Novel routes

Electroreductive coupling of ben2otrifluorides with sacrificial aluminum or magnesium anodes in the presence of acetone, carbon dioxide, or /V, /V-dimethylformamide provides a novel route to ArCF2-derivatives (310). 

Blotra.nsforma.tlon, Enzymatic oxidation of ben2otrifluoride forms 3-trifluoromethyl-i7j -l,2-dihydrocatechol dehydration (acid pH) provides a novel route to 3-hydroxyben2otrifluoride [98-17-9] (171). 

A novel route to ammonia synthesis using methane, but without first producing hydrogen, has been proposed (101). 

A significant use of dkect-process waste is realized by C H -Si bond formation via silylative decarbonylation (Fig. 2) (49,50). A novel route to CgHg—Si bond formation has also been described (eq. 2) (51). 

A novel route to azelaic acid is based on butadiene. Butadiene is dimerized to 1,5-cyclooctadiene, which is carbonylated to the monoester in the presence of an alcohol. Hydrolysis of this ester foUowed by a caustic cleavage step produces azelaic acid in both high yield and purity (56). 

Fluorodediazoniation of alkyl carbamates in hydrogen fluonde/pyndine (70/30) represents a novel route to alkyl fluoroformates [6, 9] (equation 4)... 

A novel route to 2-fluoropyridines involved the base-induced decomposition of substituted N-fluoropyridinium salts. Abstraction of the 2-H produces a singlet carbene (11) that removes F from a counterion. This is in contrast to the reaction with C nucleophiles, which are fluorinated, and is attributed to the high stability of C—F compared to O—F and N—F (89JOC1726). 

The ring-opening polymerization of ketene acetals (45, X=0) provides a novel route to polyesters and many examples have now been reported (Scheme 4.27). " "7 A disadvantage of these systems is the marked acid sensitivity of the monomers which makes them relatively difficult to handle and complicates characterization. This area is covered by a series of reviews by Bailey ct a/.177 228 ... 

More recently, another sulfoxide- sulfine photoconversion has been reported by Franck-Neumann and Lohmann223. These authors have shown that the photolysis of allylsulfinylpyrazolenines (167) provides a novel route to vinyl sulfines 168, presumably via ring-opening to a-diazosulfoxides and their a-sulfinylcarbene intermediates (equation 67). 

Scheme 51 Synthesis of novel (E)-9,10-dehydro analogs 251 of epoD, and a novel route to epoD (237d) via RCM between C9 and CIO [119]...

Tetra Acetyl Glucosone Hydrate. A Novel Route to the Syntheses of Analogues of Ascorbic Acid and a Possible Mechanism for the Transformation of Hexoses into Kojic Acid, M. Stacey and L. M. Turton, J. Chem. Soc., (1946) 661 -664. 

Treatment of bicyclic lactones 66, derived from Diels-Alder reaction of 3-carboxy-2-pyrone under standard radical conditions using (TMSlsSiH, leads to bridged lactones 67, which can smoothly be converted to bicyclo[3.3.0]-lactones 68 (Scheme 10). For X = CHaOMe, this cascade of rearrangements took place in a 78% overall yield, providing 68 in diastereomerically pure form. Three additional steps provided a novel route toward Corey s lactone 69. 

Mixed arene-2,5-dihydro-l,2,5-thiadiborole-iron complexes have been synthesized by a novel route thermally unstable bis(arene)iron sandwich complexes, prepared by cocondensation of iron atoms with arene, react in the temperature range of -100 to -60°C with free Et2C2B2Mc2S to form reactive intermediates that decom-... 

A novel route to indoles and quinolines has been developed by sequential Wiltig and Heck reactions <96CC2253>. Thus, treatment of o-bromo- or iodo-lV-lrifluoroaceiylanilines (86) with a stabilized phosphorane affords the corresponding enamines 87 as a mixture of isomers. Cyclization to 88 is effected by heating with palladium acetate, tri phenyl phosphine, and bu.se. 

A novel route to 2-fhioromethyl- and 2-hydroxymethyl-4-alkylfurans was reported. Treating a-alkylacroleins with 1-bromo-l-trimethylsilylethylene in the presence of butyllithium yields 33. Oxidation of both double bonds followed by reaction with MsCl provides the key intermediate 34 vkdiich on treatment with TBAF produces the desired conqioimds <96TL7437>. 

A novel route to functionalised 3-aminq)yridazines 77 is the reaction of 3-chloro-6-phenyl-1,2,4-triazine with C-nucleq)hiles. The mechanism proposed for this reaction is shown in Scheme 13 <96TL5795>. 

Milanova R, M Moore, Y Hirai (1994) Hydroxylation of synthetic abietane diterpenes by Aspergillus and Cunninghamella species novel route to the family of diterpenes isolated from Tripterygium wilfordii. J Nat Prod 5T 882-889. 

Where an unusual excipient is chosen, or where an established excipient is chosen for a dosage form that results in its administration by a novel route of administration, then additional data will need to form part of the application. In effect, a novel excipient will need to be supported by data similar to those required for a new drug, with full supporting data including composition, function, and safety. Novel excipients include the components of the matrix in prolonged release products, new propellants, and new permeability enhancers. The exception to this need for extensive supporting data would be for a material already approved for food use and administered by the oral route or a material already approved for cosmetic use with a topical route of administration. In all cases the quality of the excipients has to be described adequately and shown to be satisfactory (which will depend on its role). 

The NOx storage was investigated at first. The collected results showed that a dual pathway is operating when starting from N0/02 mixtures the first route implies the well-known oxidation of NO to N02, and its subsequent adsorption via disproportionation to form nitrates (nitrate route), whereas the second novel route consists of a stepwise oxidation of NO in the presence of oxygen to form nitrite ad-species, which are progressively oxidized to nitrates (nitrite route). 

Jiang LP, Wang AN, Zhao Y et al (2004) A novel route for the preparation of monodisperse silver nanoparticles via a pulsed sonoelectrochemical technique. Inorg Chem Commun 7 506-509... 

Xia B, Lenggoro IW, Okuyama K (2001) Novel route to nanoparticle synthesis by salt-assisted aerosol decomposition. Adv Mater 13 1579-1582... 

Transannular cyclizations of nine-membered cyclic sulfides provided a novel route to thioanalogues of swainsonine derivatives. Treatment of the enantiopure polyhydroxylated thiacyclononane derivative 48a with trimethylsilyl iodide yielded the bicyclic sulfonium salt 49a as a single diastereomer, as shown in Equation (16) <2003JOC3311 >. The presence of a C2-axis and the complete regio- and stereoselectivity of the transannular substitution led to a single configurationally homogeneous product irrespective of the fact that the sulfur atom would attack C-5 or C-6. 

Thermal [2+3] cycloaddition reactions of 4jt-electron component 3-benzylidene-5-phenyl-3/7-l,2-dithiole 189 with 2Jt-electron component heterocumulenes 190 provided a novel route to 2-(substituted amino)-trithiapentalenes 191a and 2-(substituted amino)-dithia-l-selenapentalenes 191b (see Equation 49 and Table 26) <1997HAG233>. 

K. E. Thummel, and P. B. Watkins. Identification of a novel route of extraction of sirolimus in human small intestine roles of metabolism and secretion, J. Pharmacol. Exp. Ther. 2002, 301, 174-186... 

Eq. (57), R = p-HC6F4 or C6F5) (66). The reactions provide a novel route to a new class of air-stable organoamidoplatinum(II) complexes. 

A novel route to 3,4-disubstituted piperidines 206 via ring transformation of 2-(haloalkyl)azetidines 207 is shown below. During these reactions, bicyclic azetidinium intermediates are formed and then ring opened by a variety of nucleophiles generating stereospecific substituted piperidines in excellent yields <06OLl 105>. 

Aside from the pyrimidine preparations which follow well-established strategies, several new pathways have been developed. In model studies for the synthesis of cylindrospermopsin, Weinreb and Keen reported a novel route to N-hydroxydihydrouracil 33 from a,P-unsaturated ester 30 followed by aromatization to give pyrimidone 34 <00TL4307>. 

The traditional Stille-type cross coupling of stannane 88 with bromopyrimidine 89 was reported by Fort and co-workers to provide pyrimidine 90 in 80% yield <00OL803>. This illustrates a novel route to heterocyclic chlorobiaryls. 

Azizian, Mehrdad, and co-workers reported a novel route to quinazolinones 123 through a Baeyer-Villiger pathway starting from isatin derivatives 120 <00TL5265>. The initial... 

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