Improved synthesis

Furalazine, Acetylfuratrizine, Panfuran-S. Heating nitrovin in butanol or dimethylformamide at 100—130°C affords furalazine, 6-[2-(5-nitro-2-furanyl)ethenyl]-l,2,4-triazine-3-amine (34). An improved synthesis originates with 5-nitro-2-furancarboxaldehyde and acetone, proceeds through 4-(5-nitro-2-furanyl)-3-buten-2-one followed by a selenium dioxide oxidation to the pymvaldehyde hydrate, and subsequent reaction with aininoguariidine (35). Furalazine, acetylfuratrizine (36), and the A[-A/-bis(hydroxymethyl) derivative, Panfuran-S, formed from the parent compound and formaldehyde (37), are systemic antibacterial agents. 

In some cases, impurities in the ionic liquids resulted in dramatic pH shifts, causing enzyme inactivation. This could sometimes be overcome simply by titration or higher buffer concentrations. In other cases, purification of the ionic liquid or an improved synthesis might be necessary. 

Improved Synthesis for TNT Production , SRI Project PYU-7360-011, Final Report, Contract No DAAG 05-68-C-0723, Menlo Park, Calif (1972), 59 18) B.S. Thyagarajan K.C. 

A much improved synthesis of perfluoroalkanesulphonyl fluorides from sulphones has been published. This involves the electrolysis of cyclic unsaturated sulphones in anhydrous HF at 8-10°C using a potential of 5-7 volts. Thus, butadiene sulphone was oxidized to perfluorobutanesulphonyl fluoride in quantitative yield211 (equation 94). 

Scheme 71 Improved synthesis of (E)-stilbenoids by olefin CM on a solid phase [154]...

AN IMPROVED SYNTHESIS OF BIARYL DERIVATIVES VIA THE PALLADIUM CATALYZED COUPLING OF ARYL BROMIDES... 

Scheme 17. Improved synthesis of optically active secondary phosphine-boranes...

This was obviously a major improvement over the original procedure, which involved many more steps, some of them quite difficult. We happily reported this improved synthesis and undertook to use it to produce uranium(IV) borohydride for large-scale testing. 

In 1996, Fu et al. reported the S3mthesis of the planar chiral heterocycles 64, formally DMAP fused with a ferrocene core [82]. While the original synthesis provided racemic 64a in only 2% overall yield requiring a subsequent resolution by preparative HPLC on a chiral stationary phase, a recently improved synthesis furnished the racemic complexes 64 in 32-40% yield over seven steps. A subsequent resolution with di-p-toluoyltartaric or dibenzoyltartaric acid gave access to the enantiomers with >99% ee (28 14% yield for each isomer in this step) [83]. 

R. B Morland, Heteroadamantanes, The Improved Synthesis and Some Reactions of 2-Hetero-adamantanes, RhD Dissertation, Chemistry, Kent State University, 1976. 

Busbee, B. D., Obare, S. O. and Murphy, C. J. (2003) An improved synthesis of high-aspect-ratio gold nanorods. Adv. Mater., 15, 414- 16. 

Khan KM et al. (2005) A facile and improved synthesis of sildenafil (Viagra) analogs through solid support microwave irradiation possessing tyrosinase inhibitory potential, their conformational analysis and molecular dynamics simulation studies. Mol Divers 9(l-3) 15-26... 

A New Improved Synthesis of Tricycle Thienobenzazepines Apphcation of chemistry recently developed by Knochel" combined with the well-described halogen dance (HD) reaction, allowed preparation of our key intermediate A in only three synthetic transformations (Scheme 6.4). In this respect, treatment of 2-bromo-5-methylthiophene with hthium diisopropylamide followed by dimethylformamide afforded aldehyde 11 in good yield, lodo-magnesium exchange with conunercial 4-iodo-3-nitro anisole followed by reaction with 11 afforded the thiophene catbinol 12. Dehydroxylation of 12 provided our key intermediate A which presented the requisite functionality to examine our approach to the construction of the seven-member ring system. 

SCHEME 8.9 Improved synthesis of taxodione 1 by Motsumoto and coworkers. 

The excellent total synthesis of strigol developed by Sih and co-workers (7) formed the basis for our efforts to devise an improved synthesis. The general synthetic plan involves consecutive A+B+C+D-ring formation as shown. 

Process development of the synthesis of iodoaniline 28 began with an improved synthesis of l-(4 -aminobenzyl)-l,2,4-triazole (6) (Scheme 4.7), which was prepared in the medicinal chemistry synthesis, albeit with poor regioselectivity (Scheme 4.1). We found that this aniline intermediate 6 could be readily prepared in three steps in >90% overall yield from 4-amino-l,2,4-triazole (30) and 4-nitrobenzyl bromide (4) based on a modified literature procedure [9]. The condensation of 30 and 4 in isopropyl alcohol followed by deamination gave the nitro... 

The completion of the synthesis required removal of the tert-butyl group and crystallization of 1 as the HC1 salt. Reaction of crude 80 with TFA in DCE at 75 °C gave the free base of 1 in near quantitative yield. The free base was not crystalline, but was converted to its crystalline HC1 salt by treatment with 2 M HC1 in MTBE. The product was isolated in 85% yield after filtration and drying. These conditions were also successfully transferred to the kilogram scale, providing 1 in the expected yields. Thus, the final overall optimized route to 1 is summarized in Scheme 7.25. The improved synthesis of 1 proceeded in 14 steps and in 22% overall yield from 35. 

Feast, W. J. et al J. Chem. Soc., Chem. Comm., 1985, 202-203 The second stage of an improved synthesis of poly(acetylene), which involves disproportionation of a soluble polymer by heating a thin film at 75°C to give 1,2-bis(trifluoromethyl)benzene and poly(acetylene), must not be done in bulk because the reaction then becomes explosive. The earlier synthesis by direct polymerisation of acetylene was considerably more dangerous... 

Mori reported an improved synthesis of (3S,4P,6 ,10Z)-faranal (37), the trail pheromone of the Pharaoh s ant (Monomorium pharaonis) [84]. As summarized in Scheme 55, the key-reaction was the coupling of iododiene A with iodide E. The geometrically pure A was prepared by the zirconocene-mediated carbo-alumination reaction, and E was prepared from B by the asymmetric cleavage of its epoxy ring to give C (77% ee), which could be purified via its crystalline 3,5-dinitrobenzoate D. 

S)-3,7-Dimethyl-2-oxo-6-octene-l,3-diol (39) was recently identified as the aggregation pheromone of the Colorado potato beetle (Leptinotarsa decem-lineata), and synthesized by Oliver et al., starting from (S)-linalool [86]. An improved synthesis of (S)-39 by Mori is shown in Scheme 57 [87]. Enzymatic acetylation of ( )-2,3-epoxynerol (A) with vinyl acetate and lipase PS gave B together with C. The acetate B was converted to a multi-gram quantity of (S)-39 according to Oliver [86]. 

An improved synthesis of dithieno[3,2-A2, 3 -<7]thiophene 15a has been achieved from 2,3-dibromothiophene 304 (Scheme 57). Lithiation of 2,3-dibromothiophene 304 using -butyllithium followed by oxidative coupling with cupric chloride provided 3,3 -dibromo-2,2 -bithiophene 305 in 79% yield. Treatment of 305 with 2 equiv of -butyllithium in ether at —78 °C under nitrogen for 40 min and then adding benzenesulfonic acid thioanhydride and leaving the reaction mixture to reach room temperature afforded dithieno[3,2-A2, 3 -<7]thiophene 15a in 70% yield <2002TL1553>. 

Finally, an improved synthesis of (rj6-l, 3,5-cyclooctatriene)-(i74-l,5-cyclooctadiene)ruthenium(0) has been reported which utilizes a cleaning bath to hasten the Zn reduction of RuCl3 in the presence of 1,5-cyclooctadiene (240). The use of ultrasound in simple reductions using Zn are a likely area for further development. 

An improved synthesis of 3,4-dihydro-2,l-benzothiazine 2,2-dioxide was reported by Togo and co-workers using photochemical conditions . Treatment of A-alkyl 2-(aryl)ethanesulfonamides 18 with (diacetoxyiodo)arenes under irradiation with a tungsten lamp at 20-30 °C afforded 2,1-benzothiazines 19 and 20. Chemical yields and selectivities were dependent upon the choice of solvents and the reactant s substituents 18 (Table 1). When THF and EtOH were used as solvents, the reactions failed to give the cyclized products, since their a-hydrogen was abstracted by the intermediate sulfonamidyl radical. Compound 20 was obtained as a major product when 1,2-dichloroethane was employed as a solvent. In contrast, in the case of EtOAc as solvent, compound 19 was obtained as the major product. 

An improved synthesis of li/-2,l-benzothiazine 4(3i/)-one 2,2-dioxide 33 that results in a relatively high overall yield was developed by Lombardino s group <710PP33 72JHC315>. This general method offered an easier entry into the 2,1-benzothiazine 2,2-dioxide heterocyclic system <67JHC403>. Treatment of methyl A-benzyl-A-methylsulfonylanthranilate 35 with sodium hydride led to 1-benzyl-4-oxo-l//-2,l-benzothiazine-4(3/7)-one 2,2-dioxide 36 in 68% yield. Reduction of 36 gave 4-oxo-17/-2,1 -... 

An improved synthesis of nC-2 thymine 49, for use in PET scans, was made possible by an efficient and rapid synthesis of nC-phosgene, previously reported <02NMB345> by the same authors. nC is a particularly interesting challenge due to its very short half life (20 minutes) and the whole sequence and purification from the end of the bombardment took 16 minutes. The scale was necessarily small (0.2 mg) <06TL5321>. 

---