8-Methoxycarbonyl- -3-oxid

Piperidine, l-(2-hydroxythiobenzoyI)-neutron diffraction, 2, 116 Piperidine, 4-hydroxy-2,2,6-trimethyI-as local anaesthetic, 1, 179 Piperidine, JV-methoxycarbonyl-electrolytic oxidation, 2, 374 Piperidine, 2-methyl-synthesis, 2, 524 Piperidine, 3-methyI-mass spectrometry, 2, 130 Piperidine, C-methyl-NMR, 2, 160 Piperidine, JV-methyl- C chemical shifts, 2, 15 catalyst... 

Alkyl-1,4-dihydropyridines on reaction with peracids undergo either extensive decomposition or biomimetic oxidation to A-alkylpyridinum salts (98JOC10001). However, A-methoxycarbonyl derivatives of 1,4- and 1,2-dihydro-pyridines (74) and (8a) react with m-CPBA to give the methyl tmns-2- 2>-chlorobenzoyloxy)-3-hydroxy-1,2,3,4-tetrahydropyridine-l-carboxylate (75) and methyl rran.s-2-(3-chlorobenzoyloxy)-3-hydroxy-l,2,3,6-tetrahydropyridine-l-carboxylate (76) in 65% and 66% yield, respectively (nonbiomimetic oxidation). The reaction is related to the interaction of peracids with enol ethers and involves the initial formation of an aminoepoxide, which is opened in situ by m-chlorobenzoic acid regio- and stereoselectively (57JA3234, 93JA7593). 

V,7V-dimethylaminopyridme provides l-(2-methoxycarbonyl)ethoxy- (40,69%) and l-(2-methoxycarbonyl-l-methyl)ethoxytryptamine (41, 72%), respectively (Scheme 4). The conjugate addition to mesityl oxide proceeds successfully as well, giving iVb-acetyl-1-(1, l-dimethyl-3-oxo)butoxytryptamine (42,49%), while the reaction with methyl 3-methylcrotonate affords 43 in a miserable yield (1.6%). Addition to acrolein results in failure, and 44 is not yet obtained. 

Kondo maintained his interest in this area, and with his collaborators [62] he recently made detailed investigations on the polymerization and preparation of methyl-4-vinylphenyl-sulfonium bis-(methoxycarbonyl) meth-ylide (Scheme 27) as a new kind of stable vinyl monomer containing the sulfonium ylide structure. It was prepared by heating a solution of 4-methylthiostyrene, dimethyl-diazomalonate, and /-butyl catechol in chlorobenzene at 90°C for 10 h in the presence of anhydride cupric sulfate, and Scheme 27 was polymerized by using a, a -azobisi-sobutyronitrile (AIBN) as the initiator and dimethylsulf-oxide as the solvent at 60°C. The structure of the polymer was confirmed by IR and NMR spectra and elemental analysis. In addition, this monomeric ylide was copolymerized with vinyl monomers such as methyl methacrylate (MMA) and styrene. 

Allylic oxidation, 25 Aluminum chloride, 28 Amine, dnsopropyl- [2-Propanamine, Af-(l-methylethyl)-], 36 Ammonium, (methoxycarbonylsulfamoyl)-tnethyl-, hydroxide [Ethanaminium, W.W-diethyl-A-t [ (methoxycarbonyl)-amino] sulfonyl] -, hydroxide, inner salt], 41... 

Dimethyl-2-phenyl- 365 6-Nitro-3-oxo-2-methoxycarbonyl- 568 6-Nitro-3-oxo-2-methoxycarbonyl- -1-oxid 568... 

Oxo-2-methoxycarbonyl -1-oxid 568 3-Phenylimino-2-phenyl- -1-oxid 698 3-Phenylnitrono-2-phenyl- -1-oxid 698... 

Only one procedure has been reported recently within this category. Thus 7-chloro-l-methyl-5-phenyl-2,3-dihydro-lH-benzodiazepin-2-one 4-oxide (437) with dimethyl acetylenedicarboxylate in methylene chloride at 20° C for 3 days gave a separable mixmre of the primary tricyclic adduct, dimethyl lO-chloro-6-oxo-llb-phenyl-5,6,7, 1 lb-tetrahydroisoxazolo[2,3-t/] [ l,4]benzodiazepine-1,2-dicarboxylate (438), and its rearrangement product, 6-chloro-4-(2-methoxalyl-2-methoxycarbonyl-l-phenylvinyl)-l-methyl-3,4-dihydro-2(lT0-quinoxalinone (439) each product afforded 6-chloro-l-methyl-2(l//)-quinoxalinone (440) on refluxing in ethanol (see also Section 1.7.13). However, the final quinoxaline (440) was best obtained in 75% yield) by simply heating the initial substrate (437) and dimethyl... 

Chloro-2-[l,4-dimethyl(thiosemicarbazido)]quinoxaline 4-oxide (250) with dimethyl acetylenedicarboxylate gave 6-chloro-2-[A-(5-methoxycarbonyl-methylene-3-methyl-4-oxo-2-thioxoimidazolidin-l-yl)-A-methylammo]quinoxa-line 4-oxide (251) (EtOH, reflux, 5 h 54%) a homolog likewise." ... 

Unsubstituted benzobicyclo[2.2.2]octatriene 76a bearing two methoxycarbonyl groups at the and C3 positions exhibited strong anti preference (with respect to the benzene moiety) with two oxidative electrophilic reagents, m-chloroperbenzoic acid (mCPBA) and osmium tetroxide. 

Whereas 2-methylpyridine-N-oxide 881a reacts rather slowly with TCS 14/ NaCN/NEt3 in DMF at 100-110°C, sterically hindered 2-methoxycarbonyl- 881b, 2-isopropyl- 881c, or 2-tert-butylpyridine-N-oxide 881d have not yet been reacted in the presence of NEts or DBU in DMF with the much less bulky but apparently as yet unknown dimethylsilyl cyanide Me2HSiCN 883 (which can probably be gener-... 

The N-oxide of l-pyrrolo[2,3-b]pyridine 936 is converted by the combination tri-methylsilylisothiocyanate Me3SiNCS 937/MeOCOCl to 21% 6-isothiocyanato-l-methoxycarbonyl-pyrrolo[2,3-b]pyridine 938 and 18% 6-chloro-l-methoxycarbonyl-pyrrolo[2,3-F]pyridine 939 [51] (Scheme 7.14). To avoid formation of the chloro compound 939 a reagent combination of MesSiNCS 937 with triethylamine or DBU, which lacks any competing chloride ion, might give much higher yields of... 

A rich family of 2-alkoxycarbonyl-l,3,2-oxazaphospholidine-2-oxides 179-181 was prepared from the reaction of camphor derived aminoalcohols 177 and 178 with either methoxycarbonyl phosphonic dichloride or ethyl dichlorophosphite followed by the reaction with methyl bromoacetate. The reaction with aminoalcohol 177a afforded the phosphorus epimers 179 and 180, in ratios from 1/1 to 12/1 depending on the iV-substituent which could be separated easily by column chromatography. The reaction with aminoalcohols 178a-c, however, gave a single epimer 181a-c in each case (Scheme 50) [81]. 

Cycloalkene Derivatives Cyclopropenes readily interact with nitrile oxides. Reactions of a broad series of 3,3-disubstituted cyclopropenes with 4-substituted benzonitrile, methoxycarbonyl- and cyanoformonitrile oxides (229) as well as with di(isopropoxy)phosphorylformonitrile oxide (230) give 2-oxa-3-azabicyclo[3.1.0]hexene derivatives 62. Stereoselectivity of the cycloaddition is governed by both steric and polar factors. In particular, steric factors are supposed to prevail for 3-methyl-3-phenylcyclopropene affording 62 [R1 =... 

Heterocycles Both non-aromatic unsaturated heterocycles and heteroaromatic compounds are able to play the role of ethene dipolarophiles in reactions with nitrile oxides. 1,3-Dipolar cycloadditions of various unsaturated oxygen heterocycles are well documented. Thus, 2-furonitrile oxide and its 5-substituted derivatives give isoxazoline adducts, for example, 90, with 2,3- and 2,5-dihydro-furan, 2,3-dihydropyran, l,3-dioxep-5-ene, its 2-methyl- and 2-phenyl-substituted derivatives, 5,6-bis(methoxycarbonyl)-7-oxabicyclo[2.2.1]hept-2-ene, and 1,4-epoxy-l,4-dihydronaphthalene. Regio- and endo-exo stereoselectivities have also been determined (259). 

Pentanenitrile oxide, BuCNO, formed in situ from 1-nitropentane, PhNCO and Et3N in benzene, added stereo- and regioselectively to 8-.vv7/-(dimethoxymethyl)-3-oxo-2-oxabicyclo[3.2. l]oct-6-ene to give 75% of the tricyclic lactone 111 (276). Introduction of a methoxycarbonyl group into the plane asymmetrical double bond of 2,3-dioxa- and 2,3-oxazabicyclo[2.2.2]oct-5-enes, brought about a clear-cut increase in syn selectivity of their reactions with 1,3-dipoles (277). 

Heat 3-nitrophthalic anhydride with ammonium carbonate to get 3-nitrophthalimide (I). Dissolve 4.3 g (I) in 50 ml 90% methanol and add 1.9 g sodium borohydride over 30 minutes while stirring vigorously at room temperature. Stir 2 hours, acidify with 20% HCI, evaporate in vacuum and treat the dry residue with acetone. Evaporate in vacuum to get 3.9 g (88%) 3-OH-4-nitrophthal-imidine (II) (recrystallize from acetone). Dissolve 3.9 g (II) in 40 ml 20% HCI and stir for 10 hours on water bath at 80-90°. Distill off HCI and stir residue with acetone. Filter and evaporate in vacuum to get 3.4 g 3-OH-4-nitrophthalide (III) (recrystallize from CHC 3 and can purify on column). Prepare an ether solution of CH2N2 and add to 1.93 g (III) in a 100 ml flask until a reaction is no longer evident. Add acetic acid to decompose excess diazomethane and evaporate in vacuum to get about 2 g of 2-methoxycarbonyl-6-nitrostyrene oxide (IV) (can purify on column). Dissolve 560 mg (IV) in 50 ml absolute methanol, add 50 mg Pt02 and hydrogenate as described elsewhere here (other reducing methods should work). Filter,... 

FIGURE 6.23 The synthesis of insulin, starting with a cystine-containing peptide. [Kamber et al., 1977]. Moc = methoxycarbonyl, Bpoc = biphenylisopropoxycarbonyl, Trt = trityl, Acm = acetamidomethyl. (a) HOBt-assisted carbodiimide-mediated coupling (b) removal of Trt by HC1 in CF3CH2OH-CH2Cl2 (9 1) at pH 3.5 (c) removal of Bpoc by CF3CH2OH-CH2 Cl2 (9 1) at 60°C (d) removal of Acm and oxidation by iodine. 

Diethyl N-(4-Aminophenyl)aminomethylenemalonate (167, R = H) was reacted with N, Af -bis(methoxycarbonyl)-5-methylisothiourea in the presence of p-toluenesulfonic acid in boiling methanol for 4 hr to afford the guanidine derivative (1590) in 50% yield. The guanidine (1590) was oxidized in chloroform with lead tetraacetate to the quinoline diimine (1591), which cyclized to 1592. After methanolysis, the 2-(methoxycarbon-ylamino)benzimidazole derivative (1593) was obtained in 41% yield [86JCR(S)161]. 

Further studies demonstrated the influence of the double-bond substitution on both the reactivity and the stereoselectivity of the reaction [78-81]. Tamaru and co-workers reported then that using the same PdCl2/CuCl2/MeOH system on butenol derivatives, with the double bond in either the terminal or an internal position, furnished selectively y-butyrol-actones. This dicarbonylation process most probably includes (i) a lactoniza-tion step and (ii) a methoxycarbonylation step, as displayed in Scheme 11 in which we clarify some intermediate steps on a representative example [82, 83]. The use of propylene oxide as an additive promotes this Pd-catalyzed dicarbonylation by playing the role of an HC1 quencher to maintain neutral conditions. 

Intramolecular alkoxycarbonylation of alkynols is parallel to what has been described for alkenols except that functionalization of the triplebond produces a double bond. No lactone formation is observed in the Pd(II)-catalyzed oxidative cyclization-carbonylation of alkynes. Instead [(methoxycarbonyl)methylene]tetrahydrofurans are selectively formed [134, 135]. Moreover, starting from an enynol, furan-2-acetic ester is obtained resulting from a final aromatization step [136]. 

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