Question

Show how you would synthesize the following compounds from the indicated starting materials and any desired inorganic reagents. (a) di-n-octyl sodium sulfosuccinate, \(\mathrm{CH}_{3}\left(\mathrm{CH}_{2}\right)_{7} \mathrm{O}_{2} \mathrm{CCH}_{2} \mathrm{CH}\left(\mathrm{SO}_{3} \mathrm{Na}\right)-\mathrm{CO}_{2} \cdot\left(\mathrm{CH}_{2}\right)_{7} \mathrm{CH}_{3}\) ("Aerosol" detergent) from maleic anhydride and n-octyl alcohol. (b) \(\left(\mathrm{CH}_{2}\right)_{3}\left(\mathrm{SO}_{3} \mathrm{H}\right)_{2}\) from \(\left(\mathrm{CH}_{2}\right)_{3} \mathrm{Br}_{2}\) (c) methyl 1 -butanesulfinate from \(\mathrm{n}\) -butyl bromide (a) from C=Cc1ccccc1 (e) optically active ethyl benzenesulfinate from optically active 2-octyl- benzenesulfinate.

Short answer

(a) Synthesis of di-n-octyl sodium sulfosuccinate: 1. Heat maleic anhydride and n-octyl alcohol with an acid catalyst to form di-n-octyl maleate. 2. Add aqueous sodium bisulfite to the di-n-octyl maleate to form di-n-octyl sodium sulfosuccinate. (b) Synthesis of \(\left(\mathrm{CH}_{2}\right)_{3}\left(\mathrm{SO}_{3}\mathrm{H}\right)_{2}\): 1. React \(\left(\mathrm{CH}_{2}\right)_{3} \mathrm{Br}_{2}\) with sodium sulfite to form \(\left(\mathrm{CH}_{2}\right)_{3}\left(\mathrm{SO}_{3}\mathrm{H}\right)_{2}\). (c) Synthesis of methyl 1-butanesulfinate: 1. Perform a nucleophilic substitution (SN2) reaction of n-butyl bromide with methyl sulfonate anion to form methyl 1-butanesulfinate. (d) Synthesis of a compound from C=Cc1ccccc1: 1. Perform electrophilic addition of bromine to the alkene in C=Cc1ccccc1 to form BrCH-CHBr-c1ccccc1. (e) Synthesis of optically active ethyl benzenesulfinate: 1. Oxidize optically active 2-octyl benzenesulfinate with H2O2/OH- to form optically active benzenesulfinic acid. 2. Esterify the resulting benzenesulfinic acid with ethyl alcohol to obtain optically active ethyl benzenesulfinate.

Step-by-step solution

Reaction with maleic anhydride and n-octyl alcohol

\ Heat maleic anhydride and n-octyl alcohol together in the presence of a catalyst (e.g. acidic catalyst) to form di-n-octyl maleate. \[ \ce{C4H2O3 + 2(CH3(CH2)7OH) -> (CH3(CH2)7O2CCH=CHCO2(CH2)7CH3)} \]

Hydrolyze the resulting ester to form di-n-octyl sodium sulfosuccinate

\ React the di-n-octyl maleate obtained in Step 1 with aqueous sodium bisulfite to perform a nucleophilic addition reaction and hydrolyze the ester, forming di-n-octyl sodium sulfosuccinate: \[ \ce{(CH3(CH2)7O2CCH=CHCO2(CH2)7CH3) + 2 NaHSO3 -> CH3(CH2)7O2CCH2CH(SO3Na)CO2(CH2)7CH3}\] (b) \(\left(\mathrm{CH}_{2}\right)_{3}\left(\mathrm{SO}_{3}\mathrm{H}\right)_{2}\) from \(\left(\mathrm{CH}_{2}\right)_{3} \mathrm{Br}_{2}\)

Reaction with sodium sulfite

\ Perform a nucleophilic substitution reaction by reacting \(\left(\mathrm{CH}_{2}\right)_{3} \mathrm{Br}_{2}\) with sodium sulfite: \[ \ce{(CH2)3Br2 + 2 Na2SO3 -> (CH2)3(SO3H)2 + 2 NaBr}\] (c) methyl 1-butanesulfinate from n-butyl bromide

Reaction with sodium sulfite

\ Nucleophilic substitution (SN2) of n-butyl bromide by methyl sulfonate anion: \[ \ce{CH3(CH2)3Br + CH3OSO2Na -> CH3(CH2)3OSO2CH3 + NaBr}\] (d) a compound from C=Cc1ccccc1

Reaction with bromine

\ Perform electrophilic addition of bromine to the alkene in C=Cc1ccccc1: \[ \ce{C=Cc1ccccc1 + Br2 -> BrCH-CHBr-c1ccccc1}\] (e) optically active ethyl benzenesulfinate from optically active 2-octyl benzenesulfinate

Oxidation of 2-octyl benzenesulfinate

\ Oxidize optically active 2-octyl benzenesulfinate to an optically active benzenesulfinic acid: \[ \ce{ 2-Octyl-Benzenesulfinate ->[H2O2/OH^-] Benzenesulfinic Acid}\]

Esterification with ethyl alcohol

\ Perform an esterification reaction with ethyl alcohol: \[ \ce{ Benzenesulfinic Acid + CH3-CH2-OH ->[H^+] Optically Active Ethyl Benzenesulfinate + H2O}\]

Key concepts

Nucleophilic Substitution

Nucleophilic substitution is a fundamental reaction where a nucleophile, a chemical species with high electron density, attacks a positively charged or partially positive atom in a compound to replace another group. Typically, an atom with an accessible pair of electrons, like sulfur or nitrogen, acts as the nucleophile. This reaction is widely used in organic synthesis to modify molecules, making it a key tool for chemists.

In the case of synthesizing compounds, such as in exercise (b) and (c), we see a practical example. For instance, in part (b), the reaction involves replacing bromine atoms in propyl dibromide with sulfonate groups derived from sodium sulfite. This is an example of a nucleophilic substitution reaction and results in the formation of 1,3-propane disulfonic acid.

Similarly, in part (c), nucleophilic substitution is employed to create methyl 1-butanesulfinate, where the bromine atom of n-butyl bromide is exchanged with a methoxy sulfinate group. These reactions are often classified either as Sn1 or Sn2, depending on the mechanism. Here, the methyl sulfonate acts directly on the carbon-bromine bond, allowing the switch.

Esterification

Esterification is a chemical reaction that forms an ester as the main product. This reaction typically occurs between an alcohol and a carboxylic acid in the presence of an acid catalyst. Esterification is a fundamental process in chemistry used to create esters, which are significant in both industrial and biological contexts.

In the exercise's synthetic pathway (e), esterification is demonstrated towards the end. After oxidizing 2-octyl benzenesulfinate to benzenesulfinic acid, an esterification reaction is performed with ethyl alcohol. This step transforms benzenesulfinic acid into optically active ethyl benzenesulfinate, highlighting the use of such reactions to obtain target molecules with specific functional groups.

Esterification is heavily influenced by the reaction conditions such as temperature and the presence of your acid catalyst. The acid catalyst, like sulfuric acid or hydrochloric acid, protonates the carboxylic acid, making it more electrophilic and thus ready to react with the alcohol to form the ester. Water is a byproduct of these reactions, which needs to be managed for the reaction to go in the forward direction.

Electrophilic Addition

Electrophilic addition is a type of reaction where an electrophile, a chemical species with a tendency to accept electrons, reacts with an alkene or alkyne. This process is crucial in converting double or triple bonds into saturated compounds by electrophiles such as halogens or acids, effectively "adding" atoms across the bonds.

In the given exercise, electrophilic addition is illustrated in part (d), using the alkene compound depicted by the SMILES string. When this alkene is treated with bromine, the double bond opens up and bromine atoms add across it, forming a dibromo structure. This action is classical electrophilic addition and is useful in altering the chemical structure of molecules to change their properties and reactivity.

Electrophilic addition reactions take place in two stages: the formation of a carbocation intermediate when the electrophile adds to the double bond, and then the nucleophile adds to this intermediate. Understanding these steps is vital in predicting product structures and yields.

Oxidation Reactions

Oxidation reactions are processes where a molecule loses electrons, which often results in an increase in its oxidation state. These reactions are central in transforming functional groups within organic molecules, frequently turning them into more oxidized forms like acids or ketones.

In exercise part (e), the oxidation of an organic sulfinate to an acid is demonstrated. Optically active 2-octyl benzenesulfinate oxidizes to benzenesulfinic acid using an oxidizing agent like hydrogen peroxide in an alkaline solution. This showcases how oxidation can be used to promote significant structural changes in organic molecules.

Oxidative reactions are instrumental in organic synthesis for converting initial compounds into desired more oxidized products. Understanding the conditions and selecting the proper oxidizing agent are both essential for achieving the specific transformation needed in organic synthesis.