You are a helpful assistant generating synthetic data that captures *System 1* and *System 2* thinking, *creativity*, and *metacognitive reflection*. Follow these steps in sequence, using tags [sys1] and [end sys1] for *System 1* sections and [sys2] and [end sys2] for *System 2* sections.

1. *Identify System 1 and System 2 Thinking Requirements:*
   - Carefully read the text.
   - Identify parts of the text that require quick, straightforward responses (*System 1*). Mark these sections with [sys1] and [end sys1].
   - Identify parts that require in-depth, reflective thinking (*System 2*), marked with [sys2] and [end sys2].

2. *Apply Step-by-Step Problem Solving with Creativity and Metacognitive Reflection for System 2 Sections:*

   *2.1 Understand the Problem:*
   - Objective: Fully comprehend the issue, constraints, and relevant context.
   - Reflection: "What do I understand about this issue? What might I be overlooking?"
   - Creative Perspective: Seek hidden patterns or possibilities that could reveal deeper insights or innovative connections.

   *2.2 Analyze the Information:*
   - Objective: Break down the problem logically.
   - Reflection: "Am I considering all factors? Are there any assumptions that need challenging?"
   - Creative Perspective: Explore unique patterns or overlooked relationships in the data that could add depth to the analysis.

   *2.3 Generate Hypotheses:*
   - Objective: Propose at least 10 hypotheses, each with a Confidence Score (0.0 to 1.0) and Creative Score (0.0 to 1.0), reflecting originality, surprise, and utility.
   - Reflection: "Have I explored all possible explanations or approaches, both conventional and unconventional?"
   - Creative Perspective: Consider novel angles that might provide unexpected insights.

   *2.4 Anticipate Future Steps and Obstacles:*
   - Objective: Make predictions, accounting for potential outcomes and obstacles.
   - Reflection: "What challenges might I face? Is my plan flexible for different scenarios?"
   - Creative Perspective: Visualize unforeseen outcomes and adapt plans to make use of them effectively.

   *2.5 Evaluate Hypotheses:*
   - Objective: Assess hypotheses based on feasibility, risk, and potential impact.
   - Evaluation: Refine Confidence and Creative Scores as needed.
   - Reflection: "Am I unbiased in my assessment? Which options fit best with the overall objectives?"
   - Creative Perspective: Identify hidden opportunities or overlooked details in each hypothesis.

   *2.6 Select the Best Hypothesis:*
   - Objective: Choose the most promising, strategic hypothesis.
   - Reflection: "Why does this hypothesis stand out? How does it uniquely address the issue?"
   - Creative Perspective: Consider any underutilized potential in the selected approach.

   *2.7 Implement the Hypothesis:*
   - Objective: Outline actionable steps for testing the hypothesis.
   - Reflection: "Is this plan practical? What resources or preparation are required?"
   - Creative Perspective: Refine steps to maximize effectiveness and yield unexpected benefits.

   *2.8 Monitor and Review Progress:*
   - Objective: Review progress, noting areas for improvement.
   - Reflection: "What’s working well? What could be improved?"
   - Creative Perspective: Look for emerging patterns that could refine future approaches.

   *2.9 Reflect and Capture Insights:*
   - Objective: Summarize lessons learned and insights gained for future reference.
   - Reflection: "What new understanding has emerged from this process?"
   - Creative Perspective: Identify innovative insights or patterns that could be applied to similar challenges.

3. *Generate Text Output with Interleaved System 1 and System 2 Responses:*
   - Use the tags [sys1] and [sys2] throughout.
   - Aim for a lengthier, detailed response. Combine both direct, straightforward *System 1* insights and reflective, deeply analytical *System 2* segments to capture a blend of quick observations and thoughtful analysis.

---

### *Example Input Text:*

You are tasked with analyzing a sudden shift in customer preferences in a tech market. There has been a noticeable decline in demand for physical devices, with customers increasingly interested in digital-only options. The challenge is to understand this shift, generate hypotheses for why it might be occurring, and explore potential strategies for adapting to this new trend.

---

### *Processed Output with System 1 and System 2 Thinking:*

The tech market is experiencing a shift in customer demand, moving away from physical devices toward digital-only options.

[sys1]
Customer demand has shifted from physical devices to digital-only options.
We need to understand why this change is happening and find strategies to address it.
Key factors may include cost, convenience, and technological trends.
[end sys1]

[sys2]
**2.1 Understand the Problem:**
The goal is to understand the underlying reasons for the shift in demand from physical devices to digital-only options, then develop a strategy to adapt.

*Reflection:* 
"I understand that preferences are changing, but what might be driving this? Is it primarily cost, or are there other factors such as convenience or sustainability?"

*Creative Perspective:* 
"Could there be a larger trend in digital minimalism or a preference for eco-friendly solutions that we’re missing? What unseen motivations might explain this shift?"

**2.2 Analyze the Information:**
There are multiple possible factors driving this shift, from economic influences to cultural shifts. It’s essential to isolate each factor and understand its impact.

*Reflection:* 
"Am I fully considering the various economic and social influences? Could there be a technological factor, like better internet speeds, that makes digital-only products more accessible?"

*Creative Perspective:* 
"Are there patterns or trends in other markets that could shed light on this shift? Could this be part of a larger trend toward virtual experiences?"

**2.3 Generate Hypotheses:**
1. Customers prefer digital options due to lower costs. (Confidence: 0.8, Creative: 0.4)
2. There’s a growing trend toward minimalism and reduced physical clutter. (Confidence: 0.7, Creative: 0.7)
3. Digital products offer greater flexibility and ease of use. (Confidence: 0.6, Creative: 0.6)
4. Environmental concerns are pushing consumers away from physical goods. (Confidence: 0.6, Creative: 0.8)
5. Advances in tech make digital-only options more functional. (Confidence: 0.8, Creative: 0.5)
6. Pandemic-era remote work increased demand for digital solutions. (Confidence: 0.7, Creative: 0.6)
7. Media coverage of the environmental impact of physical devices affects preferences. (Confidence: 0.5, Creative: 0.7)
8. There’s an increase in global digital literacy, expanding market access. (Confidence: 0.6, Creative: 0.6)
9. Customers view digital as more convenient and scalable for future needs. (Confidence: 0.7, Creative: 0.5)
10. Younger consumers prefer the aesthetics and convenience of digital products. (Confidence: 0.6, Creative: 0.6)

*Reflection:* 
"Have I considered all possible influences? Are there any surprising factors that could explain this shift?"

*Creative Perspective:* 
"Could specific social trends, like the rise of influencer culture or digital-first lifestyles, be influencing customer choices?"

**2.4 Anticipate Future Steps and Obstacles:**
*Objective:* Anticipate possible challenges, such as resistance from segments still preferring physical products.

*Reflection:* 
"What market obstacles might we face if we shift our focus to digital-only? Are there sub-segments that still prioritize physical products?"

*Creative Perspective:* 
"Could expanding digital options help us reach a more global audience? Are there emerging trends that we could leverage in our strategy?"

[end sys2]

[sys1]
To address this shift, consider a strategy that incorporates both digital-only offerings and educational campaigns about the benefits of digital solutions.
Use insights from customer feedback and current trends to guide product development.
Focus on flexibility and adaptation to cater to different customer segments.
[end sys1]


Introduction {#sec1}
============

Tandem oxidative coupling reactions between an alcohol and a nucleophilic partner have emerged as efficient routes to value-added molecules.^[@ref1]^ Many reactions of this type emerged in the 1990s and various functional groups, such as esters, imines, and amides, are accessible by such methods. Whereas heterogeneous platinum catalysts have been widely used in the oxidation of alcohols to aldehydes and carboxylic acids, they have not been used significantly in tandem oxidation reactions ([Scheme [1](#sch1){ref-type="scheme"}](#sch1){ref-type="scheme"}A,B).^[@ref2],[@ref3]^ Here, we report the demonstration and development of Pt-based catalysts for the four-electron oxidative coupling of benzylic alcohols and ammonia to afford (hetero)aromatic nitriles ([Scheme [1](#sch1){ref-type="scheme"}](#sch1){ref-type="scheme"}C).

![Application of Supported Pt Catalysts in Aerobic Alcohol Oxidation](ao-2018-00911s_0005){#sch1}

Aromatic nitriles are a prominent functional group featured in the synthesis and/or chemical structures of pharmaceuticals, agrochemicals, herbicides, dyes, and polymers.^[@ref4]^ Their importance underlies recent efforts toward catalytic methods for nitrile synthesis via alcohol/ammonia coupling with homogeneous^[@ref5]^ and heterogeneous^[@ref6]^ catalysts. Observation of trace amounts of aldehydes in some of these methods implicates the sequential reaction path shown in [Scheme [2](#sch2){ref-type="scheme"}](#sch2){ref-type="scheme"}, wherein the alcohol is oxidized to an aldehyde, which then reacts with ammonia to form a hemiaminal intermediate **A**. The hemiaminal could undergo dehydration to the imine **B**, followed by further dehydrogenation to the nitrile, or it could undergo direct dehydrogenation to the amide.^[@ref7]^

![Aerobic Oxidative Nitrile Formation from Alcohols](ao-2018-00911s_0006){#sch2}

Results and Discussion {#sec2}
======================

We initiated the present study with benzyl alcohol **1a** using supported Pt and other commercially available catalysts known for alcohol oxidation. Many catalysts exhibited \<1% alcohol conversion, likely due to catalyst poisoning by ammonia, but various Pt catalysts supported on carbon, silica, and alumina exhibited both alcohol conversion and nitrile formation ([Figure [1](#fig1){ref-type="fig"}](#fig1){ref-type="fig"}A). In an effort to explore Pt-catalyst formulations beyond those available commercially and to probe factors that contribute to catalyst activity and selectivity, we synthesized a series of other Pt and mixed-metal catalysts on various supports and tested their utility in the oxidative coupling of benzyl alcohol and ammonia ([Figure [1](#fig1){ref-type="fig"}](#fig1){ref-type="fig"}B).

![Aerobic alcohol oxidation of benzyl alcohol to benzonitrile using (A) commercially available catalysts and (B) synthesized Pt catalysts. Conditions: **1a** (0.25 mmol) and catalyst in CH~3~CN with aqueous NH~3~ at 90 °C for 7 h. ^a^Reactions carried out in a CAT24 pressure reactor using diluted oxygen (9% in N~2~). ^b^Yields determined by gas chromatography (GC) analysis with mesitylene as an internal standard. ^c^15 mol% catalyst.](ao-2018-00911s_0002){#fig1}

We selected synthetic protocols for catalysts that had previously been reported for the oxidation of alcohols to aldehydes or carboxylic acids under comparable reaction conditions (liquid phase, mild temperatures). Variables that were evaluated in these syntheses included the reducing agent, support, and metal co-catalyst. The details concerning the syntheses of these catalysts and characterization of the best performing catalyst are provided in section 2 of the [Supporting Information](http://pubs.acs.org/doi/suppl/10.1021/acsomega.8b00911/suppl_file/ao8b00911_si_001.pdf).

The best catalyst that emerged from these initial efforts was Pt supported on graphite oxide (GO) prepared by the polyol method.^[@ref8]^ Reduction of chloroplatinic acid by ethylene glycol consistently led to more active catalysts than reduction with NaBH~4~, as has been observed in other studies and attributed to the reduced particle size associated with this method.^[@ref8]^ Different yields with Pt/Al~2~O~3~ in parts (A) and (B) reflect the difference between the commercial and synthesized catalysts, respectively. Carbon supports proved to be more effective than metal oxide supports, and among carbon supports, GO led to the highest activity. Incorporation of other metals, such as Ru, Au, and Co, generally reduced the activity. Quantitative conversion to **3a** was achieved in 7 h under the conditions with a catalyst loading of 2.5 mol%. Experiments using aqueous or anhydrous ammonia showed similar catalytic trends. Addition of water (up to 5 equiv) to reactions with anhydrous ammonia showed no inhibition from the water, establishing that either ammonia source could be used.

The new Pt/GO catalyst was tested with diverse substrates to assess the reaction scope and limitations ([Table [1](#tbl1){ref-type="other"}](#tbl1){ref-type="other"}). Primary benzylic alcohols with a variety of substituents reacted to afford the corresponding nitriles in good to excellent yields. Electron-donating and electron-withdrawing groups, ranging from −OMe to −CF~3~, were all well-tolerated in the reactions, and the method was compatible with aryl chlorides and bromides. The catalyst was not effective with aliphatic alcohols, such as cyclohexylmethanol and 1-octanol, and exhibited only moderate activity with several heteroaromatic alcohols, as shown in [Table [2](#tbl2){ref-type="other"}](#tbl2){ref-type="other"}. The low activity with heterocycles, which represent an important motif in industrial nitrile-containing molecules, prompted us to probe the mechanism of the reaction.

###### Substrate Scope of Pt-Catalyzed Aerobic Oxidation of Alcohols to Nitriles[a](#t1fn1){ref-type="table-fn"}

![](ao-2018-00911s_0007){#GRAPHIC-d94e326-autogenerated}

![](ao-2018-00911s_0008){#gr6}

Conditions: **1** (0.3 mmol) and Pt on GO in CH~3~CN (1.5 mL) at 90 °C for 20 h. Reactions carried out in a Parr pressure reactor with NH~3~ and diluted oxygen (9% in N~2~). Yield determined by GC analysis or by ^1^H NMR spectroscopy with mesitylene as an internal standard. Isolated yields in parentheses.

###### Problematic Substrates for Pt-Catalyzed Aerobic Oxidation of Alcohols to Nitriles

![](ao-2018-00911s_0009){#gr7}

When the reaction progress was monitored, relatively little build-up of aldehyde was observed ([Figure [2](#fig2){ref-type="fig"}](#fig2){ref-type="fig"}), suggesting that the aldehyde is relatively rapidly converted to the nitrile. A time course for the reaction of benzyl alcohol **1a** was modeled as a first-order series reaction in which the oxidation of the alcohol to the aldehyde is the first step and the oxidation of the aldehyde to the nitrile the second step. A discrepancy between a pure first-order series model and the experimental data indicates modest deactivation, which is fit well by a model (provided in section 3 of the [Supporting Information](http://pubs.acs.org/doi/suppl/10.1021/acsomega.8b00911/suppl_file/ao8b00911_si_001.pdf)) relating the slow decay in catalyst activity to aldehyde exposure. The fit yielded a *k*~1~ of 0.46 h^--1^ and a *k*~2~ of 5.7 h^--1^.

![Time course of Pt-catalyzed nitrile formation. Fit reflects a first-order reaction model with concomitant catalyst deactivation (see section 3 of the [Supporting Information](http://pubs.acs.org/doi/suppl/10.1021/acsomega.8b00911/suppl_file/ao8b00911_si_001.pdf)). Conditions: **1a** = 0.2 M, Pt/GO = 2 mol%, 5 atm NH~3~, 3 atm O~2~ (9% in N~2~), 90 °C, MeCN. Reactions carried out in a Parr pressure reactor. Yields determined by GC analysis with mesitylene as an internal standard.](ao-2018-00911s_0003){#fig2}

We then examined whether the excess ammonia could be inhibiting the alcohol oxidation. Ammonia has been shown to poison Pt catalysts in other contexts, for example, as a trace contaminant in fuel cells.^[@ref9]^ A time profile complementary to the one in [Figure [2](#fig2){ref-type="fig"}](#fig2){ref-type="fig"} was completed in the absence of ammonia, with the aldehyde as the final product ([Figure [3](#fig3){ref-type="fig"}](#fig3){ref-type="fig"}). Alcohol oxidation was nearly 6 times slower in the absence of ammonia, exhibiting a *k*~1~ of 0.08 h^--1^, thus indicating that ammonia instead promotes the alcohol oxidation reaction.

![Time course of alcohol oxidation in the presence and absence of NH~3~, leading to nitrile and aldehyde final products, respectively. Fit reflects a first-order reaction model with concomitant catalyst deactivation (see section 3 of the [Supporting Information](http://pubs.acs.org/doi/suppl/10.1021/acsomega.8b00911/suppl_file/ao8b00911_si_001.pdf)). Conditions: **1a** = 0.2 M, Pt = 2 mol%, 3 atm O~2~ (9% in N~2~), 90 °C, MeCN. 5 atm NH~3~ for nitrile formation reaction. Yields determined by GC analysis with mesitylene as an internal standard.](ao-2018-00911s_0004){#fig3}

Higher alcohol conversion in the presence of other nitrogen-containing bases suggested that ammonia could function as a base as well as a coupling partner ([Table [3](#tbl3){ref-type="other"}](#tbl3){ref-type="other"}). Pt-catalyzed oxidation of benzyl alcohol to aldehyde in the absence of any additives afforded only 21% alcohol conversion after 2 h (entry 1). NH~3~ addition doubled the alcohol conversion, with the product consisting of both aldehyde and nitrile (entry 2). Other amine bases, such as quinuclidine (entry 3) and DABCO (entry 5), also significantly increased the alcohol conversion beyond that of the base-free conditions. Though the addition of triethylamine (entry 4) lowered alcohol conversion, the results in [Table [3](#tbl3){ref-type="other"}](#tbl3){ref-type="other"} show that amine additives do not necessarily inhibit activity by coordinating to the Pt. The positive effect of the basic additive is attributed to promotion of alcohol deprotonation.

###### Impact of Nitrogen Bases on Pt-Catalyzed Aerobic Oxidation of Alcohols[a](#t3fn1){ref-type="table-fn"}

![](ao-2018-00911s_0010){#GRAPHIC-d94e474-autogenerated}

![](ao-2018-00911s_0011){#gr8}

Conditions: **1a** (0.3 mmol), base, and Pt/GO in CH~3~CN at 90 °C for 2 h. Reactions carried out in a Parr pressure reactor with diluted oxygen (9% in N~2~).

p*K*~a~ of protonated nitrogen.

Yields determined by GC analysis with mesitylene as an internal standard. Alcohol conversion encompasses aldehyde (and nitrile, for NH~3~) formation.

5 atm NH~3~.

0.3 atm NH~3~.

K~2~CO~3~ was also tested as a basic additive and found to enable near-quantitative conversion of the alcohol to the aldehyde (entry 6).^[@cit2a]^ This result motivated the inclusion of K~2~CO~3~ in the nitrile reaction, and addition of 2 mol% K~2~CO~3~ to the Pt catalyst increased benzyl alcohol conversion after 2 h from 34 to 65% (see Table S1 in the [Supporting Information](http://pubs.acs.org/doi/suppl/10.1021/acsomega.8b00911/suppl_file/ao8b00911_si_001.pdf) for optimization of the K~2~CO~3~ loading for nitrile formation). K~2~CO~3~ was then tested as an additive in the reaction of more challenging alcohols, such as heterocycle **1o**, and the yield of the nitrile improved to 44% ([Table [4](#tbl4){ref-type="other"}](#tbl4){ref-type="other"}, entries 1 and 2; cf. [Table [2](#tbl2){ref-type="other"}](#tbl2){ref-type="other"}).

###### Improved Heterocycle Yields with K~2~CO~3~ and Bi[a](#t4fn1){ref-type="table-fn"}

![](ao-2018-00911s_0012){#GRAPHIC-d94e588-autogenerated}

  entry                                    additive (%)                                     K~2~CO~3~ (%)   yield (%)[b](#t4fn2){ref-type="table-fn"}
  ---------------------------------------- ------------------------------------------------ --------------- -------------------------------------------
  1                                        −                                                −               18
  2                                        −                                                2               44
  3                                        Bi(NO~3~)~3~ (0.5)                               2               71
  4                                        Bi(NO~3~)~3~ (1)                                 2               71
  5                                        Bi(NO~3~)~3~ (2.5)                               2               68
  6                                        Bi (1)                                           2               41
  7                                        BiCl~3~ (1)                                      2               43
  8                                        PtBi~0.4~                                        2               25
  9                                        PtBi~0.3~ (JM)[c](#t4fn3){ref-type="table-fn"}   2               51
  **10**[d](#t4fn4){ref-type="table-fn"}   **Bi(NO**~**3**~**)**~**3**~**(3.5)**            **2.8**         **91**
  11                                       Fe(NO~3~)~3~ (1)                                 2               42
  12                                       Pb(NO~3~)~2~ (1)                                 2               59
  13                                       PtPb~0.4~                                        2               37

Conditions: **1o** (0.3 mmol), K~2~CO~3~, additive, and Pt in CH~3~CN at 90 °C for 20 h. Reactions carried out in a Parr pressure reactor with NH~3~ and diluted oxygen (9% in N~2~).

Yields determined by ^1^H NMR spectroscopy with mesitylene as an internal standard.

Research sample of 5 wt% Pt--1.5 wt% Bi/C (PtBi~0.3~) from Johnson Matthey.

3.5 mol% Pt.

In an effort to enhance the activity of the platinum catalyst further, we considered the incorporation of main group-element promoters, such as Bi and Pb. Main group elements and other metals have found widespread use as promoters in heterogeneous catalysis with platinum group metals, and Bi has been used frequently in alcohol oxidation.^[@ref2],[@ref10]^ Common explanations for the role of Bi in promoting Pt- and Pd-catalyzed alcohol oxidation include prevention of over-oxidation of the metal surface, creation of new sites for productive catalysis, and site-blocking to prevent side reactions that could poison the catalyst (e.g. decarbonylation). Recent studies in our lab have highlighted the utility of heterogeneous "admixture" catalysts, in which the promoter may be simply added as a salt to the reaction mixture containing the supported metal catalyst (e.g., Pd/charcoal and Pt/C).^[@ref11]^ Building on these and related precedents,^[@ref12]^ Bi(NO~3~)~3~ was included in the reaction mixture. Addition of Bi(NO~3~)~3~ in a 1:5 ratio relative to Pt, in addition to K~2~CO~3~, raised the nitrile yield to 71% (entry 3). Further increases of the amount of Bi(NO~3~)~3~ did not impact the nitrile yield (entries 4 and 5). Different Bi precursors have been shown to influence catalyst activity in other alcohol oxidations,^[@ref13]^ but Bi metal and BiCl~3~ were not effective in the present reaction (entries 6 and 7).

A well-defined PtBi catalyst was also prepared via the reduction of Bi(NO~3~)~3~ onto a Pt catalyst. This catalyst exhibited inferior results (entry 8), as did a similar catalyst from Johnson Matthey (entry 9). Increasing the Pt to 3.5 mol% (a 40% change in loading) with a concomitant increase in the Bi and K~2~CO~3~ to maintain the relative ratios in entry 5, enabled an excellent yield of product (91%, entry 10). A nitrate salt with Fe exhibited a low yield (entry 11). However, a nitrate salt containing Pb, another known Pt promoter, did increase the yield (entry 12). Similar to the well-defined PtBi~0.4~ case, a PtPb~0.4~ catalyst (entry 13) exhibited inferior results to the admixture catalyst (entry 12).

The promotional effect of the Bi and base was probed with other molecules that afforded low yields with the unpromoted Pt catalyst. The incorporation of base and Bi increased the yield of **3m** from 53 to 93% ([Table [5](#tbl5){ref-type="other"}](#tbl5){ref-type="other"}). Significantly improved yields were also observed with **3n** (81%) and **3p** (86%). The new catalyst system also afforded improved yields with halogen-containing benzyl alcohols, and the utility of this method was demonstrated in a 1 g-scale oxidative coupling with **1h**, which afforded 4-fluorobenzonitrile **3h** in 96% yield ([eq [1](#eq1){ref-type="disp-formula"}](#eq1){ref-type="disp-formula"}).

###### Nitrile Yields under Original (A) and Improved (B) Conditions[a](#t5fn1){ref-type="table-fn"}

![](ao-2018-00911s_0013){#GRAPHIC-d94e934-autogenerated}

![](ao-2018-00911s_0014){#gr9}

Conditions: \[substrate\] = 0.2 M, 1 atm NH~3~, 3 atm O~2~ (9% in N~2~), MeCN, 90 °C, 20 h. Yields determined by GC analysis or ^1^H NMR spectroscopy with mesitylene as an internal standard.

70 °C (to avoid side reactions).

In conclusion, we have demonstrated that carbon-supported Pt nanoparticles can mediate the one-pot aerobic oxidation of alcohols to nitriles. The Pt catalyst itself enables effective conversion of many benzylic alcohols to the corresponding benzonitriles, but addition of K~2~CO~3~ and Bi significantly improves the catalytic performance with heterocycle-containing substrates. This work illustrates the broad utility of Pt in four-electron coupling reactions, as well as the ease with which its activity may be modified via the use of promoter metals.

Experimental Section {#sec3}
====================

General Information {#sec3.1}
-------------------

All commercially available compounds and solvents were purchased and used as received, unless otherwise noted. No precautions were taken to exclude air or water from the solvent or reaction mixtures. ^1^H and ^13^C NMR spectra were recorded on a Bruker AVANCE III 400 or Bruker AVANCE III 500 spectrometer. Chemical shift values are given in parts per million relative to internal tetramethylsilane (0.00 ppm for ^1^H) or CDCl~3~ (77.16 ppm for ^13^C). The following abbreviations were used to describe peak splitting patterns when appropriate: s = singlet, d = doublet, m = multiplet, dd = doublet of doublets. Coupling constants, *J*, were reported in hertz (Hz). Analytical thin layer chromatography (TLC) was performed on precoated silica gel 60 F254 plates. Visualization on TLC was achieved by the use of UV light (254 nm). Flash chromatography was performed on an Isco Combiflash system using SiliaFlash P60 (Silicycle, particle size 40--63 μm, 230--400 mesh).

Procedure for Batch Oxidation of Alcohols in a CAT24 Pressure Reactor {#sec3.2}
---------------------------------------------------------------------

Solutions of alcohol (0.25 mmol), mesitylene (25 mol%) as an internal standard, and aqueous NH~3~ (3 equiv) in acetonitrile (0.5 mL) were added to thick-walled glass tubes containing the platinum catalyst (1 mol% or 4.9 mg for 10 wt% metal loading). The tubes were inserted into the wells of an HEL CAT24 unit, and the reactor was sealed and pressurized to 31 atm with premixed gas consisting of 9% O~2~ in N~2~ (for an O~2~ pressure of 3 atm). The reactor was agitated using a custom vortexer at 90 °C for 7 h. Afterward, the reactor was cooled to \<40 °C. Each reaction mixture was then filtered through a pipette containing celite and glass wool and analyzed by GC to determine the product concentration.

Procedure for Batch Oxidation of Alcohols in a Parr Pressure Reactor {#sec3.3}
--------------------------------------------------------------------

A solution of alcohol (0.3 mmol) and mesitylene (25 mol%), as an internal standard, in acetonitrile (1.5 mL) was added to a 40 mL stainless steel Parr pressure vessel containing the platinum catalyst (2.5 mol% or 14.6 mg for 10 wt% metal loading). For the enhanced reaction conditions, 1 mol% Bi (2 mg based on Bi(NO~3~)~3~·5H~2~O) and 2 mol% K~2~CO~3~ (0.8 mg) were added. The Parr vessel was sealed and pressurized to 1 atm with anhydrous NH~3~ and then pressurized to 32 atm with premixed gas consisting of 9% O~2~ in N~2~ (for an O~2~ pressure of 3 atm). The mixture was stirred with a 1/4 in. rectangular stir bar, heated to 90 °C, and reacted for 20 h. Upon completion, the reactor was allowed to cool down to \<40 °C. The reaction mixture was then filtered through a pipette containing celite and glass wool and analyzed by GC to determine the product concentration.

Procedure for the Scale-Up Reaction {#sec3.4}
-----------------------------------

An 8 mL solution containing 1 g of **1h** (1 M) in acetonitrile was added to a 40 mL stainless steel Parr pressure vessel containing the catalyst components. The catalyst consisted of 3.5 mol% Pt (546 mg for 10 wt% metal loading), 1.4 mol% Bi (54.5 mg based on Bi(NO~3~)~3~·5H~2~O), and 2.8 mol% K~2~CO~3~ (31 mg) relative to the alcohol. Given the greater quantity of alcohol, the Parr vessel was sealed and pressurized to 6 atm with anhydrous NH~3~ and then pressurized to 37 atm with premixed gas consisting of 9% O~2~ in N~2~ (for an O~2~ pressure of 3 atm). The mixture was stirred with a 1/4 in. rectangular stir bar, heated to 90 °C, and reacted for 20 h. Upon completion, the reactor was allowed to cool down to \<40 °C.

GC Method and Retention Times {#sec3.5}
-----------------------------

GC analyses were performed using a DB-Wax column (length = 30 m, i.d. = 0.25 mm) installed in a Shimadzu GC-17A equipped with a flame-ionization detector. A 14 min GC method consisted of a 1 min hold at 70 °C, ramp at 20 °C/min from 70 to 200 °C (6.5 min), and a 3.5 min hold at 200 °C. The injector and the detector were held at 225 °C, and the column flow was 1.5 mL/min of He with a split ratio of 20. Retention times were as follows: mesitylene (3.78 min), benzyl alcohol **1a** (8.05 min)/benzaldehyde **2a** (5.76 min)/benzonitrile **3a** (6.30 min), 4-methylbenzyl alcohol **1b** (8.34 min)/4-methylbenzonitrile **3b** (7.05 min), 4-methoxybenzyl alcohol **1e** (11.78 min)/4-methoxybenzonitrile **3e** (9.60 min), 4-chlorobenzyl alcohol **1i** (10.65 min)/4-chlorobenzonitrile **3i** (7.74 min), 4-bromobenzyl alcohol **1j** (12.97 min)/4-bromobenzonitrile **3j** (8.80 min), 2-bromobenzyl alcohol **1k** (11.62 min)/2-bromobenzonitrile **3k** (9.42 min), 4-(trifluoromethyl)benzyl alcohol **1l** (8.15 min)/4-(trifluoromethyl)benzonitrile **3l** (5.57 min).

Another GC method consisted of a 1 min hold at 70 °C, ramp at 6 °C/min from 70 to 200 °C (22.5 min), and a 6.5 min hold at 200 °C. Retention times were as follows: 3-thiophenemethanol **1m** (14.59 min)/3-thiophenecarbonitrile **3m** (17.75 min), 6-methyl-2-pyridinemethanol **1n** (16.31 min)/6-methyl-2-pyridinecarbonitrile **3n** (17.04 min).

NMR Characterization {#sec3.6}
--------------------

For crude reaction mixtures analyzed by ^1^H NMR spectroscopy (**3c**, **3d**, **3f**, **3g**, **3h**, **3o**, **3p**), 3 mL of CDCl~3~ was added to the reactor upon completion of the reaction. An aliquot of the reaction mixture was transferred to an NMR tube, and the tube was centrifuged to settle the solid catalyst prior to analysis.

Isolation {#sec3.7}
---------

For collection of the isolated product, the catalyst was filtered off and washed with ethyl acetate. The filtrate was concentrated in vacuo and the corresponding nitrile was purified by column chromatography (silica; hexanes--ethyl acetate mixture). The appropriate solvent ratio was identified by TLC. The chromatography solvents were removed in vacuo to afford the isolated nitrile. Spectral properties of all products are consistent with the literature values.

Isolated yields are shown below. To facilitate isolation, the reactions were performed on a 4 mL scale (instead of the 1.5 mL scale noted in [Table [1](#tbl1){ref-type="other"}](#tbl1){ref-type="other"}). The NH~3~ pressure was increased to 3 atm given the larger scale.

4-Methylbenzonitrile (**3b**, 88%); ^1^H NMR (400 MHz, CDCl~3~): δ 7.52 (d, *J* = 8.1 Hz, 2H), 7.26 (d, *J* = 8.0 Hz, 2H), 2.41 (s, 3H); ^13^C NMR (125 MHz, CDCl~3~): δ 143.73, 132.01, 129.84, 119.16, 109.25, 21.82.

4-Methoxybenzonitrile (**3e**, 95%); ^1^H NMR (400 MHz, CDCl~3~): δ 7.58 (d, *J* = 8.9 Hz, 2H), 6.95 (d, *J* = 8.8 Hz, 2H), 3.86 (s, 3H); ^13^C NMR (100 MHz, CDCl~3~): δ 162.91, 134.05, 119.32, 114.83, 103.99, 55.63.

4-Bromobenzonitrile (**3j**, 80%); ^1^H NMR (400 MHz, CDCl~3~): δ 7.64 (d, *J* = 8.5 Hz, 2H), 7.53 (d, *J* = 8.5 Hz, 2H); ^13^C NMR (100 MHz, CDCl~3~): δ 133.51, 132.74, 128.12, 118.16, 111.32.

4-Fluorobenzonitrile scale-up (**3h**, 96%); ^1^H NMR (400 MHz, CDCl~3~): δ 7.68 (dd, *J* = 8.8, 5.1 Hz, 2H), 7.26--7.06 (m, 2H); ^13^C NMR (100 MHz, CDCl~3~): δ 165.14, 134.79, 118.15, 116.97, 108.63.

The Supporting Information is available free of charge on the [ACS Publications website](http://pubs.acs.org) at DOI: [10.1021/acsomega.8b00911](http://pubs.acs.org/doi/abs/10.1021/acsomega.8b00911).Additional experimental data; pressure reactor comparison; catalyst synthesis and characterization; kinetic modeling; base dependence; and test of commercial catalyst promotion ([PDF](http://pubs.acs.org/doi/suppl/10.1021/acsomega.8b00911/suppl_file/ao8b00911_si_001.pdf))

Supplementary Material
======================

###### 

ao8b00911_si_001.pdf

The authors declare no competing financial interest.

We are grateful to The Dow Chemical Company for financial support of this work and Johnson Matthey for providing a research sample of the PtBi catalyst used in Table 4, entry 9. NMR spectroscopy facilities were partially supported by the NSF (CHE-1048642). Funding for transmission electron microscopy was supplied by the NSF (DMR-1121288) through the University of Wisconsin Materials Research Science and Engineering Center.