, halogen, C=C. Good dienophiles are for example maleic anhydride, acrolein, acrylonitrile, dehydrobenzene, tetracya-noethylene (TCNE), acetylene dicarboxylic esters. The diene preferentially is of the electron-rich type thus it should not bear an electron-withdrawing substituent. 

Self-condensation of the substituted propiophenone, 15, by the pinacol reaction proceeds to give the glycol, 16, as the meso isomer. (If it is assumed that the transition state for this reaction resembles product, this stereoselectivity can be rationalized on the grounds of steric interaction compare A, which leads to the observed product, with B.) Dehydration under very specialized conditions (acetyl chloride, acetic anhydride) affords the bisstyrene-type diene (17). Removal of the acyl groups by means of base affords the synthetic estrogen, dien-... 

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