A cyclic ketene acetal is an olefin that is substituted at one end by two electrondonating hetero atoms, like O, N, S, where these heteroatoms are connected together by a chain. Delocalization of the lone pair electrons of the two hetero atoms to the double bond makes the β-carbon (the exocyclic methylene carbon) electron rich and nucleophilic. A major goal of cyclic ketene acetal chemistry is to provide functionalized cyclic ketene acetal monomers as precursors to polymers of desired properties. The cyclic ketene-N,O-acetal 3-methyl-2-methylene-oxazolidine, generated in situ from 2-methyl-2-oxazolinium iodide and triethylamine, reacted with aryl isocyanates in refluxing THF to give α,α-bis(N-arylamido) lactams via the iodide-catalyzed rearrangement of β,β–bis(N-arylamido) cyclic ketene-N,O-acetal intermediates. However, similar β,β–bis(N-arylamido) cyclic ketene-N,O-acetals having two methyl substituents at C-4, did not rearrange due to hindrance of the iodide attack on C-5. 3,4,4-Trimethyl-2-methylene-oxazolidine reacted with aryl chloroformates to form both mono- and di-aryloxycarbonylation adducts. The two methyl groups at C-4 Template Created By: Damen Peterson 2009 hindered the alternative polymerization route. 3-Methyl-2-methylene-oxazolidine, which does not have two methyl groups at C-4, underwent cationic polymerization under identical conditions. Benzoylation of 2-methyl-2-oxazoline with benzoyl chloride gave a ring-opened N,C,O-trisbenzoylation product via O-benzoylation of the N,C-bisbenzoylated intermediate, followed by chloride attack on C-5. The N,C,O-trisbenzoylated product underwent N,O-double debenzoylation by KOH to give the cyclic ketene-N,O-acetal, 2- oxazolidin-2-ylidene-1-phenylethanone. This compound (an ambident nucleophile), upon deprotonation, reacted with benzoyl chloride to give the β,β-bisbenzoylated cyclic ketene-N,O-acetal, and reacted with phenyl chloroformate to give a novel heterocycle, [1,3]oxazine-2,4-dione. The benzoylation of 2-methyl-2-oxazine gave a similar ringopened N,C,O-trisbenzoylation product. Reactions of 2-methyl-2-oxazoline, 2,4,4-trimethyl-2-oxazoline and 2-methyl-2- thiazoline with trifluoroacetyl anhydride gave C-trifluoroacetylated cyclic ketene-N,O(S)- acetals. However, trifluoroacetylation of 2-methyl-2-oxazine gave the β,β- bistrifluoroacetylated cyclic ketene-N,O-acetal. In summary, a novel iodide-catalyzed rearrangement of β,β–bis(N- arylamido)- cyclic ketene-N,O-acetals was found. The [1,3]oxazine-2,4-dione heterocycle synthesized during this research also demonstrates the synthetic potential of cyclic ketene acetal chemistry in pharmaceutical industry. Functionalization of cyclic ketene acetals based on the chemistry developed in this work will find applications in polymer industry.

This dissertation research is based on two reactions, including those of cyclic ketene acetals with acid chlorides and acid catalyzed olefination reactions in bio-oil. In first four chapters, reactions of in situ generated cyclic ketene acetals were explored. Highly functionalized heterocycles such as pyrrollo-[1,2-c]imidazolediones, were synthesized in one-pot reactions of 2-alkylimidazoles or 2-methylbenzimidazoles with 1,3-diacid chlorides. Some reactions proceed through in situ generated cyclic-N,N′-ketene acetal intermediates. 2-Alkylimidazoles and 2-methylbenzimidazole can be considered as tridentate nucleophiles in these reactions that can give four consecutive attacks on electrophiles which ultimately generate new heterocycles. Reactions of substituted oxazoles and thiazoles with different acid chlorides in the presence of different bases were explored. Arylvinyl esters of substituted benzoic acids containing substituted oxazoles or thiazoles were formed when aroyl chlorides were used. Most reactions occurred through in situ generated cyclic ketene acetals. Reactions of 2-methylbenzoxazole and 5-phenyl-2-methylbenzoxazole with acid chlorides and base in THF generated a series of ortho-amidoesters. All of these reactions showed that aromatic heterocycles based in situ generated cyclic ketene acetals could be used to make highly functionalized heterocycles under mild conditions. These one-pot reactions generated various heterocycles, which might have useful bioactivities. For example, arylvinyl esters of substituted benzoic acids have been reported to show insecticidal activities. The last two chapters describe the olefinations of bio-oil and model bio-oil compounds using acid catalysts. Two different branched olefins were used, representative of those available at petroleum refineries. Amberlyst-15 and Nafion NR-50 were used as heterogeneous acid catalysts. The acid catalyzed olefination of bio-oil was explored using an excess of 1- octene. Some olefinations were performed in the presence of ethanol. Ethanol was used to make the olefin and bio-oil phases partially miscible. Acid catalyzed olefination of raw bio-oil induced some changes in the resulting bio-oil by generating variety of alcohols, ethers and oligomeric mixtures of the starting olefin. Olefination with excess 1-octene showed the decrease of the water content and the acid value and increase of the heating value of the bio-oil. Thus, the acid catalyzed olefination of bio-oil can be considered as a potential bio-oil upgrading technique.

There are two sections to this research dissertation. Part one includes syntheses of fused-ring heterocycles derived from thiazole, oxazole, benzoxazole and benzothiazole derivatives and trifluoroacetylations of in situ generated N-methyl cyclic ketene-N,O/Sacetals. Attempted functionalized polymer syntheses from plant-derived 5-(hydroxymethyl) furfural are discussed in part two. Three 2-methylthiazoles, 2,4,5-trimethyloxazole, 2-methylbenzoxazole and 2- methyl-benzothiazole were each reacted with benzoyl chloride in acetonitrile/triethylamine to generate benzyl-vinyl esters. Base hydrolysis of these benzyl-vinyl esters formed 2-(heterocyclic)-1-phenylethenols which exist in both ketoenol tautomeric forms. These tautomers were used as starting materials for fused-ring heterocycle syntheses. Each tautomeric pair react with dimethyl acetylenedicarboxylate in methanol giving the 5,6-ringused 8-benzoyl-5-oxo-5H-thiazolo-, 8-benzoyl-5-oxo-5H-oxazolo-, 4-benzoyl-1-oxo-1H-benzo[4,5]oxazolo- and 4-benzoyl-1-oxo-1H-benzo[4,5]thiazolo [3,2-a]pyridinecarboxylate derivatives. Two novel 5,7-ringused 9-benzoyl-2,3- dimethyl-5,6-dihydrothiazolo- and 9-benzoyl-2,3-dimethyl-5,6-dihydrooxazolo[3,2-a] azepine-5,6,7,8-tetracarboxylates formed when the tautomers formed from 2,4,5- trimethyl thiazole and 2,4,5-trimethyl oxazole were reacted with DMADC. These tautomers react with 1,3-diacid chlorides in acetonitrile/triethylamine affording the 5,6-ringused 8-benzoyl-6,6-dialkyl-6H-thiazolo- and 8-benzoyl-6,6- dimethy-6H-oxazolo-, 4-benzoyl-2,2-dimethyl-1H-benzo[4,5]thiazolo- and 4-benzoyl- 2,2-dimethyl-1H-benzo[4,5]oxazolo[3,2,-a]pyridinedione derivatives. Functionalized 5,6- ringused 8-benzoyl-6H-thiazolo- and 8-benzoyl-6H-oxazolo[3,2]pyrimidine-5,7- diones, and 4-benzoyl-1H-benzo[4,5]thiazolo- and 4-benzoyl-1H-benzo[4,5]oxazolo[3,2- c]pyrimidine-1,3(2H)-diones formed reacting the tautomers with N-chlorocarbonyl isocyanate in THF/triethylamine. Significant ring size and substituent effects were observed in trifluoroacetylations of in situ-generated cyclic ketene-N,O/S acetals. In situ-generated 3,4,4-trimethyl-2- methylene-oxazolidine, 3-methyl-2-methylene-oxazolidine and 3-methyl-2-methylene- 1,3-oxazinane each formed β,β-bistrifluoroacetylated products. However, 3-methyl-2- methylene-oxazolidine also afforded a γ-lactam by an iodide-catalyzed rearrangement of its β,β-bistrifluoroacetylated derivative. In situ-generated 3-methyl-2-methylenethiazolidine gave both β-mono- and β,β-bistrifluoroacetylation products. 5-(Hydroxymethyl)furfural synthesized from sucrose was converted to 2,5- bis(hydroxymethyl)furan (2,5-BHMF). 7-Oxanorbornene-type Diels-Alder adducts synthesized from 2,5-BHMF were used as monomers for both ring opening metathesis polymerizations (ROMPs) and polycondensations. ROMP, followed by polycondensation or vise versa were expected to give highly functionalized cross-linked polymers. ROMP of the monomers using three Grubbs’ 1st, 2nd and 3rd generation catalysts were unsuccessful due to the presence of hydroxymethyl groups at one or both bridgeheads that could coordinate Ruthenium. With one bridgehead methyl present ROMP proceeded. Low molecular weight polyesters were synthesized via polycondensation. One was crosslinked using ROMP, but not to its gel point.

La Polymérisation Radicalaire par Ouverture de Cycle (R-ROP) est une méthode de synthèse de polymères contenant des fonctions chimiques de choix dans le squelette carboné grâce à un mécanisme d'addition-fragmentation. L'utilisation de monomères spécifiques, les Acétals Cétènes Cycliques (CKA), permet dans certaines conditions l'obtention de polyesters aliphatiques dont la propriété de (bio)dégradation présente de nombreuses applications. Cette méthode relativement peu étudiée depuis les années 1980 présente un fort potentiel mais également de nombreuses limites. Ce travail de thèse a consisté à comprendre l'origine de ces limites pour tenter d'y apporter des solutions, grâce à une approche combinée expérience-théorie.Nous avons montré que l'obtention exclusive de polyesters découle d'une compétition cinétique et que le comportement des différents monomères s'explique par des interactions orbitalaires dépendant de la géométrie, la flexibilité et la substitution des cycles. D'autre part, nous avons mis en évidence l'extrême difficulté de propagation des monomères propageant via des radicaux stabilisés par des cycles aromatiques. Cette faible réactivité inhérente à la double liaison riche en électrons des CKA est également la cause de l'incorporation restreinte des monomères cycliques en copolymérisation avec des monomères vinyliques usuels. La rationalisation de la copolymérisation a été mise à profit pour réaliser des copolymérisations de type statistique et alternée. Enfin, l'étude du contrôle de la R-ROP par les nitroxydes a montré la présence de réactions secondaires propres à ce système et permettant actuellement un contrôle partiel de la polymérisation. / The Radical Ring-Opening Polymerization (R-ROP) is a synthetic pathway to introduce chemical functions into a polymer backbone due to an addition-fragmentation mechanism. Using specific monomers like Cyclic Ketene Acetals (CKA) in the right conditions allows preparing aliphatic polyesters which have numerous applications thanks to their (bio)degradability. This method has been quite faintly investigated since the 1980s and even if it has a great potential, it suffers of numerous limitations. This PhD work consisted in the understanding of those limitations to try bringing solutions to them, with a combined approach of experiments and theory.We first demonstrated that the exclusive preparation of polyesters comes from a kinetic competition. The behavior of the distinct monomers is explained by orbital interactions depending on the geometry, flexibility and substitution of the cycles. Then, we highlighted the extremely difficult propagation of the monomers propagating with stabilized aromatic radicals. This low reactivity inherent to the electron-rich double link of the CKAs is also the cause of low polyester introduction during the copolymerization with usual vinyl monomers. We took advantage of the CKA copolymerization rationalization to realize statistical and alternate copolymerizations. At last, the study of the nitroxide mediated R-ROP demonstrated the occurrence of side reactions characteristic of this system that allow at present a partial control of the polymerization.