Bis intermediate

Cyclic amidines (213) react with chlorocarbonylsulfenyl chloride to give bicyclic 1,2,4-thia-diazoles. The product isolated from this reaction depends on the mode of addition. When (213) is added to chlorocarbonylsulfenyl chloride, 3-oxo derivatives (214) are isolated via the postulated intermediate (215). Addition of chlorocarbonylsulfenyl chloride to (213) leads to 5-oxo derivatives (216), via the proposed bis(intermediate) (217) (Scheme 47) <84CHEC-I(6)463). Cyclic amidines (213) have also been treated with 1-chloro-l-phenyliminomethanesulfenyl chloride (210) to afford 2>H-1,2,4-thiadiazoles (218). The other possible product from this reaction, the 2/7-isomer (219) has been shown to be unstable, rearranging to a benzothiazole. Heterocycles (213) which have been used in this transformation include 2-aminopyridine, 3-aminopyridazine, 2-aminobenzothiazole, 2-aminopyrimidine and 2-aminothiazole (Equation (33)) <86S1027>. 

This dependence of product distribution on reaction conditions is also evident when 2-mercaptobenzothiazole is oxidized under acidic conditions. The material will form the disulfide provided a stoichiometric amount of hydrogen peroxide is employed.364 However, when excess hydrogen peroxide is used, the sulfinic acid will be formed, which upon acidification liberates sulfur dioxide to give the benzothiazole.365 Thus 2-mercaptothiazoles, under certain conditions, will undergo desulfurization, which is an important step in the preparation of chlormethiazol,366 a vitamin Bi intermediate (Figure 3.94). 

In these (and other) solid superacid catalyst systems, bi- or multi-dentate interactions are thns possible, forming highly reactive intermediates. This amounts to the solid-state equivalent of protosolvation resulting in superelectrophilic activation. 

In the synthesis of morphine, bis-cyclization of the octahydroisoqtiinolinc precursor 171 by the intramolecular Heck reaction proceeds using palladium trifluoroacetate and 1,2,2,6,6-pentamethylpiperidine (PMP). The insertion of the diene system forms the rr-allylpalladium intermediate 172, which attacks the phenol intramolecularly to form the benzofuran ring (see Section 1.1.1.3). Based on this method, elegant total syntheses of (-)- and (+ )-dihydrocodei-none and (-)- and ( + )-morphine (173) have been achieved[141]. 

Pd-cataly2ed reactions of butadiene are different from those catalyzed by other transition metal complexes. Unlike Ni(0) catalysts, neither the well known cyclodimerization nor cyclotrimerization to form COD or CDT[1,2] takes place with Pd(0) catalysts. Pd(0) complexes catalyze two important reactions of conjugated dienes[3,4]. The first type is linear dimerization. The most characteristic and useful reaction of butadiene catalyzed by Pd(0) is dimerization with incorporation of nucleophiles. The bis-rr-allylpalladium complex 3 is believed to be an intermediate of 1,3,7-octatriene (7j and telomers 5 and 6[5,6]. The complex 3 is the resonance form of 2,5-divinylpalladacyclopentane (1) and pallada-3,7-cyclononadiene (2) formed by the oxidative cyclization of butadiene. The second reaction characteristic of Pd is the co-cyclization of butadiene with C = 0 bonds of aldehydes[7-9] and CO jlO] and C = N bonds of Schiff bases[ll] and isocyanate[12] to form the six-membered heterocyclic compounds 9 with two vinyl groups. The cyclization is explained by the insertion of these unsaturated bonds into the complex 1 to generate 8 and its reductive elimination to give 9. 

An active catalytic species in the dimerization reaction is Pd(0) complex, which forms the bis-7r-allylpalladium complex 3, The formation of 1,3,7-octa-triene (7) is understood by the elimination of/5-hydrogen from the intermediate complex 1 to give 4 and its reductive elimination. In telomer formation, a nucleophile reacts with butadiene to form the dimeric telomers in which the nucleophile is introduced mainly at the terminal position to form the 1-substituted 2,7-octadiene 5. As a minor product, the isomeric 3-substituted 1,7-octadiene 6 is formed[13,14]. The dimerization carried out in MeOD produces l-methoxy-6-deuterio-2,7-octadiene (10) as a main product 15]. This result suggests that the telomers are formed by the 1,6- and 3,6-additions of MeO and D to the intermediate complexes I and 2. 

Two moles of /3-alkoxyaicene can condense on each other by means of their a- and /3-carbon atoms. The resulting intermediate reacts on the anhydrobase by elimination of a molecule of ethanol resulting in a neocyanine formation (Schemes 59 and 60). Both monoanilino and bis-anilino derivatives resulting from the condensation of dimethylform-amide have been isolated. They are capable of furnishing various condensations on either ketomethylene or another reactive nucleus (Scheme 61). 

The ethylene glycol liberated by reaction (5.L) is removed by lowering the pressure or purging with an inert gas. Because the ethylene glycol produced by reaction (5.L) is removed, proper stoichiometry is assured by proceeding via the intermediate, bis(2-hydroxyethyl) terephthalate otherwise the excess glycol used initially would have a deleterious effect on the degree of polymerization. Poly(ethylene terephthalate) is more familiar by some of its trade names Mylar as a film and Dacron, Kodel, or Terylene as fibers it is also known by the acronym PET. 

The main intermediates in the pentaerythritol production reaction have been identified and synthesized (50,51) and the intermediate reaction mechanisms deduced. Without adequate reaction control, by-product formation can easily occur (52,53). Generally mild reaction conditions are favored for optimum results (1,54). However, formation of by-products caimot be entirely eliminated, particularly dipentaerytbritol and the linear formal of pentaerythritol, 2,2 -[meth5lenebis(oxymethylene)]bis(2-hydroxymethyl-1,3-propanediol) [6228-26-8] ... 

Several appHcations have been found for bis(2-chloroethyl) vinylphosphonate as a comonomer imparting flame retardancy for textiles and specialty wood and paper appHcations. Its copolymerization characteristics have been reviewed (76,109). This monomer can be hydrolyzed by concentrated hydrochloric acid to vinylphosphonic acid, polymers of which have photoHthographic plate coating utiHty (see Lithography). It is also an intermediate for the preparation of an oligomeric vinylphosphonate textile finish, Akzo s Fyrol 76 [41222-33-7] (110). 

One of the first attempts to produce polyurethane was from the reaction of an intermediate polyol of 1,3- and l,4-bis(hydroxyhexa uoroisopropyl)benzene m- and -12F-diols) by reaction with epichlorohydrin. This polyol was subsequentiy allowed to react with a commercial triisocyanate, resulting in a tough, cross-linked polyurethane (129,135,139). ASTM and military specification tests on these polyurethanes for weather resistance, corrosion prevention, bUster resistance, and ease of cleaning showed them to compare quite favorably with standard resin formulations. 

The first detailed investigation of the reaction kinetics was reported in 1984 (68). The reaction of bis(pentachlorophenyl) oxalate [1173-75-7] (PCPO) and hydrogen peroxide cataly2ed by sodium saUcylate in chlorobenzene produced chemiluminescence from diphenylamine (DPA) as a simple time—intensity profile from which a chemiluminescence decay rate constant could be determined. These studies demonstrated a first-order dependence for both PCPO and hydrogen peroxide and a zero-order dependence on the fluorescer in accord with an earher study (9). Furthermore, the chemiluminescence quantum efficiencies Qc) are dependent on the ease of oxidation of the fluorescer, an unstable, short-hved intermediate (r = 0.5 /is) serves as the chemical activator, and such a short-hved species "is not consistent with attempts to identify a relatively stable dioxetane as the intermediate" (68). 

Peroxyoxalate chemiluminescence is the most efficient nonenzymatic chemiluminescent reaction known. Quantum efficiencies as high as 22—27% have been reported for oxalate esters prepared from 2,4,6-trichlorophenol, 2,4-dinitrophenol, and 3-trif1uoromethy1-4-nitropheno1 (6,76,77) with the duorescers mbrene [517-51-1] (78,79) or 5,12-bis(phenylethynyl)naphthacene [18826-29-4] (79). For most reactions, however, a quantum efficiency of 4% or less is more common with many in the range of lO " to 10 ein/mol (80). The inefficiency in the chemiexcitation process undoubtedly arises from the transfer of energy of the activated peroxyoxalate to the duorescer. The inefficiency in the CIEEL sequence derives from multiple side reactions available to the reactive intermediates in competition with the excited state producing back-electron transfer process. 

The facile reaction of metallic tin in the presence of hydrogen chloride with acryUc esters to give high yields of bis( P-alkoxycarbonyleth5l)tin dichlorides is reported in References 115 and 116. This reaction proceeds at atmospheric pressure and room temperature and has been practiced commercially. Halogenostaimanes have been postulated as intermediates (105). 

Preparation of (14) and treatment with A[,A[-bis(ttimethylsily)fomiamide (BSF) and triethylamine provided (16) in 84% yield via the putative imine intermediate (15). The trifliioromethyl group could be replaced by other moieties such as 2,4,5 trichlorophenyl, pentafluorophenyl, or nonafluorobutyl with increasing effectiveness. 

Iminoboianes have been suggested as intermediates in the formation of compounds derived from the pyrolysis of azidoboranes (77). The intermediate is presumed to be a boryl-substituted nitrene, RR BN, which then rearranges to the amino iminoborane, neither of which has been isolated (78). Another approach to the synthesis of amino iminoboranes involves the dehydrohalogenation of mono- and bis(amino)halobotanes as shown in equation 21. Bulky alkah-metal amides, MNR, have been utilized successfully as the strong base,, in such a reaction scheme. Use of hthium-/i /f-butyl(ttimethylsilyl)amide yields an amine, DH, which is relatively volatile (76,79). 

Many of the surfactants made from ethyleneamines contain the imidazoline stmcture or are prepared through an imidazoline intermediate. Various 2-alkyl-imidazolines and their salts prepared mainly from EDA or monoethoxylated EDA are reported to have good foaming properties (292—295). Ethyleneamine-based imida zolines are also important intermediates for surfactants used in shampoos by virtue of their mildness and good foaming characteristics. 2- Alkyl imidazolines made from DETA or monoethoxylated EDA and fatty acids or their methyl esters are the principal commercial intermediates (296—298). They are converted into shampoo surfactants commonly by reaction with one or two moles of sodium chloroacetate to yield amphoteric surfactants (299—301). The ease with which the imidazoline intermediates are hydrolyzed leads to arnidoamine-type stmctures when these derivatives are prepared under aqueous alkaline conditions. However, reaction of the imidazoline under anhydrous conditions with acryflc acid [79-10-7] to make salt-free, amphoteric products, leaves the imidazoline stmcture essentially intact. Certain polyamine derivatives also function as water-in-oil or od-in-water emulsifiers. These include the products of a reaction between DETA, TETA, or TEPA and fatty acids (302) or oxidized hydrocarbon wax (303). The amidoamine made from lauric acid [143-07-7] and DETA mono- and bis(2-ethylhexyl) phosphate is a very effective water-in-od emulsifier (304). 

Pyridazin-3(2H)-ones rearrange to l-amino-3-pyrrolin-2-ones (29) and (30) upon irradiation in neutral methanol (Scheme 10), while photolysis of 5-amino-4-chloro-2-phenylpyridazin-3(2H)-one gives the intermediate (31) which cyclizes readily to the bis-pyridazinopyrazine derivative (32 Scheme 11). 

Other reactions with their counterparts in the pyridine series are also well known. Thus, 2,3-dimethylpyrazine 1,4-dioxide reacts with acetic anhydride to yield 2,3-bis(acetoxy-methyl)pyrazine (S3) in good yield (72KGS1275). Pyrazine 1-oxide also reacts directly with acetic anhydride to yield 2(ljH)-pyrazinone by way of the intermediate acetate (Scheme 22). The corresponding reaction in the quinoxaline series is not so well defined and at least three products result (Scheme 23) (67YZ942). 

Other methods of generating a-aminoketones in situ are common, if somewhat less general than the methods already described. 2-Nitrovinylpyrrolidine, which is readily available, yields 2,3-bis(3-aminopropyl)pyrazine on reduction and this almost certainly involves ring opening of the intermediate enamine to an a-aminoketone which then dimerizes under the reaction conditions (Scheme 59) (78TL2217). Nitroethylene derivatives have also served as a-aminoketone precursors via ammonolysis of the derived epoxides at elevated temperatures (Scheme 60) (76S53). Condensation of 1,1-disubstituted hydrazine derivatives with a-nitro-/3-ethoxyethylene derivatives has been used in the synthesis of l,4-dialkylamino-l,4-dihydropyrazines (Scheme 61) (77S136). 

An oxidative cyclization, (151) -> (152), with azodicarboxylate (78CC764) is balanced by the synthesis of 5-deazaalloxazines from aryl bis(6-aminouracilyl)methanes, which involves azodicarboxylate in an intermediate electrophilic capacity (153 -> 154) (79CPB2507). Other methods involve reductive cyclizations (72AP751). 

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