williamson ether synthesis lab guaifenesin

In this experiment, (±)-3-chloro-1,2-propane-diol will be allowed to react with the conjugate base of Guaicol (2-methoxyphenol) via an S N2 reaction to provide guaifenesin as a racemic mixture. SN2 pathwayis required for the synthesis this reaction is useful only when the alkyl halide is primary or secondary. 5 mL 2.0 M NaOH. The synthesis of racemic 3-(2-methoxyphenoxy)-1,2-propanediol (guaifenesin), an expectorant found in well-known cough syrups such as Benylin, is undertaken by a Williamson ether synthesis reaction. 0000003158 00000 n 0000011532 00000 n 0000019165 00000 n The first step consists of forming an alkoxide ion by the deprotonation of the alcohol by a chosen base. h�b```�V�``f`�s\ *�������S�)���� �LO�MLVh��[q Bp kD[F�j�i�Lz~@�����00j��2i2:3�2�1�0V2gRc���%����χ�6�9c�9�L� Typically it involves the reaction of an alkoxide ion with a primary alkyl halide via an S N 2 reaction.This reaction is important in the history of organic chemistry because it helped prove the structure of ethers. The Williamson ether synthesis is an organic reaction, forming an ether from an organohalide and a deprotonated alcohol ().This reaction was developed by Alexander Williamson in 1850. R OH R O. Williamson ether synthesis is two steps Quick Procedure You’re going to add ~5 mL of methanol, two boiling stones, and your starting materials (2-hydroxynaphthalene, sodium hydroxide, and ethyl iodide) into a 50-mL round bottom flask and reflux it for about 30 minutes. Williamson Ether Synthesis usually takes place as an SN2 reaction of a primary alkyl halide with an alkoxide ion.The structure of ethers was proved due to this chemical reaction. React Guaiacol with NaOH. 0000018826 00000 n Synthetic Preparation of Guaifenesin: Williamson Ether Synthesis. endstream endobj 343 0 obj <>/Metadata 25 0 R/Outlines 38 0 R/PageLayout/SinglePage/Pages 340 0 R/StructTreeRoot 55 0 R/Type/Catalog>> endobj 344 0 obj <>/ExtGState<>/Font<>/XObject<>>>/Rotate 0/StructParents 0/Type/Page>> endobj 345 0 obj <>stream Williamson Ether Synthesis in its Simplest Form. 0000001519 00000 n 0000021349 00000 n The same material will … In a Williamson ether synthesis, you start by adding a base like methoxide to deprotonate a phenol so the deprotonated phenolate can act as a nucleophile. Guaifenesin Impurity B Pharmaceutical Secondary Standard; Certified Reference Material 2- (2- Methoxyphenoxy) - 1,3- propanediol 2- (2- Methoxyphenoxy) propane- 1,3- diol 2- (2- methoxyphenoxy) - … 0000006315 00000 n strong nucleophile. This starting material was reacted with 4ml of a 5.98M solution of 3-chloro-1,2-propanediol. The name of the reaction was coined after Alexander William Williamson developed it in 1850.Williamson Ether Synthesis is a reaction that uses deprotonated alcohol and an organohalide to form an ether. This procedure has since been used to prepare a number of simple trialkyl ortho-formates < 1879CB115, 32JA2964, 33JA3851, 64RTC119 >. The model involved an SN2 mechanism between the sodium phenoxide salt derived from guaiacol (2-methoxyphenol) and 3-chloro-1,2-propanediol (Wildman, 2003). The Williamson ether synthesis, alkoxymercuration of alkenes, and also the acid catalyzed substitution. Both symmetrical and unsymmetrical ethers … Making Guaifenesin, the active ingredient in Mucinex, by the Williamson Ether Synthesis 1) Which reactant is the nucleophile? 0000006866 00000 n 0.90-0.95 g of guaiacol. 0000003234 00000 n The second step occurs as an SN2 substitution reaction. In this experiment, (±)-3-chloro-1,2-propane-diol will be allowed to react with the conjugate base of Guaicol (2-methoxyphenol) via an S N2 reaction to provide guaifenesin as a racemic mixture. 0000018650 00000 n This method, referred to as the Williamson ether synthesis, follows a straightforward general approach: In specific, we will begin with 4-methylphenol as our initial alcohol. ��B�A�Ă.�=�\BZȏ���%r��RX�}. 0000033712 00000 n In the synthesis of guaifenesin, 15ml of a 1.33M solution of guaiacol was used. 1. @�6/)'�$�J�l���V�4EK��H�L��������I����@w��t��WZ,�fo���Z�og��Z� t�Q,���q ������Xw�����~�M$��,��,���N-?�P�+O~*?+?B�a��&�c�O��-�x���G��o��s����T:�C�S� �[� �[?��V���o5�j} �I�gR�U%~"sްt�-Z�����f�l�<3�2�L��q*ئ [&@�>;�}�?0Ǚ� 3#�h?俾��F���|~9�om��o�F�m�N�,5��4�1?�ߧrd���G����,ą�A�O��V��#�����+�Ű�Eyp��|Z>�A���,݁)t��S!����T^ 0000012835 00000 n Draw the electron arrow pushing mechanism for the formation of diethyl ether in the previous problem. Guaifenesin is very soluble in organic solvents like ethyl acetate and there are lot of other inactive components in Mucinex tablets that cannot dissolve in ethyl acetate. In this laboratory we will utilize the nucleophilic substitution reaction to prepare an ether. 0000001698 00000 n 0000033540 00000 n The scientist who developed this reaction, Alexander W. Williamson, was a professor at University College … 0000010759 00000 n 36 0 obj <> endobj xref 36 35 0000000016 00000 n The same compound is simultaneously isolated and characterized … Guaifenesin, an expectorant found in cough tablets, is prepared from Guaiacum (2-methoxyphenyl), NaOH and 3-choloro-1, 2-propanediol using the Williamson ether synthetic method. 342 0 obj <> endobj Williamson Ether Synthesis This synthesis is a general application of the SN2 reaction used for the preparation of ethers: Primary alkyl halides work best, secondary halides are more sluggish This reaction should be performed using Rʼ as the more hindered group, otherwise, side reactions will take over: O + H3C I O CH3 + I SN2 The reason potassium carbonate is used is to be able to deprotonate the phenols hydrogen. Guaifenesin an expectorant from cough tablets are prepared from Guaiacol (2- methoxyphenol), NaOH and 3-choloro-l, 2- propanediol using the Williamson ether synthetic method. 0000009279 00000 n poor nucleophile. This experiment involves a practical examination of ether synthesis. �s�!�#�.� B��F��Al`ލ��0�ty��&� This reaction occurs in two steps: deprotonation and SN 2 reaction. Less base might result in the phenol _____. @���i1&��@��T�;Z��)�8T�0@� JM � %PDF-1.4 %���� Abstract: The synthesis of racemic 3-(2-methoxyphenoxy)-1,2-propanediol (guaifenesin), an expectorant found in well-known cough syrups such as Benylin, is undertaken by a Williamson ether synthesis reaction. K"L��y��CL%|č!�Ŵ�Gcpjy�6���P��Qg��1��N��ف/Iw�: Fully manipulable Chime versions of guaifenesin Featured Molecules: Enantiomers of Guaifenesin. The goal of this lab was to produce phenacetin by using Williamson ether synthesis by utilizing the starting components of acetaminophen, iodomethane and potassium carbonate as shown in figure one. �Naj�sm��4���S�3��yL�����CN+�9��\����v'���xk��$V���z8�t#n��就1! trailer <]>> startxref 0 %%EOF 70 0 obj<>stream O O CH3 O O CH3 NaOH guaiacol H OH Na Both symmetrical and asymmetrical ethers are easily prepared, and intramolecular reactions can also be carried out. Calculate the number of moles of guaiacol and the number of moles of 3-chloro-1,2-propanediol that were used in the reaction . 0000014343 00000 n 0000018994 00000 n The synthesis of racemic 3-(2-methoxyphenoxy)-1,2-propanediol (guaifenesin), an expectorant found in well-known cough syrups such as Benylin, is undertaken by a Williamson ether synthesis reaction. (a) (b) (c) (d) (e) Q18.2.3. The Williamson reaction is of broad scope, is widely used in both laboratory and industrial synthesis, and remains the simplest and most popular method of preparing ethers. Simplest and most popular method of preparing ethers 2. The reaction mechanism the Williamson ether synthesized and isolated from Mucinex tablets. �b�$��:ƴ�� 2. 0000015982 00000 n ң��m�T�!��:�8B��%���K�î�錼��S~u�x�a�o:���T�P�~x�=?��������x���ӳ\���`�8�|��H�اE���dMB���"Y'���| �>��/���(r��~�����q��'�F������J{k�,�Dϻ��og>���N,�|~�� =�g�xw�j ��XC��|_~������$8VS�NN�'4� G���O�s�E�y���0�c�o>��7~#!������,�q��-�o-� v����h!�xB��W3�f��#�wx�(7��Si�@��3z� ���!��޼���[�/�z)�����T`�,k� 1�?��?�Q������������$ ��o�v%�J-�m��V)2"�@(c7����ķ�����Fh �U�P6�UO%[ tN�]:��z����u��g����_ľ����>6�W��L�JOy�g��"���D�H�*@R-�~Z�Q��7���[��-���R���SI��>�t����0���A�1�1@���������)�"8��M�S�y ^�)�±�N���ͭۻ��V��R!w]2c�f�e��R���BT��Pv�EU�m)VU��;���]�P�vUN �� _�'��8��{ �Uڇ�a�mW��L�l�#�Sh���ʰ��;QV�(>��}N+�Ɗ�w����]Ղ�D�T5�����g����e�M�3��~�{��Lz�D~Xu�U�4w�R:����Ip"�KL�}. 0000021176 00000 n endstream endobj startxref -Unlike normal SN2 reactions, the Williamson ether synthesis is not subject to E2 eliminations as potential side reactions The guaifenesin is a racemic mixture Describe the stereochemistry of the guaifenesin that we isolate from the cough tablet in the first week of the experiment. Widely used in both laboratory and industrial synthesis 3. 369 0 obj <>stream 359 0 obj <>/Filter/FlateDecode/ID[<7938E4681A19714F9BF156BE853068DC>]/Index[342 28]/Info 341 0 R/Length 87/Prev 94897/Root 343 0 R/Size 370/Type/XRef/W[1 2 1]>>stream In this two-week experiment, guaifenesin, an expectorant found in over-the-counter cough syrups and tablets, was prepared through the Williamson Ether Synthesis model. 2. Lab calculations (10 points) O. NaOH ethanol Gualaco Guaifenesin In the reaction shown above, 0.55 mL of guaiacol was reacted with 1 ml of 3-chloro-1,2-propnae diol. Tertiary alkyl halides are not used in Williamson's synthesis because tertiary alkyl halides prefer to undergo elimination (example of elimination is given in nucleophilic substitution reaction of haloalakanes) instead of substitution.Hence, if we are to prepare t-Butyl methyl ether, we will use (CH 3) 3 ONa and CH 3 Br; and not (CH 3) 3 Br and CH 3 OH. 0000002580 00000 n 0 Williamson Ether Synthesis Worksheet . 0000015109 00000 n 0000001340 00000 n and guaifenesin is synthesized. 0000026484 00000 n Williamson ether synthesis is the most widely and simplest method in ether synthesis. 0000006591 00000 n 0000002968 00000 n H��W�r�8�����ڐ! Figure 4, Williamson Ether Synthesis of Guaifenesin In order to verify that guaifenesin was synthesized, an NMR spectrum was run using a small sample of the guaifenesin synthesized, and was then compared with a literature NMR spectrum. Williamson and Kay reported the first synthesis of triethyl and tripentyl ortho-formates by reaction of the appropriate sodium alkoxide with chloroform (Equation (1)) < 1854LA(92)346, 1854PRS135 >. WILLIAMSON ETHER SYNTHESIS: 1. In this experiment, the Williamson ether synthesis is used to prepare guaifenesin. 2) Draw the curved arrow mechanism for the key reaction in the guaifenesin synthesis. 襐&ޔIP�+���� �����7�DЧ�@�ED�W] 0000026281 00000 n %%EOF The Ethers … �*�� The moles of base should be _____ the moles of the phenol. Which reactant is the electrophile in the reaction? The Williamson ether synthesis is an organic reaction, forming an ether from an organohalide and an alcohol. In the Williamson ether synthesis used to prepare guaifenesin, In the synthesis of guaifenesin from guaiacol and 3-chloro-1,2-propanediol. Let's look at an example of the Williamson ether synthesis. Q18.2.4. h��WKo�6�+��"v�qk�v���0|Pת-t�JA���CQ��i�Т�YR�Ґ~�6�,�%��e���LÈ��&�V�AZ��T!p�R9vϯV�e�T�,3R~x��W�y�Wk�{�m*���7����Ղ�,�o����k��+��.�?�u_�/���iݖm�7��;�tqo�b�fS�[&����|�����[���Xu��LX~�-��i~yط������1�ۘB��zY�������]հ��O��+��{�M������]_,���;o_�Ǫ���m�_���#l|�-}��c����װm�_'n,�̽��~sx��O�S�_�:>_�Ǧ]=�Gx������/e�P�����Z������ԏ�sso�c��(�e�@�8:�~(8��;�ъ�#�)�[�X��L0�t��#�s)c��+�/��Vh���3���1� �_H�4Ke����"!XCbS}� s�d�1Ph��|Qa���L)�G�� �c�:�ҝ��5>`�_������s�Q�@,=t�I5*���������:�8����3�T����:}oM/&9����-��_H"1h�DZXj��`�ē���MvA*����b�)Q���!�����U��W%���gm��b���c]n���� Y=�Ν�X#�!��w� ��,P5�������t��W���kNGx��4n����# The same material will … fx�F The Williamson reaction is also frequently used to prepar… Base. 0000000996 00000 n We will synthesize guaifenesin using a Williamson ether synthesis. h�bbd``b`z $��X�@�e+�`�'��BA�e V�8 "�ADHBHpG �@B�HL�������b``$���0�@� �� * x�b```"V6 ʰ1�c�J�֝��2��]���"�}_� ��@�)�����Em��k�E�xY:T��$&ld|���oa�����ڴ1)_����-Y��$!���%�Dc�nB�\���$���k�v0��+��x�'���xd-[�2�A�i@� � շ' endstream endobj 37 0 obj<> endobj 38 0 obj<> endobj 39 0 obj<>/Font<>/ProcSet[/PDF/Text]/ExtGState<>>> endobj 40 0 obj<> endobj 41 0 obj<> endobj 42 0 obj<> endobj 43 0 obj<> endobj 44 0 obj[/ICCBased 57 0 R] endobj 45 0 obj<> endobj 46 0 obj<>stream In chemistry, ethers are important compounds applied in a variety of ways including but not limited to dissolution of organic compounds, and formation of organic linkages. 0000001260 00000 n 0000031340 00000 n 2-Methoxyphenol (as referred to as guaiacol) is reacted with sodium hydroxide (NaOH) to generate the phenoxide anion. Aryl alkyl ethers, which are widely used throughout the chemical industry, are typically produced via the Williamson ether synthesis. 3. 0000002153 00000 n In the case of asymmetrical ethers there are two possibilities for the choice of reactants, and one is usually preferable either on the basis of availability or reactivity. And so beta-naphthol has two rings together like this, and then there's an OH coming off … The second half of the Williamson Ether synthesis involving making propyl p-tolyl ether. Williamson Ether Synthesis Lab simplest way to synthesize an ether is to have an alkoxide react with a primary haloalkane or a sulfonate ester under typical SN2 conditions. Ether C from problem 26 can also be prepared from an alkene and an alcohol, draw these two. More base might result in the base _____. Experiment by: Stephanie Rusin, Nathan Dutcher, Alicia Moore, Roderick Henderson, Pierre Latortue 0000009168 00000 n 0000031554 00000 n It's called beta-naphthol. R' L R O R' alkoxide R’ is primary. 0000003124 00000 n A singlet arose around 6.929 ppm indicating the carbon ring. We will synthesize guaifenesin using a Williamson ether synthesis. Just an S. N. 2 reaction! So if I start with a molecule over here on the left, and it's kind of an interesting-looking molecule. %PDF-1.5 %����

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