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Synthesis of imidazoles
Van Leusen Imidazole Synthesis
Van Leusen Three-Component Reaction
Starting from 1,2-diketones and urotropine in the presence of ammonium acetate, a simple and efficient solventless microwave-assisted enabled the synthesis of 4,5-disubstituted imidazoles.
G. Bratulescu, Synthesis, 2009, 2319-2320.
A NHC-copper-catalyzed isocyanide insertion into alcohol to form an N-arylformimidate intermediate and subsequent base-promoted cycloaddition with benzyl isocyanide derivatives enables a straightforward and high-yielding synthesis of 1,4-diaryl-1H-imidazoles.
B. Pooi, J. Lee, K. Choi, H. Hirao, S. H. Hong, J. Org. Chem., 2014, 79, 9231-9545.
A one-pot, four-component synthesis of 1,2,4-trisubstituted 1H-imidazoles was achieved in very good yields by heating a mixture of a 2-bromoacetophenone, an aldehyde, a primary amine, and ammonium acetate under solvent-free conditions.
M. Adib, S. Ansari, S. Feizi, J. A. Damavandi, P. Mirzaei, Synlett, 2009, 3263-3266.
A simple and efficient approach allows the preparation of biologically active 2,4(5)-diarylimidazoles by parallel synthesis. The formation of 2-aroyl-4(5)-arylimidazoles as side products strongly depends on the reaction conditions employed.
V. Zuliani, G. Cocconcelli, M. Fantini, C. Ghiron, M. Rivara, J. Org. Chem., 2007, 72, 4551-4553.
An improved and rapid one-pot synthesis of 2,4,5-triaryl imidazoles in a room temperature ionic liquid does not need any added catalyst. This one-pot methodology offers excellent isolated yields, simple work up procedures and efficient recovery and recycling of the ionic liquid.
S. A. Siddiqui, U. C. Narkhede, S. S. Palimkar, T. Daniel, R. J. Lahoti, K. V. Srinivasan, Tetrahedron, 2005, 61, 3539-3546.
A Schiff’s base complex nickel catalyst (Ni-C) enables a highly efficient one-pot microwave-assisted synthesis of 2,4,5-trisubstituted imidazoles in excellent yields from aldehydes, benzil, and ammonium acetate. The catalyst could be easily recovered by simple filtration and reused.
T. S. Chundawat, N. Sharma, P. Kumari, S. Bhagat, Synlett, 2016, 27, 404-408.
A simple route via a copper-catalyzed [3 + 2] cycloaddition reaction provides multisubstituted imidazoles in good yields and high regioselectivity using oxygen as an oxidant without the addition of expensive catalysts.
D. Tang, P. Wu, X. Liu, Y.-X. Chen, S.-B. Guo, W.-L. Chen, J.-G. Li, B.-H. Chen, J. Org. Chem., 2013, 78, 2746-2750.
The copper-catalyzed reaction between two different isocyanides produces imidazoles in good yields. The mechanism is discussed.
C. Kanazawa, S. Kamijo, Y. Yamamoto, J. Am. Chem. Soc., 2006, 128, 10662-10663.
A rhodium(II)-catalyzed reaction of stable and readily available 1-sulfonyl triazoles with nitriles gives the corresponding imidazoles in good to excellent yields via rhodium iminocarbenoids intermediates.
T. Horneff, S. Chuprakov, N. Chernyak, V. Gevorgyan, V. V. Fokin, J. Am. Chem. Soc., 2008, 130, 14972-14974.
An efficient copper-catalyzed regioselective diamination of terminal alkynes with amidines in the presence of Na2CO3, pyridine, a catalytic amount of CuCl2·2H2O, and oxygen (1 atm), allows the synthesis of diverse 1,2,4-trisubstituted imidazoles in good yields.
J. Li, L. Neuville, Org. Lett., 2013, 15, 1752-1755.
The use of a copper catalyst allows the construction of aryl imidazolium salts in good yields from N-substituted imidazoles and diaryliodonium salts. The reaction tolerates a broad range of functional groups and provides a straightforward, efficient, and versatile route to unsymmetric aryl imidazolium as well as triazolium salts.
T. Lv, Z. Wang, J. You, J. Lan, G. Gao, J. Org. Chem., 2013, 78, 5723-5730.
A practical three-component domino reaction of α-nitroepoxides and cyanamide with a series of amines enables the synthesis of functionalized 2-aminoimidazole derivatives under mild conditions without any additives.
X. Guo, W. Chen, B. Chen, W. Huang, W. Qi, G. Zhang, Y. Yu, Org. Lett., 2015, 17, 1157-1159.
Reactions of propargylamines with carbodiimides, in the presence of 5 mol% of the titanacarborane monoamide [σ:η1:η5-(OCH2)(Me2NCH2)C2B9H9]Ti(NMe2), afford a new class of substituted 2-aminoimidazoles via [3+2] annulation in good to excellent yields. A possible reaction mechanism is proposed.
Y. Wang, H. Shen, Z. Xie, Synlett, 2011, 969-973.
A highly efficient and convenient method for the synthesis of 1,2,4,5-tetrasubstituted imidazoles from readily accessible 2-azido acrylates and nitrones proceeded under mild conditions without the assistance of any metal, acid, or base.
B. Hu, Z. Wang, N. Ai, J. Zheng, X.-H. Liu, S. Shan, Z. Wang, Org. Lett., 2011, 13, 6362-6365.
A convenient and efficient FeCl3/I2-catalyzed aerobic oxidative coupling of amidines and chalcones provides tetrasubstituted imidazoles in high regioselectivity and yields. The reaction offers good functional group tolerance, and mild reaction conditions.
Y. Zhu, C. Li, J. Zhang, M. She, W. Sun, K. Wan, Y. Wang, B. Yin, P. Liu, J. Li, Org. Lett., 2015, 17, 3872-3875.
A multicomponent protocol enables the synthesis of highly substituted imidazole derivatives in excellent yield from various α-azido chalcones, aryl aldehydes, and anilines in the presence of erbium triflate as a catalyst.
K. Rajaguru, R. Suresh, A. Mariappan, S. Muthusubramanian, N. Bhuvanesh, Org. Lett., 2014, 16, 744-747.
A gold-catalyzed selective [3 + 2] annulation of 1,2,4-oxadiazoles with ynamides enables an atom-economical synthesis of fully substituted 4-aminoimidazoles. The reaction proceeds with 100% atom economy, exhibits good functional group tolerance, and can be conducted in gram scale.
Z. Zeng, H. Jin, J. Xie, B. Tian, M. Rudolph, F. Rominger, A. S. K. Hashmi, Org. Lett., 2017, 19, 1020-1023.
A step-economical access to polysubstituted aminoimidazoles via alkene vicinal C-N bonds formation of 2-bromo-2-alkenones with guanidine avoids a NH-protection/derivatization strategy. The reaction involves a tandem pathway of aza-Michael addition, SN2, and a unique redox-neutral process and offers an excellent substrate scope.
S. K. Guchhait, N. Hura, A. P. Shah, J. Org. Chem., 2017, 82, 2745-2752.
In a gold-catalyzed synthesis of bicyclic imidazoles, a highly electrophilic α-imino gold carbene intermediate can react with a weakly nucleophilic nitrile, which is used as the reaction solvent, to deliver the desired product rapidly in an overall bimolecular [2 + 2 + 1] cycloaddition and in good yield. The competing intramolecular azide-alkyne click reaction, although likely also catalyzed by gold, is minimized by using AuCl3 as the catalyst.
Y. Xiao, L. Zhang, Org. Lett., 2012, 14, 4662-4665.
2-Imidazolines were easily prepared in good yields from the reaction of aldehydes and ethylenediamine with iodine in the presence of potassium carbonate. The 2-imidazolines were smoothly oxidized to the corresponding imidazoles in good yields using (diacetoxyiodo)benzene at room temperature.
M. Ishihara, H. Togo, Synlett, 2006, 227-230.
A number of new reactions of IBX with heteroatom-containing substrates were discovered and their utility was demonstrated. IBX was used for the generation of imines from secondary amines in notably high yields, for the oxidative aromatization of nitrogen heterocycles and for the cleavage of dithianes.
K. C. Nicolaou, C. J. N. Mathison, T. Montagnon, Angew. Chem. Int. Ed., 2003, 42, 4077-4082.
A versatile and modular one-pot method allows the preparation of differently substituted symmetrical and unsymmetrical imidazolium salts from readily available formamidines and α-halo ketones. For many substitution patterns of the imidazolium salt products, this efficient strategy compares favorably with well-known processes in terms of yield, ease of synthesis, and robustness.
K. Hirano, S. Urban, C. Wang, F. Glorius, Org. Lett., 2009, 11, 1019-1022.
An efficient copper(I) bromide catalyzed N-arylation of azoles with a variety of aromatic bromides and iodides under mild conditions displayed great functional group compatibility and excellent reactive selectivity.
H. Chen, D. Wang, X. Wang, W. Huang, Q. Cai, K. Ding, Synthesis, 2010, 1505-1511.
A copper-catalyzed N-arylation reaction of imidazole proceeds under very mild conditions in the absence of additional ligand. This protocol tolerates an array of thermally sensitive functional groups, but also achieves high chemoselectivity.
L. Zhu, G. Li, L. Luo, P. Guo, J. Lan, J. You, J. Org. Chem., 2009, 74, 2200-2202.
N-Arylation of azoles and amines with arylboronic acids was efficiently carried out with heterogeneous copper(I) oxide in methanol at room temperature under base-free conditions. Various arylboronic acids and amines were converted to the corresponding N-arylazoles and N-arylamines in very good yields, demonstrating the versatility of the reaction.
B. Sreedhar, G. T. Venkanna, K. B. S. Kumar, V. Balasubrahmanyam, Synthesis, 2008, 795-799.
A simple and efficient method enables the synthesis of N-alkynylheteroarenes from 1,1-dibromo-1-alkenes via a copper-catalyzed cross-coupling reaction. Good yields and functional-group tolerance were obtained with TMEDA as ligand using imidazole and benzimidazole substrates in dioxane.
M.-G. Wang, J. Wu, Z.-C. Shang, Synlett, 2012, 23, 589-594.
A series of N,N′-asymmetrically substituted imidazolium iodides have been synthesized, starting from N-arylimidazoles and the less expensive, but less reactive, 1-chlorobutane or (3-chloropropyl)trimethoxysilane. The addition of potassium iodide and the use of 1,2-dimethoxyethane as a solvent allowed the synthesis of multigram quantities of these salts.
A. M. Oertel, V. Ritleng, M. J. Chetcuti, Synthesis, 2009, 1647-1650.
N-Methylimidazole is a promising catalyst for aza-Michael reactions. Various N-heterocycles were introduced to α,β-unsaturated carbonyl compounds employing N-methylimidazole in a highly efficient, rapid and high yielding synthesis of N-heterocyclic derivatives.
B. K. Liu, Q. Wu, X. Q. Qian, D. S. Lv, X. F. Lin, Synthesis, 2007, 2653-2659.
2-Lithioimidazole was prepared using lithium metal in the presence of a catalytic amount of isoprene in THF at room temperature. By reacting this organolithium compound with carbonyl electrophiles 2-(hydroxyalkyl)imidazoles and 2-(aminoalkyl)imidazoles were obtained in good yields.
R. Torregrosa, I. M. Pastor, M. Yus, Tetrahedron, 2005, 61, 11148-11155.
First of all, it is important to explain what the word "synthesis" means. It is a mix of elements used to draw the whole picture. That is how one can conclude that a synthesis essay stands for the sort of essay which combines various points into a whole to defend so-called thesis statement. A thesis is the main idea of the essay. Students should write it in the last sentence of their introduction. Frequently, it comes with a piece that a student has to observe.
The main success factor of writing a good synthesis essay is an in-depth research based on the relevant sources. A student has to perceive the goal of the analyzed content, its rhetoric, and the arguments suggested by the author. To make it short, the writer simply has to provide an answer to the question: "So what?" Type in your personal claim. The rest of your synthesis essay in English should be built around that main sentence.
Choose Synthesis Essay Topic Before You Write the First Page
Sometimes, the teacher does not provide a specific topic or question to answer. In that cases, the student has a right to select any topic for his synthesis essay. Mind that your entire writing will be limited to the chosen question, so make your decision wisely. Select a topic for which it would be easy to write as many arguments as needed. Usually, there are 3-5 arguments in the academic essay.
The prompt has to be debatable. It has to motivate the readers to continue the discussion. Several centuries ago, the US population would support the ideas of Andrew Jackson concerning the negative sides of Native American people. However, today the situation is completely different. Any sort of discrimination is forbidden in the United States. The way you select the primary questions depends on your specific task. Make sure to decide on the text that may have opposing views. In other words, choose an article with the strong argument which may encourage your readers not just to read the synthesis essay from cover to cover, but also go on discussing the selected questions.
The best topics for your essay writing would always sound negotiable like these examples:
- Minimum salary
- For and against abortions
- Global warming
- Regulations for immigrants
- Daylight storage
- Gun control
- Drug abuse
- Social media
- Artificial intelligence
- Political authorities
- Alcohol and tobacco restrictions
- Anorexia nervosa
It is easy to find the sufficient amount of information on any of these essay topics as they are relevant for people of all times, ages, and nationalities.
Writing Thesis Statement and Outline Page
After you decide on your topic or main questions to discuss, move to your sources. Make sure all gathered sources are related to your essay topic. Also, they have to be no older than 5-10 years as things change dynamically.
Thoroughly study all sources to get the main point. Select the best sources to use citations from them in your essay. It will serve as a perfect evidence to support your argument. Structure your claim. Write down thesis statement which is the main idea of the whole synthesis essay.
Thesis example: With the help of historical episodes, it is possible to point to the human evolution based on how infinity was interpreted in different epochs.
Another example: Only through an understanding of the causes of medical mistakes and their prevention on the early stages, the number of medical gaps will go down as well as the number of unintentional deaths in the United States.
You can view more example online without paying a cent.
As for the outline, this is a plan of your synthesis essay. Writing this part will assist you in maintaining the structure of your essay. In case your essay is going to have three main sections, divide the outline into three chunks respectively. Insert evidence to support your thesis, include sub-arguments along with all specific points. Every part should have a name (except for the introduction and conclusion- you may leave them this way). Every point (which is also an argument) must prove the major claim of your essay. Avoid additional information or tangents as these elements may hinder the essay. It is recommended to write down the information which contradicts with your thesis. It will make the essay more persuasive. Your synthesis essay has to be as strong as possible.
The Structure of Any Type of a Good Academic Essay
Read all sources thoroughly, especially when you work with articles instead of the thick books. Never summarize sources or copy-paste ideas of other authors. It is strictly forbidden. You may write summaries only if you have to write an annotated bibliography. Synthesis denotes analysis instead of the abstracts of your readings.
The example of your essay structure may be:
- Argument #1
- Argument #2
- Argument #3
- Argument 1
- Evidence (cite a source)
- Analysis of Evidence
- Argument 2
- Evidence (cite a source)
- Analysis of Evidence
- Argument 3
- Evidence (cite a source)
- Analysis of Evidence
- Argument 1
- Restate thesis and answer all the questions left behind
What about the Writing Style?
Formatting is an important condition of the successful synthesis essay. Academic writing defines several formats. Their names are related to the scientific or educational organizations that established these styles.
The most widespread formats are:
The first one is applied to the essays in Humanities. The second one is used while writing essays on Education, Psychology, and Science. Turabian or Chicago format is excellent for Business, History, and Fine Arts.
There is a Purdue Owl guide available online for free which can tell more about each of the existing academic writing styles. It has all the details about MLA and APA, while Easybib and some other online citation generators help students to format essays automatically. Simply insert your external sources to get proper citations for them.
Here are the basic nuances to consider:
- Times New Roman
- 12 pt font
- Double-spaced text
- 1" margins all around
- Top right of the page should have student's last name and page number
- Titles and headings are put in the center
- The header must have your name, your professor's name, course number, and the full date (dd/mm/yy)
- The last page is Bibliography page (a.k.a. Works Cited or References)
It is an example of MLA synthesis essay. Other examples and templates are available online for free. You can find an example of a page in APA style here.
Features of an AP Synthesis Essay in English
AP English Language and Composition is a separate academic course. Students who are enrolled in this class must perform a deep understanding of the subject matter through using various sources and operating with the information they already know. Grammar, spelling, structure, and originality might be insufficient to receive the highest score on your AP exam. The writing has to be "defending, challenging, qualifying the claim." Once you obtain the course syllabus, it is better to study it to learn the exact test dates and what it would look like.
It is important to concentrate on three main branches of the AP English and Composition. Those are argument, synthesis, and rhetoric. That is why all three elements should be present in your synthesis essay. Let’s have a closer look.
The argument is the simplest part; it's about writing your thesis and gathering evidence from the selected sources to defend your ideas. Prove to your reader that your point of view is correct.
Synthesis demands that a student reads multiple sources and defines pros and cons of the chosen topic (or for and against, if you wish). It is critical as it helps to create your personal claim.
Rhetorical analysis is all about the author and his goals. It has to explain the purpose of writing as well as describe the target audience. Finally, it explains the ways in which the writer attracts the readers and structures the claim.
Useful Prompts Associated with Writing Synthesis Essay
Memorize these acronyms to be able to answer all questions of your synthesis essay properly.
Advice #1: SOAPS
It's all about determining the speaker, occasion, audience, purpose, and subject.
Have a look at our example: The American Health Association believes that only through an understanding of the causes of medical mistakes and their prevention on the early stages, the number of medical gaps will go down as well as the number of unintentional deaths in the United States.
Speaker: The American Health Association has a bias against the inexperienced medical personnel.
Occasion: The American Health Association has held its meeting on Abbey Square, New York, on the 10th of November 2016.
Audience: The report written by The American Health Association was addressed to the doctors of the main regional hospitals in NY.
Purpose: The American Health Association tries to point to the main causes of unintentional deaths in the US hospitals. It performs against the improper medical treatment.
Subject: The subject is the increased number of fatal outcomes due to the lack of healthcare education and professionalism of the local personnel.
Advice #2: Logos, Ethos, and Pathos
We are speaking about the reasons, philosophy, and emotion respectively. AP Lang exam requires you to deal with all three Latin words effectively.
When there are some facts and statistics in the chosen text, the writer deals with Logos. Return to the background information all the time to make your synthesis essay as persuasive a possible.
The vivid imagery and powerful words are the signs of Pathos. It is effective for relating the readers to the essay on the emotional level.
If you aim to show the accountability and credibility of your synthesis essay, you deal with Ethos. State some facts that prove your competence in the chosen field so that the audience will have no doubt that you are right.
Watch out as often, Logos, Ethos, and Pathos may lead to the usage of logical fallacies.
It would be a great strategy for any sort of textual analysis. When you are reading the selected piece, make an attempt to pinpoint Diction, Imagery, Details, Language, and Sentence Structure. Add whatever seems more vivid to you into your analysis.
As you can see, it is not that easy to write a synthesis essay. Many students have problems either with writing or analyzing sources. Luckily, there is an opportunity to order an instant help with synthesis essay for an affordable price. When you face any doubts, turn to the expert online service which will write the whole essay to bring you to the highest score!
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