Substituent sequencing

Thus, 2-nitropropylene can be initiated to polymerize with a base as weak as KHCO3. Indeed, only the very weak Lewis bases, water, alcohols, or ketones, are needed for vinylidene cyanide. In contrast, methyl methacrylate is more difficult to polymerize anionically than acrylonitrile because of the presence of the electron-donating methyl group, even though ester and nitrile groups have about the same electron accepting properties. With olefin derivatives, CH2=CHR, the capacity to polymerize anionically decreases with the R substituent sequence... 

The central carbon atom C-2 of molecule II (Figure 3-1) has the clockwise substituent sequence H -> CH2 Cl the C-4 carbon atom of molecule II (Figure 3-2), however, has the clockwise sequence CH3 CH2 H. 

In a more extended chain with the same configuration, the C-6 atom would have the substituent sequence H CH2 CH3 and the C-8 atom would have the sequence CH3 CH2 H, etc. Such sequences of configurative diads are called syndiotactic diads. Thus molecules II and III (Figure 3-2) are also syndiotactic. 

When the molar ratio MejAl ketone was approximately unity, ketones (134)— (137) gave 96% axial alcohols 2,2,6-trimethylcyclohexanone, with an axial methyl, gave 88% axial alcohol. Axial attack decreased in the substituent sequence 4-t-butyl-, 2-methyl-, ds-2,6-dimethyl. The decrease with successive introduction of 2-and 6-equatorial methyl groups was paralleled by a decrease in axial attack with decreased flexibility of the ring system in the sequence 2-methyl-, ds-2-methyl-4-t-butyl-cyclohexanones, and rrans-decalone. With cis-2,6-dimethyl- and 2,2,6-tri-methyl-cyclohexanones, at a MejAl ketone ratio of 2 1, the percentage of axial alcohol... 

If the seed atom is in a ring, the unplaced neighbors are sequenced by means of the master substituent sequencing algorithm (above), and placed at regular intervals within the seed atom s CFS (Algorithm 8). 

Let P be the angular separation calculated from Algorithm 6. Also calculate the substituent sequence using Algorithm 7. 

Invoke Algorithms 6 and 7 to get the substituent sequence and residual angular spacing. 

The Wiswesser Line Notation (WLN) was introduced in 1946, in order to organize and to systematically describe the cornucopia of compounds in a more concise manner. A line notation represents a chemical structure by an alphanumeric sequence, which significantly simplifies the processing by the computer [9-11], (n many cases the WLN uses the standard symbols for the chemical elements. Additionally, functional groups, ring systems, positions of ring substituents, and posi-... 

They deactivate all positions, overall reactivities depending upon the substituent in the sequence F I > Cl Br. 

The o p-ratio is always less than unity and varies with the substituent in the sequence I > Br > Cl > F. 

The halogen substituents ( — 7 +M) owe their o p-orientating effect, achieved in spite of the deactivation, to polarisability by the conjugative process. The strength of the inductive deactivation is seen in the sequence of the two ratios quoted. 

TrialkyIboranes (p. 9), which can be synthesized from olefins and diborane, undergo alkyl coupling on oxidation with alkaline silver nitrate via short-lived silver organyls. Two out of three alkyl substituents are coupled in this reaction. Terminal olefins may be coupled by this reaction sequence in 40 - 80% yield. With non-terminal olefins yields drop to 30 - 50% (H.C. Brown, 1972C, 1975). 

Cis-olefins or cis./rjns-dienes can be obtained from alkynes in similar reaction sequences. The alkyne is first hydroborated and then treated with alkaline iodine. If the other substituents on boron are alkyl groups, a cis-olefin is formed (G. Zweifel, 1967). If they are cir-alkenyls, a cis, trans-diene results. The reactions are thought to be iodine-assisted migrations of the cis-alkenyl group followed by (rans-deiodoboronation (G. Zweifel, 1968). Trans, trans-dienes are made from haloalkynes and alkynes. These compounds are added one after the other to thexylborane. The alkenyl(l-haloalkenyl)thexylboranes are converted with sodium methoxide into trans, trans-dienes (E. Negishi, 1973). The thexyl group does not migrate. 

J lie decarboxylation is frequently the most troublesome step in this sequence. Attempts at simple thermal decarboxylation frequently lead to recycliz-ation to the lactam. The original investigators carried out decarboxylation by acidic hydrolysis and noted that rings with ER substituents were most easily decarboxylated[2]. It appears that ring protonation is involved in the decarboxylation under hydrolytic conditions. Quinoline-copper decarboxylation has been used successfully after protecting the exocyclic nitrogen with a phthaloyl, acetyl or benzoyl group[3]. 

Gassman and co-workers developed a synthetic route from anilines to indoles and oxindoles which involves [2.3]-sigmatropic rearrangement of anilinosul-fonium ylides. These can be prepared from Ai-chloroanilines and ot-thiomcthyl-ketones or from an aniline and a chlorosulfonium salt[l]. The latter sequence is preferable for anilines with ER substituents. Rearrangement and cyclizalion occurs on treatment of the anilinosulfonium salts with EtjN. The initial cyclization product is a 3-(methylthio)indole and these can be desulfurized with Raney nickel. Use of 2-(methylthio)acetaldehyde generates 2,3-unsubstituled indoles after desulfurization[2]. Treatment of 3-methylthioindoles with tri-fiuoroacetic acid/thiosalieylie acid is a possible alternative to Raney nickel for desulfurization[3]. 

There are two sequences in which the reaction can be carried out. For most anilines the first step is /V-chlorination which can be done with t-butyl hypochlorite[9]. However, for anilines with ER substituents it may be preferable to halogenate the thioester. The halogenation can be done with Cl2[lbl or SOjCljCU]. For some anilines simply adding f-butyl hypochlorite to a mixture of the aniline and thioester is satisfactory (Entries 1, 4, Table 7.6). 

An important method for construction of functionalized 3-alkyl substituents involves introduction of a nucleophilic carbon synthon by displacement of an a-substituent. This corresponds to formation of a benzylic bond but the ability of the indole ring to act as an electron donor strongly influences the reaction pattern. Under many conditions displacement takes place by an elimination-addition sequence[l]. Substituents that are normally poor leaving groups, e.g. alkoxy or dialkylamino, exhibit a convenient level of reactivity. Conversely, the 3-(halomethyl)indoles are too reactive to be synthetically useful unless stabilized by a ring EW substituent. 3-(Dimethylaminomethyl)indoles (gramine derivatives) prepared by Mannich reactions or the derived quaternary salts are often the preferred starting material for the nucleophilic substitution reactions. 

The reaction of MeO /MeOH with 2-Cl-5(4)-X-thiazoles (122) follows a second-order kinetic law, first order with respect to each reactant (Scheme 62) (297, 301). A remark can be made about the reactivity of the dichloro derivatives it has been pointed out that for reactions with sodium methoxide, the sequence 5>2>4 was observed for monochlorothiazole compounds (302), For 2.5-dichlorothiazole, on the contrary, the experimental data show that the 2-methoxy dehalogenation is always favored. This fact has been related to the different activation due to a substituent effect, less important from position 2 to 5 than from... 

Both schemes count five carbon atoms m their longest continuous chain and bear a methyl group as a substituent at the second carbon An alternative numbering sequence that begins at the other end of the chain is incorrect... 

The reaction of an alcohol with a hydrogen halide is a substitution A halogen usually chlorine or bromine replaces a hydroxyl group as a substituent on carbon Calling the reaction a substitution tells us the relationship between the organic reactant and its prod uct but does not reveal the mechanism In developing a mechanistic picture for a par ticular reaction we combine some basic principles of chemical reactivity with experi mental observations to deduce the most likely sequence of steps... 

No locants are needed m the absence of substituents it is understood that the double bond connects C 1 and C 2 Substituted cycloalkenes are numbered beginning with the double bond proceeding through it and continuing m sequence around the ring The direction is chosen so as to give the lower of two possible numbers to the substituent... 

Because acylation of an aromatic ring can be accomplished without rearrangement it is frequently used as the first step m a procedure for the alkylation of aromatic compounds by acylation-reduction As we saw m Section 12 6 Friedel-Crafts alkylation of ben zene with primary alkyl halides normally yields products having rearranged alkyl groups as substituents When a compound of the type ArCH2R is desired a two step sequence IS used m which the first step is a Friedel-Crafts acylation... 

Sequence rule (Section 7 6) Foundation of the Cahn-Ingold-Prelog system It is a procedure for ranking substituents on the basis of atomic number... 

In a syndiotactic arrangement, the substituents are in an ordered alternating sequence, appearing alternately on one side and then on the other side of the chain, thus... 

In an atactic arrangement, substituents are in an unordered sequence along the polymer chains. 

This particular sequence of conformations-trans bonds that advance the helix along the axis, alternating with gauche bonds which provide the twist-takes the chain through a series of relatively low potential energy states and generates a structure with minimum steric hindrance between substituents. If the polymer series is extended to include bulkier substituents, for example. 

R = -CH2CH(CH3)2, there occurs a modest deviation from a strict 0°-120° alternation which characterizes the trans-gauche sequence. This produces a helical structure with seven repeat units occurring in two turns. Even bulkier substituents, for example, o-methyl phenyl, produce still more open helices... 

This tendency is related to the polarization properties of the monomer substituents (42). Monomers that are dissimilar in polarity tend to form alternating monomer sequences in the polymer chain. An example is the monomer pair acrylonitrile—styrene. Styrene, with its pendent phenyl group, has a relatively electronegative double bond whereas acrylonitrile, with its electron-withdrawing nitrile group, tends to be electropositive. 

Mass spectral fragmentation patterns of alkyl and phenyl hydantoins have been investigated by means of labeling techniques (28—30), and similar studies have also been carried out for thiohydantoins (31,32). In all cases, breakdown of the hydantoin ring occurs by a-ftssion at C-4 with concomitant loss of carbon monoxide and an isocyanate molecule. In the case of aryl derivatives, the ease of formation of Ar—NCO is related to the electronic properties of the aryl ring substituents (33). Mass spectrometry has been used for identification of the phenylthiohydantoin derivatives formed from amino acids during peptide sequence determination by the Edman method (34). 

Acylation. Acylation is the most rehable means of introducing a 3-substituent on the indole ring. Because 3-acyl substituents can be easily reduced to 3-aLkyl groups, a two-step acylation—reduction sequence is often an attractive alternative to direct 3-aLkylation. Several kinds of conditions have been employed for acylation. Very reactive acyl haUdes, such as oxalyl chloride, can effect substitution directiy without any catalyst. Normal acid chlorides are usually allowed to react with the magnesium (15) or 2inc (16) salts. The Vilsmeier-Haack conditions involving an amide and phosphoms oxychloride, in which a chloroiminium ion is the active electrophile, frequentiy give excellent yields of 3-acylindoles. 

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