C2 substitution

Ci Substitution given in the text C2 Substitution given in the text CD Drag coefficient dimensionless d Diameter of the bubble, drop, droplet, cm... 

Keeley, D.F., Hoffpauir, M.A., and Meriwether, J.R. Solubility of aromatic hydrocarbons in water and sodium chloride solutions of different ionic strengths C2-substituted benzenes, / Chem. Eng. Data, 36(4) 456-459, 1991. 

The ionic liquid [bmim][BF ] is known to catalyze the aza-Diels-Alder reaction in the synthesis of pyrano- and furanoquinolines [190]. This reaction was also catalyzed by the enantiopure bis-imidazolinium salt 67 in 67% yield with an endo. exo ratio of 60 40 (Scheme 69) [191]. The product was obtained as a race-mate. In addition the aza-Diels-Alder reaction with imines and Danishefsky s diene was catalyzed by the salt 67 giving racemic product. The salt and its analogues could be easily prepared via the oxidation of the corresponding aminals [192]. Investigation of the influence of the counter anion in achiral C2-substituted imidazolinium salts, which can be also described as 4,5-dihydroimidazolium or saturated imidazolium salts, in the aza-Diels-Alder reaction showed, that the catalytic activity increased, the more lipophilic the counter anion and therefore the more hydrophobic the salt was [193]. 

Evans and co-workers were also successful in extending this methodology to the diastereoselective rhodium-catalyzed [4-1-2-i-2] reaction, which probed the influence of a C2-substituted tethered enyne (Eq. 15). Treatment of the substituted enyne 90, under optimized conditions, furnished the 5,8-bicycHc product 91 in a highly efficient and diastereoselective manner. The observed stereoselectivity is in strong agreement with the selective formation of a single metallacycle intermediate as originally outlined. 

The subsequent paragraphs will focus on the preparation of C2-substituted malonyl derivatives for the incorporation into PMRI-peptides. In the classical method, C2 alkylation of a malonic acid diester is followed by partial hydrolysis to generate the C2-alkylated monoalkyl malonate (Scheme 7). The malonyl-derived topochemical replacements for Phe, Lys, Trp, Leu, Ala, His, and Met residues have been successfully prepared by this strat-egyJ48 57 ... 

Campbell et al.[97] found that the yield of the Goldschmidt-Wick-type reaction was lower with C2-substituted monoalkyl malonates than with unsubstituted monoalkyl malonates. They therefore suggest selective C2 alkylation of a malonyl residue already incorporated into a PMRI-dipeptide (Scheme 8)J73] Unfortunately, no experimental details are available for what might potentially be an important synthetic manipulation. 

C2 Alkylation of cyanoacetates followed by hydrolysis results in C2-substituted malonamic acids suitable for incorporation at the C-terminus of PMRI-peptides. However, due to the higher acidity of the C2 protons, dialkylation at the C2 position may occur. 103 Cushman et al.Pl successfully applied this strategy for the synthesis of a terminal mMet-amide-modified bombesin derivative (Scheme 9). 

Verdini and co-workers 71,81 107 were able to silylate the amine with Af,0-bis(trimethylsilyl)-acetamide 108 (BTMSA) and to ring-open Meldrum s acid in a one-pot procedure without isolating the labile Af-silyl derivative. Additional, less frequently employed methods for the synthesis of C2-substituted malonic acids are summarized in a review. 73 ... 

Interesting solutions to the spontaneous epimerization of C2-substituted malonyl residues, to provide configurational stability, were explored independently by Dal Pozzo and Laurita 111 and Abouabdellah and Welch. 30 Replacement of the C2 hydrogen in C2-alkyl-substituted malonyl residues by either methyl 111 or fluorine 30 stabilized the configurational integrity of the C2 chiral center in the malonyl derivatives. 

The intense interest in y - am i n o - (i -hydroxy acid related peptides has led to a great deal of effort devoted to their synthesis. Statine analogues Ahppa (11), Achpa (12), and Dahoa (13) (Scheme 2), which correspond to the replacement of the chain equivalent of leucine in statine by those of phenylalanine, cyclohexylalanine, and lysine, respectively, were used to synthesize inhibitors of pepsin, renin, and penicillinopepsinJ1314] With the objective of developing highly specific inhibitors, C2-substituted analogues have also been introduced into short, substrate-derived inhibitors, e.g. the a,a-difluoro statine 14 in renin inhibitors,1151 and N -substituted statine derivatives like 15 in HIV-1 protease inhibitors.[16]... 

The dilithium derivatives of 2-alkyl-N-trimethylsilylanilines condense with esters to give C2-substituted indoles in generally satisfactory yield.1... 

Due to the preference for a cis-amide bond[93] with the preceding residue of C2-substituted pseudoprolines, their incorporation results in a kink conformation of the peptide backbone, thus preventing peptide aggregation, self-association, or (3-structure formation. 

Extensive use of Pd-catalyzed reactions was included in the synthesis of 2,6,8-trisubstituted purines (Fig. II).33 The synthesis started by anchoring dichloropurine to Rink resin via N9 linkage. Polymer-bound 2,6-dichloropurine (63) was selectively substituted at C6 via acid-catalyzed SNAr substitutions. In the absence of Pd catalysis, the substitution on C2 could be performed only with strongly nucleophilic amines. To expand the scope of C2 substitution, catalytic amounts of Pd were used. Under these reaction conditions arylboronic acids and amines successfully substituted the chloro atom on C2 to afford C2-C and C2-N bonds. Subsequently, the C8 position was brominated with a bromine-lutidine complex33 (66) to give resin 67. 

The intermediate derived from attack at the C2 position has greater delocalisation of the positive charge (mesomeric forms 2.28a,b,c) than that derived from attack at the C3 position (mesomeric forms 2.29a,b). As the charge is more extensively delocalised in the former, this intermediate is at lower energy. This in turn is reflected in a lower activation energy for this pathway and manifested in a selectivity for electrophilic substitution at the C2 position over the C3 position. The actual isomer ratio depends on the heterocycle, the electrophile, and the precise conditions, although in many cases such reactions are virtually regiospecific, and only the C2 substitution... 

Starting from C4-epimeric C2-substituted a,P-unsaturated bromolactones 28 and 33, readily available from 7-bromo-7-deoxy-D-glycero-D-galacto-heptono-1,4-lactone, the radical cyclization was performed by using tributyltin hydride/AIBN mixture (Scheme 5). 

Isopropylpyrocatechol may be included in this as well in the system being compared the isopropyl group was considered as alkyl group C2 substituted on the a-carbbn atom. The relative activities of... 

Photo-oxidation has been reported at crude-oU spills. It results in depletion of n-aUcanes below nCi5 and alkylaromatics such as C - and C2-substituted naphthalenes relative to unoxidized oil (Payne and Phillips, 1985). In terms of a material balance, photo-oxidation has been found to be a minor process (NRC, 1985) but does result in changes in the residual oil composition and can affect the subsequent behavior of an oil spill on the open ocean (Payne and Phillips, 1985). Autooxidation reactions of hydrocarbons in the absence of hght have not been well studied. 

Thus, both conditions result in the same value for the constant C,. but ho value for C2. Substituting, the specific solution in this case is determined to be... 

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