Organic Chemistry II Lecture Notes 6th Lecture 2024-2025 PDF

ORGANIC CHEMISTRY II College of Pharmacy 2nd Stage/1st semester Lecturer :Mohammed S. Nawrooz Pharmacognosist 6th Lecture 2024-2025 ...

ORGANIC CHEMISTRY II College of Pharmacy 2nd Stage/1st semester Lecturer :Mohammed S. Nawrooz Pharmacognosist 6th Lecture 2024-2025  Mohammed Deyaa Reactions of carboxylic Acid.‫ ﯾﻤﻜﻦ إزاﻟﺔ اﻟﺒﺮوﺗﻮﻧﺎت ﻣﻦ اﻷﺣﻤﺎض اﻟﻜﺮﺑﻮﻛﺴﯿﻠﯿﺔ ﻹﻋﻄﺎء اﻷﻧﯿﻮﻧﺎت‬،‫ ﻣﺜﻞ اﻟﻜﺤﻮل‬.‫ﺗﺸﺒﮫ اﻷﺣﻤﺎض اﻟﻜﺮﺑﻮﻛﺴﯿﻠﯿﺔ ﻓﻲ ﺑﻌﺾ اﻟﻨﻮاﺣﻲ ﻛﻞ ﻣﻦ اﻟﻜﺤﻮل واﻟﻜﯿﺘﻮﻧﺎت‬ Carboxylic acids are similar in some respects to both alcohols and ketones. Like alcohols, carboxylic acids can be deprotonated to give anions..‫ ﺗﺨﻀﻊ اﻷﺣﻤﺎض اﻟﻜﺮﺑﻮﻛﺴﯿﻠﯿﺔ ﻹﺿﺎﻓﺔ اﻟﻨﻮﻛﻠﯿﻮﻓﯿﻼت إﻟﻰ ﻣﺠﻤﻮﻋﺔ اﻟﻜﺮﺑﻮﻧﯿﻞ‬،‫ ﻣﺜﻞ اﻟﻜﯿﺘﻮﻧﺎت‬ Like ketones, carboxylic acids undergo addition of nucleophiles to the carbonyl group..‫ ﺗﺨﻀﻊ اﻷﺣﻤﺎض اﻟﻜﺮﺑﻮﻛﺴﯿﻠﯿﺔ ﻟﺘﻔﺎﻋﻼت أﺧﺮى ﻣﻤﯿﺰة ﻻ ﻟﻠﻜﺤﻮل وﻻ اﻟﻜﯿﺘﻮﻧﺎت‬،‫ ﺑﺎﻹﺿﺎﻓﺔ إﻟﻰ ذﻟﻚ‬ In addition, carboxylic acids undergo other reactions characteristic of neither alcohols nor ketones.  / ‫ اﻟﻤﺮﻛﺒﺎت اﻟﺘﻲ ﺗﺮﺗﺒﻂ ﻓﯿﮭﺎ ﻣﺠﻤﻮﻋﺔ اﻷﺳﯿﻞ ﺑﺬرة ﺳﺎﻟﺒﺔ ﻟﻠﻜﮭﺮﺑﺎء أو ﺑﺪﯾﻞ ﯾﻤﻜﻦ أن ﯾﻌﻤﻞ ﻛﻤﺠﻤﻮﻋﺔ‬،‫ﻣﺸﺘﻘﺎت ﺣﻤﺾ اﻟﻜﺮﺑﻮﻛﺴﯿﻞ‬.‫ﻣﻐﺎدرة ﻓﻲ ﺗﻔﺎﻋﻞ اﺳﺘﺒﺪال أﺳﯿﻞ اﻟﻨﻮاة‬ carboxylic acid derivatives, compounds in which an acyl group is bonded to an electronegative atom or substituent that can act as a leaving group in the nucleophilic acyl substitution reaction.  ‫ ﻓﻲ ﺣﯿﻦ أن اﻹﺳﺘﺮات واﻷﻣﯿﺪات ﺷﺎﺋﻌﺔ ﻓﻲ ﻛﻞ ﻣﻦ اﻟﻜﯿﻤﯿﺎء اﻟﻤﺨﺘﺒﺮﯾﺔ‬،‫ﺗﺴﺘﺨﺪم اﻟﮭﺎﻟﯿﺪات اﻟﺤﻤﻀﯿﺔ واﻷﻧﮭﯿﺪرﯾﺪات اﻟﺤﻤﻀﯿﺔ ﻓﻘﻂ ﻓﻲ اﻟﻤﺨﺘﺒﺮ‬.‫واﻟﺒﯿﻮﻟﻮﺟﯿﺔ‬ Acid halides and acid anhydrides are used only in the laboratory, while esters and amides are common in both laboratory and biological chemistry..‫ ﺗﺘﻢ ﻣﻮاﺟﮭﺔ ﻣﺸﺘﻘﺎت ﺣﻤﺾ اﻟﻜﺮﺑﻮﻛﺴﯿﻞ اﻟﺘﻲ ﺗﺴﻤﻰ ﺛﯿﻮﺳﺘﺮ وﻓﻮﺳﻔﺎت اﻷﺳﯿﻞ ﻓﻲ اﻟﻤﻘﺎم اﻷول ﻓﻲ اﻟﻜﯿﻤﯿﺎء اﻟﺒﯿﻮﻟﻮﺟﯿﺔ‬،‫ﺑﺎﻹﺿﺎﻓﺔ إﻟﻰ ذﻟﻚ‬ In addition, carboxylic acid derivatives called thioesters and acyl phosphates are encountered primarily in biological chemistry..‫ﻻﺣﻆ اﻟﺘﺸﺎﺑﮫ اﻟﮭﯿﻜﻠﻲ ﺑﯿﻦ أﻧﮭﯿﺪرﯾﺪات اﻟﺤﻤﺾ وﻓﻮﺳﻔﺎت اﻷﺳﯿﻞ‬ Note the structural similarity between acid anhydrides and acyl phosphates.  Naming Carboxylic Acid Derivatives.‫ ﻋﻦ طﺮﯾﻖ ﺗﺤﺪﯾﺪ ﻣﺠﻤﻮﻋﺔ اﻷﺳﯿﻞ أوﻻ ﺛﻢ اﻟﮭﺎﻟﯿﺪ‬RCOX ‫ ﯾﺘﻢ ﺗﺴﻤﯿﺔ ھﺎﻟﯿﺪات ﺣﻤﺾ‬:‫ ھﺎﻟﯿﺪات اﻟﺤﻤﺾ‬.1 1.Acid Halides: RCOX Acid halides are named by identifying first the acyl group and then the halide. 2. Acid Anhydrides, RCO2COR′  3.Esters, RCO2R′ 4. Amides, RCONH2  5. Thioesters, RCOSR′ 6.Acyl Phosphates, RCO2PO3-2 and RCO2PO3R-′  ‫ﺗﻔﺎﻋﻼت اﺳﺘﺒﺪال أﺳﯿﻞ اﻟﻨﻮﻛﻠﯿﻮﻓﯿﻠﯿﻚ‬ Nucleophilic Acyl Substitution Reactions.‫ اﻟﻘﻄﺒﯿﺔ ھﻲ اﻟﺨﻄﻮة اﻟﺮﺋﯿﺴﯿﺔ ﻓﻲ ﺛﻼﺛﺔ ﻣﻦ ﺗﻔﺎﻋﻼت ﻣﺠﻤﻮﻋﺔ اﻟﻜﺮﺑﻮﻧﯿﻞ اﻟﺮﺋﯿﺴﯿﺔ اﻷرﺑﻌﺔ‬C=O ‫ﺗﻌﺪ إﺿﺎﻓﺔ ﻧﻮﻛﻠﯿﻮﻓﯿﻞ إﻟﻰ راﺑﻄﺔ‬ The addition of a nucleophile to a polar C=O bond is the key step in three of the four major carbonyl-group reactions..‫ ﻣﻤﺎ ﯾﺆدي إﻟﻰ ﺗﻔﺎﻋﻞ ﺑﺪﯾﻞ أﺳﯿﻞ ﻣﺤﺐ ﻟﻠﻨﻮاة‬،‫ﯾﺰﯾﻞ اﻟﻮﺳﯿﻂ رﺑﺎﻋﻲ اﻟﺴﻄﻮح اﻟﺬي ﺗﻢ ﺗﺸﻜﯿﻠﮫ ﻓﻲ اﻟﺒﺪاﯾﺔ أﺣﺪ اﻟﺒﺪاﺋﻞ اﻟﻤﺮﺗﺒﻄﺔ ﻓﻲ اﻷﺻﻞ ﺑﻜﺮﺑﻮن اﻟﻜﺮﺑﻮﻧﯿﻞ‬ The initially formed tetrahedral intermediate eliminates one of the two substituents originally bonded to the carbonyl carbon, leading to a net nucleophilic acyl substitution reaction..‫ وﻏﺎﻟﺒﺎ ﻣﺎ ﺗﻜﻮن أﻧﯿﻮن ﻣﺴﺘﻘﺮ‬،‫ ﯾﻤﻜﻦ أن ﺗﻌﻤﻞ ﻛﻤﺠﻤﻮﻋﺔ ﻣﻐﺎدرة‬Y- ‫ﺗﺤﺘﻮي ﻣﺸﺘﻘﺎت ﺣﻤﺾ اﻟﻜﺮﺑﻮﻛﺴﯿﻞ ﻋﻠﻰ ﻛﺮﺑﻮن أﺳﯿﻞ ﻣﺮﺗﺒﻂ ﺑﻤﺠﻤﻮﻋﺔ‬ Carboxylic acid derivatives have an acyl carbon bonded to a group -Y that can act as a leaving group, often as a stable anion. Nucleophilic Acyl Substitution Reactions of Carboxylic Acids.‫ ھﻲ ﻣﺠﻤﻮﻋﺔ ﻣﻐﺎدرة ﻓﻘﯿﺮة‬OH ‫ﻣﻦ اﻟﺼﻌﺐ اﺳﺘﺒﺪال أﺳﯿﻞ اﻟﻨﻮاة اﻟﻤﺒﺎﺷﺮ ﻟﺤﻤﺾ اﻟﻜﺮﺑﻮﻛﺴﯿﻞ ﻷن‬ The direct nucleophilic acyl substitution of a carboxylic acid is difficult because OH is a poor leaving group. ‫ إﻣﺎ ﺑﺎﺳﺘﺨﺪام ﻣﺤﻔﺰ ﺣﻤﻀﻲ ﻗﻮي ﻟﺒﺮوﺗﻮن اﻟﻜﺮﺑﻮﻛﺴﯿﻞ وﺟﻌﻠﮫ ﻣﺘﻘﺒﻼ أﻓﻀﻞ‬،‫ ﻋﺎدة ﻣﺎ ﯾﻜﻮن ﻣﻦ اﻟﻀﺮوري ﺗﻌﺰﯾﺰ ﺗﻔﺎﻋﻞ اﻟﺤﻤﺾ‬،‫وﺑﺎﻟﺘﺎﻟﻲ‬ Thus, it’s usually necessary to enhance the reactivity of the acid, either by using a strong acid catalyst to protonate the carboxyl and make it a better acceptor or.‫ إﻟﻰ ﻣﺠﻤﻮﻋﺔ ﻣﻐﺎدرة أﻓﻀﻞ‬OH- ‫ﻋﻦ طﺮﯾﻖ ﺗﺤﻮﯾﻞ‬ by converting the -OH into a better leaving group.  ‫ ﺗﺤﻮﯾﻞ اﻷﺣﻤﺎض اﻟﻜﺮﺑﻮﻛﺴﯿﻠﯿﺔ إﻟﻰ ﻛﻠﻮرﯾﺪات ﺣﻤﻀﯿﺔ‬.1 1.Conversion of Carboxylic Acids into Acid Chlorides.(SOCl2) ‫ ﯾﺘﻢ ﺗﺤﻮﯾﻞ اﻷﺣﻤﺎض اﻟﻜﺮﺑﻮﻛﺴﯿﻠﯿﺔ إﻟﻰ ﻛﻠﻮرﯾﺪات ﺣﻤﻀﯿﺔ ﻋﻦ طﺮﯾﻖ اﻟﻤﻌﺎﻟﺠﺔ ﺑﻜﻠﻮرﯾﺪ ﺛﯿﻮﻧﯿﻞ‬،‫ﻓﻲ اﻟﻤﺨﺘﺒﺮ‬ In the laboratory, carboxylic acids are converted into acid chlorides by treatment with thionyl chloride(SOCl2).  ‫ ﺗﺤﻮﯾﻞ اﻷﺣﻤﺎض اﻟﻜﺮﺑﻮﻛﺴﯿﻠﯿﺔ إﻟﻰ أﻧﮭﯿﺪرﯾﺪات ﺣﻤﻀﯿﺔ‬.2 2.Conversion of Carboxylic Acids into Acid Anhydrides ‫ﻣﻦ‬.‫اﻟﻄﺮﯾﻘﺔ‬ 1 ‫ﯾﻤﻜﻦ اﺷﺘﻘﺎق أﻧﮭﯿﺪرﯾﺪات اﻟﺤﻤﺾ ﻣﻦ ﺟﺰﯾﺌﯿﻦ ﻣﻦ ﺣﻤﺾ اﻟﻜﺮﺑﻮﻛﺴﯿﻞ ﻋﻦ طﺮﯾﻖ اﻟﺘﺴﺨﯿﻦ ﻹزاﻟﺔ ﻣﺎ ﯾﻌﺎدل‬ ‫ ﻋﺎدة ﻣﺎ ﯾﺘﻢ ﺗﺤﻀﯿﺮ أﻧﮭﯿﺪرﯾﺪ اﻟﺨﻞ ﻓﻘﻂ ﺑﮭﺬه‬،‫ ﺑﺴﺒﺐ ارﺗﻔﺎع درﺟﺎت اﻟﺤﺮارة اﻟﻤﻄﻠﻮﺑﺔ‬،‫ وﻣﻊ ذﻟﻚ‬.‫اﻟﻤﺎء‬ Acid anhydrides can be derived from two molecules of carboxylic acid by heating to remove 1 equivalent of water. Because of the high temperatures needed, however, only acetic anhydride is commonly prepared this way.  ‫ ﺗﺤﻮﯾﻞ اﻷﺣﻤﺎض اﻟﻜﺮﺑﻮﻛﺴﯿﻠﯿﺔ إﻟﻰ اﺳﺘﺮات‬.3 3.Conversion of Carboxylic Acids into Esters.‫ وھﻲ ﻋﻤﻠﯿﺔ ﺗﺴﻤﻰ ﺗﻔﺎﻋﻞ اﻷﺳﺘﺮة ﻓﯿﺸﺮ‬،‫ﯾﻤﻜﻦ أﯾﻀﺎ ﺗﺼﻨﯿﻊ اﻹﺳﺘﺮات ﻋﻦ طﺮﯾﻖ ﺗﻔﺎﻋﻞ اﺳﺘﺒﺪال أﺳﯿﻞ ﻧﻮﻛﻠﯿﻮﻓﯿﻠﻲ ﻣﺤﻔﺰ ﺑﺎﻟﺤﻤﺾ ﻟﺤﻤﺾ اﻟﻜﺮﺑﻮﻛﺴﯿﻞ ﻣﻊ اﻟﻜﺤﻮل‬ Esters can also be synthesized by an acid-catalyzed nucleophilic acyl substitution reaction of a carboxylic acid with an alcohol, a process called the Fischer esterification reaction..‫ ﻓﺈن اﻟﺤﺎﺟﺔ إﻟﻰ اﺳﺘﺨﺪام ﻓﺎﺋﺾ ﻣﻦ اﻟﻜﺤﻮل اﻟﺴﺎﺋﻞ ﻛﻤﺬﯾﺐ ﺗﺤﺪ ﺑﺸﻜﻞ ﻓﻌﺎل ﻣﻦ اﻟﻄﺮﯾﻘﺔ ﻟﺘﺨﻠﯿﻖ اﻟﻤﯿﺜﯿﻞ واﻹﯾﺜﯿﻞ واﻟﺒﺮوﺑﯿﻞ وإﺳﺘﺮات اﻟﺒﻮﺗﯿﻞ‬،‫ﻟﺴﻮء اﻟﺤﻆ‬ Unfortunately, the need to use an excess of a liquid alcohol as solvent effectively limits the method to the synthesis of methyl, ethyl, propyl, and butyl esters. 4.Conversion of Carboxylic Acids into Alcohols ‫ واﻟﺬي ﯾﺘﻢ ﺗﻘﻠﯿﻠﮫ إﻟﻰ ﻛﺤﻮل أوﻟﻲ ﻋﻦ طﺮﯾﻖ إﺿﺎﻓﺔ ﻣﺤﺐ‬،‫ ﻹﻋﻄﺎء أﻟﺪھﯿﺪ‬H -OH- ‫ ﻓﺈن اﻟﺘﺨﻔﯿﺾ ھﻮ ﺗﻔﺎﻋﻞ اﺳﺘﺒﺪال أﺳﯿﻞ ﻣﺤﺐ ﻟﻠﻨﻮاة ﯾﺤﻞ ﻓﯿﮫ ﻣﺤﻞ‬،‫ﻓﻲ اﻟﻮاﻗﻊ‬ In fact, the reduction is a nucleophilic acyl substitution reaction in which.‫ﻟﻠﻨﻮاة‬ -H replaces -OH to give an aldehyde, which is further reduced to a primary alcohol by nucleophilic addition..‫ ﻟﺬﻟﻚ ﯾﺘﻔﺎﻋﻞ ﻋﻠﻰ اﻟﻔﻮر وﻟﯿﺲ ﻣﻌﺰوﻻ‬،‫اﻷﻟﺪھﯿﺪ اﻟﻮﺳﯿﻂ أﻛﺜﺮ ﺗﻔﺎﻋﻼ ﺑﻜﺜﯿﺮ ﻣﻦ ﺣﻤﺾ اﻟﺒﺪاﯾﺔ‬ The aldehyde intermediate is much more reactive than the starting acid, so it reacts immediately and is not isolated.  ‫ ﻓﺈن ﺧﻄﻮة اﺳﺘﺒﺪال أﺳﯿﻞ اﻟﻨﻮﻛﻠﯿﻮﻓﯿﻠﻲ اﻟﻔﻌﻠﯿﺔ ﺗﺤﺪث ﻋﻠﻰ أﯾﻮن اﻟﻜﺮﺑﻮﻛﺴﯿﻞ ﺑﺪﻻ ﻣﻦ اﻟﺤﻤﺾ اﻟﻜﺮﺑﻮﻛﺴﯿﻠﻲ اﻟﺤﺮ‬،‫ﻧﻈﺮا ﻷن أﯾﻮن اﻟﮭﯿﺪرﯾﺪ ھﻮ ﻗﺎﻋﺪة وﻛﺬﻟﻚ ﻧﻮﻛﻠﯿﻮﻓﯿﻞ‬ Because hydride ion is a base as well as a nucleophile, the actual.‫وﯾﻌﻄﻲ وﺳﯿﻄﺎ ﻋﺎﻟﻲ اﻟﻄﺎﻗﺔ‬ nucleophilic acyl substitution step takes place on the carboxylate ion rather than on the free carboxylic acid and gives a high-energy dianion intermediate. ‫ اﻷﻛﺴﺠﯿﻨﺎن ﺑﻼ ﺷﻚ‬،‫ﻣﻌﻘﺪ إﻟﻰ أﻧﻮاع اﻷﻟﻮﻣﻨﯿﻮم اﻟﺤﻤﻀﯿﺔ ﻟﻮﯾﺲ ﻓﻲ ھﺬا اﻟﻮﺳﯿﻂ‬ In this intermediate, the two oxygens are undoubtedly ‫بال شك‬ complexed to a Lewis acidic aluminum species..‫ وﺗﺘﻄﻠﺐ ﺗﺨﻔﯿﻀﺎت اﻟﺤﻤﺾ درﺟﺎت ﺣﺮارة أﻋﻠﻰ وأوﻗﺎت ﺗﻔﺎﻋﻞ ﻣﻤﺘﺪة‬،‫ ﻓﺈن اﻟﺘﻔﺎﻋﻞ ﺻﻌﺐ ﻧﺴﺒﯿﺎ‬،‫وﺑﺎﻟﺘﺎﻟﻲ‬ Thus, the reaction is relatively difficult, and acid reductions require higher temperatures and extended reaction times.  BH3 / THF ‫ ﯾﺤﺪث ﺗﻔﺎﻋﻞ اﻟﺤﻤﺾ ﻣﻊ‬.‫( ھﻮ ﻛﺎﺷﻒ ﻣﻔﯿﺪ ﻟﺘﻘﻠﯿﻞ اﻷﺣﻤﺎض اﻟﻜﺮﺑﻮﻛﺴﯿﻠﯿﺔ إﻟﻰ اﻟﻜﺤﻮﻻت اﻷوﻟﯿﺔ‬BH3/THF) ‫ﺑﻮران ﻓﻲ رﺑﺎﻋﻲ ھﯿﺪروﻓﯿﻮران‬. Alternatively, ‫بدال عن ذلك‬ borane in tetrahydrofuran (BH3/THF) is a ،‫ )ھﯿﺪرﯾﺪ اﻷﻟﻮﻣﻨﯿﻮم اﻟﻠﯿﺜﯿﻮم( ﺑﺴﺒﺐ ﺳﮭﻮﻟﺘﮫ اﻟﻨﺴﺒﯿﺔ وﺳﻼﻣﺘﮫ ﺑﺪﻻ ﻣﻦ ذﻟﻚ‬LiAlH4 ‫ وﻏﺎﻟﺒﺎ ﻣﺎ ﯾﻔﻀﻞ اﻹﺟﺮاء ﻟﻠﺘﺨﻔﯿﺾ ﻣﻊ‬،‫ﺑﺴﺮﻋﺔ ﻓﻲ درﺟﺔ ﺣﺮارة اﻟﻐﺮﻓﺔ‬ useful reagent for reducing carboxylic acids to primary alcohols. Reaction of an acid with BH3/THF occurs rapidly at room temperature, and the procedure is often preferred to reduction with LiAlH4(Lithium aluminium hydride) because of its relative ease and safety. ‫ ﻣﻤﺎ ﯾﺴﻤﺢ ﺑﺎﻟﺘﺤﻮﻻت اﻻﻧﺘﻘﺎﺋﯿﺔ ﻣﺜﻞ ﺗﻠﻚ اﻟﻤﻮﺟﻮدة ﻋﻠﻰ ﺣﻤﺾ‬،‫ﯾﺘﻔﺎﻋﻞ اﻟﺒﻮران ﻣﻊ اﻷﺣﻤﺎض اﻟﻜﺮﺑﻮﻛﺴﯿﻠﯿﺔ ﺑﺸﻜﻞ أﺳﺮع ﻣﻦ أي ﻣﺠﻤﻮﻋﺔ وظﯿﻔﯿﺔ أﺧﺮى‬ Borane reacts with carboxylic acids faster than with any other.‫اﻟﻨﯿﺘﺮوﻓﯿﻨﯿﻞ اﻷﺳﯿﺘﯿﻚ‬ functional group, thereby allowing selective transformations such as that on p-nitrophenylacetic acid..‫ ﻓﺴﯿﺘﻢ ﺗﻘﻠﯿﻞ ﻛﻞ ﻣﻦ ﻣﺠﻤﻮﻋﺎت اﻟﻨﯿﺘﺮو واﻟﻜﺮﺑﻮﻛﺴﯿﻞ‬،LiAlH4 ‫ ﺑﺎﺳﺘﺨﺪام‬p-nitrophenylacetic ‫إذا ﺗﻢ ﺗﻘﻠﯿﻞ ﺣﻤﺾ‬ If the reduction of p-nitrophenylacetic acid were done with LiAlH4, both nitro and carboxyl groups would be reduced.