Intermolecular ester

Anthramycin methyl ester Intermolecular HR of an alkenyl triflate [73]... 

Qavicipitic acids (445) and their methyl esters Intermolecular HR of an aryl bromide [454-456] ( ), (440[ (-]... 

An example of an intermolecular aldol type condensation, which works only under acidic catalysis is the Knoevenagel condensation of a sterically hindered aldehyde group in a formyl-porphyrin with a malonic ester (J.-H. Fuhrhop, 1976). Self-condensations of the components do not occur, because the ester groups of malonic esters are not electrophilic enough, and because the porphyrin-carboxaldehyde cannot form enolates. 

The synthesis of five-, six-, and seven-membered cyclic esters or timides uses intramolecular condensations under the same reaction condifions as described for intermolecular reactions. Yields are generally excellent. An example from the colchicine synthesis of E.E. van Ta-melen (1961) is given below. The synthesis of macrocyclic lactones (macrolides) and lactams (n > 8), however, which are of considerable biochemical and pharmacological interest, poses additional problems because of competing intermolecular polymerization reactions (see p. 246ff.). Inconveniently high dilution, which would be necessary to circumvent this side-... 

The acylpalladium complex formed from acyl halides undergoes intramolecular alkene insertion. 2,5-Hexadienoyl chloride (894) is converted into phenol in its attempted Rosenmund reduction[759]. The reaction is explained by the oxidative addition, intramolecular alkene insertion to generate 895, and / -elimination. Chloroformate will be a useful compound for the preparation of a, /3-unsaturated esters if its oxidative addition and alkene insertion are possible. An intramolecular version is known, namely homoallylic chloroformates are converted into a-methylene-7-butyrolactones in moderate yields[760]. As another example, the homoallylic chloroformamide 896 is converted into the q-methylene- -butyrolactams 897 and 898[761]. An intermolecular version of alkene insertion into acyl chlorides is known only with bridgehead acid chlorides. Adamantanecarbonyl chloride (899) reacts with acrylonitrile to give the unsaturated ketone 900[762],... 

Enamines derived from ketones are allylated[79]. The intramolecular asymmetric allylation (chirality transfer) of cyclohexanone via its 5-proline ally ester enamine 120 proceeds to give o-allylcyclohexanone (121) with 98% ee[80,8l]. Low ee was observed in intermolecular allylation. Similarly, the asymmetric allylation of imines and hydrazones of aldehydes and ketones has been carried out[82]. 

Lactides, intermolecular cyclic esters, are named as heterocycles. Lactams and lactims, containing a —CO—NH— and —C(OH)=N— group, respectively, are named as heterocycles, but they may also be named with -lactam or -lactim in place of -olide. For example. 

Nitrocellulose is among the least stable of common explosives. At 125°C it decomposes autocatalyticaHy to CO, CO2, H2O, N2, and NO, primarily as a result of hydrolysis of the ester and intermolecular oxidation of the anhydroglucose rings. At 50°C the rate of decomposition of purified nitrocellulose is about 4.5 x 10 %/h, increasing by a factor of about 3.5 for each 10°C rise in temperature. Many values have been reported for the activation energy, E, and Arrhenius frequency factor, Z, of nitrocellulose. Typical values foiE and Z are 205 kj/mol (49 kcal/mol) and 10.21, respectively. The addition of... 

Lipase-catalyzed intermolecular condensation of diacids with diols results in a mixture of macrocycUc lactones and liuear oligomers. Interestingly, the reaction temperature has a strong effect on the product distribution. The condensation of a,(D-diacids with a,(D-dialcohols catalyzed by Candida glindracea or Pseudomonas sp. Upases leads to macrocycUc lactones at temperatures between 55 and 75°C (91), but at lower temperatures (<45°C) the formation of oligomeric esters predorninates. Optically active trimers and pentamers can be produced at room temperature by PPL or Chromobacterium viscosum Upase-catalyzed condensation of bis (2,2,2-trichloroethyl) (+)-3-meth5ladipate and 1,6-hexanediol (92). 

The formation of ethyl cyano(pentafluorophenyl)acetate illustrates the intermolecular nucleophilic displacement of fluoride ion from an aromatic ring by a stabilized carbanion. The reaction proceeds readily as a result of the activation imparted by the electron-withdrawing fluorine atoms. The selective hydrolysis of a cyano ester to a nitrile has been described. (Pentafluorophenyl)acetonitrile has also been prepared by cyanide displacement on (pentafluorophenyl)methyl halides. However, this direct displacement is always aecompanied by an undesirable side reaetion to yield 15-20% of 2,3-bis(pentafluoro-phenyl)propionitrile. 

Unreacted Starting Material S Intermolecular Reaction Product Keto Ester Product ... 

Methyl salicylate is the methyl ester of o-hydroxybenzoic acid. Intramolecular (rather than intermolecular) hydrogen bonding is responsible for its relatively low boiling point. 

Yet another distinction is between intermolecular catalysis, in which the catalytic function and the reaction site are on different molecules, and intramolecular catalysis, in which the catalytic function and the reaction site are within the same molecule. All of the above examples constitute intermolecular catalyses. The following reaction, the hydrolysis of a monomaleate ester, is an intramolecular nucleophilic catalysis. 

The effect of a carboxy group is illustrated by the reactivity of 2-bromopyridine-3- and 6-carboxylic acids (resonance and inductive activation, respectively) (cf. 166) to aqueous acid under conditions which do not give hydroxy-debromination of 2-bromopyridine and also by the hydroxy-dechlorination of 3-chloropyridine-4-car-boxylic acid. The intervention of intermolecular bifunctional autocatalysis by the carboxy group (cf. 237) is quite possible. In the amino-dechlorination (80°, 4 hr, petroleum ether) of 5-carbethoxy-4-chloropyrimidine there is opportunity for built-in solvation (167) in addition to electronic activation. This effect of the carboxylate ion, ester, and acid and its variation with charge on the nucleophile are discussed in Sections I,D,2,a, I,D,2,b, and II,B, 1. A 5-amidino group activates 2-methylsulfonylpyridine toward methanolic am-... 

Unexpectedly strong intermolecular hydrogen bonding has been reported by IR spectroscopic studies for tetrahydro-4,7-phenanthroline-l,10-dione-3,8-dicarboxylic acids, which exist in the oxo-hydroxy form 165 in both solid state and in solution [78JCS(CC)369].Tlie conclusion was based on comparison of B-, C-, and D-type bands for 165 and their dimethyl esters (detection of hydrogen bonding) and on analysis of IR spectra in the 6 /xm region (pyridine- and pyridone-like bands). 

There is quite some evidence for a mechanism as formulated above,especially for the six-membered transition state—the Barton reaction is observed only with starting materials of appropriate structure and geometry, while the photolysis of nitrite esters in general seldom leads to useful products formed by fragmentation, disproportionation or unselective intermolecular hydrogen abstraction. 

The Barton reaction is usually carried out by irradiation of a nitrite ester 1 dissolved in a hydroxyl-free solvent under nitrogen atmosphere. Possible side-reactions can be decomposition reactions and intermolecular reactions sometimes the disproportionation may even predominate ... 

The utility of base catalyzed condensations of esters to give jS-ketoesters is well known. A straightforward example of this reaction is the intermolecular cyclization of diethyl succinate giving 2,5-dicarbethoxy-l,4-cyclohexanedione, which can in turn be easily decarboxylated to give 1,4-cyclohexanedione. 

The strained bicyclic carbapenem framework of thienamycin is the host of three contiguous stereocenters and several heteroatoms (Scheme 1). Removal of the cysteamine side chain affixed to C-2 furnishes /J-keto ester 2 as a possible precursor. The intermolecular attack upon the keto function in 2 by a suitable thiol nucleophile could result in the formation of the natural product after dehydration of the initial tetrahedral adduct. In a most interesting and productive retrosynthetic maneuver, intermediate 2 could be traced in one step to a-diazo keto ester 4. It is important to recognize that diazo compounds, such as 4, are viable precursors to electron-deficient carbenes. In the synthetic direction, transition metal catalyzed decomposition of diazo keto ester 4 could conceivably furnish electron-deficient carbene 3 the intermediacy of 3 is expected to be brief, for it should readily insert into the proximal N-H bond to... 

Intramolecular and intermolecular 1,3-dipolar cycloadditions of aziridine-2-car-boxylic esters with alkenes and alkynes have been investigated [131, 132]. Upon heating, aziridine-2-carboxylates undergo C-2-C-3 bond cleavage to form azome-... 

In the Michael addition of achiral enolates and achiral Michael acceptors the basic general problem of simple diastereoselection (see Section D.1.5.1.3.2.), as described in Section 1.5.2.3.2. is applicable. Thus, the intermolecular 1,4-addition of achiral metal enolates to enones, a.jS-unsat-urated esters, and thioamides, results in the formation of racemic syn-1,2 and/or anti-3,4 adducts. 

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